Gleb Oleinik is a freelance health writer from Vancouver, Canada. He’s read thousands of research studies about CBD and other supplement ingredients, allowing him to translate complex scientific information into plain language. Gleb is knowledgeable about the ins and outs of the CBD industry and the science behind this popular natural remedy. When he’s not writing, Gleb likes to spend his time traveling, kickboxing, and telling people how awesome intermittent fasting is.
CBD And THC: What's The Difference?
Most people are familiar with THC and CBD: the two main active components of cannabis. They belong to a class of natural compounds called cannabinoids, which interact with your body’s endocannabinoid system. THC is best known for its psychoactive effects and is largely responsible for the marijuana high. Meanwhile, CBD is the most abundant cannabinoid in hemp: a variety of cannabis with extremely low THC levels. Unlike its psychoactive cousin, CBD is completely non-intoxicating. However, the two also differ in many other ways. Here’s everything you need to know about CBD and THC and what sets them apart. Difference Between CBD and THC Aside from intoxication, CBD and THC are also different in their effects, uses, benefits, side effects, plant sources, legality, and product forms. CBD vs THC Effects CBD and THC have the same chemical formula (C21H30O2), but their atoms are arranged differently, so they affect the body in different ways. Since they’re similar in structure to your body’s own endocannabinoids, this allows CBD and THC to interact with endocannabinoid system receptors. THC binds directly to these receptors, producing the characteristic cannabis high and activating various biological pathways linked to your endocannabinoid system. CBD affects your endocannabinoid system differently. It doesn’t bind to cannabinoid receptors but influences their function instead (1). More importantly, it increases the levels of the endocannabinoids produced by your own body (2). CBD vs THC Uses THC can be used both medically and recreationally in the form of whole-plant cannabis or prescription drugs. The medication can contain THC alone or include other cannabis compounds. Although CBD is also present in whole-plant cannabis preparations, it’s mostly used in the form of CBD oil and other dietary supplements CBD vs. THC Health Benefits CBD and THC have many potential health benefits. Some of these are similar, while others are unique to each cannabinoid. Both CBD and THC are used to relieve pain, inflammation, nausea, anxiety, and sleep issues, with a growing volume of research evidence backing these effects (3, 4, 5). However, whereas CBD’s anxiety-relieving properties are well-documented, THC seems to either lower or increase anxiety depending on the dosage, person, and other factors (6, 7). Studies suggest that CBD may also help with other issues such as seizures. In particular, there is strong evidence that CBD relieves epileptic seizures, and the FDA recently approved the drug Epidiolex — the only prescription medication containing pure CBD — for treating rare types of epilepsy. Meanwhile, ongoing research suggests that THC may be an option to temporarily reduce eye pressure in glaucoma patients and stimulate appetite in people suffering from weight loss caused by chronic health disorders such as cancer (5, 8). CBD vs. THC Side Effects THC and CBD can cause adverse effects, but they’re not quite the same. THC is best known for its psychoactive side effects, which include anxiety, paranoia, euphoria, and impaired memory, and reaction time. It can also cause red eyes, increased heart rate, dry mouth, sleepiness, and dizziness. CBD doesn’t have any mind-altering effects but may cause low blood pressure (hypotension), diarrhea, dry mouth, lightheadedness, and sleepiness. However, medical studies looking at the benefits of CBD for individuals suffering from epilepsy and psychotic disorders suggest that these side effects are not consistent across populations and may be considered mild, especially when compared to other drugs that are used to treat similar conditions. (9). CBD vs. THC: The High As noted earlier, the biggest difference between CBD and THC is that the latter causes intoxication. CBD, on the other hand, cannot make you high. In fact, research suggests that CBD counteracts THC’s psychoactivity by indirectly preventing it from binding to your body’s cannabinoid receptors (10). This may explain why cannabis strains with higher CBD levels are not as intoxicating. CBD vs. THC Sources Another major difference between CBD and THC is in how they’re sourced. Cannabis plants come in two main varieties: marijuana and hemp. Most THC products are made from marijuana, which is high in THC. Conversely, most CBD products are extracted from hemp, a variety of cannabis with high CBD but extremely low (<0.3%) THC levels. CBD vs. THC Legality The 2018 Farm Bill made hemp and hemp-derived products such as CBD oil legal at the federal level in the United States. Hemp is also legal in many other countries because it doesn’t contain enough THC to cause intoxication. Marijuana and THC, on the other hand, are illegal in the U.S. at the federal level and in most places around the world because of their potential psychoactive effects. This means that any CBD products made from marijuana plants are also illegal. However, many American states allow access to marijuana for medical reasons and some have even completely legalized it for recreational use. CBD vs. THC Product Forms CBD and THC can also differ in the kind of products they appear in. THC is most commonly used in the form of dried, whole-plant cannabis which also contains smaller amounts of CBD. Meanwhile, most people use CBD in the form of CBD oil, which can either have pure CBD or whole-plant extract providing the full range of cannabinoids, terpenes, and other active compounds found in hemp. Both THC and CBD can also appear in other whole-plant cannabis preparations such as tinctures, capsules, edibles, and topical products. Furthermore, the two cannabinoids can be used in purified preparations called isolates, which contain only that single cannabinoid. Examples of these isolates include pharmaceutical drugs containing man-made forms of THC to help with nausea and vomiting caused by chemotherapy. The CBD isolate drug Epidiolex is used for treatment-resistant epilepsy. This wide variety of forms means that CBD and THC can be smoked, vaped, eaten, applied to the skin, or used sublingually (under the tongue). CBD vs. THC Chart CBD vs. THC: Main Differences CBD THC Source Usually extracted from hemp Usually extracted from marijuana Can make you high No Yes Uses Used as a dietary supplement and medical products Used in recreational and medical products Benefits Some similar and some unique benefits Some similar and some unique benefits Legality Legal in the U.S. and many other countries Illegal in most U.S. states and most countries Side effects Minor side effects Psychoactive side effects Most common product form CBD oil Dried, whole-plant cannabis, and THC-only drugs Summing Up CBD and THC are different in many ways. Most importantly, hemp-derived CBD products are legal and don’t make you high, whereas THC is a controlled substance because of its intoxicating effects. Consequently, CBD oil and similar products are growing increasingly popular as a way to enjoy the benefits of cannabis without the mind-altering effects. Still, the beneficial effects of THC should not be overlooked. And as shown by research, THC, CBD, and other cannabis-derived compounds work best in combination. References Chung, Hery, Angelica Fierro, and C. David Pessoa-Mahana. "Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study." PloS one 14.7 (2019). Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94. Nagarkatti, Prakash, et al. "Cannabinoids as novel anti-inflammatory drugs." Future medicinal chemistry 1.7 (2009): 1333-1349. Vu?kovi?, Sonja, et al. "Cannabinoids and pain: new insights from old molecules." Frontiers in pharmacology 9 (2018): 1259. Abrams, Donald I. "The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report." European journal of internal medicine 49 (2018): 7-11. Blessing, Esther M., et al. "Cannabidiol as a potential treatment for anxiety disorders." Neurotherapeutics 12.4 (2015): 825-836. Viveros, M. P., Eva M. Marco, and Sandra E. File. "Endocannabinoid system and stress and anxiety responses." Pharmacology Biochemistry and Behavior 81.2 (2005): 331-342. Bridgeman, Mary Barna, and Daniel T. Abazia. "Medicinal cannabis: history, pharmacology, and implications for the acute care setting." Pharmacy and Therapeutics 42.3 (2017): 180. Iffland, Kerstin, and Franjo Grotenhermen. "An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies." Cannabis and cannabinoid research 2.1 (2017): 139-154. Niesink, Raymond JM, and Margriet W. van Laar. "Does cannabidiol protect against adverse psychological effects of THC?." Frontiers in psychiatry 4 (2013): 130.
How Much CBD Should I Take? CBD Dosage Guide
The list of health benefits associated with CBD use continues to grow, but knowing exactly how much to take for specific ailments can be a challenge. In many cases, we end up relying on the advice of a friend or even just our own best guess when in fact we may be taking far too much or far too little CBD. To complicate matters even further, CBD does not have a recommended daily intake from the FDA unlike other supplements out there, so appropriate dosages can be difficult to determine. While ongoing research aims to shed more light on the benefits and optimal doses of CBD, there is currently no hard and fast rule to determine how much CBD is right for you. However, there are several pieces of information that can help you make an educated decision about your dose. Important CBD Dosage Considerations Each person’s appropriate CBD dose will be different based on their specific body weight, genetics, the severity and type of symptoms, and the specific product they’re using. As a result, it’s difficult to suggest an amount that will work for everyone and there are no official, clinician-backed CBD dosage recommendations at this time. Here’s a closer look at the factors that can affect CBD dosage. Body Weight Bodyweight can have a significant effect on the optimal dosage for many medications,1 and CBD is no different. Generally speaking, people who weigh more will need to take more CBD to feel the same effects as someone of a lower weight. For an average dose of CBD, the general rule of thumb is to add 3mg of CBD for every 10 pounds you weigh (or 1mg for every kilogram). Here’s a table showing the average CBD doses that can be taken by people of specific bodyweight. Keep in mind these are just general recommendations. General CBD Doses by Body Weight Body Weight (lbs) Average CBD dose (mg) 100 lbs 30 mg 125 lbs 38 mg 150 lbs 45 mg 175 lbs 52 mg 200 lbs 60 mg 225 lbs 67 mg 250 lbs 75 mg CBD Genetics Your specific body chemistry plays a big role in how you respond to CBD and other cannabinoids. One helpful comparison is to think of caffeine. Some people can drink coffee regularly and have few side effects. Others will get anxious and jittery from a single cup. Similarly, your unique genetics can make you either more or less responsive to the effects of CBD. The key genetic factor in how your body responds to CBD is your unique set of genes that give rise to your endocannabinoid system (ECS). This includes the genes behind your cannabinoid receptors, endocannabinoids, and special enzymes involved in the ECS. For example, research shows that some people have a genetic variation that leads to suppressed activity of FAAH, which is the enzyme that breaks down the endocannabinoid anandamide.2 As a result, they tend to have higher anandamide levels than people without that specific gene variant. As it happens, CBD also reduces the activity of the FAAH enzyme and increases anandamide levels.3 This means that individuals with this specific genetic variation may be less responsive to the effects of CBD and require larger doses to notice any effects beyond those attributed to their naturally higher anandamide levels. On the flip side, if research determines that the effects of CBD are additive, it could mean the opposite, where those individuals may be more sensitive to CBD since their already higher levels of anandamide may be exacerbated with CBD use. But that’s far from the only possible genetic difference. The gene for FAAH alone can have 30 variations.4 Meanwhile, the genes that control your two cannabinoid receptors — CB1 and CB2 — can also come in dozens of variations. These differences can also affect how your body responds to CBD. In short, many genetic factors can influence your sensitivity to CBD. As a result, a dose that works for one person could be insufficient for someone else. Your Symptoms and Their Severity Another major determining factor for CBD dosage is the medical condition or symptoms for which you’re trying to find relief. For starters, clinical trials and treatment plans for certain serious conditions such as Parkinson’s disease, Huntington’s disease, schizophrenia, and some cancers, are using much higher doses compared to general-use doses. 5 6 17 On the other hand, a healthy individual taking CBD to support their overall health and wellness will generally require smaller doses. The severity of your symptoms plays a role as well. For instance, someone experiencing mild, occasional anxiety, may require lower CBD doses than a person with a diagnosed anxiety condition such as post-traumatic stress disorder (PTSD). Similarly, a person suffering from severe chronic pain from fibromyalgia or another serious condition will likely need to consult a doctor for an appropriate treatment plan. That plan may then be complemented by CBD use with a “start low and go slow” approach to increasing the dose. Whereas the dose and approach to relieve exercise-induced muscle pain and soreness may different. The bottom line is that the severity and type of issue you hope to relieve will have an impact on the correct dosing for you. Type of CBD Product Even after we account for all of the above factors, the concentration, formulation, and way you take a CBD product will also affect how much you should take. CBD Concentration Concentration refers to the amount of CBD (in milligrams) present in one ml of CBD oil, one capsule, one gummy, or another type of product. Also known as potency, concentration is a major factor in determining your ideal CBD dosage. For example, let’s take two 30 ml bottles of CBD oil: one contains 600 mg of CBD, while the other has 1200 mg. Taking one ml (one full dropper) of the second oil will produce much stronger effects because its concentration is twice as high — 40 mg of CBD per one ml versus only 20 mg. This means you’ll need to take smaller amounts of it to achieve the same results. Similarly, a gummy containing 20 mg of CBD is much stronger than one with only 5 mg. The amount of CBD within a product will usually be listed on the label. But if it’s not, simply divide the total amount of CBD by the volume. Many CBD brands also label their products as having low, medium, or high strength. Although it’s always best to check (or calculate) the exact CBD concentration yourself, this information can also help you figure out the ideal dosage and product for yourself. CBD Extract Type Another crucial factor in determining dosage is the type of CBD extract in your product. There are three main kinds of CBD: isolate, full-spectrum, and broad-spectrum. CBD isolate is pure CBD, whereas full-spectrum preparations provide the full range of cannabinoids, terpenes, and other active hemp compounds found in the plant. Broad-spectrum CBD is similar to full-spectrum, except for completely removing THC. Preliminary research on CBD use for treating seizures in certain epileptic populations suggest that CBD-rich Cannabis extracts are more potent and have a better safety profile (but not higher efficacy) than products with purified CBD. Researchers speculate that this may be attributed to the synergy between the plant’s many components— the so-called “entourage effect.”7 18 This means you may need to take higher doses of CBD isolate to experience the same effects as an equal dose of a full-spectrum product. On top of that, research suggests that taking more than a certain amount of CBD isolate will result in reduced effects, whereas full-spectrum CBD was shown to provide stronger effects even at higher dosages.8 CBD Delivery Method Last but not least, you have to consider how you’re taking the CBD. There are four main ways: sublingual (under the tongue), inhalation, ingestion (oral), and topical. Each of these methods varies in absorption, which not only affects the dosage but also the duration and onset of the effects. Of these options, inhaling CBD through vaping or smoking tends to have the highest bioavailability, which is a measure of the portion of CBD you take that actually reaches your bloodstream.9 The effects of vaping CBD are also instantaneous and last for only about one hour. The sublingual method used by CBD oil tinctures, where the oil is held under the tongue and allowed to absorb directly into the blood vessels, also allows for efficient absorption. However, it takes about 10-30 minutes to kick in and the effects can last for about four hours. Meanwhile, ingested (oral) CBD products such as capsules, gummies, and other edibles tend to have the lowest absorption because they have to get through the digestive tract and liver before the CBD is distributed into the blood, a phenomenon known as first-pass metabolism.10 Estimates of their bioavailability range from 13% to 19%.11 Ingested CBD also takes the longest time to be felt — anywhere from 30 minutes to over an hour — depending on when and how much you ate. However, the effects can last upwards of six hours. Finally, topical CBD products applied to the skin, such as creams and balms, vary in their absorption and effects. Except for transdermal patches, topical products have fairly low absorption and their effects can last for many hours. Topicals are great for those who struggle with muscle and joint pain or related conditions, such as arthritis. General CBD Dosing Guidelines As we can see, there are many factors to consider when figuring out the optimal CBD dosage. That’s why the best option is to consult your doctor before using CBD for the first time. It’s also helpful to know that most people take 20–50 mg doses of CBD one or two times daily. Aside from that, the most popular and safe method of figuring out the best CBD dosage for yourself is to start with a small dose (10–15 mg) and see how you feel. If that’s not enough, you can either take a bigger dose a few hours later or experiment with taking the same dose for a few days before increasing it. Use this method to gradually increase the CBD dosage until you find the amount that provides you with relief. Keep in mind that the effects of CBD are not always apparent right away; it may take you a few days or even weeks of taking it to notice an effect. Suggested CBD Product Doses Another helpful recommendation to be aware of is the dosage suggested by your particular CBD product. Virtually any reputable CBD company will provide a serving size on their product labels. For CBD oil tinctures, this will usually be equivalent to one half or a full dropper. Some products may also have a “suggested use” or a similar section with further instructions. These suggestions can help you figure out your CBD dosage. For example, you can use the serving size and its associated amount of CBD as the starting point for the “start small” method described above. However, you should also keep in mind the concentration of the product. For example, one full dropper of a high-concentration tincture will provide a much higher dose of CBD than a low-strength product. CBD Dosages for Specific Health Conditions Although more research is needed to figure out the optimal CBD dosage for specific symptoms and conditions, there are some early indications. For example, here are the oral dosages used by successful research studies of certain conditions:12 Schizophrenia: 200–1500 mg of CBD daily Certain types of epilepsy and seizures: 5–25 mg/kg body weight daily Dystonia: 100–600 mg daily Social anxiety disorder and insomnia: 150–600 mg daily13 Most of the current high-quality research is restricted to difficult-to-treat conditions such as rare types of epilepsy, which is why there isn’t much evidence for issues such as pain or general anxiety. We can also see that these dosage ranges are not only very broad but also extremely high. This is largely because researchers are using pure CBD and administering it orally (typically as capsules), which isn’t always the best representation of real-world CBD use. The bottom line is that these numbers should only be used to help you gain a better understanding of the kind of CBD doses used for severe symptoms. Can You Take Too Much CBD? CBD is a remarkably safe substance and it’s difficult to use too much of it. Scientific studies have shown that even daily doses as high as 1,500mg of CBD were well-tolerated by humans.14 Studies using high CBD dosages (300 mg and above) have reported only mild side effects, including:15 Tiredness Low blood pressure Lightheadedness Dry Mouth Diarrhea Changes in weight or appetite Reduced activity of CYP450 enzymes Perhaps the most notable of these is the reduction of CYP450 activity. These enzymes metabolize the majority (79%) of drugs people consume,16 including caffeine, NSAIDs (like ibuprofen), antidepressants, and much more. Alterations in CYP450 activity can drastically affect the amount of these substances in your bloodstream, possibly producing unwanted effects. However, keep in mind that these effects have only been reported at high CBD doses. Besides, grapefruit juice and some other substances, such as St. John’s Wort, have equally potent effects on the CYP450 enzyme system, so it’s not anything unheard of or unnatural. As one final tip, be sure to consult your healthcare provider before embarking on any natural products regimen, and take care! Frequently Asked Questions How Much CBD Isolate Should I Take? It depends on many factors, such as the benefit you’re hoping to gain, and how you use the isolate. The main thing to keep in mind is that you’ll have to take higher doses than full-spectrum CBD products because CBD isolate has weaker effects. How Much CBD Should I Take Per Day? As a general guideline, most people take 10–40 mg of CBD once or twice daily. However, the precise amount will depend on your body weight, the type of CBD product you’re using, and other factors. How Much CBD Gummies Should I Take? It depends on the amount of CBD in each gummy, the symptoms you’re trying to address, and other considerations. If you’re new to CBD, it’s best to start with one gummy or follow the dosing recommendations on your product label. References 1. Pan, Sheng-dong, et al. "Weight-based dosing in medication use: what should we know?." Patient preference and adherence 10 (2016): 549. 2. Dincheva, Iva, et al. "FAAH genetic variation enhances fronto-amygdala function in mouse and human." Nature communications 6.1 (2015): 1-9. 3. Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94. 4. https://www.ncbi.nlm.nih.gov/clinvar/?term=faah+%5Bgene%5D 5. Peres, Fernanda F., et al. "Cannabidiol as a promising strategy to treat and prevent movement disorders?." Frontiers in pharmacology 9 (2018): 482. 6. Batalla, Albert, et al. "The potential of cannabidiol as a treatment for psychosis and addiction: who benefits most? A systematic review." Journal of clinical medicine 8.7 (2019): 1058. 7. Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969. 8. Gallily, Ruth, Zhannah Yekhtin, and Lumír Ond?ej Hanuš. "Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol." Pharmacology & Pharmacy 6.02 (2015): 75. 9. Bruni, Natascia, et al. "Cannabinoid delivery systems for pain and inflammation treatment." Molecules 23.10 (2018): 2478. 10. Huestis, Marilyn A. "Human cannabinoid pharmacokinetics." Chemistry & biodiversity 4.8 (2007): 1770. 11. Mechoulam, Raphael, Linda A. Parker, and Ruth Gallily. "Cannabidiol: an overview of some pharmacological aspects." The Journal of Clinical Pharmacology 42.S1 (2002): 11S-19S. 12. Millar, Sophie A., et al. "A systematic review of cannabidiol dosing in clinical populations." British journal of clinical pharmacology 85.9 (2019): 1888-1900. 13. Zhornitsky, Simon, and Stéphane Potvin. "Cannabidiol in humans—the quest for therapeutic targets." Pharmaceuticals 5.5 (2012): 529-552. 14. Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. "en Crippa, JA (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent." Current Drug Safety 6.4: 237-249. 15. Iffland, Kerstin, and Franjo Grotenhermen. "An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies." Cannabis and cannabinoid research 2.1 (2017): 139-154. 16. McDonnell, Anne M., and Cathyyen H. Dang. "Basic review of the cytochrome p450 system." Journal of the advanced practitioner in oncology 4.4 (2013): 263. 17. Corroon, Jamie., Sexton, Michelle., and Bradley, Ryan “Indications and administration practices amongst medical cannabis healthcare providers: a cross-sectional survey.” BMC Family Practice (2019) 18. Pamplona, Fabricio A. et al., “Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.” Frontiers of Neurology (2018)
CBD And The Endocannabinoid System: How Does It Work?
A Comprehensive Guide to the Endocannabinoid System Discovered in the 1990s, the endocannabinoid system (ECS) is one of the major systems of the human body. It has an immense impact on our health by regulating key physiological processes, including: Mood Stress Metabolism Brain function Immune function Pain Sleep In doing so, the ECS helps keep your body in a healthy state of balance. Throughout this article, we’re going to discuss how the ECS works, how CBD affects it, how you can keep it in balance, and why it holds so much promise in improving human health. What Does the Endocannabinoid System Do? The main role of the ECS is maintaining what’s called homeostasis: a state of internal balance. When something upsets this delicate balance, such as stress, injury, or illness, the ECS is activated to help steer things back to normal. A simple way to imagine this is to consider inflammation. Inflammation is our body's natural defense mechanism to help identify and eliminate "harmful" agents, following injury or infection. Ultimately, the inflammatory response eliminates what our body perceives as a harmful agent, removes damaged tissue, and allows the body to begin healing. But too much inflammation is bad for the body and plays a major role in most chronic diseases. The ECS regulates inflammation and many other processes to keep them functioning at just the right level — not too much and not too little. This helps maintain your overall health and well-being. Research suggests that the ECS influences a wide variety of critical processes, including:1 Metabolism, appetite, and digestion Mood, stress, and emotions Memory, learning, neuronal development, and other brain functions Inflammation and other immune system functions Cardiovascular system function Liver function Pain perception Sleep Skin function Thermogenesis and body temperature These findings explain why researchers are excited about the potential therapies targeting the ECS to help with a wide variety of health disorders. How Does the Endocannabinoid System Work? The endocannabinoid system is composed of three major elements: cannabinoid receptors, endocannabinoids, and special enzymes that create and break down these compounds. This biological system is incredibly old, having evolved over 500 million years ago, which is why it's present in many other animals, including mammals, birds, fish, and reptiles.2 Endocannabinoids Cannabinoids are compounds that bind to and activate cannabinoid receptors. THC and CBD from cannabis are not the only cannabinoids out there; the human body also makes its own endogenous cannabinoids, called endocannabinoids (endo meaning “within”). The two main endocannabinoids are called anandamide and 2-arachidonoylglycerol (2-AG). They’re produced by our bodies as needed and broken down shortly after, which is why they were difficult for scientists to discover. Cannabinoid Receptors Receptors are protein molecules found in cells that can interact with specific compounds, producing a variety of biological effects. So far, researchers have identified two main cannabinoid receptors which they named CB1 and CB2. However, further research suggests there are other receptors that could eventually be recognized as part of the ECS, such as GPR55.3 Anandamide and 2-AG can bind to these cannabinoid receptors, influencing a wide variety of biological responses including anxiety and pain perception. Phytocannabinoids (cannabinoids sourced from plants) such as THC can also interact with cannabinoid receptors. Cannabinoid receptors are found in all major body tissues, including the brain, spinal cord, skin, immune cells, bones, fat, liver, pancreas, muscle, heart, blood vessels, kidneys, and the digestive tract. However, CB1 receptors are especially abundant in the brain and other parts of the central nervous system, whereas CB2 is most common in immune system cells and tissues.4 Enzymes The third major component of the ECS are the enzymes that make and break down endocannabinoids. The two most important of these enzymes are monoacylglycerol lipase (MGL), currently thought to break down the majority of 2-AG, and fatty acid amide hydrolase (FAAH), which breaks down anandamide.5 These enzymes help regulate the levels of endocannabinoids in our bodies at a given time and place, which makes sense given the role of the ECS in maintaining a delicate state of balance. How Does THC Affect the Endocannabinoid System? Tetrahydrocannabinol (THC) is the main psychoactive cannabinoid found in cannabis. THC is similar in structure to anandamide and binds mainly to the CB1 receptor. This produces the mind-altering “high” experienced by cannabis users as well as other effects, such as increased appetite and pain relief. THC can also cause some people to feel increased feelings of anxiety or paranoia. The effects of THC last longer than endocannabinoids because it’s not regulated and broken down by ECS enzymes. How Does CBD Affect the Endocannabinoid System? Unlike THC, cannabidiol (CBD) is a non-intoxicating cannabinoid, which means it doesn’t get you high. CBD is also unique because it doesn’t directly bind to cannabinoid receptors. Rather, CBD’s main effect is reducing the activity of FAAH, the enzyme that breaks down the endocannabinoid anandamide. This results in higher anandamide levels, which may be beneficial for some individuals. Research on the potential benefits continues to show promise (e.g., antipsychotic effects for schizophrenic patients). Aside from this, research shows that CBD changes the function of the CB1 receptor,6 which may explain how it counteracts THC’s intoxicating effects. CBD also seems to interact with other receptors7 that may eventually be recognized as being part of the ECS. How Was the Endocannabinoid System Discovered? The ECS was discovered by accident. Researchers wanted to find out how THC produced its effects on the brain and in 1990 they discovered that it binds to a specific receptor, which they called the first cannabinoid receptor (CB1).8 This was a groundbreaking development because it meant that the human body must produce its own cannabinoids to interact with this receptor. In the next several years, researchers confirmed the existence of the endocannabinoids anandamide and 2-AG, the second cannabinoid receptor (CB2), and the enzymes that break them down: all of the major components of the ECS. As we can see, the ECS is a relatively recent discovery, which is why we’re still learning more about it. Clinical Endocannabinoid Deficiency Research suggests that dysfunction of the ECS called clinical endocannabinoid deficiency (CECD) may be responsible for a variety of difficult-to-treat disorders. This theory was first proposed by leading cannabis researcher Dr. Ethan Russo in 2001. Scientific evidence for CECD has been steadily growing. One 2016 paper detailed the findings of more than a decade of studies,9 suggesting that this deficiency may be responsible for migraines, fibromyalgia, irritable bowel syndrome, and many other chronic conditions. These findings suggest that targeting the ECS could be a groundbreaking way to treat disorders that don’t seem to have a clear cause and have largely stumped conventional medicine. The Amazing Potential of the Endocannabinoid System The fact that the ECS is involved in virtually every important bodily function and that its dysfunction may have major negative effects, suggests that this system has immense therapeutic potential to benefit human health. That’s why researchers are hopeful that therapies aimed at the ECS, such as CBD-rich cannabis preparations or compounds that reduce the breakdown of endocannabinoids, may be used to help with disorders affecting everything from metabolism to sleep. There’s still a lot more to learn about the ECS and scientists are discovering something new every day. So far, there’s evidence10 that influencing ECS function may help with mental disorders, neurodegenerative conditions such as Alzheimer’s disease, cardiovascular conditions, spinal cord injury, multiple sclerosis, arthritis, osteoporosis, hypertension, and glaucoma. The ECS may hold the key for better treatment of obesity, diabetes, and even cancer. Endocannabinoid System Genetics Everybody’s body is different, so it’s not surprising that the ECS can differ as well. This may explain why people respond to cannabis differently and might even offer a clue to differences in brain function and predisposition to certain disorders. For example, some people have a genetic variation in the gene that produces the FAAH enzyme11 which leads to a decreased activity of the enzyme. As a result, these individuals have naturally higher anandamide levels, which may contribute to lower overall anxiety and other effects. Similarly, there's research showing that certain variations of ECS genes may contribute to drug addiction and other health disorders, including ADHD, PTSD, depression, and obesity.12 How to Stimulate the Endocannabinoid System Emerging research suggests that there are many ways to promote a healthy endocannabinoid system, aside from what is known of the effects of cannabis-based products. Omega-3 Fatty Acids Your body uses fatty acids from dietary sources to make endocannabinoids. There’s some early evidence that reducing the ratio of omega-6/omega-3 fatty acids by increasing your intake of omega-3 and decreasing omega-6 fatty acids may help optimize the endocannabinoid system for some individuals.13 In particular, research suggests that excessive intake of omega-6 fatty acids can desensitize and downregulate (reduce the number of) your cannabinoid receptors.14 Improving the omega-6/omega-3 ratio is also widely recognized as one of the best ways to reduce systemic inflammation and the risk of many chronic health disorders15 that are particularly common in Western countries, such as cardiovascular disease and cancer. Herbs Many plant-based compounds can also interact with the endocannabinoid system: A 2010 study reported that compounds called catechins found in tea can bind to cannabinoid receptors16 Curcumin, the main active ingredient of the popular anti-inflammatory herb turmeric, has been shown to increase brain levels of endocannabinoids17 Several studies have shown that the terpene compound beta-caryophyllene, found in many edible plants, stimulates CB2 receptors18 Panaxynol, one of the compounds in Asian ginseng, can bind to cannabinoid receptors19 Moderate amounts of caffeine may stimulate the ECS, whereas high, chronic doses may have the opposite effect20 Dark Chocolate Furthermore, research shows that chocolate contains several compounds similar in structure to our body’s endocannabinoids.21 These compounds may be able to mimic the effects of cannabinoids by activating cannabinoid receptors or reducing the breakdown of anandamide. Their levels are highest in raw cacao and dark chocolate and may offer an explanation for the strong cravings for chocolate experienced by many people. Getting Exercise We all know that exercise is great for your health, and here’s another reason why. Studies in rodents suggest that physical activity and long-term exercise in particular lead to a more balanced endocannabinoid system. Similarly, human studies report that medium to high-intensity exercise such as running, hiking, and biking can boost anandamide levels and potentially increase the number of CB1 receptors.22 These findings also suggest that anandamide could be the molecule responsible for the “runner’s high,” the feeling of euphoria often experienced after prolonged cardiovascular exercise. Managing Stress Chronic stress is known to cause a wide range of negative effects on our health. As such, it’s not surprising that some rodent studies have shown that chronic stress can lead to decreased endocannabinoid levels.23 Conversely, managing, and relieving stress can help reverse these effects. There are many ways to achieve this, including getting regular exercise, meditating, doing yoga, and socializing. There’s even evidence that acupuncture, a common stress relief practice, can boost endocannabinoid levels.24 Avoiding Alcohol Consumption Studies suggest that alcohol consumption can influence the ECS. In one study, researchers gave rats a high dose of ethanol and found reduced levels of anandamide in the brain and other tissues.25 Furthermore, chronic consumption of alcohol has been shown to reduce the density of CB1 receptors.26 The Endocannabinoid System: Summing Up Consisting of cannabinoid receptors, endocannabinoids, and the enzymes that control their metabolism, the ECS has a major impact on our health by helping maintain whole-body homeostasis. We know that it plays a role in regulating everything from pain to sleep and that its dysfunction may be an important link for many difficult-to-treat disorders such as migraines and fibromyalgia. As such, researchers and clinicians are hopeful that therapies targeting the ECS may offer novel solutions to a wide variety of health issues in the future. There are many ways to keep your ECS in balance, such as using CBD and other cannabis-derived preparations, as well as eating specific foods and herbs, and making positive lifestyle changes. References 1. Aizpurua-Olaizola, Oier, et al. "Targeting the endocannabinoid system: future therapeutic strategies." Drug discovery today 22.1 (2017): 105-110. 2. McPartland, John M., et al. "Evolutionary origins of the endocannabinoid system." Gene 370 (2006): 64-74. 3. Brown, A. J. "Novel cannabinoid receptors." British journal of pharmacology 152.5 (2007): 567-575. 4. Kendall, Debra A., and Guillermo A. Yudowski. "Cannabinoid receptors in the central nervous system: their signaling and roles in disease." Frontiers in cellular neuroscience 10 (2017): 294. 5. NAAA, MGL FAAH1 FAAH. "Endocannabinoid-metabolising enzymesbph_506_110 220.. 221." (2009). 6. Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. "Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study." PloS one 14.7 (2019): e0220025. 7. Ryberg, E., et al. "The orphan receptor GPR55 is a novel cannabinoid receptor." British journal of pharmacology 152.7 (2007): 1092-1101. 8. Alger, Bradley E. "Getting high on the endocannabinoid system." Cerebrum: the Dana forum on brain science. Vol. 2013. Dana Foundation, 2013. 9. Russo, Ethan B. "Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes." Cannabis and cannabinoid research 1.1 (2016): 154-165. 10. Pacher, Pál, Sándor Bátkai, and George Kunos. "The endocannabinoid system as an emerging target of pharmacotherapy." Pharmacological reviews 58.3 (2006): 389-462. 11. Dincheva, Iva, et al. "FAAH genetic variation enhances fronto-amygdala function in mouse and human." Nature communications 6.1 (2015): 1-9. 12. Onaivi, E. S., et al. "Cannabinoid receptor gene variations in drug addiction and neuropsychiatric disorders." Journal of Drug and Alcohol Research 2.1 (2013): 1-11. 13. Bosch-Bouju, Clémentine, and Sophie Layé. "Dietary Omega-6/Omega-3 and endocannabinoids: Implications for brain health and diseases." Cannabinoids in Health and Disease (2016): 111-142. 14. McPartland, John M., Geoffrey W. Guy, and Vincenzo Di Marzo. "Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system." PloS one 9.3 (2014): e89566. 15. Simopoulos, Artemis P. "The importance of the ratio of omega-6/omega-3 essential fatty acids." Biomedicine & pharmacotherapy 56.8 (2002): 365-379. 16. Korte, G., et al. "Tea catechins’ affinity for human cannabinoid receptors." Phytomedicine 17.1 (2010): 19-22. 17. Hassanzadeh, Parichehr, and Anna Hassanzadeh. "The CB 1 receptor-mediated endocannabinoid signaling and NGF: the novel targets of curcumin." Neurochemical Research 37.5 (2012): 1112-1120. 18. Gertsch, Jürg, et al. "Beta-caryophyllene is a dietary cannabinoid." Proceedings of the National Academy of Sciences 105.26 (2008): 9099-9104. 19. Sharma, Charu, et al. "Small molecules from nature targeting G-protein coupled cannabinoid receptors: potential leads for drug discovery and development." Evidence-Based Complementary and Alternative Medicine 2015 (2015). 20. Rossi, Silvia, et al. "Caffeine drinking potentiates cannabinoid transmission in the striatum: interaction with stress effects." Neuropharmacology 56.3 (2009): 590-597. 21. di Tomaso, Emmanuelle, Massimiliano Beltramo, and Daniele Piomelli. "Brain cannabinoids in chocolate." Nature 382.6593 (1996): 677-678. 22. Sparling, P. B., et al. "Exercise activates the endocannabinoid system." Neuroreport 14.17 (2003): 2209-2211. 23. Hill, Matthew N., et al. "Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment." Journal of neurochemistry 106.6 (2008): 2322-2336. 24. Chen, Lin, et al. "Endogenous anandamide and cannabinoid receptor-2 contribute to electroacupuncture analgesia in rats." The Journal of Pain 10.7 (2009): 732-739. 25. Ferrer, Belen, et al. "Regulation of brain anandamide by acute administration of ethanol." Biochemical Journal 404.1 (2007): 97-104. 26. Basavarajappa, Balapal S., Thomas B. Cooper, and Basalingappa L. Hungund. "Chronic ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic plasma membrane." Brain research 793.1-2 (1998): 212-218.
What Is The CBD Entourage Effect?
The Cannabis Entourage Effect Explained You’ve probably heard the term “entourage effect.” It gets thrown around quite frequently in the CBD industry, but what does it mean? The entourage effect is the idea that whole-plant cannabis preparations work better than those containing only THC or CBD. It’s the result of the synergy between the hundreds of active compounds found in the plant. That’s why it’s thought best to use full-spectrum CBD products rather than those containing CBD isolate whenever possible. Read on to learn more about the entourage effect, how it was discovered, how it works, and why it’s so important. What is the Entourage Effect? The entourage effect is the theory that cannabis provides the most benefits when used as a whole-plant extract. It’s what happens when you use all of the cannabinoids, terpenes, and other active phytochemicals in cannabis together. You’re getting not just the individual benefits of each compound in this entourage, but, more importantly, their synergistic relationships with each other. As the popular saying goes, “the whole is greater than the sum of its parts.” One of the best examples of the entourage effect is the synergy between THC and CBD. If you were to take pure THC, especially in large doses, there’s a good chance you’d feel its notable mind-altering effects. But when you pair it with CBD, something happens. CBD reduces THC’s intoxicating effects such as anxiety and psychosis.¹ That’s why cannabis — and especially strains rich in CBD — is less intoxicating than pure THC. Not only that, but CBD and THC also strengthen each other’s beneficial effects. For example, a 2010 study in patients with treatment-resistant cancer pain found that combining THC with CBD greatly enhanced its pain-relieving therapeutic effects. Individuals in the study treated with THC on its own did not differ significantly from the placebo treatment group. However, 43% of the people in the THC plus CBD group had a 30% or greater improvement in pain.² It’s also important to note that the entourage effect applies to both marijuana and hemp, the two main types of cannabis. Whereas marijuana is rich is in THC and low in CBD, hemp is high-CBD and low-THC. Aside from that major difference, they both contain similar compounds. The Discovery of the Entourage Effect The entourage effect was first proposed in 1998 by Israeli researchers Raphael Mechoulam and Shimon Ben-Shabat. They coined the term after performing a study of 2-AG, one of the main endocannabinoids made by our bodies. The researchers noticed that when 2-AG was given to mice alongside other closely related molecules, its effects were stronger.³ Yet, by themselves, these related endocannabinoid compounds showed no activity. In the years since, numerous studies have provided further evidence for the entourage effect. The Cannabis Entourage When we think of cannabis, we tend to associate most of its effects with THC and CBD. It’s easy to think this way because THC and CBD are the two most abundant active compounds in the plant and have received the most attention from researchers and the media. However, cannabis plants contain dozens of other cannabinoids, as well as many other classes of compounds, including terpenes, flavonoids, fatty acids, minerals, and vitamins. All in all, cannabis plants are made up of over 400 chemical compounds.? All of them can have benefits and more importantly modify or amplify each other’s effects — what scientists call synergy. Let’s take a closer look at these different chemicals and how they contribute to the entourage effect. Cannabinoids Cannabinoids are believed to play a pivotal role in the entourage effect. In a nutshell, cannabinoids can enhance each other’s effects when used together. We already discussed the prime example of this: the synergy between THC and CBD. Another lesser-known example of cannabinoid synergy occurs between THC and cannabinol (CBN). When researchers studied the effects of these two cannabinoids, CBN did not produce any notable effects by itself. Yet, when taken together with THC, it enhanced feelings of dizziness, drowsiness, and drunkenness.? Keep in mind that the cannabis plant contains over 120 different cannabinoids, most of which (like CBN) are considered “minor” because they’re present in very small quantities. All of these cannabinoids could potentially be interacting or indirectly with THC, CBD, and each other.? That means the list of potential cannabinoid synergies that we don’t yet know about is immense. And we haven’t even touched on terpenes. Terpenes Without a doubt, terpenes are the most overlooked component of the entourage effect. These natural aromatic compounds are found in many plants - including fruits, trees, spices, and cannabis. Terpenes are responsible for the unique aromas of plants, such as the distinct smells of different strains of cannabis. For example, pinene is one of the main compounds responsible for the characteristic smell of pine trees. Terpenes contribute to the entourage effect not only through their distinct effects on health but also by synergizing with cannabinoids. Examples of cannabis terpenes and various studies highlighting their potential benefits include: Linalool - may have sedative, anxiolytic (anxiety-reducing),? anti-inflammatory, and antioxidant effects that can contribute to the effects of CBD and other cannabinoids.? Myrcene - may provide anti-inflammatory, muscle-relaxing,? sedative, and anticancer¹? properties and may also make it easier for cannabinoids to cross the blood-brain barrier, enhancing their effects.¹¹ It might also contribute to the “couch lock” often experienced by cannabis users.¹² Pinene - may have anti-inflammatory,¹³ bronchodilating,¹? and memory-aiding properties. It may also help offset the short-term memory impairment from THC intake.¹? Limonene - may have anxiolytic properties and pair well with CBD.¹? Caryophyllene – may provide anti-inflammatory effects and stimulate CB2 receptors.¹? It’s also been shown to reduce alcohol intake in a mouse study, potentially pairing well with efforts to use CBD for anti-addiction.¹? Again, these are just a few preliminary studies highlighting various examples of terpenes. There are many other terpenes and related compounds called terpenoids in cannabis, all of which can have potential synergies with cannabinoids and other compounds present in the plant. Other Phytochemicals Although cannabinoids and terpenes play the most important role in the entourage effect, we shouldn’t forget the remaining chemicals in cannabis. These include flavonoids, fatty acids, minerals, vitamins, and other phytochemicals such as chlorophyll. For example, it’s common knowledge that fatty acids, minerals, and vitamins play an essential role in human health, so we know they can have effects of their own. But it’s also possible that they could synergize with cannabinoids or terpenes in some way. At this time, research is limited about how these compounds contribute to the cannabis entourage effect. However, scientists are continuing to explore their effects as it’s possible that they do play a role. The Endocannabinoid System Most of the effects of cannabis are the result of the interaction between cannabinoids and the endocannabinoid system (ECS). This system is composed of three key elements: Endocannabinoids — cannabinoids made by our bodies Metabolic enzymes that make and break down endocannabinoids Cannabinoid receptors (CB1 & CB2) that respond to cannabinoids The ECS is thought to play a large role in maintaining homeostasis in our bodies, a scientific term for a state of internal balance where everything is functioning as it should — not too much and not too little. Put simply, the ECS helps maintain your overall health by regulating major processes, including immunity, inflammation, pain, sleep, mood, cognitive function, metabolism, and stress.¹? Although the ECS is activated by our body’s endocannabinoids, it can also respond to phytocannabinoids — cannabinoids coming from plants such as cannabis. For example, some phytocannabinoids, such as THC, can bind directly to the body’s cannabinoid receptors. Others, like CBD, don’t bind to cannabinoid receptors. Instead, CBD can change how the CB1 receptor responds to other cannabinoids.²? It remains to be researched and confirmed whether this can explain how CBD may synergizes with THC and potentially counteracts its psychotropic side effects. CBD can also suppress the enzyme that breaks down endocannabinoids, potentially enhancing their effects.²¹ Full and Broad Spectrum CBD Oils vs Isolates You may have heard that there are three kinds of CBD oil: full-spectrum, broad-spectrum, and isolate. Full-spectrum and broad-spectrum oils are both whole-plant extracts, which means they contain all of the beneficial components of hemp and make use of the entourage effect. The only difference between these two extracts is that full-spectrum CBD contains small amounts (<0.3%) of THC, which is completely removed in broad-spectrum CBD. Meanwhile, isolate is a pure form of CBD without any other cannabis compound. As such, it doesn’t benefit from the entourage effect. This explains why it’s commonly recommended to use CBD products formulated with full-spectrum or at least a broad-spectrum CBD extract over those made with isolate. Of course, whole plant CBD products are not without their downsides. For example, full-spectrum CBD might not be the best choice for someone who’s extremely sensitive to THC or has to pass drug tests for work. However, when we’re talking about the effectiveness of CBD for various purposes, whole-plant CBD tends to be the winner compared to other hemp plant extracts. Possibly due to the entourage effect, full and broad-spectrum CBD products tend to produce greater desired effects, require smaller doses, and have a smaller chance of causing side effects than those formulated with CBD isolate.²² Whole-Plant Medicine: The Way Of the Past and the Future? To sum up, the entourage effect is the proposed scientific theory that the effects of cannabis may be most effective when used in the form of a whole-plant extract. Perhaps what’s most interesting about this idea is that it lines up with anecdotal evidence throughout history. If we look back at thousands of years, we can see that human civilization always used cannabis and other herbal medicines in their whole-plant form. These herbal remedies must carry some merit, or we wouldn’t find written and archaeological records of their use. In that sense, the entourage effect may be more of a rediscovery of one of nature’s greatest gifts to mankind. Which raises an important question for the future of healthcare: is the single-molecule approach championed by modern medicine, where most pharmaceutical drugs contain a single active compound, taking us in the wrong direction? Frequently Asked Questions What Does the Entourage Effect Feel Like? The entourage effect doesn’t really produce any discernible feeling. However, its overall impact is much more complex and varied than isolated THC or CBD because you’re simultaneously experiencing the individual effects and synergies of dozens of compounds. What is Needed to Add to Isolate to Create an Entourage Effects? If you want to get the entourage effect, you’d have to at least add all of the other cannabinoids and terpenes naturally present in cannabis to CBD or THC isolate. What Does the Entourage Effect Mean? The entourage effect is the idea that whole-plant cannabis preparations containing all of the plant’s active components may provide a greater or different effect than isolated CBD (e.g., CBD isolate). What Plants Have an Entourage Effect? So far, the entourage effect has only been demonstrated in cannabis. However, considering that humans have successfully used herbal medicines in their whole-plant form for millennia, we can speculate that many other medicinal plants also benefit from an entourage effect of their own. References 1. Niesink, Raymond JM, and Margriet W. van Laar. "Does cannabidiol protect against adverse psychological effects of THC?." Frontiers in psychiatry 4 (2013): 130. 2. Johnson, Jeremy R., et al. "Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain." Journal of pain and symptom management 39.2 (2010): 167-179. 3. Ben-Shabat, Shimon, et al. "An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity." European journal of pharmacology 353.1 (1998): 23-31. 4. Atakan, Zerrin. "Cannabis, a complex plant: different compounds and different effects on individuals." Therapeutic advances in psychopharmacology 2.6 (2012): 241-254. 5. Karniol, Isac G., et al. "Effects of Δ9-tetrahydrocannabinol and cannabinol in man." Pharmacology 13.6 (1975): 502-512. 6. Morales, Paula, Dow P. Hurst, and Patricia H. Reggio. "Molecular targets of the phytocannabinoids: a complex picture." Phytocannabinoids. Springer, Cham, 2017. 103-131. 7. Costa, Celso ARA, et al. "Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT 1A-receptors and reduces cholesterol after repeated oral treatment." BMC complementary and alternative medicine 13.1 (2013): 42. 8. Sabogal-Guáqueta, Angélica Maria, Edison Osorio, and Gloria Patricia Cardona-Gómez. "Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice." Neuropharmacology 102 (2016): 111-120. 9. Pacher, Pál, Sándor Bátkai, and George Kunos. "The endocannabinoid system as an emerging target of pharmacotherapy." Pharmacological reviews 58.3 (2006): 389-462. 10. Sobral, Marianna Vieira, et al. "Antitumor activity of monoterpenes found in essential oils." The Scientific World Journal 2014 (2014). 11. Hartsel, Joshua A., et al. "Cannabis sativa and Hemp." Nutraceuticals. Academic Press, 2016. 735-754. 12. Russo, Ethan B. "Taming THC: potential cannabis synergy and phytocannabinoid?terpenoid entourage effects." British journal of pharmacology 163.7 (2011): 1344-1364. 13. Gil, M. L., et al. "Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck." Die Pharmazie 44.4 (1989): 284-287. 14. Falk, Agneta A., et al. "Uptake, distribution and elimination of α-pinene in man after exposure by inhalation." Scandinavian Journal of Work, Environment & Health (1990): 372-378. 15. Perry, Nicolette SL, et al. "In?vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes." Journal of pharmacy and pharmacology 52.7 (2000): 895-902. 16. Carvalho-Freitas, Maria Isabel Roth, and Mirtes Costa. "Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L." Biological and Pharmaceutical Bulletin 25.12 (2002): 1629-1633. 17. Gertsch, Jürg, et al. "Beta-caryophyllene is a dietary cannabinoid." Proceedings of the National Academy of Sciences 105.26 (2008): 9099-9104. 18. Al Mansouri, Shamma, et al. "The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice." Pharmacology Biochemistry and Behavior 124 (2014): 260-268. 19. Aizpurua-Olaizola, Oier, et al. "Targeting the endocannabinoid system: future therapeutic strategies." Drug discovery today 22.1 (2017): 105-110. 20. Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. "Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study." PloS one 14.7 (2019): e0220025. 21. Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94. 22. Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969.
Terpenes in CBD - A Complete Guide
We often recognize plants by their unique smell — the refreshing, earthy aroma of pine, or the fruity smell of lemon. These two scents might not smell similar, but behind the scenes, the same group of compounds is responsible: terpenes. Terpenes are found in virtually all plants, playing a major role in their distinct aromas. What’s more, they seem to contribute to the beneficial health effects of CBD oil and other cannabis-derived products. In this guide, we’re going to explain what are terpenes in CBD, and why they’re an important component of CBD oil. You’ll also find a terpenes chart focusing on the most common ones found in cannabis. What Are Terpenes? Terpenes are aromatic compounds found in a wide variety of plants, including cannabis. They form the largest and most diverse group of natural chemicals, with over 20,000 terpenes discovered to date. Terpenes are sometimes interchangeably called terpenoids, although this related class of compounds has a slightly different structure. Scientists believe plants evolved to produce terpenes primarily as a defensive strategy to repel herbivores and attract the predators and parasites that prey on these animals. Terpenes are best known for their distinct smells and tastes which contribute to the unique aromas of individual plants. Pinene, for example, is responsible for the fresh, earthy scent of pine and other evergreen trees. Terpenes in Cannabis Although the cannabis plant contains over 150 known terpenes, the most common are myrcene, pinene, linalool, caryophyllene, limonene, and humulene. Some terpenes come in multiple forms called isomers. Isomers have the same molecular formula but a different structure. For example, caryophyllene comes in the form of alpha-caryophyllene (better known as humulene) and beta-caryophyllene. Like CBD, THC, and other cannabinoids, terpenes are most abundant in the hair-like trichomes that cover the cannabis plant. Each “strain” of cannabis has a distinct terpene composition, which contributes to its exclusive flavor and aroma. What are terpenes in CBD? Well, without terpenes, cannabis and CBD aficionados would never be able to enjoy the hints of pine, citrus, or berry. More importantly, terpenes can have advantageous properties and work together with cannabinoids to produce the unique health effects of marijuana, CBD oil, and other whole-plant cannabis preparations. Lastly, terpenes can also be made in a lab rather than being extracted from plants. Such synthetic terpenes are starting to be utilized in the pharmaceutical, cosmetic, vaping, and cannabis industries when there’s a need for specific terpenes that might be too difficult to purify from plants. Some companies are also attempting to mimic or recreate the terpene profile of cannabis with these man-made creations. But for now, it’s best to stay away from these synthetic alternatives as not enough research has been completed to validate their safety. Terpenes & The Entourage Effect The real value of cannabis terpenes comes from their role in the “entourage effect.” First proposed in 1998, this evidence-based theory argues that cannabis works best when used as a whole-plant extract. In other words, the “entourage” of all the different cannabinoids, terpenes, and other cannabis phytochemicals working together in synergy may produce greater effects and benefits than any of these compounds on their own. Terpenes are believed to contribute to the entourage effect in two ways. First, each terpene provides distinct effects, such as anti-inflammatory, sedative, antibacterial, antioxidant, and other beneficial properties. Second, many terpenes are thought to work synergistically with cannabinoids. For instance, let’s take a look at the common cannabis terpene, myrcene. Firstly, it adds muscle-relaxing, sedative, and anti-inflammatory properties to the plant and may play a notable role in the “couch lock” sometimes experienced after smoking cannabis. Secondly, myrcene may enhance the effects of cannabinoids by making it easier for them to cross the blood-brain barrier. This means more cannabinoids can be absorbed, increasing its potency. Similarly, the terpene linalool is known to have anxiety-reducing properties, which may complement the similar effects of CBD. In fact, many of the unique, complex effects cannabis users ascribe to particular strains — such as reduced anxiety, sleepiness, or increased relaxation, energy, or creativity — may come largely from terpenes. The cannabis entourage effect and the role terpenes play in it have been demonstrated by multiple studies.  Although there’s much more research needed to completely unravel how terpenes and cannabinoids work together, it’s clear that terpenes play a major role in the medicinal and recreational benefits of cannabis. What are Terpenes in CBD Products? Terpenes are not only found in marijuana — the intoxicating form of cannabis used primarily for its recreational effects. They’re also present in hemp — the low-THC, high-CBD variety of cannabis that was recently made legal in the United States. Hemp has a similar terpene makeup to regular cannabis, with the most common terpenes being beta-caryophyllene, linalool, caryophyllene oxide, humulene, myrcene, and pinene. As such, terpenes can contribute to the health benefits of CBD oil and other hemp-derived CBD products that have skyrocketed in popularity over the past few years. That’s why you may have heard the entourage effect mentioned with full-spectrum and broad-spectrum CBD — two types of whole-plant extract that contain the complete entourage of hemp compounds, including terpenes. Terpenes are only present in three kinds of CBD product formulations: Full-spectrum CBD, which contains all hemp cannabinoids (CBD and THC), terpenes, and other phytochemicals. Broad-spectrum CBD, which is the same as full-spectrum but with THC completely removed. Any other type of product where terpenes were added separately, such as a CBD isolate vape e-liquid infused with a specific blend of terpenes. That means products containing isolate — a purified form of CBD — will not contain any terpenes unless they were blended in during a separate step. As a result, CBD isolate products lack the entourage effect of whole-plant hemp extracts, making them less effective overall. Opting for full or broad-spectrum CBD products is the best way to ensure that you’re getting all of hemp’s terpenes and getting the greatest efficacy and benefits. CBD Third-Party Terpene Testing You should also be aware that CBD companies use varying manufacturing processes to formulate full-spectrum and broad-spectrum extracts, which can influence the terpene levels of the final product. That means a full-spectrum CBD oil from one company might contain a wider variety and higher concentrations of terpenes than a tincture from another brand. The only way to know exactly which terpenes you’re getting is to look at what’s called a terpene profile test. You’ve probably heard of third-party testing — tests are done by an independent lab to confirm that a CBD product is safe and contains as much CBD as it says on the label. A terpene profile test is another type of third-party test. Instead of showing which cannabinoids are present in a CBD product and in what amounts, this test identifies the terpene levels. Although reading a test report for terpenes might sound difficult, it’s actually quite straightforward to see what are terpenes in CBD. In most cases, you’ll see the names of terpenes and a corresponding number or bar that indicates how much of that terpene is present in the CBD oil or product. Primary Cannabis Terpenes Chart This terpenes chart highlights the most common terpenes found in cannabis as well as their aromas, medicinal properties, and other plants they’re found in. Terpene Aroma/Flavor Beneficial Properties Also common in these plants Caryophyllene (beta-caryophyllene) Wood-like scent Anti-inflammatory, cardioprotective, hepatoprotective, gastroprotective, neuroprotective, immunomodulatory, nephroprotective, antioxidant, anti-inflammatory, antimicrobial, may activate CB2 cannabinoid receptors,  Pepper, basil, cinnamon, cloves, lavender, oregano, rosemary Caryophyllene oxide Wood-like scent Antifungal, insecticidal, anticoagulant, antioxidant, antiviral, anti-inflammatory, anticarcinogenic, analgesic (pain-relieving) Lemon balm, basil, sage Geraniol Rose-like scent and sweet, floral taste Antitumor, anti-inflammatory, antioxidative, antimicrobial hepatoprotective, cardioprotective, and neuroprotective Valerian, cinnamon Humulene (alpha-caryophyllene) Earthy, hops-like scent Anti-inflammatory Hops, sage, ginseng Limonene Citrus-like scent Anxiolytic (anxiety-reducing), immunostimulant, anti-inflammatory, anticancer, antibacterial, antifungal, may relieve heartburn and GERD Lemon, orange, lime Linalool Floral, lavender-like scent anti-inflammatory, anticancer, anti-hyperlipidemic, antimicrobial, antinociceptive, analgesic, anxiolytic, antidepressive and neuroprotective properties Lavender, coriander Myrcene Earthy, herbal scent Anti-inflammatory, analgesic, sedative, anticancer[CC3] Hops, bay Ocimene Sweet, herbal scent Anti-inflammatory Hops, mangoes, basil Pinene Fresh, pine-like scent Antibiotic resistance modulation, cytogenetic, gastroprotective, anxiolytic, cytoprotective, anticonvulsant, neuroprotective, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, analgesic anti-inflammatory, bronchodilatory, acetylcholinesterase inhibitor (may improve memory) Pine and other coniferous trees Terpineol Lilac-like scent Anti-inflammatory, anticancer Lilac, pine, lime blossom Terpinolene Pine-like scent Sedative, antioxidant, anticancer,  Lilac, nutmeg, cumin, sage, conifers Valencene Citrus-like scent Anti-inflammatory, may help with eczema Valencia oranges, nutgrass Terpenes: Beneficial Compounds with True Potential As you can see, terpenes don’t just provide a pleasant smell to plants but they also have many helpful properties. They appear to play a particularly important role in the therapeutic effects of whole-plant cannabis products such as CBD oil by working in synergy with cannabinoids. Researchers have only recently begun to explore the potential health applications of terpenes. We can expect more promising studies to come out in the near future regarding what are terpenes in CBD, shedding further light on what they are capable of and how they contribute to the beneficial effects of cannabis. Frequently Asked Questions How do I take terpenes? Similar to CBD, terpenes can be taken internally as part of an oil or edible product, inhaled through vaporization or smoking, or applied to the skin. What are synthetic terpenes? As the name implies, synthetic terpenes are man-made versions of natural terpenes. They’re starting to be used by some companies in the cannabis industry and other fields. You can often find them being sold independently or as a blend with CBD and THC. How do terpenes affect the body? Different terpenes can have different effects on the human body. Thus far, research has shown that terpenes can have anti-inflammatory, antioxidant, sedative, neuroprotective, and many other beneficial properties. References  Sahu, Pankaj K., et al. "Therapeutic and medicinal uses of Aloe vera: a review." Pharmacology & Pharmacy 4.08 (2013): 599.  Pichersky, Eran, and Robert A. Raguso. "Why do plants produce so many terpenoid compounds?." New Phytologist 220.3 (2018): 692-702.  Booth, Judith K., and Jörg Bohlmann. "Terpenes in Cannabis sativa–From plant genome to humans." Plant Science 284 (2019): 67-72.  Arendt, Philipp, et al. "Synthetic biology for production of natural and new?to?nature terpenoids in photosynthetic organisms." The Plant Journal 87.1 (2016): 16-37.  Ben-Shabat, Shimon, et al. "An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity." European journal of pharmacology 353.1 (1998): 23-31.  Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969.  Russo, Ethan B. "Taming THC: potential cannabis synergy and phytocannabinoid?terpenoid entourage effects." British journal of pharmacology 163.7 (2011): 1344-1364.  Hartsel, Joshua A., et al. "Cannabis sativa and Hemp." Nutraceuticals. Academic Press, 2016. 735-754.  Ferber, Sari G., et al. "The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders." Current Neuropharmacology 18.2 (2020): 87-96.  Machado, Keylla da Conceição, et al. "A systematic review on the neuroprotective perspectives of beta?caryophyllene." Phytotherapy Research 32.12 (2018): 2376-2388.  Sharma, Charu, et al. "Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise." Current pharmaceutical design 22.21 (2016): 3237-3264.  Fidyt, Klaudyna, et al. "β?caryophyllene and β?caryophyllene oxide—natural compounds of anticancer and analgesic properties." Cancer medicine 5.10 (2016): 3007-3017.  Chen, Weiyang, and Alvaro M. Viljoen. "Geraniol—a review of a commercially important fragrance material." South African Journal of Botany 76.4 (2010): 643-651.  Lei, Yu, et al. "Pharmacological properties of geraniol–a review." (2019).  Rogerio, Alexandre P., et al. "Preventive and therapeutic anti?inflammatory properties of the sesquiterpene α?humulene in experimental airways allergic inflammation." British journal of pharmacology 158.4 (2009): 1074-1087.  Sun, Jidong. "D-Limonene: safety and clinical applications." Alternative Medicine Review 12.3 (2007): 259.  Pereira, Irina, et al. "Linalool bioactive properties and potential applicability in drug delivery systems." Colloids and Surfaces B: Biointerfaces 171 (2018): 566-578.  https://pubmed.ncbi.nlm.nih.gov/25026734/  Salehi, Bahare, et al. "Therapeutic potential of α-and β-pinene: A miracle gift of nature." Biomolecules 9.11 (2019): 738.  Nogueira, M. N. M., et al. "Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages." Inflammation research 63.9 (2014): 769-778.  Hassan, Saadia Bashir, et al. "Alpha terpineol: a potential anticancer agent which acts through suppressing NF-κB signalling." Anticancer Research 30.6 (2010): 1911-1919.  Ito, Ken, and Michiho Ito. "The sedative effect of inhaled terpinolene in mice and its structure–activity relationships." Journal of natural medicines 67.4 (2013): 833-837.  Aydin, Elanur, Hasan Türkez, and ?ener Ta?demir. "Anticancer and antioxidant properties of terpinolene in rat brain cells." Archives of Industrial Hygiene and Toxicology 64.3 (2013): 415-424.  Yang, In Jun, Dong-Ung Lee, and Heung Mook Shin. "Inhibitory effect of valencene on the development of atopic dermatitis-like skin lesions in NC/Nga mice." Evidence-Based Complementary and Alternative Medicine 2016 (2016).
What Are The Side Effects Of CBD?
One common question beginners or new CBD users ask is "What are the side effects of CBD?" Although CBD appears to be a safer alternative to many prescription medications — especially for difficult-to-treat conditions such as rare types of epilepsy — it’s not a silver bullet with zero downsides. CBD can indeed cause some negative side effects. However, they’re considered mild, especially when compared to those caused by many pharmaceutical drugs. Here’s what we know about CBD’s side effects, drug interactions, and other safety-related concerns. Short Term Side Effects of CBD Oil Studies using high doses of CBD oil in humans have reported several mild-to-moderate, short-term side effects, including:1 Tiredness Drowsiness Diarrhea Dry mouth Low blood pressure Lightheadedness Changes in appetite or weight However, it’s important to be aware that research studies are not an accurate representation of real-world CBD use. Researchers tend to utilize a pure form of CBD called CBD isolate and administer it orally for 4 weeks or longer in very high daily doses of 300 mg or more. In comparison, most people take CBD in much smaller doses (20–100 mg daily) and use CBD oil tinctures rather than capsules or other ingested products. Many also use products containing full-spectrum hemp extract, rather than purified CBD, which contain not only CBD but other cannabinoids, terpenes, and various hemp compounds. Research evidence shows that full-spectrum CBD preparations cause fewer side effects than purified CBD, which they think may be due to requiring smaller doses for similar therapeutic outcomes. The higher potency of full-spectrum CBD is speculated to be from the synergy between the plant’s many components, what researchers call the “entourage effect”.2 The bottom line is that the side effects mentioned above are likely to be mild and have a low chance of occurring for most CBD users. Side Effects of Full-Spectrum CBD Products As we mentioned above, some CBD oil products are made with full-spectrum hemp extract, which means they contain not only CBD but many other compounds. In particular, full-spectrum CBD can contain up to 0.3% of THC, the cannabinoid largely responsible for the mind-altering “high” associated with cannabis. This amount of THC is not enough to cause intoxication in the vast majority of people. Having said that, some individuals are so sensitive to THC that they may experience unwanted effects by taking a large-enough dose of a full-spectrum CBD product. The potential side effects of full-spectrum CBD include feelings of anxiety or paranoia. Nonetheless, these effects are unlikely to occur for most individuals. Long Term Side Effects of CBD Oil CBD does not appear to cause any long-term side effects in humans. More importantly, there’s no evidence that you can become dependent on CBD, develop a tolerance to its effects, or have withdrawal symptoms if you stop taking it after prolonged use. That’s another major advantage over some prescription medications, such as opioid painkillers, which are notorious for their addictive properties. In fact, studies are suggesting that CBD might help people reduce their usage of opioids and other addictive drugs,3 making it a realistic option for tackling the opioid epidemic. Not to mention, cannabis and its many cannabinoids have been found to help reduce pain levels similarly to opioids. Having said that, most studies of CBD had a duration of 4-6 weeks, so more data about its long-term effects — after months or years of daily usage — is needed. CBD Oil Side Effects on Kidneys So far, research has not revealed any side effects of CBD oil on the kidneys in healthy individuals. If anything, it may actually be beneficial in treating symptoms of advanced chronic kidney disease including pain and reducing the need for opioids.4 One study on mice also showed that pure CBD reduced inflammation and protected kidneys from damage caused by the chemotherapy drug cisplatin.5 Is CBD Oil Bad for Your Liver? The Food and Drug Administration (FDA) has raised concerns over the safety of CBD because of the belief that it can cause liver injury. However, this claim is based largely on a single study done in mice. In this 2019 study, mice were given varying doses of CBD either acutely (one time) or for 10 days. The doses ranged from 61.5 to 2460 mg/kg. This means that at the highest dosage, mice were given almost 2.5 grams of CBD for every kilogram of body weight. In the acute experiment, only a CBD dose of 2460 mg/kg produced signs of liver toxicity. This dose is equivalent to about 200 mg/kg for humans. The researchers found similar signs of liver damage in mice given 615 mg/kg (equivalent to 50 mg/kg in humans) of CBD for 10 days. They concluded that “CBD exhibited clear signs of hepatotoxicity [liver toxicity]” but acknowledged that the high doses required for such an outcome are not applicable to most real-world scenarios.”6 The average body weight worldwide is 62 kg.7 Using the equivalent doses suggested by the study, this means the average person would have to take 12,400 mg (12.4 grams) of CBD at once or 3,100 mg (3.1 grams) for at least three days to experience liver damage. These doses are nowhere near the 20–100 mg taken by CBD users. In sum, there isn’t any evidence to suggest that CBD is bad for your liver unless you’re taking ridiculously large doses. CBD & Fertility Some people wonder if CBD has any effects on fertility. Thus far, there’s very limited evidence to indicate whether CBD has any significant impact on fertility in humans. The only thing we know for certain is that taking CBD at the commonly recommended doses doesn’t seem to have any serious negative effects on the reproductive system in healthy individuals. One 2018 study did show that male mice given CBD (15 or 30mg/kg) for 34 days straight had a 30% reduction in fertility rate.8 A similar 1987 study reported that CBD reduced the fertility of sea urchin sperm.9 However, these kinds of findings need to be confirmed by human studies before we can say anything conclusive. Can You Be Allergic to CBD? It’s highly unlikely to experience an allergic reaction to CBD itself. Scientific studies have not reported any evidence of CBD allergies. On the contrary, research on mice suggests that CBD may help with certain allergic responses by reducing inflammation.10 Nonetheless, it’s possible to have an allergic reaction to other ingredients present in CBD products. One likely culprit is terpenes — natural aromatic compounds present in many CBD oils and other CBD products. For example, one 2017 study found that some people had an allergic reaction when their skin came in contact with limonene or linalool, two common cannabis terpenes.11 There’s also some evidence that certain terpenes can be irritating to skin, eyes, and mucous membranes.12 Another possible allergic ingredient is cannabis pollen, the powdery substance produced by male cannabis plants. However, pollen is unlikely to find its way into cannabis products because male plants are not widely used in cannabis cultivation. This is even more true for hemp-derived CBD products because CBD is usually used in the form of an oil, an extract that doesn’t contain any plant parts. Finally, some CBD products — especially topicals — can also contain many other ingredients that can potentially cause allergic reactions, such as fragrances and preservatives. Vaping CBD Side Effects Vaping CBD can cause all of the same short-term side effects we discussed earlier. However, the real question is whether vaping CBD — or anything else, for that matter — is safe. Although experts agree that vaping is far safer than smoking, it’s not entirely without its risks. For instance, one study found that higher doses of propylene glycol and vegetable glycerin — the two most common ingredients in vape e-liquids, including those containing CBD — were toxic to cells.13 Another study reported that e-cigarettes can produce acetaldehyde, acrolein, and formaldehyde, three toxic compounds that contribute to cardiovascular and lung disease14 while a 2019 paper found that e-cigarettes are associated with an increased risk of a heart attack.15 Finally, a comprehensive report by the National Academies of Science, Engineering, and Medicine looked at the findings of dozens of studies and found that there’s conclusive evidence that vaping products can produce multiple potentially harmful substances, as well as substantial-to-moderate evidence that vaping carries other risks and can increase coughing, wheezing, and asthma attacks. The dangers of vaping were highlighted by the recent outbreak (from March 2019 to February 2020) of vaping-related lung injury in the US, where 2,800 people were hospitalized and 68 died.16 Although this outbreak was largely linked to products containing vitamin E acetate, it still highlights the fact that inhaling anything other than air is likely detrimental to your health. CBD Drugs Interactions CBD can interact with many prescription drugs by altering the function of certain enzymes and proteins. These natural molecules are involved in metabolizing (breaking down) a wide variety of prescription medications. As a result, CBD can drastically change the effects of many drugs. CYP450 Enzyme Inhibition Some studies have reported that CBD can suppress the activity of cytochrome P450 enzymes.17 This enzyme family is abundant in the liver, where it helps metabolize the majority of prescription drugs. Taking CBD alongside these medications can change how they are metabolized by the liver, which can modify their intended effects. Just some of the prescriptions whose effects CBD may alter include: Theophylline, used for respiratory conditions Chlorzoxazone, a muscle relaxer used for treating pain Amitriptyline, an antidepressant Ondansetron, used to relieve nausea and vomiting caused by surgery or cancer treatment Clozapine, used to treat schizophrenia The complete list involves dozens of common prescriptions used for every kind of health disorder. At the same time, this also means that many medications can affect CBD’s metabolism by interacting with the same enzymes, lowering or increasing the concentration of CBD in the blood. p-Glycoprotein Inhibition CBD can also interact with medications by inhibiting P-glycoprotein.18 This protein helps transport various drugs in and out of cells, which means CBD can have a significant impact on their effects. P-glycoprotein helps the body utilize many drugs, including HIV antivirals, epilepsy and chemotherapy medications, antihypertensive drugs, immunosuppressants, blood thinners, and steroids.19 Some drugs, such as the immunosuppressant cyclosporin, interact with both P-glycoprotein and CYP450 enzymes, which means CBD can have an even bigger impact on their effects. The bottom line is that more research needs to be done to identify CBD’s precise impact on specific medications and anyone taking prescription drugs should talk to their doctor before using CBD. Current FDA Stance on CBD Safety The FDA is taking a “better safe than sorry” approach towards CBD, claiming that there’s insufficient research to broadly label it a fully safe substance. The organization argues that CBD may: cause side effects cause liver injury affect other medications people take be dangerous when taken alongside other substances that slow brain activity, such as alcohol harm male fertility Although their areas of concern are backed by a wide range of research findings, many of them are from preliminary studies conducted on animals that don’t use common real-world doses of CBD. The FDA also stresses that we don’t know enough about CBD’s safety in specific situations, such as a growing fetus, the developing brains of children, or taking it daily for a prolonged period of time. Should You Be Concerned About CBD’s Side Effects? This list of CBD’s potential negative side effects can undoubtedly sound scary, but remember the popular saying: “The dose makes the poison.” Taken at normal dosages, CBD offers relief with minimal side effects for most people. Generally speaking, it’s only when individuals take extremely high CBD doses — such as those used for treatment-resistant epilepsy — that side effects become a more serious concern. For the average healthy person, there isn’t much to worry about when you use CBD, especially in combination with a healthy diet, lifestyle, and exercise regimen. Besides, CBD is a far safer alternative to many prescription drugs, whose effects can be worse than the issue they’re treating. Nonetheless, it’s important to stress that although CBD has an excellent and well-documented safety profile backed by decades of studies, we don’t yet know everything about its effects. That’s why you should always consult with your healthcare provider before using CBD, especially if you are currently on a prescription. Frequently Asked Questions What are the side effects of CBD hemp oil? CBD hemp oil can cause minor side effects, including tiredness, drowsiness, diarrhea, dry mouth, low blood pressure, and changes in appetite or weight. However, these effects have only been reported in studies using large doses of pure CBD. What are the bad side effects of CBD oil? CBD oil doesn’t have any severe side effects. However, it can amplify or reduce the effectiveness of many drugs, which is why it’s imperative to consult your doctor before using it if you’re taking any prescription. What are the side effects of water-soluble hemp oil? Water-soluble hemp oil containing CBD doesn’t have any additional side effects over regular CBD oil. References 1. Huestis, Marilyn A., et al. "Cannabidiol adverse effects and toxicity." Current neuropharmacology 17.10 (2019): 974-989. 2. Pamplona, Fabricio A., Lorenzo Rolim da Silva, and Ana Carolina Coan. "Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis." Frontiers in neurology 9 (2018): 759. 3. Capano, Alex, Richard Weaver, and Elisa Burkman. "Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study." Postgraduate Medicine 132.1 (2020): 56-61. 4. Rein, Joshua L. "The nephrologist's guide to cannabis and cannabinoids." Current Opinion in Nephrology and Hypertension 29.2 (2020): 248. 5. Pan, Hao, et al. "Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death." Journal of Pharmacology and Experimental Therapeutics 328.3 (2009): 708-714. 6. Ewing, Laura E., et al. "Hepatotoxicity of a cannabidiol-rich cannabis extract in the mouse model." Molecules 24.9 (2019): 1694. 7. Walpole, Sarah Catherine, et al. "The weight of nations: an estimation of adult human biomass." BMC public health 12.1 (2012): 439. 8. Carvalho, Renata K., et al. "Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice." Reproductive Toxicology 81 (2018): 34-40. 9. Schuel, Herbert, et al. "Cannabinoids reduce fertility of sea urchin sperm." Biochemistry and Cell Biology 65.2 (1987): 130-136. 10. Vuolo, Francieli, et al. "Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma." European Journal of Pharmacology 843 (2019): 251-259. 11. Nath, Neel Som, et al. "Contact allergy to hydroperoxides of linalool and D-limonene in a US population." Dermatitis 28.5 (2017): 313-316. 12. Löfstedt, Håkan, et al. "Respiratory symptoms and lung function in relation to wood dust and monoterpene exposure in the wood pellet industry." Upsala journal of medical sciences 122.2 (2017): 78-84. 13. Sassano, M. Flori, et al. "Evaluation of e-liquid toxicity using an open-source high-throughput screening assay." PLoS biology 16.3 (2018): e2003904. 14. Ogunwale, Mumiye A., et al. "Aldehyde detection in electronic cigarette aerosols." ACS omega 2.3 (2017): 1207-1214. 15. Centers for Disease Control and Prevention. "Smoking and Tobacco Use; Electronic Cigarettes." (2018). 16. Iffland, Kerstin, and Franjo Grotenhermen. "An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies." Cannabis and cannabinoid research 2.1 (2017): 139-154. 17. Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. "en Crippa, JA (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent." Current Drug Safety 6.4: 237-249. 18. Finch, Andrew, and Peter Pillans. "P-glycoprotein and its role in drug-drug interactions." Aust Prescr 37.4 (2014): 137-139. 19. Finch, Andrew, and Peter Pillans. "P-glycoprotein and its role in drug-drug interactions." Aust Prescr 37.4 (2014): 137-139
Guide to CBD Types and Extraction Methods
Millions across the world are using cannabidiol (CBD) to improve their health. Despite that, many people have lingering questions about this natural compound. One common source of confusion is the different types of CBD and the methods used to produce them. You’ve probably seen terms like “broad-spectrum CBD,” “nano CBD,” and “CO2 extraction” on CBD oil labels and product descriptions. But what do they mean? How should they affect your buying decision? Here’s a quick primer for the different types of CBD, extraction methods, and other CBD terminology to help you make an educated choice. The Different Types of CBD CBD is a non-intoxicating cannabinoid present in cannabis plants. Most CBD products are sourced from hemp, a type of cannabis with low tetrahydrocannabinol (THC) and high CBD levels. In comparison, any plant with over 0.3% THC is considered marijuana, which is illegal in the U.S. and most other countries. Although CBD is a single compound, it can come in three types: full-spectrum, broad-spectrum, and CBD isolate. All of these can be formulated into a wide array of products, including oils, capsules, gummies, topicals, vape e-liquids, beverages, and more. It’s vital to understand the difference between the three types of CBD so you can choose the one that suits your individual preferences. Keep in mind that reputable CBD companies will always make it clear what type of CBD is present in a particular product with info on the label and product description. Full Spectrum Full-spectrum is a whole-plant hemp extract that contains all of the plant’s main active compounds.1 Although CBD is still the main ingredient, this extract also carries small concentrations of THC, other cannabinoids such as CBG, CBN, and CBC, terpenes, flavonoids, fatty acids, vitamins, minerals, and other phytochemicals. Full-spectrum CBD can also contain waxes, chlorophyll, and other inactive plant material, although their presence depends on the exact manufacturing process used. CBD in the form of full-spectrum hemp extracts have been shown to have increased potency due to what researchers are speculating to be the “entourage effect” — the synergistic relationship between cannabinoids, terpenes, and other components of cannabis.2 An easy way to imagine this is to think of an orchestra. When the piano, violin, and other components of an orchestra are played together, the resulting sound is more pleasing than any instrument by itself. Similarly, whole-plant cannabis preparations may be more potent because of the interplay between all their components as well as their individual effects. It’s also possible to make a full-spectrum extract from marijuana. However, this terminology is typically used to refer to hemp products, and it will often be clear if a product is made from marijuana rather than hemp. Broad Spectrum Broad-spectrum CBD is similar to full-spectrum but includes an additional step during preparation to remove THC. Some trace amounts of THC can remain, but they’re typically below levels detectable by third-party testing. This type of extract is ideal for those who wish to completely avoid THC for any reason (e.g., employee drug testing, high sensitivity to THC). Full-spectrum CBD products can result in a positive drug test and even cause a little intoxication in susceptible people at higher doses. Still, you should verify that your broad-spectrum product is actually free of THC by checking the third-party lab test reports. Broad-spectrum CBD also benefits from the cannabis entourage effect since you’re getting numerous cannabinoids, terpenes, and other beneficial phytochemicals. However, its effects may be slightly weaker than a full-spectrum extract due to the absence of THC. Isolate As the name suggests, CBD isolate is pure CBD. It’s made by isolating CBD from all other compounds pulled from hemp during the extraction process, leaving behind a white, tasteless, odorless crystalline powder that typically contains over 99% CBD. CBD isolates can sometimes contain very small (less than 1%) amounts of other cannabinoids, particularly CBDV because it has a similar molecular structure and gets left behind during the extraction process. Since CBD isolate lacks all of the other phytochemicals found in full-spectrum and broad-spectrum extracts, researchers speculate that it doesn’t benefit from the entourage effect, leading to a lower potency compared to whole-plant hemp extracts. So you may need to take higher doses to get similar effects. Having said that, CBD isolate has several advantages: It’s free of THC It’s easy to formulate into oils, capsules, gummies, and other products It tends to be cheaper than full-spectrum CBD You can use it in a wide variety of ways and can even make DIY CBD preparations Carrier Oils Aside from cannabidiol, every CBD oil will contain another key ingredient called a carrier oil. Carrier oils may help the body absorb CBD by binding to it and encouraging the release of enzymes involved in fat absorption. Carrier oils also make it easier to dose CBD by diluting it and can offer health benefits of their own. Thanks to its affordability, long shelf-life, effective absorption, and other favorable properties, the most popular carrier oil for CBD is coconut-derived medium-chain triglyceride (MCT) oil. However, any other plant-based oil can work just as well, including hemp seed oil, grape seed oil, olive oil, black cumin oil, as well as vegetable glycerin. CBD Extraction Another concept to be aware of is CBD extraction. Before formulating CBD oil, capsules, or other CBD products, you first need to pull CBD and other beneficial compounds out of the hemp plant. This process is called extraction and it can be done via different methods. Hemp extraction usually involves a solvent — a compound that helps isolate the CBD-rich oil from the hemp plant. The two most popular CBD extraction methods use alcohol or CO2 as solvents. Neither method is superior to the other as they both have their strengths and limitations. Other solvent extractions, such as butane, hexane, and propane, can be used as well. However, they’re not widely utilized by the CBD industry due to their high flammability and the possibility of leaving harmful residual solvents. Alcohol Extraction One of the crudest ways of creating cannabis extracts in the industry is by using alcohol as a solvent. Ethanol is usually the alcohol of choice but isopropyl alcohol is also used. For this method, cannabis plant material is soaked in ethanol to dissolve cannabis trichomes — the hair-like structures abundant on the flowers and leaves of the plant. Trichomes are rich in cannabinoids, terpenes, and other active ingredients.3 After this, the plant material is removed, and the alcohol is purged to leave behind a full-spectrum CBD extract. Alcohol extraction is popular because of its relative safety, effectiveness, and ease, allowing it to be done at home or scaled up to meet the high-volume needs of a CBD company. Although it started out as the go-to extraction method for marijuana, it has since grown equally common for CBD-rich hemp extraction. CO2 Extraction Although CBD extraction using ethanol is an effective method, most companies these days opt for carbon dioxide (CO2) extraction. This advanced and highly efficient extraction method involves pressurizing and heating CO2 to turn it into a supercritical fluid and passing it over hemp plant material to dissolve the trichomes and create a CBD-rich oil. The main advantage of the CO2 extraction method is that it’s highly tuneable — by adjusting the temperature and pressure, you can choose which compounds to target and what to leave behind.4 However, the CO2 extraction method requires expensive equipment, which is why it’s favored by bigger CBD companies. Some brands even utilize both ethanol and CO2 extraction. Nano Processing Another concept that can create confusion is what’s called nano CBD or water-soluble CBD. The truth is, CBD can never truly become water-soluble. But the industry uses the term when nanotechnology is being used to improve the absorption of CBD. You’ll sometimes see the term used in various CBD products like CBD oils, capsules, beverages, and other liquid CBD preparations. Nanotechnology is already widely utilized in the pharmaceutical industry to enhance the oral and topical delivery of drugs into the body.5 The central idea behind nano CBD is to break down the active plant compounds into tiny (nano) sized bits to increase their surface area and make them more bioavailable — that is, to increase how quickly and to what extent they’re absorbed by your body.6 There are two main approaches to increasing their bioavailability. The first is to protect the tiny CBD molecules with nano-sized fatty shells called liposomes, allowing more CBD to reach their destination. The second is the nanoemulsion method, where CBD oil is broken down into even smaller, nanosized particles, making them behave very similarly to water-soluble compounds, increasing your body’s ability to absorb it. These approaches are especially beneficial for CBD because of its naturally low bioavailability from being a fat-soluble compound that doesn’t dissolve in water and first-pass metabolism – needing to be processed through the digestive tract and liver .7 11 For example, oral CBD has an estimated bioavailability of 13–19%, which means you’re losing out on over 80 percent of the CBD you ingest.8 Simply put, CBD is difficult for our water-based bodies to absorb. Companies using nanotechnology claim that they can solve this issue, enhancing CBD’s effectiveness in the process. Does Nano CBD Work? This brings us to the key question — does nanotechnology improve CBD’s effectiveness? One study compared the absorption of cannabis-based drug Sativex to a nanoemulsion drug containing the same active ingredients: THC and CBD. The nanoemulsion had greater absorption, with 31% higher bioavailability for CBD and 16% for THC than Sativex.9 A similar study compared Sativex with a THC/CBD nanoemulsion infused with piperine — a black pepper compound used to enhance the bioavailability of supplements. Here again, the nanoemulsion showed much higher bioavailability.10 While these findings are certainly promising, the studies were conducted on very small groups using a very specific nanoemulsion drug. Nano CBD products may vary in their formulation methods, making it difficult to conclude which form of CBD on the market is superior. For now, take any claims you see on nano CBD products with a grain of salt. Watch Out for High-THC Cannabis Products Another thing to keep in mind is that because CBD is present in both hemp and marijuana, you should always take care to check which type of cannabis a given product is derived from. Although the vast majority of CBD products are sourced from hemp, this isn’t always the case. For example, it’s possible to find marijuana-derived oils, capsules, gummies, and similar products in states where recreational marijuana is legal, such as Colorado and Washington. Your best bet is to only buy products that come with third-party lab tests so you can confirm that they contain minimal THC. Rick Simpson Oil One prominent example of a marijuana-derived product that resembles CBD oil is Rick Simpson Oil (RSO). Although RSO is a full-spectrum cannabis oil that contains CBD, its levels are relatively low and THC is the main active ingredient. It was invented by Canadian cannabis activist Rick Simpson, who reportedly used RSO to cure his skin cancer and help other cancer sufferers. RSO and other marijuana-derived products are not the same thing as CBD oil and other high-CBD, low-THC preparations. Get the Knowledge Before Buying CBD Concepts like different CBD types, extraction methods, and nano CBD shouldn’t be intimidating. In fact, they can help you make a better decision by finding a safe, high-quality product that meets your specific needs. As one final tip, we recommend doing some research before buying a CBD product. You should check where it’s sourced from, which extraction method is used, and any other manufacturing information. Some companies, such as CBDistillery, the same products in different extract types. If you're interested in selections as such, we invite you to use our CBDistillery coupon code. Frequently Asked Questions What are the two types of CBD? The two main types of CBD are whole-plant CBD extract and CBD isolate. Whereas isolate contains pure CBD, whole-plant extracts contain CBD plus a wide range of hemp cannabinoids, terpenes, and other active compounds. What are the forms of CBD? CBD can come in many different product forms, including CBD oil tinctures, capsules, softgels, gummies, chocolate, vape e-liquids, beverages, isolates, topicals, and even smokable hemp flower. These products represent the four main ways of using CBD: sublingually, orally, topically, and through inhalation. What's the best form of CBD? There’s no “best” form of CBD because it depends on your particular goals. All-around, however, full-spectrum CBD oil is the most efficient, versatile way to use CBD. References 1. Marinotti, Osvaldo, and Miles Sarill. "Differentiating full-spectrum hemp extracts from CBD isolates: implications for policy, safety and science." Journal of Dietary Supplements (2020): 1-10. 2. Russo, Ethan B. "Taming THC: potential cannabis synergy and phytocannabinoid?terpenoid entourage effects." British journal of pharmacology 163.7 (2011): 1344-1364. 3. Happyana, Nizar, et al. "Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR." Phytochemistry 87 (2013): 51-59. 4. Rovetto, Laura J., and Niccolo V. Aieta. "Supercritical carbon dioxide extraction of cannabinoids from Cannabis sativa L." The Journal of Supercritical Fluids 129 (2017): 16-27. 5. Patra, Jayanta Kumar, et al. "Nano based drug delivery systems: recent developments and future prospects." Journal of nanobiotechnology 16.1 (2018): 71. 6. Price, Gary, and Deven A. Patel. "Drug Bioavailability." StatPearls [Internet]. StatPearls Publishing, 2020. 7. Millar, Sophie A., et al. "A systematic review on the pharmacokinetics of cannabidiol in humans." Frontiers in pharmacology 9 (2018): 1365. 8. Mechoulam, Raphael, Linda A. Parker, and Ruth Gallily. "Cannabidiol: an overview of some pharmacological aspects." The Journal of Clinical Pharmacology 42.S1 (2002): 11S-19S. 9. Atsmon, Jacob, et al. "PTL401, a new formulation based on pro-nano dispersion technology, improves oral cannabinoids bioavailability in healthy volunteers." Journal of Pharmaceutical Sciences 107.5 (2018): 1423-1429. 10. Cherniakov, Irina, et al. "Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration." Journal of Controlled Release 266 (2017): 1-7. 11. Huestis, Marilyn A. "Human cannabinoid pharmacokinetics." Chemistry & biodiversity 4.8 (2007): 1770.
CBD Legality Worldwide
CBD Legality Worldwide: Is CBD Legal In My Country? Is cannabidiol (CBD) legal in the United States? Yes, but there are some caveats that we’ll get into. The legal status of CBD worldwide, however, differs drastically by country and can be classified into four areas: Completely banned Legal grey area (no clear law saying whether CBD is legal or illegal) Restricted use (typically means CBD is only available to medical patients) Unrestricted use (available over-the-counter without any prescription) It’s easy to get confused when trying to figure out if CBD is legal in your country or one that you’re traveling to. That’s why we put together this guide with the most up-to-date information. Read on for a detailed look at CBD’s legal status around the world. Legal Status of CBD: Hemp vs Marijuana To get an overview of CBD’s legality it’s important to understand that there are two main varieties of the cannabis plant: marijuana and hemp. Marijuana is high in THC, which means it’s capable of causing intoxication. Hemp, on the other hand, is a type of cannabis with no more than 0.3% of THC, which isn’t enough to make people high. How these two cannabis varieties are regulated has a direct effect on whether CBD is legal in a given country. That’s because CBD products are almost always made from hemp. Many countries ban only marijuana because of its intoxicating effects but allow for the cultivation of hemp, which makes hemp-derived CBD legal. However, some countries ban all cannabis outright, not making a distinction between marijuana and hemp. In such cases, hemp-derived CBD products become illegal by extension. History & Current CBD Legalization in the United States The United States government made cannabis illegal in 1937 with the passing of the Marihuana Tax Act. Although this legislation was meant to outlaw marijuana due to fears over its mind-altering effects, it also indiscriminately banned hemp. This ban was in place until the 2018 Farm Bill that reclassified hemp as an agricultural commodity, making hemp-derived CBD legal on the federal level. It also removed restrictions on the sale, transport, and possession of hemp and hemp-derived products. However, this legislation has several key stipulations: The plants must contain 0.3% or less of THC to be considered hemp The hemp can only be cultivated by approved and licensed growers The hemp must adhere to shared state-federal regulations The bottom line is that CBD products made from hemp are legal in the United States. However, the Federal Food and Drug Administration (FDA) doesn't currently regulate the CBD industry, with the exception of the approved medication Epidiolex. Not to mention, CBD products derived from marijuana plants are a different story. Marijuana-Derived CBD The legal status of CBD products derived from marijuana depends on individual U.S. state laws. Some states ban marijuana completely, many allow patients access to medical marijuana, and others have made it legal for both medical and recreational use. Here’s a detailed breakdown: States Where Marijuana-Derived CBD is Legal for Medical Use Most American states allow for the medical use of marijuana. These 33 states include Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Oklahoma, Pennsylvania, Rhode Island, Vermont, Washington, West Virginia, and Utah. In these states, qualifying patients with a doctor’s prescription and a medical marijuana card can gain access to marijuana-derived CBD products. Furthermore, 17 states have special laws allowing for the medical use of CBD products with minimal THC levels: Alabama, Florida, Georgia, Indiana, Iowa, Kentucky, Mississippi, Missouri, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Utah, Virginia, Wisconsin, and Wyoming. States Where Marijuana-Derived CBD is Legal Marijuana is currently completely legal for both medical and recreational use in the District of Columbia and 11 U.S. states: Alaska, California, Colorado, Illinois, Oregon, Massachusetts, Maine, Michigan, Nevada, Vermont, and Washington. States Where Marijuana-Derived CBD is Illegal Marijuana is completely banned in Idaho, Kansas, Nebraska, and South Dakota. This means marijuana-derived CBD products are also illegal. However, these four states are expected to create medical cannabis programs in the near future. Legal Complications of CBD Unfortunately, legal complications can arise even in countries where CBD is supposedly legal. The United States is the best example of this, with some reports of people getting arrested and CBD businesses being raided and forced to stop selling CBD products. For example, a CBD store owner in Iowa was arrested in December 2019 for alleged “controlled substance violations and unlawful tax stamp violations.” The police claimed that the CBD products being sold at her store were illegal because any part of marijuana is illegal in the state of Iowa. Meanwhile, truckers were arrested that same year for transporting hemp in Idaho because the police thought they were carrying marijuana. Although cases such as these are rare, they still highlight the legal grey area that remains due to differences in state and federal regulations and the personal discretion of law enforcement. CBD Legality and Shopping Online Before we get into the legal status of CBD around the world, it’s important to mention that just because a country bans CBD, or only allows for its use through a strict medical program, doesn’t mean that you can’t buy it online. In fact, many people in these countries do just that. Having said that, doing so does carry some risks, especially in countries with more strict cannabis laws. It’s not unheard of for CBD product packages to be seized at the border. CBD Legality in North & Central America CBD is legal in the three major North American countries: Canada, the United States, and Mexico. However, the situation is more strict further south (e.g., Central America and the Caribbean), with most countries either banning all types of cannabis and by extension CBD, or restricting its use to medical patients. The history of cannabis in Canada, the U.S., and Mexico has a similar trajectory. Following the steps of the United States, Canada banned cannabis in 1938 but made it legal to cultivate in 1997, growing into one of the world’s major producers. In 2018, Canada became the second country to legalize cannabis, which also made CBD products legal. Similarly, Mexico banned cannabis in 1920 but legalized its medical use in 2017, provided that it contains less than 1% THC. This effectively made CBD oil legal in the country, although the law is currently in a bit of a grey area. Mexico’s Supreme Court has repeatedly ruled that prohibiting the recreational use of cannabis is unconstitutional and the government is expected to completely legalize cannabis by the end of 2020, which would also make CBD completely legal. CBD Legality in South America The legal status of CBD in South America differs drastically from country to country. CBD is banned in some countries, such as Ecuador and Suriname, legal only for medical use with a doctor’s prescription in others, such as Brazil, and fully legal in Uruguay and Colombia. These differences aren’t surprising because the continent has a complicated history with cannabis due to the burgeoning illegal drug trade, with some countries choosing a tougher stance and others opting in favor of decriminalization and eventual legalization. The three major South American countries — Brazil, Argentina, and Peru — only allow medical access to CBD. This means patients have to go through the appropriate application process and get a doctor’s prescription. CBD Legality in Europe Although there are some exceptions, CBD is legal in most European countries. There are several reasons for this but, to begin with, most European nations didn’t follow in the footsteps of the U.S. when it banned cannabis in the 1930s. Further, Europe has a long history of hemp cultivation. Hemp is legal in the European Union (EU) and the UK as long as it contains no more than 0.2% of THC. As such, hemp-derived CBD products are legal as well. Having said that, both the EU and the UK recently classified hemp-derived CBD with the Novel Food status, which introduces certain regulatory complexities that make it more difficult for companies to sell their products. Regardless, hemp-derived CBD products are completely legal in Germany, the UK, and the Netherlands, which means you can buy them without a prescription at over-the-counter stores and online. CBD products are also legal in France and Sweden as long as they’re completely free of THC. CBD is also partially legal or in a legal grey area in many other countries. In Italy, for example, CBD oil products containing anywhere from 0.2% to 0.6% of THC are considered legal. However, the country’s Supreme Court ruled in 2019 that only cannabis products without narcotic effects are legal. This has created confusion because it’s not clear whether CBD oils with 0.2–0.6% of THC fall under this definition or not. Spain has a similarly confusing situation. While topical CBD products are entirely legal, food supplements containing CBD, such as CBD oil, are technically illegal, even though they’re available in many places. CBD Legality in Africa Africa has some of the most strict cannabis laws in the world. As a result, cannabis products, including CBD, are illegal in almost all countries on the continent. This may be because cannabis has been used for centuries for its recreational effects in many African countries. Hemp, on the other hand, has been grown only in recent times and in a limited number of countries, so there isn’t much recognition of its value and difference from marijuana. South Africa is one of the few exceptions, making an amendment in 2019 that allows for the over-the-counter sale of CBD products as long as they meet several requirements, such as providing doses of no more than 20 mg of CBD daily. Other CBD products require a doctor’s prescription. CBD Legality in Asia & the Middle East Although hemp originated in Asia, the laws surrounding its legality vary wildly in the region. In the Middle East and some other countries such as Singapore, cannabis laws are very strict and CBD is completely illegal. China’s case is a little more complicated. Although CBD is not strictly illegal in the county, for now, it’s only allowed to be sold in cosmetic products. In addition, you can be penalized for trying to import CBD oils and other CBD products that are considered food items. Meanwhile, CBD in India is in somewhat of a legal grey area; there’s no official ruling on the legality of hemp and CBD, although individual states are working on creating regulations for hemp cultivation. CBD is in a similar situation in Russia. While THC is prohibited, there are no explicit rulings for CBD. Meanwhile, in Japan and Hong Kong, CBD products are completely legal as long they contain zero THC. CBD Legality in Australasia CBD is legal for medical use in Australasia, the region that consists of Australia, New Zealand, Papua New Guinea, and some island nations. Hemp was introduced to this part of the world by the British and when the U.S. banned cannabis in the 1930s, Australia followed suit. Today, CBD products can only be accessed through medical programs in both Australia and New Zealand. This may soon change, however, as the Australian government is considering making low-dose CBD products legal over-the-counter while New Zealand will hold a referendum on whether cannabis should be made legal in September of 2020. Conclusion As we can see, the legality of CBD differs drastically by country. In some places, hemp-derived CBD products are completely legal, while in others there are specific restrictions, and some places ban CBD outright. Many countries are also stuck in a legal grey area without a clear indication of whether CBD is legal or not. There are even cases of legal complications in countries where CBD is supposedly legal due to confusing laws. Whatever the case, we can certainly expect CBD to continue becoming legal in more countries as attitudes towards hemp and cannabis as a whole continues to change, with increased recognition of the plant’s beneficial effects. For now, you should exercise caution and be aware of the specific laws of your country and keep them in consideration, especially if you want to purchase a CBD oil product online. Frequently Asked Questions What Is CBD Oil And Is It Legal? CBD oil is a supplement made by combining CBD-rich extracts of the hemp plant with a carrier oil that improves CBD’s absorption, such as coconut-derived MCT oil. CBD oil is legal in many places around the world. Where Is CBD Oil Legal? Hemp-derived CBD oil is legal in the United States and many other countries, including Canada, the UK, Germany, and the Netherlands. Some countries have specific restrictions on the legality of CBD oil, such as requiring it to contain 0% THC or only allowing its use for medical patients, while others completely ban it. How Much THC Is Legal In CBD Oil? CBD oil is allowed to contain 0.3% or less of THC in Canada and the U.S. and 0.2% or less in the UK and most European countries. However, some countries only allow CBD oils that contain zero THC. What Is The Best Legal CBD Oil? There are many brands of CBD oil out there, but some stand out as the best. These include reputable, experienced companies such as Nuleaf Naturals, Endoca, Lazarus Naturals, and PlusCBD Oil.
CBD for Sleep
Scientific Confidence Grade Effect Size Rating Editorial Note C ** CBD may help with sleep disorders by targeting their underlying causes. However, most of the current evidence is limited to animal and low-quality human studies. The available human research evidence is promising but of relatively low quality. Research suggests that CBD may significantly improve sleep problems. CBD for Sleep Disorders: Can It Help? (January 2021) Early human studies suggest that cannabidiol (CBD) may improve sleep disorders. Researchers believe it works by influencing our endocannabinoid system and addressing the underlying causes of sleep problems, such as anxiety. We’ve all dealt with occasional sleeplessness and other sleep-related issues. However, when these problems become a regular occurrence, you may be suffering from a sleep disorder, such as insomnia. While these conditions can be treated, standard medications often come with unwanted side effects and cannot be used long-term. Besides, many drugs only treat the symptoms of sleep disorders — such as difficulty falling asleep — rather than the underlying causes. As a result, there’s increasing interest in alternative, natural solutions like cannabis and CBD. There’s some evidence that CBD can help with insomnia and other sleep disorders, particularly by targeting their underlying causes. Read on for a look at what researchers say about CBD’s potential to aid healthy sleep. Sleep Disorders Overview Sleep disorders affect your sleeping patterns and make it difficult to get the right amount of quality sleep. They can decrease the quality of life and harm your overall health, particularly through sleep deprivation. There are many types of sleep disorders, but insomnia — difficulty falling and staying asleep — is the most common. Sleep disorders typically manifest as excessive daytime drowsiness due to a lack of quality sleep at night. Sleep Disorder Subtypes Sleep disorders can be grouped into several types:  Insomnia: the most common type of sleep disorder, characterized by difficulty falling and staying asleep. Breathing related sleep disorders: sleep apnea and other disorders linked to difficulty breathing during sleep. Hypersomnia: conditions such as narcolepsy and idiopathic hypersomnia that make it difficult to stay awake during the day. People with these disorders can fall asleep at any time. Parasomnia: disorders characterized by abnormal behaviors when you’re falling asleep, sleeping, or waking up, such as sleepwalking and sleep terrors. Circadian rhythm sleep disorders: sleep disorders where your body’s internal 24-hour sleep-wake clock is out of sync with your environment’s light-dark cycle, causing you to feel disoriented and sleepy. Sleep Movement disorders: conditions that make it difficult to get restful sleep by causing movements, such as restless leg syndrome and bruxism. Sleep Disorder Symptoms & Pathology The most common symptom of sleep disorders is excessive daytime sleepiness and associated problems such as difficulty concentrating, irritability, and feeling very tired. Depending on the exact type, sleep disorders can also cause movement during sleep, irregular breathing, and other issues. Can CBD Help With Sleep Disorders? Alleviating insomnia and improving overall sleep quality is one of the most common reasons people turn to CBD products. What’s so promising about CBD is that it seems to work by tackling the underlying causes of sleep disorders instead of just their symptoms. For example, anxiety, depression, and other conditions such as post-traumatic stress disorder, are known to either cause or contribute to insomnia and other sleep problems.   Preliminary studies have suggested that CBD may help alleviate anxiety, PTSD, and possibly have antidepressant-like effects as shown in a mouse study.   That means people whose sleep issues are related to these conditions can potentially benefit from CBD. Anxiety, in particular, is one of the leading causes of insomnia. Similarly, chronic pain is another reason many people struggle to get good sleep. In this case, CBD’s pain-relieving properties may be beneficial.  Another interesting finding is that CBD may have a biphasic effect on sleep. This means that low doses of CBD at certain times may actually promote wakefulness, as demonstrated by a study in rats.  Furthermore, higher doses of CBD may act as a sedative, as shown by a small study on humans, where 160 mg doses increased total sleep time and reduced sleep disturbances.  These preliminary findings merit further research to confirm whether CBD can be taken at night to promote sleep or be used in lower doses during the day to counteract the excessive daytime sleepiness caused by most sleep disorders. Not to mention, it's unclear how much of an effect other hemp properties - such as flavonoids and terpenes - have on sleep. The Endocannabinoid System and Sleep We also know that the body’s endocannabinoid system (ECS) plays an important role in regulating the sleep-wake cycle. This crucial system helps your body maintain a balanced state called homeostasis by regulating a wide range of essential processes, such as immunity, metabolism, and brain function.  The ECS consists of endocannabinoids made in our bodies, the enzymes that build and break them down, and the cannabinoid receptors (CB1 & CB2) they activate. The most popular theory is that the ECS plays a role in the effects of the suprachiasmatic nucleus — the part of the brain which controls an individual’s 24-hour circadian rhythm — on sleep and other processes.  This means the ECS may help maintain and promote sleep. Researchers are working hard to clarify the connection between the ECS and sleep. A study in rats revealed that the levels of endocannabinoids, their associated enzymes, and even cannabinoid receptors appear to fluctuate throughout the day, with a marked difference between the day and night.  The results from a study of healthy humans showed that levels of the endocannabinoid anandamide are three times higher when waking up versus going to sleep and that this relationship is dysregulated by sleep deprivation.  Furthermore, there’s evidence that activation of CB1 receptors via THC — the main intoxicating cannabinoid — can promote sleep. This may begin to describe the correlation between people feeling sleepy after taking cannabis with high levels of THC.  A study in rats also found a strong correlation between the light-dark cycle, sleep, and levels of ECS components. Specifically, CB1 receptor density increased in the pons area of the brain during REM rebound — the period of increased REM sleep that follows sleep deprivation.  Taken together, all of these findings suggest that our endocannabinoid system plays an important role in regulating our sleep cycle and making sure we get enough sleep. Since more and more evidence is showing how CBD can interact with this system in various ways (e.g., by suppressing the enzyme that breaks down anandamide, altering the function of the CB1 receptor), CBD may provide a possible avenue to help with sleep disorders.   What Does the Research Say? There’s a growing volume of human research suggesting that CBD can help with sleep disorders. One 2019 study out of Colorado looked at the effects of CBD on 72 people with anxiety and poor sleep. CBD decreased anxiety in 79% of the study participants for all three months of treatment. Sleep was improved in 67% of the subjects during the first month but fluctuated for the remaining two months.  A different study of 21 adults with PTSD reported that 38% experienced improvements in sleep after taking CBD.  There are also multiple case reports of individuals who improved their sleep by taking CBD. One such report discussed the cases of four Parkinson’s disease patients with REM sleep behavior disorder (RBD), a type of parasomnia characterized by acting out vivid, violent dreams during rapid eye movement (REM) sleep. All four patients experienced a significant improvement in RBD after taking CBD.  Another case report discussed a woman with restless leg syndrome (RLS) who relieved her symptoms and improved sleep by using CBD oil.  Finally, a case report of a ten-year-old girl with PTSD noted that CBD oil improved her insomnia.  In short, the available human research evidence of CBD’s positive effects on sleep disorders is promising. Having said that, there’s a lack of high-quality evidence and the type of rigorous research needed like randomized controlled trials (RCTs), to confirm findings and provide specific therapeutic guidance on the use of CBD for improving sleep. How Much CBD Should I Take for Sleep? There’s no consensus on the right amount of CBD to take to promote good sleep. There simply isn’t enough research in this area. Besides, your ideal CBD dosage for sleep or any other issue depends on many variables, such as body weight, genetics, symptom severity, and the type of product you’re using. As such, it’s hard to suggest a CBD dosage that will work for everyone. If you’re new to CBD, it’s best to start with a small dose (10-15 mg) and see how it makes you feel. If you don’t notice any effect, you should gradually raise the dosage over a few hours or days, making sure to stop in between doses to see if you feel anything. Once you find the CBD dose that provides you with the relief you’re looking for, stick to it. Also, keep in mind that it’s best to take CBD about 20-60 minutes before sleep to give it time to start working. Some products are (such as CBD gummies and tinctures) make it easier to measure out doses. We highly suggest finding a CBD product that's designed for sleep aid. Are There Any Side Effects? According to numerous research studies, CBD is a generally safe substance with few side effects and was even tolerated well at daily dosages as high as 1500 mg.  Although CBD can cause issues such as tiredness, drowsiness, diarrhea, dry mouth, low blood pressure, dizziness, and changes in appetite or weight, these effects are relatively mild and have only been reported by studies using very high doses of pure CBD (300 mg and up).  Most people take no more than 100 mg of CBD at a time, so they’re unlikely to experience these side effects. Additionally, instead of pure CBD, many individuals use whole-plant, full-spectrum CBD extracts which have been shown to have a lower risk of side effects.  Conclusion Although more high-quality research is needed, early findings suggest that CBD oils can have a beneficial effect on sleep problems and full-on sleep disorders such as insomnia. This isn’t all that surprising as CBD: Interacts with the endocannabinoid system, which is known to regulate the sleep-wake cycle May improve many of the health issues that can cause or worsen sleeping problems, such as chronic pain, anxiety, and depression Although figuring out the right CBD dosage can take some experimentation, CBD is a safe, natural substance with few and minor side effects. In comparison, many of the prescription medications used for sleep disorders cannot be used in the long-term due to significant adverse effects and the possibility of addiction and withdrawal. Not to mention, CBD products for sleeping are often made with a number of other sleep-promoting all-natural ingredients, such as melatonin. References  Chokroverty, Sudhansu. "Overview of sleep & sleep disorders." Indian J Med Res 131.2 (2010): 126-140.  Oh, Chang-Myung, et al. "The effect of anxiety and depression on sleep quality of individuals with high risk for insomnia: a population-based study." Frontiers in neurology 10 (2019): 849.  Maher, Michael J., Simon A. Rego, and Gregory M. Asnis. "Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management." CNS drugs 20.7 (2006): 567-591.  Masataka, Nobuo. "Anxiolytic effects of repeated cannabidiol treatment in teenagers with social anxiety disorders." Frontiers in Psychology 10 (2019): 2466.  Sales, Amanda J., et al. "Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels." Progress in Neuro-Psychopharmacology and Biological Psychiatry 86 (2018): 255-261.  Vu?kovi?, Sonja, et al. "Cannabinoids and pain: new insights from old molecules." Frontiers in pharmacology 9 (2018): 1259.  Murillo-Rodríguez, Eric, et al. "The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent." Behavioral neuroscience 122.6 (2008): 1378.  CARLINI, ELISALDO A., and JOMAR M. CUNHA. "Hypnotic and antiepileptic effects of cannabidiol." The Journal of Clinical Pharmacology 21.S1 (1981): 417S-427S.  Skaper, Stephen D., and Vincenzo Di Marzo. "Endocannabinoids in nervous system health and disease: the big picture in a nutshell." (2012): 3193-3200.  Babson, Kimberly A., James Sottile, and Danielle Morabito. "Cannabis, cannabinoids, and sleep: a review of the literature." Current psychiatry reports 19.4 (2017): 23.  Valenti, M., et al. "Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain." Cellular and Molecular Life Sciences CMLS 61.7-8 (2004): 945-950.  Vaughn, Linda K., et al. "Endocannabinoid signalling: has it got rhythm?." British journal of pharmacology 160.3 (2010): 530-543.  Murillo-Rodríguez, Eric. "The role of the CB1 receptor in the regulation of sleep." Progress in Neuro-Psychopharmacology and Biological Psychiatry 32.6 (2008): 1420-1427.  Martnez-Vargas, M., et al. "Sleep modulates cannabinoid receptor 1 expression in the pons of rats." Neuroscience 117.1 (2003): 197-201.  Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.  Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. "Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study." PloS one 14.7 (2019): e0220025.  Shannon, Scott, et al. "Cannabidiol in anxiety and sleep: a large case series." The Permanente Journal 23 (2019).  Elms, Lucas, et al. "Cannabidiol in the treatment of post-traumatic stress disorder: a case series." The Journal of Alternative and Complementary Medicine 25.4 (2019): 392-397.  Chagas, Marcos HN, et al. "Cannabidiol can improve complex sleep?related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series." Journal of clinical pharmacy and therapeutics 39.5 (2014): 564-566.  Megelin, Thomas, and Imad Ghorayeb. "Cannabis for restless legs syndrome: a report of six patients." Sleep medicine 36 (2017): 182.  Shannon, Scott, and Janet Opila-Lehman. "Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: a case report." The Permanente Journal 20.4 (2016).  Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. "en Crippa, JA (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent." Current Drug Safety 6.4: 237-249.  Huestis, Marilyn A., et al. "Cannabidiol adverse effects and toxicity." Current neuropharmacology 17.10 (2019): 974-989.  Pamplona, Fabricio A., Lorenzo Rolim da Silva, and Ana Carolina Coan. "Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis." Frontiers in neurology 9 (2018): 759.
CBD for Psoriasis
Scientific Confidence Grade Effect Size Rating Editorial Note C ** CBD may help relieve the symptoms and underlying causes of psoriasis. However, much of the evidence is limited to test-tube studies. There’s only one, low-quality human study. CBD for Psoriasis: Can It Help? Early research suggests that CBD may have a positive effect on psoriasis. These findings highlight the involvement of the body's endocannabinoid system (ECS) in overall skin health. However, it remains too early to tell whether or not you should use CBD for psoriasis over traditional medication. Psoriasis is a common skin condition characterized by scaly, itchy patches of skin. It’s usually treated by topical creams and ointments, but the condition is not curable and standard treatments are not always effective. That’s why many people turn to alternative options such as cannabis and hemp-derived cannabidiol (CBD) products. Research suggests that CBD may alleviate the symptoms of psoriasis and perhaps even address the overactive immune responses that underlie this condition. In particular, it seems that applying CBD topically may have a positive effect. Here’s what the science says about the potential of using CBD for psoriasis. Psoriasis Overview Psoriasis is an autoimmune skin disorder that causes red, itchy marks covered by flaking silvery scales. It most commonly affects the knees, elbows, scalp, and torso. Health experts believe the main cause of psoriasis is the rapid growth of skin cells resulting from an overactive immune system.  Psoriasis is a chronic condition that goes through cycles of flaring up and receding. Psoriasis Subtypes There are several types of psoriasis:  Plaque psoriasis (psoriasis vulgaris): the most common type of psoriasis (90% of cases), distinguished by raised, red, itchy patches covered in white scales. Inverse psoriasis: inflamed, shiny marks that occur in areas where your skin folds, such as the armpits, groin, and the inner thighs. Guttate Psoriasis: this type of psoriasis is marked by small red spots and tends to affect children and adolescents. Pustular Psoriasis: characterized by red, scaly patches with pustules that affect the hands and feet. Erythrodermic psoriasis: a short-term condition distinguished by red, inflamed skin present on over 90% of the body. It can occur in any type of psoriasis as a result of sunburn, certain medications, and other factors. Some people also develop psoriatic arthritis, a form of arthritis that occurs in about 20% to 30% of psoriasis sufferers. Psoriasis Symptoms and Pathology The most common symptom of psoriasis is raised, red, flaky skin patches. These patches can be small in size or affect large areas. Psoriasis can also cause soreness, itching, and burning around the spots, pitted nails, and dry, cracked skin that can bleed. These symptoms are worst during a flare-up and can disappear completely when psoriasis subsides. Can CBD Help With Psoriasis? There’s a growing number of test-tube studies suggesting that CBD may have a positive effect on psoriasis. One 2007 study looked at the effects of CBD, THC, and other cannabinoids on keratinocytes: the skin cells whose rapid growth — what scientists call proliferation — is the main cause of psoriasis. All of the cannabinoids reduced keratinocyte proliferation, leading the researchers to conclude that there’s a “potential role for cannabinoids in the treatment of psoriasis.”  More recently, the authors of a 2017 paper proposed that cannabinoids can help with psoriasis by addressing two key processes involved in its development: inflammation and angiogenesis, the formation of new blood vessels.  As it happens, CBD has been demonstrated to have both anti-inflammatory and antiangiogenic effects.   Additionally, a 2020 study looked at the effects of CBD on isolated human keratinocytes. The researchers found that cannabidiol affected the cells’ differentiation, leading them to conclude that it could be useful for treating various skin disorders.  CBD, The Endocannabinoid System, and Your Skin Researchers theorize that the potential benefits of CBD in treating psoriasis may come from its interaction with the body’s endocannabinoid system (ECS). The ECS consists of three parts: endocannabinoids produced by our bodies, the enzymes that make and break them down, and cannabinoid receptors (CB1 & CB2). CBD interacts with the ECS in two major ways: Suppressing an enzyme (FAAH) that breaks down the endocannabinoid anandamide, boosting its levels and prolonging its effects  Altering the function of the CB1 receptor  Discovered only recently, this important system plays a role in regulating everything from brain function to immunity to maintaining what’s called homeostasis — a state of internal balance.  Each component of the ECS can also be found in the skin — your largest organ — with growing evidence that this system may be involved in maintaining skin health. In particular, studies have shown that the ECS is involved in skin cell proliferation, differentiation, survival, and immune responses, all of which can play a role in psoriasis.  There’s also an indication that malfunction of the ECS may be associated with the development of skin conditions, including psoriasis.  For example, one study found that people with psoriasis and a related condition called psoriatic arthritis had elevated endocannabinoid levels in various blood cells.  The bottom line is that the ECS may play an essential role in skin health and the processes that underlie psoriasis and other skin conditions. Although dosages, timing, and method of intake are yet to be determined for effective treatment, the preliminary evidence suggests that using CBD may have a positive effect on psoriasis and its symptoms through its effect on the ECS. Anandamide and the Skin When it comes to the role of the ECS on skin health, the endocannabinoid anandamide may be particularly interesting. One study found that it reduced the release of pro-inflammatory molecules called cytokines by immune cells in the skin, a process that seems to be involved in causing psoriasis and other inflammatory skin conditions.  There’s also proof that anandamide can reduce itching — one of the symptoms of psoriasis — as demonstrated by a study where suppressing the FAAH enzyme reduced the itching response in mice.  As we highlighted earlier, CBD has the same effect on this enzyme and can result in increased anandamide levels. As such, increasing anandamide levels could be a major factor in how CBD may help treat psoriasis. Additionally, a recent 2020 review paper summarizing the results of various studies on the effects of anandamide, THC, CBD, and other cannabinoids, concluded that they all may have an important role in reducing skin inflammation, cell proliferation, fibrosis, pain, and itching, all of which may help with treating psoriasis and other skin conditions.  What Does the Research Say? There isn’t much human or clinical research looking at the use of CBD for treating psoriasis patients. One 2019 Italian study examined the effects of a CBD-infused ointment on 20 people with psoriasis, eczema, or scarring as a result of these conditions. The study participants applied the ointment to affected skin areas two times a day for 90 days. The treatment improved the symptoms and severity of psoriasis and several measures of skin health, such as elasticity and hydration.  The researchers concluded that applying CBD topically is a safe and effective way to improve the quality of life in people with skin disorders. Although these findings are promising, more high-quality studies, and especially randomized controlled trials (RCTs) — the gold standard of clinical research — are needed. How Much CBD Should I Take for Psoriasis? There isn’t enough research to suggest the ideal CBD dosage for psoriasis. This is especially true when applying CBD topically since most studies use either capsules or CBD oil. Besides, CBD dosage can vary depending on genetic factors, the type of product you’re using, and other variables. Your best option is to start by applying the amount of CBD recommended by your topical product to the affected skin areas. If you don’t notice any effects after a few days or weeks, you can try to raise the dose, making sure to try it for at least a few days before raising again if needed. If you’re using a topical product, you can estimate your CBD dose by dividing the total CBD content by the container volume. For example, if a 30 ml cream contains 600 mg of CBD, that’s 20 mg per ml. Next, you can estimate how much of an ml of the product you’re using to arrive at your estimated CBD dose. Are There Any Side Effects? One of the great things about CBD is that it’s a remarkably safe compound. Although it can cause some side effects, they are relatively mild in nature and have only been reported by studies using high dosages.  More importantly, CBD and hemp's other cannabinoids can only produce side effects when they reach the bloodstream. When applied topically in the form of a cream, ointment, or another product, CBD and other cannabinoids are highly unlikely to penetrate deep enough into the skin to reach the blood. Having said that, other ingredients in topical CBD preparations — such as terpenes or fragrances — may cause allergic reactions or other adverse effects in rare cases.  Conclusion More research is needed to show that CBD or other cannabinoids can provide relief for psoriasis. In particular, high-quality human studies are lacking, and most of the findings are restricted to test-tube studies. Nonetheless, the current evidence suggests that CBD may help alleviate psoriasis symptoms and address its underlying causes, such as an overactive immune response in the skin and a rapid build-up of keratinocyte cells. Given that it’s relative safety — especially when applied topically — CBD represents a promising, natural option for alleviating psoriasis. This is especially true for cases where standard pharmaceutical treatments are either ineffective or produce significant side effects. References  Lowes, Michelle A., Mayte Suárez-Fariñas, and James G. Krueger. "Immunology of psoriasis." Annual review of immunology 32 (2014): 227-255.  Rendon, Adriana, and Knut Schäkel. "Psoriasis pathogenesis and treatment." International journal of molecular sciences 20.6 (2019): 1475.  Tiwari, V., & Brent, L. H. (2019). Psoriatic Arthritis.  Wilkinson, Jonathan D., and Elizabeth M. Williamson. "Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis." Journal of dermatological science 45.2 (2007): 87-92.  Norooznezhad, Amir Hossein, and Fatemeh Norooznezhad. "Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation." Medical Hypotheses 99 (2017): 15-18.  Atalay, Sinemyiz, Iwona Jarocka-Karpowicz, and Elzbieta Skrzydlewska. "Antioxidative and anti-inflammatory properties of cannabidiol." Antioxidants 9.1 (2020): 21.  Solinas, M., et al. "Cannabidiol inhibits angiogenesis by multiple mechanisms." British journal of pharmacology 167.6 (2012): 1218-1231.  Casares, Laura, et al. "Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1." Redox biology 28 (2020): 101321.  Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.  Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. "Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study." 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"Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus." Journal of Pharmacology and Experimental Therapeutics 329.1 (2009): 314-323.  Cintosun, Amber, Irene Lara-Corrales, and Elena Pope. "Mechanisms of Cannabinoids and Potential Applicability to Skin Diseases." Clinical Drug Investigation (2020): 1-12.  Palmieri, B., C. Laurino, and M. Vadalà. "A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars." Clin Ter 170.2 (2019): e93-e99.  Iffland, Kerstin, and Franjo Grotenhermen. "An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies." Cannabis and cannabinoid research 2.1 (2017): 139-154.  Nath, Neel Som, et al. "Contact allergy to hydroperoxides of linalool and D-limonene in a US population." Dermatitis 28.5 (2017): 313-316.
CBD for Inflammation
Scientific Confidence Grade Effect Size Rating Editorial Note B + ** CBD seems to reduce inflammation and has beneficial effects on a long list of disorders with a significant inflammatory component. Nonetheless, more human studies are needed to confirm its efficacy across individuals. Multiple high-quality clinical trials lay the ground-work to reveal the potential of CBD in treating inflammatory conditions. The evidence suggests that CBD may play a key role in regulating inflammation in various populations. Can CBD Help With Inflammation? Cannabidiol (CBD) is widely recognized for its anti-inflammatory properties. Research shows that it has the potential to help with a lengthy list of conditions marked by chronic inflammation, ranging from autoimmune to neurodegenerative conditions. We’ve all experienced inflammation as part of our body’s healing process (e.g., after stubbing our toe, an accidental cut, or getting sick). Inflammation is a perfectly normal immune system response meant to help you recover. But when inflammation becomes chronic, it can have a detrimental effect and is a contributing factor to a wide range of medical conditions that can affect any part of the body. There are many medications used to reduce inflammation and help with specific inflammatory conditions, such as nonsteroidal anti-inflammatory drugs (NSAIDs). However, these drugs (e.g., aspirin, ibuprofen) are often limited in scope and come with side effects. That’s why people are increasingly turning to safer, natural alternatives. With that, many wonder if you can use cannabis and CBD for inflammation. CBD and other cannabinoids are arguably best known for their anti-inflammatory effects and have shown great potential in many diseases with a chronic inflammatory component. Here’s what the research says about using CBD for inflammation. Inflammation Overview Inflammation is your immune system’s natural response to injury, infections, and harmful substances. Inflammation is meant to help the body remove whatever may be causing harm and help repair the damage. When it operates as intended, the inflammatory response is activated in response to tissue damage by bacteria, toxins, heat, or trauma, and subsides within a couple of days. Unfortunately, when your body’s inflammatory response is not well regulated and becomes chronic, it can harm rather than protect you. This type of inflammation plays an important role in many serious health conditions. Inflammatory Disorders Chronic inflammation can affect virtually any part of the body, including the digestive tract, joints, skin, brain, and other organs. It plays a particularly notable role in autoimmune conditions such as multiple sclerosis and type 1 diabetes, which are characterized by the body’s immune system mistakenly attacking its own cells. Chronic inflammation is also involved in a wide variety of other conditions, including arthritis, allergies, stroke, respiratory conditions, inflammatory bowel disease, cardiovascular diseases, neurodegenerative conditions, and even cancer.  Low-grade chronic inflammation also plays a role in obesity and type 2 diabetes. Inflammation Symptoms & Pathology Signs of acute inflammation include swelling, pain, heat, redness, and loss of function in the affected area. Meanwhile, the most common symptoms of chronic inflammation are body, joint, and muscle pain, chronic fatigue, insomnia, depression, anxiety, gastrointestinal issues such as diarrhea and constipation, weight loss or weight gain, and frequent infections. Can CBD Help With Inflammation? CBD and other cannabinoids are perhaps best known for their anti-inflammatory effects. Most notably, research suggests that CBD can suppress certain immune system activities, many of which are related to inflammation. For example, CBD has been shown to lower the levels of pro-inflammatory molecules called cytokines by reducing the migration and activity of immune cells involved in releasing them. CBD’s anti-inflammatory properties have been explored in various animal and test-tube studies for multiple inflammatory conditions including arthritis, allergic contact dermatitis, type 1 diabetes, skin inflammation, neuroinflammation, asthma, and inflammatory bowel disease.        CBD, the Endocannabinoid System, and Inflammation Research suggests that most of CBD’s anti-inflammatory effects come from its interaction with the body’s endocannabinoid system (ECS). The ECS has three major components: Endocannabinoids produced by our bodies: anandamide and 2-AG. Special enzymes that build and break down endocannabinoids. Cannabinoid receptors (CB1 & CB2) that interact with both endocannabinoids and phytocannabinoids such as CBD and THC. Although studies have yet to confirm its role, this essential system may be involved in regulating the immune system and, by extension, the inflammatory response. However, there’s evidence that immune cells are not only influenced by but also make and release their own endocannabinoids. Furthermore, the CB2 receptor, which is abundant in immune system cells, seems to play a particularly key role in regulating inflammation. Multiple studies have shown that mice without this receptor suffer from increased inflammation. Additionally, an investigation in rats demonstrated that activation of CB2 receptors in immune cells suppressed the release of pro-inflammatory molecules. Other studies have also shown that CB2 activation can reduce pain and inflammation. Other parts of the ECS have also been studied and shown to have the capacity to influence inflammation. For instance, in a test-tube study, the endocannabinoid anandamide was revealed to be capable of inhibiting the activation of (NF)-κB, a major proinflammatory pathway. CBD can have an impact on these and other inflammation-regulating ECS activities by suppressing the enzyme that breaks down the endocannabinoid anandamide and by altering the function of the CB1 receptor.  Other Anti-Inflammatory Mechanisms of CBD Aside from its effects on the ECS, researchers have also discovered other ways that CBD can potentially lower inflammation. Here’s a look at the most prominent findings: CBD can interact with glycine, TRPV1, and other receptors involved in regulating inflammation CBD may be able to increase adenosine which can, in turn, activate adenosine receptors to reduce inflammation CBD may inhibit the (NF)-κB pro-inflammatory pathway CBD may stimulate the PPARγ receptor, which can reduce inflammation What Does the Research Say? Most of the evidence for CBD’s anti-inflammatory properties are limited to animal and petri dish research. However, the list of human studies is steadily growing. For starters, clinical trials suggest that CBD-rich cannabis preparations can help people with either type of inflammatory bowel disease (IBD): ulcerative colitis and Crohn’s disease. In one 2019 pilot study, CBD-rich cannabis extract capsules improved subjective ratings of disease severity and quality of life in ulcerative colitis sufferers when compared to the placebo group. The results were nearing statistical significance but were limited due the small number of participants (n=39) that completed it.  Additionally, a highly scrutinized and yet-to-be-published study presented at the 2017 International Association of Cannabis Medicine found that CBD-rich cannabis oil (15% CBD and 4% THC) improved quality of life and disease severity in 50 Crohn’s disease patients. A follow-up publication in 2020 by the same researcher revealed that 65% of the people in their CBD group achieved disease remission, compared to only 35% for placebo. Studies of CBD in neurodegenerative conditions — which have a significant inflammatory component — have also reported positive findings. In one 2014 trial, CBD treatment improved quality of life ratings in Parkinson’s disease patients compared to those taking the placebo. Furthermore, a 2019 pilot study in people with severe dementia found that cannabis oil containing a 2:1 ratio of CBD to THC had a positive effect on behavior, daily care needs, and prescription medication use. Another area where CBD’s anti-inflammatory properties have shown promise is autoimmune disorders. In particular, studies of the drug Sativex, which contains equal amounts of THC and CBD, have reported positive effects in some individuals suffering from multiple sclerosis and rheumatoid arthritis.  All in all, while more research is needed, multiple human studies and reviews, including high-quality randomized controlled trials (RCTs), suggest that CBD products can have beneficial effects on inflammatory conditions. How Much CBD Should I Take for Inflammation? There’s no “right” dose of CBD for inflammation that will work for everyone. It can vary depending on many factors, such as your unique body chemistry, body weight, the specific inflammatory condition you’re dealing with, and its severity. CBD products also come in many different forms which can influence the optimal dosage for your needs. For this reason, it’s best to follow the “start low and go slow” approach. You can begin with a small dose of CBD (10-15 mg) and wait for a few hours to see if you notice any effects. If the dose is too small, you can slowly raise it in small increments of 5 to 10mg. Be sure to wait and see if a dose affects you before increasing it again until you find the amount that provides the anti-inflammatory effect you’re looking for. Are There Any Side Effects? Research indicates that CBD is a very safe substance. General safety studies of CBD have only reported mild-to-moderate side effects such as sleepiness, tiredness, diarrhea, dry mouth, low blood pressure, dizziness, and changes in appetite or weight. Even a study using dosages as high as 6000 mg did not report any serious complications in healthy individuals. Some of these issues, notably sleepiness and fatigue, were also noted by a study of CBD in people with inflammatory bowel disease. Besides, most studies of CBD use high dosages, so the likelihood of side effects is fairly low for the average CBD user. This is especially true when using full-spectrum CBD preparations, which have been reported to have a lower risk of side effects than pure CBD. Conclusion Like most cannabinoids, CBD may possess potent anti-inflammatory properties that could potentially be helpful for inflammatory conditions. While more high-quality research needs to be done, there’s already solid evidence that merits further research to confirm how CBD may reduce inflammation and potentially help treat a wide variety of conditions marked by chronic inflammation including autoimmune, digestive, and neurodegenerative disorders. On top of that, there continues to be more animal and test-tube studies that are revealing CBD’s potential to help with other types of inflammation and inflammatory disorders, such as asthma, skin conditions, and arthritis. If you want to try CBD for inflammation, it may take some trial and error to find the right dosage. Having said that, CBD is a perfectly safe, natural compound with only minor side effects. 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"Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS." Proceedings of the National Academy of Sciences 100.18 (2003): 10529-10533.  Kinsey, Steven G., et al. "The CB2 cannabinoid receptor-selective agonist O-3223 reduces pain and inflammation without apparent cannabinoid behavioral effects." Neuropharmacology 60.2-3 (2011): 244-251.  Sancho, Roc??o, et al. "Anandamide inhibits nuclear factor-κB activation through a cannabinoid receptor-independent pathway." Molecular pharmacology 63.2 (2003): 429-438.  Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.  Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. 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"Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-κB and interferon-β/STAT proinflammatory pathways in BV-2 microglial cells." Journal of biological chemistry 285.3 (2010): 1616-1626.  Esposito, Giuseppe, et al. "Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement." PloS one 6.12 (2011): e28668.  Irving, Peter M., et al. "A randomized, double-blind, placebo-controlled, parallel-group, pilot study of cannabidiol-rich botanical extract in the symptomatic treatment of ulcerative colitis." Inflammatory bowel diseases 24.4 (2018): 714-724.  Kafil, Tahir S., et al. "Cannabis for the treatment of Crohn's disease." Cochrane Database of Systematic Reviews 11 (2018).  Naftali, Timna. "An overview of cannabis based treatment in Crohn’s disease." Expert Review of Gastroenterology & Hepatology 14.4 (2020): 253-257.  Chagas, Marcos Hortes N., et al. 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CBD for Acne
Scientific Confidence Grade Effect Size Rating Editorial Note C ** CBD might reduce acne by addressing its underlying causes, such as sebum overproduction and inflammation. However, there’s a lack of conclusive, high-quality evidence. There are only two human studies. CBD may significantly improve acne. CBD for Acne: Can It Help? (January 2021) Researchers believe CBD may be able to treat acne. However, its benefits have only been demonstrated in two relatively small human studies. Cannabidiol (CBD) products are most commonly used to relieve pain, calm anxiety, and improve sleep. Yet, many people also take it for other conditions, including acne. This isn’t surprising as there’s growing interest in natural alternatives to prescription medications, which are often ineffective or come with notable side effects. Evidence from test-tube and early clinical studies suggests that CBD may help reduce acne when applied directly to the affected skin. Does CBD work? What’s the ideal way to use it? Here’s a closer look at CBD for acne, the research evidence, dosage recommendations, and other helpful tips. Acne Overview Acne (acne vulgaris) is a common skin condition where your hair follicles become clogged with sebum and dead skin cells, causing pimples to form. Sebum is the oily, waxy substance produced by your sebaceous glands to protect and moisturize the skin. Acne typically affects the face and forehead but can also occur on other parts of the body that have many sebaceous glands, such as your chest, upper arms, and upper back. Acne can be caused by bacteria, inflammation, and excess sebum (oil) production. It’s most common in teenagers because puberty causes a rise in androgen (sex hormone) levels, which stimulate sebum production, but can also occur in other age groups. It’s estimated to affect about 9.4% of the world’s population, making it the 8th most common health disorder in the world. Acne Subtypes Acne can vary in severity from mild to severe. Generally speaking, you can divide it into two types based on the kind of blemishes it produces: noninflamatory and inflammatory. Noninflammatory acne: the most common type of acne, which produces noninflammatory pimples: whiteheads and blackheads. Inflammatory acne: a more severe type of acne which produces inflammatory lesions: papules, pustules, nodules, and cysts. It can also be called cystic acne when cysts are the primary type of lesion involved. Acne Symptoms & Pathology Most commonly, acne causes pimples which can either be whiteheads or blackheads. Whiteheads form when sebum and dead skin cells clog up the opening of a pore, creating a white or flesh-colored blemish. Blackheads are similar, except the opening of the pore doesn’t get clogged, so the material inside reacts with oxygen and turns into a black color. Meanwhile, more serious forms of acne can cause inflammatory lesions marked by visible redness: Papules, which look like small, tender red bumps Pustules, which are papules filled with pus Nodules, which are large, solid, painful lumps under the skin Cysts, which are soft, painful, pus-filled lumps under the skin Can CBD Help With Acne? Early findings from test-tube studies suggest that CBD may help reduce different kinds of acne. In the most notable study on the subject, researchers applied CBD to isolated human sebocytes: the skin cells that produce sebum. CBD reduced the production of lipids that form sebum, proliferation (increase in number) of sebocyte cells, and inflammation. The combination of the lipostatic, antiproliferative, and anti-inflammatory effects led the researchers to conclude that “CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.” Other studies have also reported that CBD can affect the differentiation and proliferation of keratinocyte cells.  Since keratinocytes also play a role in acne formation by contributing to plugging pores, this suggests another way that CBD might be beneficial. Additionally, research has shown that CBD has specific yet mechanistically elusive antibacterial effects. Further studies may reveal how its antibacterial properties work which could potentially be used against P. acnes, a bacteria that can play a role in acne. Further, CBD has well-documented anti-inflammatory effects, which may be particularly helpful for more serious, inflammatory types of acne. It’s also important to note that applying CBD for acne topically rather than using CBD oil or other internal products (i.e. CBD edibles) seems to be the best way to use it. That’s because topical application allows CBD to interact directly with the affected parts of the skin. The Endocannabinoid System and Your Skin Ongoing research continues as scientists are examining how CBD can help with acne and other skin conditions by interacting with your endocannabinoid system (ECS). The ECS is a network of cannabinoid receptors, endocannabinoids made in the body (anandamide and 2-AG), and special enzymes. The main role of this recently discovered system is to maintain homeostasis, a healthy state of balance in your body. Researchers are continuing to shed light on how this state of balance is achieved. They speculate on the many possible processes that the ECS could have a hand in regulating such as inflammation and skin function.  In particular, research indicates that the ECS influences the growth and activity of many different types of skin cells, including sebocytes, the cells that make up the sebaceous glands which play a central role in acne. For example, a cell culture study showed that the CB2 endocannabinoid receptor is expressed in certain sebocytes and plays a role in the regulation of the lipids (substances that make up sebum). They also revealed that the endocannabinoids anandamide and 2-AG were present in their sebocyte cell cultures and concluded that, through the CB2 receptor, these endocannabinoids dose-dependently promoted sebum production and cell death. There’s also evidence that ECS dysfunction may be involved in numerous skin conditions, including acne. All in all, we can see that the ECS may play an important role in skin health. Other clinical studies have already shown some of the ways that CBD interacts with our ECS (e.g., suppressing an enzyme that breaks down the endocannabinoid anandamide). More research will continue to unveil how CBD can support the ECS in therapeutic treatment for various conditions including acne. What Does the Research Say? There are few human studies of CBD for acne but the findings are optimistic. In one study, 20 people with psoriasis, eczema, or scarring from these conditions applied CBD ointment daily for 90 days. Some of the study participants also had scarring from acne. After 90 days, one of the reported effects of the gel was the improvement of acne scars. The researchers attributed this to CBD’s anti-inflammatory and anti-proliferative effects. Unfortunately, this study didn’t have the most rigorous design and was primarily focused on other skin conditions. Aside from that, there’s an active clinical study looking at the effects of a pure, synthetic topical CBD preparation called BTX 1503 on people with acne. Preliminary clinical findings from a 4-week safety trial in 21 people with moderate-to-severe acne reported that this CBD-based drug was well-tolerated and significantly reduced the number of both nonimflammatory and inflammatory acne lesions as effectively as other FDA-approved drugs. These findings are promising and seem to confirm the results of research done on isolated cells. Still, larger and more high-quality research is needed before confirming that CBD can be used effectively and safely across populations suffering from acne. How Much CBD Should I Take for Acne? Due to the scarcity of research, there’s no recommended CBD dosage for acne. On top of that, the ideal amount of CBD to take can vary between individuals based on body weight, genetics, acne severity, and the type of product being used. That’s why health experts recommend to “start low and go slow” with cannabinoids like CBD. You can begin with a CBD dose of 10-15 mg (or the amount recommended by your product) and see how you respond. If there’s no improvement after several days, you can try gradually increasing the dose and assessing the effects until you find the amount that works for your acne. Having said that, this is a bit more tricky to do when dealing with topical CBD products — the preferred way to use CBD for acne. For one thing, it can take longer than other conditions to see if the product is having a positive effect. Also, it’s not as easy to increase your dosage when using a topical product. You may have to try out CBD products with varying potencies before you settle on one that has a positive effect on your acne. You will also need to estimate how much CBD you’re using by either checking the product label or dividing the total amount of CBD in the product by its volume. For example, if a 30 ml cream contains 300 mg of CBD, that means one ml of product will provide a 10 mg dose. Are There Any Side Effects? According to extensive research, CBD is a very safe, well-tolerated skin care substance. Although researchers have noted that CBD can cause side effects, most of them are considered mild and only occurred in studies using relatively high doses of pure cannabidiol. More importantly, when you apply CBD topically, it’s highly unlikely to absorb deep enough to enter your blood vessels. This means topical CBD products have a very low chance of causing the same side effects reported in studies of oral CBD preparations such as capsules. Still, it is theoretically possible for other ingredients in topical CBD preparations, like terpenes or fragrances, to cause allergic reactions or other side effects. Conclusion Early research demonstrates CBD’s potential to reduce acne. In particular, there’s some evidence that CBD may target the underlying causes of acne, such as overproduction of sebum and inflammation. Coupled with CBD’s apparent safety, that’s great news for people with both moderate and more severe, inflammatory types of acne. It’s best to apply topical CBD in the form of creams and other products when dealing with acne, although finding the right dosage may take some experimentation. Still, rigorous clinical research is lacking, so we can’t say for sure that CBD can improve acne. We’ll need to wait for results from more high-quality studies, such as the trial of the synthetic topical CBD preparation that’s currently underway. If you plan to take CBD for acne, it may be in your best interest to do so alongside traditional acne medicines. However, be sure to speak to your dermatologist prior because hemp extract may have negative interactions with these substances. References  Makrantonaki, Evgenia, Ruta Ganceviciene, and Christos C. Zouboulis. "An update on the role of the sebaceous gland in the pathogenesis of acne." Dermato-endocrinology 3.1 (2011): 41-49.  Tan, Jerry KL, and K. Bhate. "A global perspective on the epidemiology of acne." British Journal of Dermatology 172 (2015): 3-12.  Sutaria, A. H., S. Masood, and J. Schlessinger. "Acne Vulgaris [Updated 2019 Dec 13]." Treasure Island (FL): StatPearls Publishing LLC (2020): p1-6.  Oláh, Attila, et al. "Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes." The Journal of clinical investigation 124.9 (2014): 3713-3724.  Wilkinson, Jonathan D., and Elizabeth M. Williamson. "Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis." Journal of dermatological science 45.2 (2007): 87-92.  Casares, Laura, et al. "Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1." Redox biology 28 (2020): 101321.  Appendino, Giovanni, et al. "Antibacterial cannabinoids from Cannabis sativa: a structure− activity study." Journal of natural products 71.8 (2008): 1427-1430.  Bhatia, Ajay, Jean-Francoise Maisonneuve, and David H. Persing. "Propionibacterium acnes and chronic diseases." The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary., Knobler, SL et al.(eds.). 2004.  Atalay, Sinemyiz, Iwona Jarocka-Karpowicz, and Elzbieta Skrzydlewska. "Antioxidative and anti-inflammatory properties of cannabidiol." Antioxidants 9.1 (2020): 21.  Skaper, Stephen D., and Vincenzo Di Marzo. "Endocannabinoids in nervous system health and disease: the big picture in a nutshell." (2012): 3193-3200.  Bíró, Tamás, et al. "The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities." Trends in pharmacological sciences 30.8 (2009): 411-420.  Kircik, Leon H. "What’s new in the management of acne vulgaris." Cutis 104.1 (2019): 48-52.  Dobrosi, Nóra, et al. "Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor?2?mediated signaling." The FASEB Journal 22.10 (2008): 3685-3695.  Tóth, Kinga Fanni, et al. "Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C (ut) annabinoid” System." Molecules 24.5 (2019): 918.  Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.  Palmieri, B., C. Laurino, and M. Vadalà. "A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars." Clin Ter 170.2 (2019): e93-e99.  Spleman, L., et al. "1061 The safety of topical cannabidiol (CBD) for the treatment of acne." Journal of Investigative Dermatology 138.5 (2018): S180.  Lucas, Catherine J., Peter Galettis, and Jennifer Schneider. "The pharmacokinetics and the pharmacodynamics of cannabinoids." British journal of clinical pharmacology 84.11 (2018): 2477-2482.  Iffland, Kerstin, and Franjo Grotenhermen. "An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies." Cannabis and cannabinoid research 2.1 (2017): 139-154.  Nath, Neel Som, et al. "Contact allergy to hydroperoxides of linalool and D-limonene in a US population." Dermatitis 28.5 (2017): 313-316.
CBD for Migraines
Scientific Confidence Grade Effect Size Rating Editorial Note D ? CBD might help with endocannabinoid deficiency — a condition that may cause migraines. However, CBD hasn’t been studied for migraines so there isn’t any solid evidence yet. There’s no research looking specifically at CBD. However, studies have found that medical cannabis (which contains CBD, THC, and other cannabinoids) can reduce the number and severity of migraines. There aren’t any studies of CBD for migraines. CBD for Migraines: Can It Help? (January 2021) There isn't any research looking at the use of CBD for migraines. However, mounting evidence suggests that a dysfunctional endocannabinoid system can be cause, which means CBD might help with migraine treatment. Cannabis is a popular option for migraine sufferers looking for relief. As such, it’s not surprising that some turn to cannabidiol (CBD) products, which lack intoxicating effects. While early research has shown that cannabis — which contains both THC, CBD, and other active compounds — can relieve migraines, there’s a lack of research looking specifically at CBD. However, there’s growing evidence that a dysfunctional endocannabinoid system can be involved in migraines. If this holds true, CBD could be beneficial for this and other difficult-to-treat conditions. Migraines Overview Migraine is a common disorder characterized by painful headaches that usually occur on one side of the head. It can also cause nausea, sensitivity to light, and other symptoms. In some cases, migraines are preceded by or happen alongside aura symptoms, which include visual effects such as blind spots and other issues such as feeling tingling sensations and hearing noises. Migraines typically come in the form of recurrent attacks that can last anywhere from a few hours to several days. They can be triggered by certain foods, weather, stress, caffeine, sleep disturbances, and other factors. Researchers are not completely sure what causes migraines but genetics, neurochemical imbalances, and dysfunctions in certain parts of the brain appear to be involved. Migraine Subtypes Migraines can be divided into the following types: Common migraine: the most prevalent type of migraine that doesn’t involve aura symptoms. Classic migraine: migraine accompanied by aura symptoms for up to 30 minutes before headaches. Hemiplegic migraine: a more severe type of aura migraine with weakness on one side of the body. Ocular migraine: aura symptoms with partial or full loss of vision in one eye followed by migraine headaches. Menstrual migraine: migraines that occur days before, during, or after a woman’s period. Migraine equivalent: aura symptoms without any headaches. Migraines Symptoms & Pathology Although a throbbing or pulsating headache is the main symptom of migraines, you can also experience other issues. Migraine attacks typically occur in phases, although not everyone experiences all four: Prodromal phase (day or two before the headache), where people may have depression, irritability, neck stiffness, and food cravings. About 25% of sufferers also experience aura, which can include visual, auditory, sensory, and other symptoms, such as bright lines, blind spots, hearing music and other noises, and feeling tingling or numbness. The aura phase typically occurs before or as the headache starts. The headache phase, which can occur on one or both sides of the head and be accompanied by nausea, vomiting, and sensitivity to light and sound. Postdromal phase, where you may experience short-lasting headaches when moving your head and feel tired. Can CBD Help with Migraines? Researchers hypothesize that CBD and other cannabinoids may relieve migraines by interacting with the body’s endocannabinoid system (ECS). The ECS is composed of a network of cannabinoid receptors (CB1 & CB2), enzymes, and natural endocannabinoids made by the body to maintain a balanced state called homeostasis. To do so, the ECS regulates brain function, pain, immunity, metabolism, and many other processes. In particular, researchers believe that a dysfunction of the ECS called clinical endocannabinoid deficiency (CED) may be linked to migraines. First proposed by respected cannabis researcher Dr. Ethan Russo in 2001, this theory argues that deficient endocannabinoid levels could lead to certain health disorders. Since then, researchers have been finding more support for the theory. There’s particularly strong evidence that a dysfunctional ECS is linked to irritable bowel syndrome, fibromyalgia, and migraines. First off, studies show that endocannabinoids may be able to inhibit the brain’s trigeminovascular system, which is widely considered to play the central role in causing migraines. Additionally, there’s evidence that the migraine-relieving effects of drugs called triptans are at least partially dependent on the ECS. Triptans include common drugs such as Imitrex, Amerge, Zomig, Maxalt, Axert, Frova, and Relpax. Researchers also believe that a dysfunctional serotonin system may be involved in migraines. To illustrate this, one study looked at platelets, a type of blood cell which may play a role in migraines. The scientists found that endocannabinoid and serotonin levels were significantly lower in the platelets of people with chronic migraines and medication overuse headaches (MOH) as compared to healthy individuals. Another interesting link are the symptoms of migraines, which include sensitivity to light, touch, and nausea — all effects that the ECS is known to regulate. Meanwhile, genetic studies suggest that certain endocannabinoid genes may be linked to migraines. For example, one study showed that specific variations of the CB1 receptor gene were associated with an increased risk of migraines. There’s also ample evidence for the involvement of the natural endocannabinoid, anandamide, in migraines: One study found that chronic migraine sufferers had reduced cerebrospinal fluid anandamide levels compared to healthy individuals. This is considered the key piece of evidence that endocannabinoid deficiency could be a cause of migraines. Another study found that anandamide interacted with serotonin receptors in a similar way to drugs that relieve migraines. In an animal study, anandamide directly inhibited trigeminovascular neurons which when overstimulated may cause migraines. This suggests a mechanism by which endocannabinoids like anandamide can improve migraines. Researchers have used anandamide to reduce migraine-like pain in rats. In summary, research findings indicate that a dysfunctional endocannabinoid system can be involved in migraines and that plant-derived cannabinoids may be able to help. CBD is an especially promising candidate because one of its major effects is suppressing FAAH, the enzyme that breaks down the endocannabinoid, anandamide. According to a review conducted by a team of Italian and American researchers, “inhibition of AEA degradation via FAAH is a promising therapeutic target for migraine pain.” What Does the Research Say? There are currently no studies on CBD for migraines. However, we can gain some helpful insights from studies of whole-plant cannabis, which contains CBD as the second-most abundant active ingredient after THC. THC is the psychoactive cannabinoid often associated with the cannabis plant. In one Colorado trial, medical cannabis use (smoking, vaping, edibles, or topicals) improved migraines in 85.1% of 121 participants. Interestingly, cannabis not only reduced the number of migraines but also stopped them when taken during an attack. Another study found that when inhaled, whole-plant cannabis improved regular headaches and migraines in 94% of 699 study participants. Similarly, a retrospective study of 316 people with chronic migraines found that 88.3% saw improvements from using medical cannabis. The study also noted that patients using cannabis with a higher THC to CBD ratio (20:1) reported greater improvements than those using a 1:1 ratio. Another study found significant reductions in migraine and headache severity from inhaling cannabis, with concentrates being more effective than regular cannabis. In this case, CBD and THC content did not seem to influence the effectiveness of cannabis. These findings support the idea that a combination of THC and CBD can reduce the number and severity of migraines. However, there isn’t enough data to say whether THC is more effective than CBD for migraines or whether CBD-only preparations would produce similar effects. Ultimately, human studies looking specifically at CBD for migraines are needed. How Much CBD Should I Take for Migraines? There isn’t enough evidence to suggest a CBD dosage for migraines. Besides, the optimal dosage is different for everyone and depends on multiple factors, including body weight, genetics, migraine severity, and CBD product type. Your best option is to follow the “start low and go slow” approach suggested by most health experts. Ideally, you’ll want to take CBD when you feel a migraine coming on so you can see whether it helps. Start with a small amount of CBD (10-15 mg) and assess how you feel. If you don’t notice any relief, raise the dose in small increments over time until you find one that provides the desired effects. If you want to experience immediate effects, inhaling CBD by smoking or vaping is the best option. However, CBD oils, capsules, and edibles can be used as well. Are There Any Side Effects? According to decades of research, CBD is a generally safe, well-tolerated compound. While some studies have reported that CBD can cause side effects, they were mostly considered mild and occurred only when using high doses of pure CBD. The possible side effects of CBD include:  Tiredness Drowsiness Diarrhea Nausea Dry mouth Low blood pressure Lightheadedness Changes in appetite or weight Since most people use smaller doses of CBD and often opt for whole-plant formulations rich in many other natural compounds, the chances of experiencing these side effects are slim. However, it's important to note that CBD remains unapproved by the Food & Drug Administration (FDA). With that, it's unclear how safe it is for people of all categories to take. For example, pregnant women are advised to avoid CBD as there isn't enough research to suggest its safety. Conclusion At this time, there isn’t much evidence that CBD for migraines is beneficial. The only studies completed so far used whole-plant cannabis, which includes high concentrations of THC and many other active compounds, so it’s difficult to determine the effects of CBD. Still, there is some evidence that CBD can help from a theoretical standpoint. Researchers have uncovered more and more evidence that dysfunction in the endocannabinoid system is involved in migraines. Since CBD can influence this system by reducing the breakdown of endocannabinoids, it may have a positive effect on the number and severity of migraine attacks. Not to mention, it may be able to be used for therapeutic purposes alongside migraine medication. References  Nagalli, S. "Migraine with Aura." (2020).  Aizpurua-Olaizola, Oier, et al. "Targeting the endocannabinoid system: future therapeutic strategies." Drug discovery today 22.1 (2017): 105-110.  Russo, Ethan B. "Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes." Cannabis and cannabinoid research 1.1 (2016): 154-165.  Ashina, Messoud, et al. "Migraine and the trigeminovascular system—40 years and counting." The Lancet Neurology 18.8 (2019): 795-804.  Akerman, Simon, et al. "Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive traffic via CB1 and “triptan” receptors: implications in migraine." Journal of Neuroscience 33.37 (2013): 14869-14877.  Rossi, Cristiana, et al. "Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels." European journal of clinical pharmacology 64.1 (2008): 1-8.  Pacher, Pál, and George Kunos. "Modulating the endocannabinoid system in human health and disease–successes and failures." The FEBS journal 280.9 (2013): 1918-1943.  Juhasz, Gabriella, et al. "Variations in the cannabinoid receptor 1 gene predispose to migraine." Neuroscience letters 461.2 (2009): 116-120.  Sarchielli, Paola, et al. "Endocannabinoids in chronic migraine: CSF findings suggest a system failure." Neuropsychopharmacology 32.6 (2007): 1384-1390.  Boger, Dale L., Jean E. Patterson, and Qing Jin. "Structural requirements for 5-HT2A and 5-HT1A serotonin receptor potentiation by the biologically active lipid oleamide." Proceedings of the National Academy of Sciences 95.8 (1998): 4102-4107.  Akerman, Simon, Holger Kaube, and Peter James Goadsby. "Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception." Journal of Pharmacology and Experimental Therapeutics 309.1 (2004): 56-63.  Greco, Rosaria, et al. "Effects of anandamide in migraine: data from an animal model." The journal of headache and pain 12.2 (2011): 177-183.  Leweke, F. M., et al. "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia." Translational psychiatry 2.3 (2012): e94-e94.  Greco, Rosaria, et al. "Endocannabinoid system and migraine pain: an update." Frontiers in neuroscience 12 (2018): 172.  Rhyne, Danielle N., et al. "Effects of medical marijuana on migraine headache frequency in an adult population." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 36.5 (2016): 505-510.  Stith, Sarah S., et al. "Alleviative effects of Cannabis flower on migraine and headache." Journal of Integrative Medicine 18.5 (2020): 416-424.  Mechtler, Laszlo, et al. "Medical Cannabis for Chronic Migraine: A Retrospective Review (P3. 10-015)." (2019): P3-10.  Cuttler, Carrie, et al. "Short-and long-term effects of cannabis on headache and migraine." The Journal of Pain 21.5-6 (2020): 722-730.  Lucas, Catherine J., Peter Galettis, and Jennifer Schneider. "The pharmacokinetics and the pharmacodynamics of cannabinoids." British journal of clinical pharmacology 84.11 (2018): 2477-2482.  Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. "en Crippa, JA (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent." Current Drug Safety 6.4: 237-249.  Huestis, Marilyn A., et al. "Cannabidiol adverse effects and toxicity." Current neuropharmacology 17.10 (2019): 974-989.
Guide to Cannabinoids: Cannabinol (CBN)
Cannabinol (CBN) Introductory Guide Most people have heard of cannabidiol (CBD) and tetrahydrocannabinol (THC). They’re the two most abundant cannabinoids in cannabis and play a major role in its effects. But they’re not alone. Cannabis contains many other minor cannabinoids, including cannabinol (CBN). Despite being the first cannabinoid to be isolated from the plant in 1896, CBN hasn’t received much attention.1 That’s because most minor cannabinoids are present in only trace amounts. Some people recognize CBN as the compound that makes old weed more sedating, but there’s a lot more to it. And many are starting to realize this. You may have seen CBN products hit the market recently. So, what is CBN oil and what can it be used for? We invite you to follow along as we take a deeper look. What is Cannabinol (CBN)? CBN is one of more than 120 different active components, or cannabinoids, found in the cannabis plant.2 THC breaks down into CBN over time, especially when exposed to oxygen.3 This is why CBN concentrations are very small in raw cannabis but can reach significant levels in older, dried plants. Most of the cannabinoids in cannabis are considered “minor” because their concentrations are quite small — less than 1%. CBN is one such cannabinoid. Like CBD, CBN is completely non-intoxicating, so it can’t get you high. Interest in CBN has been steadily growing because it appears to have a wide variety of potential health benefits. Some people even consider CBN and other minor cannabinoids to be the “next big thing” following in the footsteps of CBD’s success. Is Cannabinol Legal? Yes, as long as CBN is derived from hemp, it’s completely legal. Hemp is one of the two main kinds of cannabis, the other being marijuana. By definition, marijuana has significant THC levels, whereas hemp contains 0.3% or less of this intoxicating cannabinoid. The 2018 Farm Bill made hemp an agricultural commodity in the United States, which means that any cannabinoid product sourced from it is also legal. CBN extracted from any type of cannabis is also legal in Canada. As for the rest of the world, the legality of CBN can vary. Some countries ban cannabis (including hemp) completely, which means any part or extract of the plant — including CBN — is illegal. Meanwhile, in other places where hemp is legal, CBD, CBN, and any other cannabinoid derived from hemp are also legal. However, because hemp plants have low THC levels and CBN comes from the breakdown of THC, it can be difficult and expensive to make CBN products from hemp. As such, most CBN products are sourced from marijuana and only sold in states and countries where it’s legal. How Does Cannabinol Work? Like most cannabinoids, CBN seems to work by interacting with your endocannabinoid system (ECS). This system regulates all major bodily processes, including brain function, metabolism, and sleep, to maintain homeostasis — a healthy state of balance. The ECS is composed of three major parts: 4 Endocannabinoids — cannabinoids produced on-demand by your body. Enzymes that help build and break down endocannabinoids. Cannabinoid receptors are found in all parts of the body. The CB1 receptor is especially common in the brain and the CB2 receptor in immune system cells.5 Cannabinoid receptors can be activated by both “endo” (naturally produced in the body) and “phyto” (plant-derived) cannabinoids. For example, the phytocannabinoid THC produces most of its effects by binding CB1.6 As for CBN, research suggests that it has a lower attraction to CB1 receptors than THC, but a higher one for CB2 receptors, which means it might have stronger effects on the immune rather than the nervous system.7 Still, we don’t know enough about how CBN works because most minor cannabinoids are not well-researched. It’s quite possible that it may affect other parts of the body aside from the ECS, similar to CBD. CBN also contributes to the “entourage effect” — the proposed synergy between cannabinoids and other active components of cannabis, which strengthen their overall effects.8 This effect means that using whole-plant cannabis is better than isolated compounds, such as CBD or CBN on their own. The entourage effect has been demonstrated by multiple studies. In the case of CBN, for example, studies in rabbits and rats have shown that it can synergize with THC, enhancing its sedating and intoxicating effects.9 However, more research is needed to explain exactly how CBN works, what it may be able to treat, and how it contributes to the entourage effect. Where to Buy CBN Oil? CBN can come in many product forms. For now, CBN oil is the most common but cannabinol can theoretically be offered in all of the same product types as CBD, including capsules, isolates, edibles, topicals, and vape products. Just like CBD products, the best place to buy CBN is online. They’re just starting to appear because most legal cannabis products are made from hemp, which has naturally lower CBN and THC levels. CBN can come in several formulations. The simplest one is isolate: pure cannabinol and nothing else. You can also find whole-plant CBN preparations. These typically combine full-spectrum hemp extract with CBN isolate to create a product that has high CBD and CBN levels and maintains all of the other cannabinoids found in hemp. This type of product shouldn’t be confused with a regular full-spectrum CBD extract. Standard full-spectrum CBD can contain CBN but only in very small amounts. Similarly, you might also be able to find broad-spectrum CBN products, which are the same as full-spectrum formulations but with zero THC. Whole-plant hemp products also contain many other natural substances, including terpenes — aromatic molecules responsible for the characteristic aromas and flavors of plants, including various cannabis strains.10 Terpenes play a notable role in the entourage effect by not only providing beneficial effects of their own but also working in synergy with cannabinoids. For example, terpenes can enhance the passage of cannabinoids across the blood-brain barrier, enhancing their efficacy.11 Finally, some products combine CBN isolate with CBD isolate for a 1:1 formula. Cannabinol Effects There are few studies of CBN and most of the research is restricted to investigations in animals. So far, all we know is that CBN can enhance the sedating and intoxicating effects of THC and may have other beneficial properties, such as suppressing appetite. With this, some researchers suggest it may be able to be used as a sleep aid or to alleviate anxiety. But we don’t know much about its potential side effects and drug interactions, especially after prolonged use. Cannabinol Dosage The right amount of CBN to take is different for everyone. That’s because the optimal dosage of any cannabinoid is influenced by many factors, such as your body weight, genetics, and medical symptoms. Additionally, CBN and other cannabinoid products can come in various formulations, concentrations, and consumption methods, which will further affect your dosage. For example, cannabinoids are known to have poor oral absorption,12 so you’ll need to take higher doses of an oral CBN product (such as capsules) to achieve the same effects as a sublingual oil. As for actual amounts, there’s very little research data for CBN dosages. However, one good starting point is the doses used for CBD, which is another non-intoxicating cannabinoid with similar effects. Most people take about 10-50 mg of CBD once or twice daily. Using this information, you can start with a CBN dose of about 10-15 mg and see how it makes you feel. If there’s no effect, you can gradually raise the dosage over time until you start noticing the desired benefits. Choosing the Right Type of CBN Extract You also have to consider what type of CBN formulation you want to use. If you want nothing but pure CBN, you should look for products containing isolate. Meanwhile, if you want to benefit from the entourage effect, you should look for a full-spectrum cannabis formulation.13 In most cases, this will be a standard whole-plant CBD extract that’s been enriched with CBN, so it will contain all of the cannabinoids, terpenes, and other potentially beneficial hemp phytochemicals. Finally, if you want to maximize the benefits of hemp but avoid ingesting THC, you should look for a broad-spectrum CBN formulation. These products will have all of the same ingredients as a full-spectrum extract but undergo an additional step to remove THC. CBN Benefits and Health Conditions CBN has been examined in multiple scientific studies. As with other cannabinoids, the research suggests that CBN may have multiple health applications. Here’s an overview of the key findings: CBN may have anti-inflammatory properties.14 CBN may have antibacterial effects.15 CBN may have anticonvulsant effects that can help with seizures, although it’s weaker than CBD and THC.16 CBN may have neuroprotective qualities. In one study, cannabinol delayed the development of the neurodegenerative condition amyotrophic lateral sclerosis (ALS) in mice.17 CBN may have appetite-stimulating properties. In one animal study, it significantly increased the food intake of mice.18 CBN may have analgesic effects; it reduced muscle pain in a rat study.19 Having said that, CBN is a relatively under-researched cannabinoid and most of these effects have not yet been studied in humans. But we can expect more findings in the years to come, especially as the interest in minor cannabinoids continues to grow. Does CBN Help with Sleep? There’s a popular belief that CBN has a potent sedative or sleep-promoting effects. Unfortunately, this is a misconception based on the observation that old, dried cannabis — which has higher CBN concentrations — seems to make people more sleepy. While it is true that CBN is higher in aged cannabis, it’s not necessarily the compound responsible for its notable sedative effects. For one, dried, old cannabis tends to contain higher levels of sedating, oxygenated sesquiterpenes, compounds closely related to terpenes.20 Also, CBN may be able to enhance the sedating effects of other cannabinoids. This was demonstrated by an older study where the researchers gave people pure THC, CBN, or both. CBN did not make people sleepy or high on its own. However, when the study participants took both cannabinoids together, they reported feeling more drugged, drunk, dizzy, and drowsy compared to THC alone.21 This is also a great example of CBN’s role in the entourage effect. Frequently Asked Questions What is CBN oil good for? We don’t know enough about the effects of CBN oil to say what it might be good for. However, it may work well for aiding sleep if it contains significant amounts of THC or other cannabinoids with sedative properties. What is the difference between CBD and CBN oil? The key difference is in the amount of CBN. CBD oil might contain low levels of CBN, whereas a proper CBN oil will have high concentrations of CBN, typically about as much or more than CBD. What are the effects of CBN? So far researchers have found that CBN may have anti-inflammatory, pain-relieving, antibacterial, neuroprotective, anticonvulsant, and appetite-stimulating effects. But these have not yet been confirmed in human studies. It also seems to enhance the intoxicating and sedating effects of THC. Which is better for sleep CBD or CBN? It’s far too early to say because there isn’t any significant research evidence backing either cannabinoid. Anecdotally, many people have found that CBD can help them sleep. Similarly, some have reported getting better sleep after taking CBN, especially when it’s combined with THC and other cannabinoids. References 1. Hanuš, Lumír Ond?ej, et al. "Phytocannabinoids: a unified critical inventory." Natural product reports 33.12 (2016): 1357-1392. 2. Morales, Paula, Dow P. Hurst, and Patricia H. Reggio. "Molecular targets of the phytocannabinoids: a complex picture." Phytocannabinoids. Springer, Cham, 2017. 103-131. 3. Brenneisen, Rudolf. "Chemistry and analysis of phytocannabinoids and other Cannabis constituents." Marijuana and the Cannabinoids. Humana Press, 2007. 17-49. 4. Lu, Hui-Chen, and Ken Mackie. "An introduction to the endogenous cannabinoid system." Biological psychiatry 79.7 (2016): 516-525. 5. Turcotte, Caroline, et al. "The CB 2 receptor and its role as a regulator of inflammation." Cellular and Molecular Life Sciences 73.23 (2016): 4449-4470. 6. Hua, Tian, et al. "Crystal structure of the human cannabinoid receptor CB1." Cell 167.3 (2016): 750-762. 7. Andre, Christelle M., Jean-Francois Hausman, and Gea Guerriero. "Cannabis sativa: the plant of the thousand and one molecules." Frontiers in plant science 7 (2016): 19. 8. Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969. 9. Takahashi, R. N., and I. G. Karniol. "Pharmacological interaction between cannabinol and D9-tetrahydrocannabinol." Psychopharmacologia (1975). 10. Cox-Georgian, Destinney, et al. "Therapeutic and medicinal uses of terpenes." Medicinal Plants. Springer, Cham, 2019. 333-359. 11. Hartsel, Joshua A., et al. "Cannabis sativa and Hemp." Nutraceuticals. Academic Press, 2016. 735-754. 12. Bruni, Natascia, et al. "Cannabinoid delivery systems for pain and inflammation treatment." Molecules 23.10 (2018): 2478. 13. Maayah, Zaid H., et al. "The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis." Inflammation Research (2020): 1-10. 14. Zurier, Robert B., and Sumner H. Burstein. "Cannabinoids, inflammation, and fibrosis." The FASEB Journal 30.11 (2016): 3682-3689. 15. Appendino, Giovanni, et al. "Antibacterial cannabinoids from Cannabis sativa: a structure− activity study." Journal of natural products 71.8 (2008): 1427-1430. 16. Karler, Ralph, William Cely, and Stuart A. Turkanis. "The anticonvulsant activity of cannabidiol and cannabinol." Life Sciences 13.11 (1973): 1527-1531. 17. Weydt, Patrick, et al. "Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival." Amyotrophic Lateral Sclerosis 6.3 (2005): 182-184. 18. Farrimond, Jonathan A., Benjamin J. Whalley, and Claire M. Williams. "Cannabinol and cannabidiol exert opposing effects on rat feeding patterns." Psychopharmacology 223.1 (2012): 117-129. 19. Wong, Hayes, and Brian E. Cairns. "Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain." Archives of oral biology 104 (2019): 33-39. 20. Russo, Ethan B. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.” British Journal of Pharmacology 163 (2011): 1244-1364. 21. Karniol, Isac G., et al. "Effects of Δ9-tetrahydrocannabinol and cannabinol in man." Pharmacology 13.6 (1975): 502-512.
CBD for Arthritis
Scientific Confidence Grade Effect Size Rating Editorial Note B ** CBD may relieve arthritis symptoms and alleviate the chronic inflammation involved in some types of arthritis. However, most of the findings are limited to animal studies, so more human evidence is needed. There are two human studies but one of them used a treatment that also contains THC. CBD may significantly improve the symptoms of arthritis. CBD for Arthritis: Can It Help? (January 2021) Research indicates that CBD might help relieve arthritis symptoms and the chronic inflammation involved in some of its forms. Nonetheless, conclusive, high-quality clinical studies are lacking. Cannabidiol (CBD) is growing in popularity as an alternative treatment for arthritis. Some people take it in the form of CBD oil, whereas others apply CBD topically to the affected joints, or use both methods. There are many reasons why CBD is becoming a sought-after option for people suffering from this condition. For one, CBD is a safe, natural compound that comes from the hemp plant, whereas prescription medications — especially opioids — come with serious side effects, can become addictive, and only treat the symptoms rather than the root of the problem. There’s also a growing volume of test-tube and animal research, with some early human studies, suggesting that you might be able to use CBD for arthritis. Can CBD relieve arthritis and its symptoms? Read on for a detailed look at the evidence. Arthritis Overview Arthritis is an umbrella term for conditions that affect your joints. It can either be non-inflammatory or involve inflammation and affect one or several joints. Inflammatory arthritis can be caused by autoimmune processes where the body’s immune system attacks the joints, infections, or crystal deposits (e.g., during gout attacks). It can also be accompanied by autoimmune diseases that affect other parts of the body, such as lupus. Arthritis Subtypes There are well over 100 different types of arthritis. However, the most prominent ones are: Osteoarthritis: Also known as non-inflammatory or degenerative arthritis, osteoarthritis is the most common form of joint disease. It’s characterized by the wearing away of cartilage — the flexible, rubber-like padding that protects the ends of bones at the joints. Rheumatoid arthritis (RA): Another common type of arthritis, where an overactive immune system attacks healthy joint tissue. Juvenile arthritis: Any type of arthritis that affects children. In most cases, it has an autoimmune cause. Gout: A form of inflammatory arthritis caused by uric acid buildup in the joints. Gout is marked by sudden and severe episodes of joint pain and inflammation. Lupus: Lupus is a systemic autoimmune disease that can affect the joints and many other parts of the body, including blood cells, the skin, kidneys, brain, and other organs. Reactive arthritis: This condition is caused by an infection elsewhere in the body, such as the gut. Infectious arthritis: Also known as septic arthritis, this kind of arthritis is caused by joint infection. Psoriatic arthritis: a form of arthritis that occurs in about 20-30% of people with psoriasis, an autoimmune skin disorder. Ankylosing spondylitis: An autoimmune disorder that causes inflammation in the spine but can also occur in other joints. Arthritis Symptoms & Pathology The main symptoms of arthritis are joint pain, stiffness, swelling, redness, weakness, reduced range of motion, and loss of function. However, depending on the underlying cause, it can also produce symptoms unrelated to the joints, such as fatigue and fever. Having arthritis can also contribute to developing depression and anxiety. Can CBD Help With Arthritis? CBD and other cannabinoids hold serious potential in the treatment of arthritis. At the most basic level, CBD has anti-inflammatory and pain-relieving properties which can help relieve the symptoms of both non-inflammatory (osteoarthritis) and inflammation-related arthritis. CBD may also address the underlying causes of joint diseases, such as the chronic inflammation seen in rheumatoid arthritis (RA). Multiple animal and test-tube studies of RA have demonstrated that CBD can have a positive effect when applied either internally or topically. In one frequently cited study from 2000, researchers examined the effects of oral or injected CBD in mice with RA. They found that it had a “potent anti-arthritic effect” through anti-inflammatory and immunosuppressive effects. Meanwhile, the researchers of a 2016 study applied a transdermal CBD-infused gel to the joints of rats affected by RA. Again, CBD reduced joint pain and inflammation. Furthermore, a 2020 test-tube study found that CBD may be able to alleviate RA by reducing the inflammatory effects of synovial fibroblast cells which play a key role in the condition. There’s also some evidence that CBD may be helpful for osteoarthritis (OA), the non-inflammatory form of the disease. In one 2017 study, CBD prevented the development of neuropathic pain and nerve damage in rats with OA. All in all, early research findings suggest that there's great potential when it comes to using CBD for arthritis. Having said that, some researchers speculate that CBD may work best in combination with other specific cannabinoids because it can also activate anti-inflammatory mechanisms not related to cannabinoid receptors. The Endocannabinoid System and Arthritis Many of CBD’s beneficial effects on arthritis and other conditions come from its interaction with the body’s endocannabinoid system (ECS). This system’s main role is to help maintain your body’s homeostasis, a healthy state of balance. The ECS has three parts: Endocannabinoids made by your body (anandamide and 2-AG) Enzymes used to make and break down endocannabinoids Cannabinoid receptors (CB1 and CB2) that interact with both phytocannabinoids such as CBD and endocannabinoids Since the ECS regulates many of the processes involved in arthritis, namely immune system function, inflammation, and pain, it offers an innovative way to alleviate and treat joint conditions. For instance, there’s evidence that activation of the CB2 receptor, which is especially abundant in immune system cells, may have a positive effect on RA by lowering the production of autoantibodies, inflammatory molecules called cytokines, and via other mechanisms. Several studies have also reported that the levels of endocannabinoids, their associated enzymes, and cannabinoid receptors in individuals with arthritis significantly differ from those of healthy individuals, suggesting that the ECS is involved in the condition. Another interesting finding is that blocking the effects of FAAH — an enzyme that breaks down the endocannabinoid anandamide — seems to alleviate arthritis symptoms. In one animal study of RA, researchers looked at mice that either lacked the enzyme completely or were given a drug to prevent its effects. They found that blocking FAAH reduced the severity of RA and associated pain. Similarly, a study in mice with OA found that a FAAH blocker lowered acute joint inflammation, prevented nerve damage, and reduced chronic joint pain. These studies are especially relevant to CBD because one of its major effects is suppressing this same FAAH enzyme.9 Other Anti-Arthritic Mechanisms of CBD As we mentioned earlier, one of the great things about CBD is that it also affects other systems aside from the ECS. For example, there’s evidence that CBD can produce anti-inflammatory, pain-relieving, and other anti-arthritic effects by acting on serotonin, TRPV1, TRPA1, and PPARγ receptors, and suppressing the pro-inflammatory (NF)-κB pathway.    What Does the Research Say? Human studies looking at CBD for arthritis are just beginning, but the findings are promising. In a 2018 trial on 320 people with knee OA, researchers compared the effects of a synthetic transdermal CBD gel with a placebo treatment. Although people in the CBD gel group reported lower average pain scores than placebo, this improvement was not statistically significant enough to rule out random chance. However, further analysis showed that some people (responders) did see significant reductions in pain when treated with the CBD gel compared to placebo. Meanwhile, a 2006 study on 58 RA sufferers compared placebo with the effects of Sativex, a drug with equal amounts of CBD and THC. Unlike placebo, the cannabinoid treatment significantly improved arthritis pain and severity. CBD also improved sleep and was associated with mostly minor side effects. There’s also a case report of a 50-year-old woman suffering from RA, lupus, and Raynard’s disease, all of which are autoimmune conditions. She took 600 mg of CBD isolate oil for 28 days, resulting in significant pain relief, better mobility and mood, improved scores on quality-of-life metrics, and lower levels of inflammation. There are also many anecdotal reports of CBD’s beneficial effects on arthritis. In particular, a survey done by the Arthritis Foundation reported that arthritis sufferers saw improvements in physical function, morning stiffness, sleep, and overall well-being by using CBD oil and topical CBD products. Overall, the evidence is promising but more well-designed, rigorous human studies of CBD’s effects on arthritis are needed. How Much CBD Should I Take for Arthritis? There are no official CBD dosage recommendations for arthritis or any other condition. Although we have no conclusive guidance for an effective way to treat arthritis with CBD, we do know that an effective CBD dosage can vary between individuals based on their weight, unique body chemistry, and arthritis type and severity. Additionally, CBD products come in a wide variety of forms, which can also influence the dosage. In general, most health experts recommend the “start low and go slow” approach to dosing CBD and other cannabinoids. In the case of arthritis, you can use CBD internally, in the form of CBD oil and other products, or apply it directly to the affected joints as a cream or another topical preparation. Start with a small amount of CBD (10-15 mg) and wait a few hours to see if you notice any effects. If that’s not enough, raise the dose in small increments over time until you settle on the amount that relieves your arthritis symptoms. Meanwhile, if you’re using a topical product, you can estimate the amount you’re using by dividing the total CBD content by the volume. For example, a 30 ml CBD cream with 900 mg of CBD provides 30 mg per ml. Are There Any Side Effects? According to decades of research, CBD is a well-tolerated, safe compound. While it can cause minor-to-moderate side effects, including sleepiness, tiredness, diarrhea, dry mouth, low blood pressure, dizziness, and changes in appetite or weight, these have only been reported in studies using high doses of pure CBD. Additionally, the study of transdermal CBD gel in OA sufferers reported skin dryness and headaches in some participants. However, most people take much lower doses of CBD and are unlikely to experience anything more than mild side effects. Conclusion Judging from preliminary research, CBD shows great promise to be developed into an alternative or complementary treatment plan for arthritis. It seems to offer beneficial effects for all types of arthritis, including its two most common forms: rheumatoid arthritis and osteoarthritis. It's worth noting that most people report the best effects through topicals rather than other consumption methods, such as CBD gummies. What’s more, full-spectrum CBD might not only alleviate arthritis symptoms, such as chronic pain, but also address the chronic inflammation that underlies rheumatoid arthritis and other inflammatory forms of the disease. Furthermore, CBD is a very safe option that’s only been associated with mild-to-moderate side effects. Still, like with most conditions people are trying to treat with CBD , there isn’t a ton of clinical research evidence. More high-quality studies are needed to confirm CBD’s anti-arthritic effects and figure out the best way to use it. If you are currently on prescription medication, we suggest consulting your doctor before taking CBD. References  Tiwari, Vivekanand, and Lawrence H. Brent. "Psoriatic Arthritis." (2019).  Senthelal, Shayan, and Mark A. Thomas. "Arthritis." StatPearls [Internet]. StatPearls Publishing, 2019.  Bruni, Natascia, et al. "Cannabinoid delivery systems for pain and inflammation treatment." Molecules 23.10 (2018): 2478.  Malfait, A. M., et al. "The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis." Proceedings of the National Academy of Sciences 97.17 (2000): 9561-9566.  Hammell, D. C., et al. "Transdermal cannabidiol reduces inflammation and pain?related behaviours in a rat model of arthritis." European Journal of Pain 20.6 (2016): 936-948.  Lowin, Torsten, et al. "Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts." Cell death & disease 11.8 (2020): 1-11.  Philpott, Holly T., Melissa O'Brien, and Jason J. McDougall. "Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis." Pain 158.12 (2017): 2442.  Lowin, Torsten, Matthias Schneider, and Georg Pongratz. "Joints for joints: cannabinoids in the treatment of rheumatoid arthritis." Current opinion in rheumatology 31.3 (2019): 271-278.  Battista, Natalia, et al. "The endocannabinoid system: an overview." Frontiers in behavioral neuroscience 6 (2012): 9.  Gui, Huan, et al. "The endocannabinoid system and its therapeutic implications in rheumatoid arthritis." International immunopharmacology 26.1 (2015): 86-91.  La Porta, Carmen, et al. "Involvement of the endocannabinoid system in osteoarthritis pain." European Journal of Neuroscience 39.3 (2014): 485-500.  Kinsey, Steven G., et al. "Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice." Pharmacology Biochemistry and Behavior 99.4 (2011): 718-725.  McDougall, Jason J., et al. "Early blockade of joint inflammation with a fatty acid amide hydrolase inhibitor decreases end-stage osteoarthritis pain and peripheral neuropathy in mice." Arthritis Research & Therapy 19.1 (2017): 1-9.  De Gregorio, Danilo, et al. "Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain." Pain 160.1 (2019): 136.  Muller, Chanté, Paula Morales, and Patricia H. Reggio. "Cannabinoid ligands targeting TRP channels." Frontiers in molecular neuroscience 11 (2019): 487.  O'Sullivan, Saoirse Elizabeth. "An update on PPAR activation by cannabinoids." British journal of pharmacology 173.12 (2016): 1899-1910.  Kozela, Ewa, et al. "Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-κB and interferon-β/STAT proinflammatory pathways in BV-2 microglial cells." Journal of biological chemistry 285.3 (2010): 1616-1626.  Hunter, D., et al. "Synthetic transdermal cannabidiol for the treatment of knee pain due to osteoarthritis." Osteoarthritis and Cartilage 26 (2018): S26.  Blake, David R., et al. "Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis." Rheumatology 45.1 (2006): 50-52.  Shaw, Christian, L. L. C. Halcyon Therapeutics, and Jahan Marcu. "Cannabidiol in the Management of Comorbid Rheumatoid Arthritis, Lupus, and Raynaud’s Disease." Pain 2.30 (2016).  Lucas, Catherine J., Peter Galettis, and Jennifer Schneider. "The pharmacokinetics and the pharmacodynamics of cannabinoids." British journal of clinical pharmacology 84.11 (2018): 2477-2482.  Huestis, Marilyn A., et al. "Cannabidiol adverse effects and toxicity." Current neuropharmacology 17.10 (2019): 974-989.
Guide to Cannabinoids: Cannabigerol (CBG)
Cannabigerol (CBG) Introductory Guide Most of us attribute the effects of cannabis to cannabidiol (CBD) and tetrahydrocannabinol (THC). After all, they’ve received the most attention from the media, health experts, and researchers. In reality, the cannabis plant contains hundreds of active compounds known as cannabinoids. This includes cannabigerol (CBG), which is present in relatively small concentrations in most cannabis plants. But what is CBG? Research suggests that CBG may have multiple potential benefits, such as stimulating appetite. As a result, CBG oil and other CBG products have been growing in popularity. In this introductory guide, we’ll cover the key facts you need to know about CBG and explain why there’s so much hype around it. What is CBG? CBG belongs to a group of more than 120 natural compounds called cannabinoids, which are largely responsible for the health effects of cannabis.  Like CBD, CBG can’t get you high because it’s non-intoxicating. It’s made from cannabigerolic acid (CBGA), which is the first cannabinoid produced by the cannabis plant.  CBGA is, in fact, the starting point for most cannabinoids. Specific enzymes turn it into tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), or cannabichromenic acid (CBCA), which are acidic forms of the cannabinoids most of us are familiar with. When these acidic cannabinoids are exposed to heat (such as when people smoke cannabis), they’re transformed into their “active” form: THC, CBD, and CBC.  Cannabis plants typically have low (<1%) CBG levels because much of the CBGA is converted into THCA, CBDA, and CBCA.  As a result, CBG is typically considered a minor cannabinoid. However, hemp producers are exploring different ways to grow the plant to obtain higher CBG levels. CBG offers many potential benefits. That’s why there’s been growing interest in this non-intoxicating cannabinoid and CBG products are beginning to appear on the market. Some people even think CBG could become the next CBD. Is CBG Legal? CBG and any other cannabinoid isolated from hemp — the variety of cannabis with extremely low (no more than 0.3%) THC levels — is legal in the U.S. Hemp was made into a legal, agricultural crop by the 2018 Farm Bill, leading to an explosion in hemp-derived, cannabinoid-rich products. On top of that, some U.S. states allow for the recreational use of marijuana (the high-THC variety of cannabis), which means marijuana-derived CBG is also legal in these states. The CBG isolated from both cannabis strains - hemp and marijuana - are also legal in Canada. Meanwhile, in other countries, the legal status of cannabis, and by extent CBG, varies drastically. In many places, such as the Middle East and most of Africa, all types of cannabis are banned and, as is CBG. Other countries may allow hemp, which means CBG products made from it are also legal. Many countries also have medical-only programs for access to cannabinoids or have a legal gray area where it’s not currently clear whether CBG and other cannabinoids are allowed. How Does CBG Work? There isn’t enough research to completely explain how CBG works. Having said that, current findings suggest that CBG produces its effects by influencing the endocannabinoid system as well as other parts of the body. The endocannabinoid system (ECS) plays an important role in our health by regulating stress, anxiety, sleep, mood, immunity, inflammation, metabolism, pain, and many other processes.  Its overall purpose is to keep our bodies in a state of healthy balance called homeostasis. You can think of homeostasis as a pair of perfectly even scales. When something tilts one of the scales, such as anxiety, stress, or inflammation, the ECS is activated to restore balance. The ECS can be stimulated by cannabinoids naturally made by our bodies (endocannabinoids) through different cannabinoid receptors (CB1 & CB2). Receptors are like locks found on different cells that only respond to specific keys; in our case, different cannabinoids. There are also enzymes that specifically create and break down these endocannabinoids to control ECS activity. Research suggests that CBG doesn’t bind very strongly to either CB1 or CB2 receptors. However, it seems to reduce the reuptake of anandamide, one of the main endocannabinoids made by your body, increasing its levels.  Studies have also shown that CBG can interact with adrenergic, serotonin, and TRPV receptors, which have a wide variety of similar health-related roles in the body.  CBG and the Entourage Effect Aside from the above, CBG is also likely to play a part in the “entourage effect” — the theory that all of the cannabinoids and other components of cannabis work together in synergy, producing greater effects than any compound alone.  As demonstrated by multiple studies, this effect seems to be responsible for the greater efficacy of whole-plant cannabis preparations in comparison to isolated cannabinoids. For example, there’s evidence that CBD enhances the therapeutic and decreases the side effects of THC, which means using them together can produce greater results.  Although further research is needed, CBG can likely have similar interactions with other compounds in cannabis. The Different Types of CBG Products Just like CBD, CBG products can come in three main extraction types: isolate, full-spectrum, and broad-spectrum. Isolate refers to the pure form of any cannabinoid. A CBG isolate would mean that it doesn’t contain any other compounds except for CBG. Isolate can be sold in a powder form or formulated into CBG oils and other products. Full-spectrum CBG is a whole-plant extract that contains CBG, CBD, THC, and all other cannabinoids found in the hemp plant. This is usually made from hemp that’s been grown specifically for high CBG content because regular hemp has low CBG levels. The amount of CBG in this extract should be higher or similar to CBD. Full-spectrum hemp extracts also contain terpenes. Terpenes are natural compounds that give cannabis and other plants their distinct aromas and flavors. They have also been demonstrated to have beneficial health effects and work in synergy with cannabinoids.  That means they can also play a major role in the entourage effect. For instance, the terpene myrcene is known for its sedative, pain-relieving, and muscle-relaxing effects, which may work together with THC to produce the “couch-lock” experienced by some cannabis users.  Another way to make full-spectrum CBG is to combine a regular full-spectrum CBD extract with CBG isolate to bring up its low CBG levels. Lastly, broad-spectrum CBG is identical to full-spectrum but with one difference: all of the THC has been removed. What is CBG Oil? The three types of CBG extract can be sold in the same wide variety of products as CBD. This includes CBG oils, capsules, edibles, topicals, and much more. Such CBG products are still relatively new so they will be harder to find than their CBD counterparts. The Effects of CBG Because CBG research is still in its infancy, we don’t know too much about CBG’s effects and side effects. One study in rats found that CBG stimulated appetite without producing any significant side effects.  Other studies have suggested other beneficial properties, such as reducing different types of inflammation. However, human research is needed before we fully understand CBG’s effects. CBG Dosage There isn’t one correct amount of CBG to take. It varies by individual, based on your body weight, body chemistry, the symptoms you’re hoping to improve, and their severity. Other factors that can influence CBG dosage include the type of product you’re taking, its concentration, and the delivery method. On top of that, CBG is a relatively new and under-examined cannabinoid, so there isn’t a lot of scientific or anecdotal data on how much you should take. Your best bet is to apply CBD’s general dosing recommendations to CBG. The vast majority of CBD users take anywhere from 10 mg to 50 mg of CBD one to two times per day. That means you can start by taking a low (10-15 mg) dose of CBG and see how it affects you. If there’s no effect, increase the dosage incrementally, making sure to stop and check how you feel after every dose. Do this until you can notice the desired effects or benefits and stick to that dosage in the future. Choosing the Right Type of CBG Extract Another important tip to keep in mind is to choose the optimal type of CBG for your needs. If you’re looking for the greatest benefits and want to get the most out of the entourage effect, then full-spectrum CBG products will be your best option. Meanwhile, if you need to avoid THC, broad-spectrum CBG products will be the better choice. Finally, if you just want pure CBG and nothing else, you should choose products containing CBG isolate. CBG Benefits and Health Conditions There isn’t a lot of research looking at CBG because it’s a minor cannabinoid. Having said that, the few studies that have been done paint a promising picture, suggesting that CBG may have multiple potential benefits: One study found that CBG and other cannabinoids may have antibacterial effects  A mouse study found that CBG reduced bladder contractions more effectively than four other cannabinoids, suggesting its potential use in bladder dysfunction disorders  Another mouse study showed that CBG had beneficial effects on inflammatory bowel disease (IBD)  Another animal study reported that CBG seemed to reduce neuroinflammation in mice with multiple sclerosis (MS)  CBG might also have neuroprotective properties, as it protected the neurons of mice with Huntington’s disease  A study of multiple cannabinoids reported that CBG can reduce keratinocyte proliferation, the process largely responsible for psoriasis  A study in rats found that CBG had appetite-stimulating effects that can have many exciting applications, such as offering a non-intoxicating alternative to THC for counteracting weight loss in people with HIV, cancer, and other serious conditions  A test-tube study found that CBG inhibited colorectal cancer cell growth while another reported similar effects on human carcinoma cells, suggesting potential anti-cancer effects   It’s far too early to conclude anything from these findings because they’re limited to animal and test-tube research. Still, they do suggest that CBG can have similar and some unique benefits when compared to CBD, paving the way for its increased use. Frequently Asked Questions What is CBG used for? CBG is used in treating potential health benefits, which include anti-inflammatory, appetite-stimulating, and neuroprotective effects. Like CBD, CBG can be used as a dietary supplement in the form of CBG oil, capsules, and many other products. What is the difference between CBD and CBG? The main difference is that CBD is typically the most abundant cannabinoid in hemp, whereas CBG is only present in small amounts. Aside from that, they seem to differ in their effects, with some being similar, and others — such as appetite stimulation — being unique to CBG. How does CBG make you feel? We don’t know enough about CBG’s effects because there’s a lack of human studies. Having said that, we know it’s non-intoxicating, so you won’t get high from taking it. In that sense, it might be as effective as CBD in reducing unwanted sensations or specific medical symptoms like inflammation. Is CBG better than CBD? There’s no such thing as the “best cannabinoid” since they all have different effects that are useful for different health issues. For example, CBG is clearly better for stimulating appetite, since there’s no evidence that CBD has a similar effect. Meanwhile, CBD is likely better for anxiety, since there are multiple studies demonstrating its effectiveness. References 1. Morales, Paula, Dow P. Hurst, and Patricia H. Reggio. "Molecular targets of the phytocannabinoids: a complex picture." Phytocannabinoids. Springer, Cham, 2017. 103-131. 2. Brenneisen, Rudolf. "Chemistry and analysis of phytocannabinoids and other Cannabis constituents." Marijuana and the Cannabinoids. Humana Press, 2007. 17-49. 3. Maroon, Joseph, and Jeff Bost. "Review of the neurological benefits of phytocannabinoids." Surgical neurology international 9 (2018). 4. Aizpurua-Olaizola, Oier, et al. "Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes." Journal of natural products 79.2 (2016): 324-331. 5. Aizpurua-Olaizola, Oier, et al. "Targeting the endocannabinoid system: future therapeutic strategies." Drug discovery today 22.1 (2017): 105-110. 6. De Petrocellis, Luciano, et al. "Effects of cannabinoids and cannabinoid?enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes." British journal of pharmacology 163.7 (2011): 1479-1494. 7. Cascio, Maria Grazia, et al. "Evidence that the plant cannabinoid cannabigerol is a highly potent α2?adrenoceptor agonist and moderately potent 5HT1A receptor antagonist." British journal of pharmacology 159.1 (2010): 129-141. 8. Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969. 9. Casey, Sherelle L., Nicholas Atwal, and Christopher W. Vaughan. "Cannabis constituent synergy in a mouse neuropathic pain model." Pain 158.12 (2017): 2452-2460. 10. Andre, Christelle M., Jean-Francois Hausman, and Gea Guerriero. "Cannabis sativa: the plant of the thousand and one molecules." Frontiers in plant science 7 (2016): 19. 11. Russo, Ethan B. "Taming THC: potential cannabis synergy and phytocannabinoid?terpenoid entourage effects." British journal of pharmacology 163.7 (2011): 1344-1364. 12. Brierley, Daniel I., et al. "Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats." Psychopharmacology 233.19-20 (2016): 3603-3613. 13. Appendino, Giovanni, et al. "Antibacterial cannabinoids from Cannabis sativa: a structure− activity study." Journal of natural products 71.8 (2008): 1427-1430. 14. Pagano, Ester, et al. "Effect of non-psychotropic plant-derived cannabinoids on bladder contractility: focus on cannabigerol." Natural Product Communications 10.6 (2015): 1934578X1501000653. 15. Borrelli, Francesca, et al. "Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease." Biochemical pharmacology 85.9 (2013): 1306-1316. 16. Granja, Aitor G., et al. "A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis." Journal of Neuroimmune Pharmacology 7.4 (2012): 1002-1016. 17. Valdeolivas, Sara, et al. "Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice." Neurotherapeutics 12.1 (2015): 185-199. 18. Wilkinson, Jonathan D., and Elizabeth M. Williamson. "Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis." Journal of dermatological science 45.2 (2007): 87-92. 19. Brierley, Daniel I., et al. "A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT] 9-tetrahydrocannabinol, elicits hyperphagia in rats." Behavioural pharmacology 28.4 (2017): 280-284. 20. Borrelli, Francesca, et al. "Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid." Carcinogenesis 35.12 (2014): 2787-2797. 21. Baek, Seung Hwa, et al. "Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells." Archives of Pharmacal Research 21.3 (1998): 353.
CBD for Back Pain
Scientific Confidence Grade Effect Size Rating Editorial Note B ** CBD may relieve back pain. However, most of the evidence comes from studies looking at other types of chronic pain, so targeted research in people with back pain is lacking. Multiple human studies have demonstrated CBD’s pain-relieving properties. CBD may significantly reduce back pain. CBD for Back Pain: Can It Help? (January 2021) Research has shown that CBD can relieve various types of pain, suggesting that it may also be beneficial for back pain. Still, studies looking specifically at the use of CBD in back pain sufferers are needed. Cannabidiol (CBD) is growing in popularity as a natural option for anxiety, inflammation, and other common issues. Many people also take CBD for back pain. There’s some evidence for CBD’s pain-relieving effects, which may help reduce various types of acute and chronic pain. More specifically, there's a lot of potentials when it comes to CBD for back pain. Besides, CBD is a relatively safe, natural compound, which makes it an attractive alternative to prescription medications. CBD can be taken in many forms, including CBD oil, capsules, and topical products that are applied directly to the painful part of the body. But does it work? Here’s what medical research tells us about using CBD for back pain. Back Pain Overview Back pain is one of the most common reasons people see their doctor. Although it typically affects the lower back, it can also occur in the middle or upper parts of the back. Back pain can be acute but for many sufferers, it’s a chronic issue that significantly reduces their quality of life. According to studies, an estimated 23% of the world’s adults suffer from chronic low back pain, and as many as 84% will experience it at some point in their lives.1 There are many causes of back pain, including muscle or ligament strain, a bulging or herniated disk in your spine, osteoporosis, arthritis, and other conditions that don’t necessarily affect the back, such as pneumonia. Back Pain Subtypes Based on what causes it, back pain can be roughly broken down into five categories: 2 Mechanical: This type of back pain is caused by damage to the spine or soft tissues. One common example is a herniated disk, a condition where the inner portion of the rubbery cushions (disks) between your spine’s vertebrae slip out. Degenerative: Back pain caused by a disease that tends to progress and get worse over time, such as osteoarthritis. Inflammatory: Back pain caused by some sort of inflammation, such as sacroiliitis (inflammation of the sacroiliac joint). Oncologic: Back pain caused by cancer, including bone marrow cancer and cancer lesions in the spine. Infectious: Back pain due to an infection or abscess in the spine or nearby muscles and other soft tissues. Back Pain Symptoms & Pathology Back pain is characterized by a painful sensation that can be described as a muscle ache or burning, shooting, or stabbing pain. Back pain may also be worse during certain movements, such as bending, standing, walking, or lifting something. In some cases, back pain can also radiate down into your leg. Can You Use CBD for Back Pain? CBD may help relieve back pain in multiple ways. First off, its analgesic (pain-relieving) properties3 can reduce back pain directly, regardless of the cause. Additionally, CBD’s anti-inflammatory4 effects may help with cases of back pain caused by inflammation. Research also suggests that anxiety and depression may be associated with lower back pain.5 6 CBD may help here as well, as it’s known for its anxiolytic (anxiety-relieving) effect and may have antidepressant properties.7 8 A growing list of animal studies have shown that CBD can alleviate pain and provide related benefits when used internally or externally: One 2017 study in rats with osteoarthritis found that CBD prevented the development of neuropathic joint pain.9 In a 2016 study, topically applied transdermal CBD gel reduced joint pain and inflammation in mice with rheumatoid arthritis.10 A 2014 study in rats found that CBD protected against damage caused by intervertebral disc degeneration, one of the most common causes of chronic low back pain.11 The Endocannabinoid System and Pain One of the main ways that CBD can relieve back pain is by interacting with your endocannabinoid system (ECS). This system regulates many processes, including inflammation, stress, mood, sleep, and pain, to maintain a balanced internal state called homeostasis.12 The ECS is made up of endocannabinoids, cannabinoid receptors, and special enzymes. Endocannabinoids are cannabinoids naturally made in the body that stimulate the ECS by binding to specific cannabinoid receptors. Most notably, CBD can inhibit the effects of FAAH, an enzyme that breaks down anandamide, one of the two main endocannabinoids produced by your body. In doing so, it can enhance anandamide’s effects, which include pain and inflammation relief.13 14 There’s already ample evidence showing that drugs that inhibit FAAH may be an effective way to relieve pain. For example, one highly cited study found that giving mice a FAAH inhibitor increased their anandamide levels and significantly lowered inflammatory pain.15 Another mouse study found that genetically removing the FAAH enzyme or using a drug to block its effects both reduced the animal’s pain from rheumatoid arthritis.16 Similarly, a study of a FAAH inhibitor in mice with osteoarthritis reported an improvement in chronic joint pain.17 Other Ways CBD Can Help With Back Pain CBD may also relieve back pain by interacting with other systems in your body. For example, there’s evidence that CBD can act on TRP receptors,18 which are involved in regulating pain and inflammation, as well as other receptors with similar functions, such as PPARγ receptors.19 An animal study also found that CBD may relieve inflammatory and neuropathic (nerve) pain by acting on a3 glycine receptors.20 Additionally, studies have shown that CBD can suppress the pro-inflammatory (NF)-κB pathway,21 which is involved in many inflammatory conditions, including those that may cause back pain, such as osteoporosis and osteoarthritis.22 What Does the Research Say? While there isn’t much human research looking specifically at the use of CBD for back pain, multiple studies have shown that CBD has pain-relieving properties. In one 2020 study, 29 people with peripheral neuropathy — a type of nerve pain that usually affects the hands and feet — applied placebo or CBD oil to their lower extremities. Unlike the placebo group, the CBD group reported a significant reduction in pain as well as unwanted cold and itchy sensations.23 Meanwhile, a 2019 study examined the impact of adding full-spectrum CBD softgels to the regimen of 97 chronic pain sufferers for 8 weeks. More than half (53%) reduced or completely stopped taking prescription painkillers (opioids), and 94% of the study participants reporting improved quality of life, particularly in terms of pain and sleep.24 Another 2018 trial looked at the effects of a synthetic transdermal CBD gel versus a placebo in 320 people with knee osteoarthritis. Although not everyone in the CBD group saw notable improvements, those that did experience a significant reduction in pain.25 Furthermore, a 2015 review paper that examined the findings of 79 clinical studies concluded that “there was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain…”26 In summary, there’s a large volume of evidence showing that CBD can relieve pain but high-quality studies looking specifically at the use of CBD for back pain are still needed. Tips on Using CBD for Back Pain If you’re interested in using CBD for back pain, you have two main options: Take CBD internally in the form of CBD oil, capsules, gummies, vape e-liquid, or a similar product Use CBD externally, as a cream or another topical preparation that’s applied directly to the affected area of the back The major difference between the two is that topical CBD only provides benefits where you applied it (unless you’re using a transdermal product). Meanwhile, taking CBD internally produces body-wide effects. It’s best to use both if you’re looking for optimal pain relief. Another way to make sure you’re getting the best possible effects is to opt for products made with full-spectrum or broad-spectrum CBD. These whole-plant extracts contain not just CBD but multiple phytocannabinoids, terpenes, and other beneficial active compounds found in hemp. Research suggests that all of these substances work together to produce a synergistic “entourage effect,” which means whole-plant CBD products may offer greater benefits than those containing CBD alone.27 How Much CBD Should I Take for Back Pain? There’s no established dosage of CBD for back pain. Firstly, there isn’t enough research evidence to make dosage recommendations, secondly, the dosage can also vary drastically from person to person. The right amount of CBD to take depends on many variables, including body weight, genetics, the severity of your back pain, and the kind of CBD product you’re taking. As a result, most experts recommend the “start low and go slow” method.28 This means starting with a small dose of CBD (10-15 mg), waiting a few hours to see the effects, and gradually increasing as needed until you achieve the desired relief. Note that if you’re using a topical product, it can be a bit more difficult to figure out the dosage. One helpful tip is to divide the total amount of CBD in the container by the volume so you know how much CBD is in one ml. For example, a 30 ml cream with 600 mg of CBD would provide 20 mg per ml (600 mg ÷ 30 ml = 20 mg/ml). Are There Any Side Effects? Research suggests that CBD is a generally safe, well-tolerated substance with mostly minor side effects. The following side effects have been reported by studies:29 Tiredness Drowsiness Diarrhea Nausea Dry mouth Low blood pressure Lightheadedness Changes in appetite or weight However, most of these effects are mild and were only found in studies using high doses of pure CBD. This means the average CBD user is unlikely to experience these side effects. Also, if you’re using a topical CBD product, it’s even less likely to cause side effects because it’s difficult for CBD to penetrate deep enough into the skin to reach the bloodstream. Conclusion There isn’t yet any direct evidence supporting the use of CBD for back pain. Still, many animal and human studies have shown that CBD can relieve various types of pain and researchers have uncovered multiple mechanisms through which it works. The bottom line is that CBD oils may help reduce back pain and neck pain, even though more rigorous studies are needed. If you want to use CBD for back pain, you can take it internally, apply it externally in the form of a topical product, or both. CBD is a natural and relatively safe compound that’s unlikely to cause any significant side effects, which isn’t the case for standard prescription painkillers and opioids in particular. If you find that CBD isn't helping, there are health options with tetrahydrocannabinol (THC), another cannabinoid found in the cannabis plant. Keep in mind that this substance isn't legal everywhere in the United States, unlike hemp-derived CBD. With that, you may need to seek medical advice from a doctor before obtaining THC. References 1. Balagué, Federico, et al. "Non-specific low back pain." The lancet 379.9814 (2012): 482-491. 2. Casiano, V. E., A. M. Dydyk, and M. Varacallo. "Back Pain [Internet]. StatPearls." (2020). 3. Russo, Ethan B. "Cannabinoids in the management of difficult to treat pain." Therapeutics and clinical risk management 4.1 (2008): 245. 4. Atalay, Sinemyiz, Iwona Jarocka-Karpowicz, and Elzbieta Skrzydlewska. "Antioxidative and anti-inflammatory properties of cannabidiol." Antioxidants 9.1 (2020): 21. 5. Sagheer, Muhammad Amir, Muhammad Farhan Khan, and Salman Sharif. "Association between chronic low back pain, anxiety and depression in patients at a tertiary care centre." J Pak Med Assoc 63.6 (2013): 688-90. 6. Bener, Abdulbari, et al. "Psychological factors: anxiety, depression, and somatization symptoms in low back pain patients." Journal of pain research 6 (2013): 95. 7. Blessing, Esther M., et al. "Cannabidiol as a potential treatment for anxiety disorders." Neurotherapeutics 12.4 (2015): 825-836. 8. Sales, Amanda J., et al. "Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels." Progress in Neuro-Psychopharmacology and Biological Psychiatry 86 (2018): 255-261. 9. Philpott, Holly T., Melissa O'Brien, and Jason J. McDougall. "Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis." Pain 158.12 (2017): 2442. 10. Hammell, D. C., et al. "Transdermal cannabidiol reduces inflammation and pain?related behaviours in a rat model of arthritis." European Journal of Pain 20.6 (2016): 936-948. 11. Silveira, João W., et al. "Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration." PLoS One 9.12 (2014): e113161. 12. Battista, Natalia, et al. "The endocannabinoid system: an overview." Frontiers in behavioral neuroscience 6 (2012): 9. 13. Clapper, Jason R., et al. "Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism." Nature neuroscience 13.10 (2010): 1265-1270. 14. Rettori, Elisa, et al. "Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat." Neuroimmunomodulation 19.5 (2012): 293-303. 15. Ahn, Kay, et al. "Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain." Chemistry & biology 16.4 (2009): 411-420. 16. Kinsey, Steven G., et al. "Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice." Pharmacology Biochemistry and Behavior 99.4 (2011): 718-725. 17. McDougall, Jason J., et al. "Early blockade of joint inflammation with a fatty acid amide hydrolase inhibitor decreases end-stage osteoarthritis pain and peripheral neuropathy in mice." Back Pain Research & Therapy 19.1 (2017): 1-9. 18. Muller, Chanté, Paula Morales, and Patricia H. Reggio. "Cannabinoid ligands targeting TRP channels." Frontiers in molecular neuroscience 11 (2019): 487. 19. O'Sullivan, Saoirse Elizabeth. "An update on PPAR activation by cannabinoids." British journal of pharmacology 173.12 (2016): 1899-1910. 20. Xiong, Wei, et al. "Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors." Journal of Experimental Medicine 209.6 (2012): 1121-1134. 21. Kozela, Ewa, et al. "Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-κB and interferon-β/STAT proinflammatory pathways in BV-2 microglial cells." Journal of biological chemistry 285.3 (2010): 1616-1626. 22. Tilstra, Jeremy S., et al. "NF-κB in aging and disease." Aging and disease 2.6 (2011): 449. 23. Xu, Dixon H., et al. "The Effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities." Current Pharmaceutical Biotechnology 21.5 (2020): 390-402. 24. Capano, Alex, Richard Weaver, and Elisa Burkman. "Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study." Postgraduate Medicine 132.1 (2020): 56-61. 25. Hunter, D., et al. "Synthetic transdermal cannabidiol for the treatment of knee pain due to osteoarthritis." Osteoarthritis and Cartilage 26 (2018): S26. 26. Häuser, W., F. Petzke, and M. A. Fitzcharles. "Efficacy, tolerability and safety of cannabis?based medicines for chronic pain management–An overview of systematic reviews." European Journal of Pain 22.3 (2018): 455-470. 27. Russo, Ethan B. "The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain." Frontiers in plant science 9 (2019): 1969. 28. Lucas, Catherine J., Peter Galettis, and Jennifer Schneider. "The pharmacokinetics and the pharmacodynamics of cannabinoids." British journal of clinical pharmacology 84.11 (2018): 2477-2482. 29. Huestis, Marilyn A., et al. "Cannabidiol adverse effects and toxicity." Current neuropharmacology 17.10 (2019): 974-989.