Calvin Chan is a researcher and medical writer from Edmonton, Canada. As a big science nerd, he loves reading and writing about everything science - from cannabis to dark matter and even alien life. Calvin has a PhD from the University of Alberta.
Research Suggest CBD May Act As Sunscreen
Research Shows CBD Can Protect Skin Cells From UV Radiation Cannabidiol (CBD) is a naturally occurring compound found in hemp and cannabis, and is used in a variety of consumer products including sunscreens. However, whether the addition of CBD offers any protection from the sun had not yet been tested — until now. According to a first-ever study, CBD can protect laboratory-grown skin cells from cell death triggered by UVB rays — the component of sunlight that causes sunburns, skin cancer, and premature aging. These findings indicate that CBD could be a beneficial additive to sunscreens and may offer more protection than sunscreen alone. The study was led by the biotechnology company Applied Biology Inc. and supported by the natural health products company, Jupiter Wellness. CBD Prevents Skin Cell Death “When we added CBD and exposed the cells to radiation, what we found was that in some cases more 50% of them survived,” Dr. Andy Goren, president and chief medical officer of Applied Biology Inc. and author of the study, tells us. “This means there’s a protective effect.” For the study, two types of laboratory-grown human skin cells — keratinocytes and melanocytes — were treated with CBD for one hour before being exposed to UVB light. These two cell types make up over 90% of the cells found in the outermost layer of the skin. In trials without any added CBD, only about 16% of cells survived a 10-second exposure to UVB. However, for cells treated with CBD, up to 65% of cells survived irradiation — a 49% increase in survival rate. However, Goren notes that CBD itself cannot physically block UVB rays, meaning the protective effects must be coming from something else. “It’s not a physical barrier,” Goren says. “It’s a biological mechanism, but we don’t know what it is yet.” “One possibility could be that it’s neutralizing reactive oxygen species,” explains Glynn Wilson, chairman and chief scientific officer of Jupiter Wellness. “But we don’t really know. There are a host of potential mechanisms which we will have to look at further.” Reactive oxygen species are high energy molecules created by UVB that can damage DNA, trigger inflammation, and cause cell death. CBD is an antioxidant and can eliminate these reactive oxygen species. Wilson said CBD may be providing protection through other processes as well such as by preventing inflammation or promoting DNA repair, only additional research can determine what exactly is at play. Sunscreen Still Important, CBD Not a Replacement When infused into sunscreen, Goren says the protective effects of CBD could potentially provide a variety of additional benefits. “This could translate to longer-lasting or higher protection SPF,” Goren discusses. “But more research is needed.” CBD may also penetrate the skin better than other antioxidants commonly used in skin care products because it’s hydrophobic — meaning it mixes better with oil than water — making it an excellent additive. But Goren notes that because CBD does not physically block any UV rays it cannot be used as a sunscreen substitute. “I see CBD as something that could potentially work synergistically to improve the efficacy of sunscreens,” Goren says. “But it’s not a replacement. All people should use sunscreen that provides sufficient SPF protection for the length of time they are outside.” For those interested in trying a CBD-infused sunscreen, both Goren and Wilson advise looking at FDA compliant companies that use a pure CBD source and is invested in using science to guide their development processes. “People have infused CBD into everything and a lot of it is just marketing claims,” Goren said. “This is the first time we’ve found a clue that CBD can improve UV protection.”
CBD for Fibromyalgia
Scientific Confidence Grade Effect Size Rating Editorial Note C ** Additional human studies are still needs to be done to determine whether CBD can be effective in treating fibromyalgia symptoms. But controlled trials using medical cannabis as well as research in animal models suggest that CBD could be worth trying. Controlled trials so far have only focused on the use of medical cannabis (contains both CBD and THC) for treating fibromyalgia symptoms. However, initial studies have had promising results. Animal studies and survey data have also shown that cannabinoids can be effective for treating pain and insomnia – common symptoms for fibromyalgia patients. CBD for Fibromyalgia (March 2021) Being as fibromyalgia is so common and without a cure, many have looked to alternative therapies as a way of reducing pain. One natural substance that's been garnering a lot of attention is cannabidiol (CBD). Unfortunately, while research concerning CBD for fibromyalgia itself is slim, we do know a decent amount about how CBD affects pain levels. Throughout this article, we're going to explore the health condition of fibromyalgia and how CBD products (such as CBD oil) may just be able to help. What is Fibromyalgia? Fibromyalgia is one of the most common syndromes of chronic pain and is thought to affect upwards of 8% of the world’s population. The disease causes physical pain all over the body as well as other symptoms including: 1 Fatigue (sometimes chronic fatigue) Migraines Insomnia Memory problems (a condition often referred to as fibro fog) 2 Researchers aren’t clear yet how fibromyalgia develops. In some cases, the disease can run in families indicating a genetic link. But in other cases, fibromyalgia can develop after a psychological or physical trauma (e.g. depression and sports injuries). With no cure yet for fibromyalgia, treatments can vary but typically involve a combination of pain medication and other rehabilitative interventions to help individuals manage their pain levels (e.g. chiropractic and aerobic exercises). 3 CBD for Fibromyalgia: What Do We Know? The medical cannabis plant contains a combination of both CBD (or cannabidiol) and THC tetrahydrocannabinol). While THC causes psychoactive effects, CBD is non-psychoactive and has been used as a treatment option for a wide range of chronic pain including joint pain, nerve pain, and even cancer pain. 4 Unfortunately, all research studies on fibromyalgia so far test a combination of both CBD and THC, so it’s not clear yet how potent CBD would be as a treatment on its own. But here’s what researchers have found so far: A 2018 study from Israel surveyed 26 fibromyalgia patients and asked them to try smoking medical cannabis as a treatment option and compare it to their previous treatments using analgesics and mild opiates. Patients received on average 26 grams of cannabis a month for approximately 10 months. 5 All patients reported an improvement in their fibromyalgia symptoms, and 13 patients chose to stop taking other medications and rely on medical cannabis alone. In 2019, a study in the Netherlands found that fibromyalgia patients who took a combination of CBD and THC reported reduced pain compared to taking a placebo (18 out of 20 patients). 6 In 2019, another Israel research study of 239 fibromyalgia patients who were given on average 20 grams of cannabis a day, found that 80% reported a “moderate” or “significant” improvement in their fibromyalgia symptoms after 6 months. 7 Of the 196 patients who also experience sleep problems, 73.4% said they saw improvement, and 13.3% claimed their sleep problems completely disappeared. Of the 125 patients who experienced depression-related symptoms, 80.0% reported some level of improvement. However, 28 participants chose to dropout due to moderate side effects, with the most common including dizziness, dry mouth, and hyperactivity. While all 3 of these studies show positive effects of cannabis on fibromyalgia symptoms, it’s important to remember that the research is still in its infancy. Studies on cannabis and fibromyalgia has just started springing up in the last couple years, and most look only at a small number of participants (< 500) and examine the effects in the short term (less than 1 year). Likewise, until studies using only CBD is done, we can’t be sure how successful CBD is as a fibromyalgia treatment on its own. Other Research on CBD and Pain While CBD studies in fibromyalgia patients are lacking, other laboratory studies using animals and brain tissue has led to some promising insights. In both mice and rats, CBD can protect the animals from brain inflammation which is part of what causes the brain damage, memory problems, and fibro fog is seen in humans patients. 8 CBD seems to reduce the activity of certain neurons in the brain, preventing them from triggering the development of chronic pain. 9 CBD has also been shown to lower the stress response in mice, and previous research has shown that chronic stress could trigger the development of fibromyalgia. 10,11 Likewise, when CBD is administered orally or applied topically to inflamed joints in rats, it reduces their pain behavior. Both joint inflammation and pain is also a key symptom of fibromyalgia. 12 Is CBD Still Worth Trying? Fibromyalgia is a chronic disease and while CBD will not cure it, studies have found that at least for some, CBD can help alleviate the associated chronic pain. 13 With that, it's assumed using CBD may work as an additional therapy for when people treat fibromyalgia. While additional research is still needed, some reports suggest that CBD may be a safer alternative as compared to other pain-relieving pharmaceuticals such as opioids and NSAIDS (non-steroidal anti-inflammatory drugs). 14 A systematic review of 275 research papers conducted by the European League Against Rheumatism found no clear evidence that either strong opioids or NSAIDS improved health outcomes for fibromyalgia patients. 3 A survey of 2897 individuals in the U.S. found that respondents overwhelmingly reported that cannabis provided pain relief better than or at least on par with opioid-based medications. 81% of respondents agreed that taking cannabis by itself was actually more effective at treating their pain then conventional opioid-based pharmaceuticals. 14 Nonetheless, what works for one person may not work for everyone else. Until additional research on the effects of CBD on fibromyalgia symptoms, it’s best to approach with caution. Always seek the advice of the medical professional treating your fibromyalgia before trying CBD. And always start with the “suggested use” amount labeled on your CBD product before trying a higher dose. References 1 Wolfe, F., K. Ross, J. Anderson, I. J. Russell, and L. Hebert. “The prevalence and characteristics of fibromyalgia in the general population.” Arthritis and Rheumatism. 38 (1995): 19-28. 2 Kravitz, Howard M., and Robert S. Katz. “Fibrofog and fibromyalgia: a narrative review and implications for clinical practice.” Rheumatology International. 35 (2015): 1115-1125. 3 Macfarlane, G. J. et al. “EULAR revised recommendations for the management of fibromyalgia.” Annals of the Rheumatic Diseases. 76 (2017): 318-328. 4 Argueta, Donovan A. et al. “A balanced approach for cannabidiol use in chronic pain.” Frontiers in Pharmacology. 11 (2020): 561. 5 Habib, George, and Suheil Artul. “Medical cannabis for the treatment of fibromyalgia.” Journal of Clinical Rheumatology. 24 (2018): 255-258. 6 Van de Donk, T. et al. “An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia.” Pain. 160 (2019): 860-869. 7 Sagy, Iftach, Lihi Bar-Lev Schleider, Mahmoud Abu-Shakra, and Victor Novack. “Safety and efficacy of medical cannabis in fibromyalgia.” Journal of Clinical Medicine. 8 (2019): 807. 8 Albrecht, Daniel S. et al. “Brain glial activation in fibromyalgia – A multiside positron emission tomography investigation.” Brain, Behavior, and Immunity. 75 (2019): 72-83. 9 Campos, Alline C., Manoela V. Fogaca, Andreza B. Sonego, and Francisco S. Guimarase. “Cannabidiol, neuroprotection and neuropsychiatric disorders.” Pharmacological Research. 112 (2016): 119-127. 10 Campos, Alline C. et al. “The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system.” International Journal of Neuropsychopharmacology. 16 (2013): 1407-1419. 11 Gupta, Anindya, and Alan J. Silman. “Psychological stress and fibromyalgia: A review of the evidence suggesting a neuroendocrine link.” Arthritis Research and Therapy. 6 (2004): 98-106. 12 Hammell, D. C. et al. “Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.” European Journal of Pain. 20 (2016): 936-948. 13 Borgelt, Laura M., Franson K., Nussbaum A., and Wang G. S. “The pharmacologic and clinical effects of medical cannabis.” Pharmacotherapy. 33 (2013): 195-209. 14 Reiman, Amanda, Mark Welty, and Perry Solomon. “Cannabis as a substitute for opioid-based pain medication: Patient self-report.” Cannabis and Cannabinoid Research. 2 (2017): 160-166.
CBD May Be Able to Reduce Lung Inflammation in COVID-19 Cases
CBD Reduces Lung Inflammation in Respiratory Illnesses Like COVID-19, Pneumonia, and More Recent research has highlighted a potential role for CBD in reducing lung damage caused by acute respiratory distress syndrome (ARDS) – a common condition seen in patients with COVID-19, lung infections, severe pneumonia, and other respiratory diseases or injuries. Cannabidiol (CBD) is one of over a hundred naturally occurring compounds found in hemp and cannabis. But unlike other cannabinoids such as THC, CBD is completely non-intoxicating. It has long been suggested that CBD can have anti-inflammatory properties due to the molecules’ ability to interact with the human endocannabinoid system – a signaling network between cells that can control immune responses. Recent studies in animals have confirmed that CBD can be used to treat excessive lung inflammation seen in ARDS and other respiratory illnesses. Studies Suggest CBD can Reduce ARDS-Associated Lung Damage Early research from the Medical College of Georgia at Augusta University has recently shown that pure CBD can help lungs recover from ARDS and restore healthy oxygen levels. “ARDS is a major killer in severe cases of some respiratory viral infections, including [COVID-19],” said immunologist and study author Babak Baban. “We have an urgent need for better intervention and treatment strategies.” ARDS trigger what researchers call a “cytokine storm.” Cytokines are important molecules secreted by immune cells to communicate and coordinate recovery efforts. However, in ARDS there is an overproduction of these cytokines, creating a dangerous overactive immune response. In the confusion, immune cells can begin inadvertently attacking the lungs, furthering the damage. No cure is currently available for ARDS, and most patients with ARDS will require ventilator support. Mechanical ventilators can take over the breathing functions for the patient, giving the lungs a chance to recover from the infection. However, studies suggest that even with ventilators, approximately 27% of patients with ARDS will die, with the risk of death increases with age and severity of illness. In their studies, the research team triggered ARDS in mice using three doses of foreign RNA molecules similar to those found in respiratory viruses such as COVID-19. Afterward, some mice were given a CBD treatment shot in the abdomen every other day for a total of three days. The timeline was specifically designed to mimic a human patient seeking medical care after experiencing troubled breathing. In mice administered pure CBD, oxygen levels went up and temperatures and cytokine levels went down over time. Additional analysis of the lung tissues further showed that CBD significantly prevented physical lung damage such as scarring and swelling. The finding suggests that CBD can quell the overactive immune response seen in ARDS. However, if CBD is given too early, co-author and physician-scientist Dr. Jack Yu said it may interfere with the body’s healthy immune response. A second study by the research team has further shown that one way CBD appears to reduce ARDS-associated lung damage is through increasing the anti-inflammatory molecule, apelin. Apelin levels decrease during viral infection, but “CBD almost brought it back to a normal level,” Yu said. Because of the association, the team suggests that low apelin levels could be an early indicator of ARDS, however, whether CBD protects the lungs through other mechanisms as well will require additional studies. Synthetic CBD for COVID-19 Currently in Phase-1 Clinical Trial The growing research interest surrounding the use of CBD to treat ARDS has led to the development of a synthetic CBD-based drug, ARDS-003, which has been granted FDA approval to begin phase-1 clinical trials. The drug is under development by Tetra-Bio-Pharma, a pharmaceutical company focused on cannabinoid-derived drug development. Unlike pure CBD, which is purified from the cannabis plant, ARDS-003 is synthetically derived but can interact with the same immune signaling network CBD does – the human endocannabinoid system. “We have extensive preclinical evidence that the active pharmaceutical ingredient in ARDS-003 has a profound effect in inhibiting factors that lead to excessive immune system activation,” Tetra Bio-Pharma CEO Guy Chamberland told Forbes. The randomized, double-blind, placebo-controlled clinical study is scheduled to begin enrollment in December 2020. If successful, the company plans to begin phase 2 studies in the second quarter of 2021. CBD May Also Prevent Lung Damage in Other Respiratory Diseases While most research on the use of CBD is currently centered around COVID-19, ARDS can be seen in a variety of respiratory illnesses such as influenza, pneumonia, sepsis, and other physical lung and chest injuries. A Brazilian research team has found that CBD can improve lung function and inflammation in mice with acute lung injuries. CBD has also been shown to reduce airway inflammation in mice with allergic asthma, the most common type of asthma that can be triggered through allergens such as pollen, dust, and smoke. Considering the positive effects observed with CBD thus far and the importance of the endocannabinoid system in the human body, Baban’s research team said in their study that “it is plausible CBD may be used as a therapeutic candidate in the treatment of various inflammatory conditions.”
CBD for Cancer
Scientific Confidence Grade Effect Size Rating Editorial Note C ** Laboratory studies and controlled trials have already shown that CBD can help reduce cancer pain and chemotherapy-induced nausea and vomiting in cancer patients. However, clinical trials are just being started to study whether CBD can be used to treat cancer directly in human patients. Promising results in both petri-dish and animal studies have led to human trials being planned to investigate the use of CBD in killing cancer cells. However, no results have been reported yet. CBD and other cannabinoids have shown to slow down and kill cancer cells in animals. But research in humans is still lacking. CBD for Cancer (March 2021) CBD can stimulate the body’s endocannabinoid system, a neuromodulatory system influencing various physiological processes and possibly disease progression. How might CBD be useful in treating cancer? Cannabis contains a variety of compounds called cannabinoids that can elicit different effects on the body through the endocannabinoid system (ECS) – a neuromodulatory system that may influence the development and progression of diseases. So far, cannabidiol (CBD) and other cannabinoids have largely only been looked at to alleviate cancer pain and to treat chemotherapy-induced nausea and vomiting. However, some cell-based and animal studies have suggested that you might be able to use CBD for cancer due to its anti-tumor effects on certain cancer types. Cancer Overview Cancer is an extremely complex group of over 100 different diseases, but they all involve the uncontrolled growth and division of the body’s cells. Normal cells in the body grow and divide in a controlled manner. They follow signals produced by the body that direct when the cells should and shouldn’t divide. For instance, cells will be instructed to grow and divide when there’s a wound to repair.1 But cancer begins when cells break free of these normal constraints and can begin growing and dividing uncontrollably. This happens through the accumulation of certain mutations or changes to the cell’s DNA. Some of these mutations can be inherited from parents, which is why family history can sometimes be an indicator of cancer risk.2 American actress Angelina Jolie famously decided to undergo a double mastectomy after having lost her mother to ovarian cancer and finding out that she inherited a mutation in the BRCA1 gene – which placed her at a higher risk of developing cancer herself. However, the National Cancer Institute estimates that only approximately 5-10% of cancers are inherited. Most mutations occur after birth and are caused by carcinogens – substances that can cause DNA damage – or other environmental factors:3,4 Alcohol – Research suggests that about 3.6% of cancers have a high correlation with chronic daily alcohol consumption. Smoking tobacco – More than 85% of all lung cancers have a high correlation with tobacco smoking. Among the 4,000 chemicals that have been identified in tobacco smoke, almost 40 of them are known to be carcinogenic. Viruses and bacteria – Some infectious agents such as HPVs (human papillomaviruses), hepatitis B and C, and helicobacter pylori can damage cells and tissues, increasing the risk of developing certain types of cancers. Ultraviolet Radiation – UV rays from the sun, sunlamps, and tanning booths can damage exposed skin and increase the risk of skin cancer. Pollutants – Many air and water pollutants are carcinogenic such as arsenic in polluted groundwater and chemicals from diesel exhaust. Aging – Most cancers occur in people over the age of 55, largely because it can take time for cells to accumulate enough mutations to become cancerous. According to the Centers for Disease Control and Prevention, cancer is the second leading cause of death in the United States and is exceeded only by heart disease. There are an estimated 1.6 million new cases of cancer every year and nearly 600,000 cancer-related deaths. Cancer Subtypes and Classification Depending on the type of cell that becomes cancerous, their behavior and response to treatment can vary. Most cancers fall into three main groups: Carcinomas – this includes approximately 90% of cancers and arise in epithelial cells that line the skin, internal organs, and blood vessels. Most lung, breast, colon, and prostate cancers are carcinomas. Leukemias and Lymphomas – these account for approximately 8% of cancers and arise from blood cells and cells from the immune system, respectively. Sarcomas – these are cancers that lead to tumors in connective tissues such as muscle, bone, cartilage, tendons, and ligaments. Cancers can then be further classified based on the tissues that they originate from. For instance, ductal breast carcinomas are a type of breast cancer that originates from cells that line the milk duct in the breast. Can CBD help with Cancer: Cancer Pain and Nausea Cannabinoids, including CBD, have gained popularity in the biomedical field due to their potential anti-cancer effects and use in managing other symptoms – such as pain and nausea – in cancer patients. Significant research has already shown that cannabinoids – particularly tetrahydrocannabinol (THC) – can be used to treat nausea caused by cancer chemotherapy. In fact, there are two FDA approved synthetic THCs – Dronabinol and Nabilone – for use in treating chemotherapy-induced nausea and vomiting.5 THC is the principal psychoactive component of cannabis and when consumed can cause the feelings of “euphoria” or “high” that is typically associated with cannabis.10 CBD is non-psychoactive and does not lead to those same sensations. Cannabinoids interact with the body’s endocannabinoid system (ECS). Endocannabinoids are naturally produced chemicals in the human body that play a role in regulating various biological processes. Research is ongoing to confirm how the ECS is involved in regulating brain function, pain, immunity, and metabolism. Cannabinoids such as THC and CBD can mimic these natural “endocannabinoids” and can bind to endocannabinoid receptors including CB1 and CB2, causing similar effects. THC can stimulate the CB1 receptor and prevent the release of hormones that trigger nausea and vomiting after chemotherapy.6 CBD is thought to elicit a similar response by preventing the breakdown of natural endocannabinoids. A 2010 randomized, double-blind, and placebo-controlled study in Spain found that patients with chemotherapy-induced nausea and vomiting benefited from using a 1:1 THC and CBD spray – 71% reported no vomiting as compared to 22% with the placebo.7 A review of 8 different clinical trials also found that cannabinoids reduced neuropathic and cancer pain in patients as compared to a placebo (37% reduction with cannabinoids versus 31% with a placebo).8 Early studies on the drug, Nabiximol, a 1:1 THC and CBD spray also found a reduction in patient-reported cancer pain as compared to a placebo.9 These studies so far suggest that THC and CBD can have anti-nausea and anti-pain effects. However, most trials have relied on using THC and CBD together, so it’s not clear yet whether CBD can elicit the same level of benefit on its own. Can CBD help with Cancer: Anti-Cancer Effects Apart from its use in managing cancer-related pain and nausea, CBD products (such as CBD oil) are also being investigated for possible anti-cancer effects. Studies on cancer cells have shown that many cancer types – including breast, prostate, and pancreatic cancer cells – all have higher than average numbers of CB1 and CB2 receptors.10 In some studies, researchers found that the elevated levels of CB receptors in certain cancer cells were correlated with more aggressive tumors. In some instances, these cells with more highly activated CB receptors were more mobile and divided faster – possibly helping them to become more invasive.11 However, in other cancer types, such as colorectal cancer, researchers have found a lower number of CB1 receptors. A study on mice with colorectal tumors showed a correlation between lower levels of CB1 receptors and faster cancer progression.12 These differences suggest there’s a lot more about how the ECS influences cancer development that has not yet been unraveled. Likewise, it remains to be determined whether CBD could be influencing other biological systems in the body outside of the ECS and CB receptors and, in general, if you can use CBD for cancer. In petri-dish studies, the addition of CBD has been shown to kill or slow down different types of cancer cells including glioblastoma, leukemia, melanoma, lung, breast, cervical, and prostate cancer cell lines.13 In mice, CBD has also been shown to slow down “angiogenesis,” a process by which new blood vessels are created to supply oxygen and nutrients to cells. Tumors rely on this process to gain access to nutrients needed for growth. By blocking angiogenesis, CBD could be useful in preventing tumors from growing.14 What Does the Research Say? Many new follow-up studies have since been done to examine how CBD and other cannabinoids influence cancer development in animals. However, some of the results have been conflicting.15 The first reported study of using CBD and other cannabinoids to slow tumor growth in animals was done in 1975. Lung cancer was transplanted into animals which were then given THC or CBD over 10 days. Researchers found that THC had a dose-dependent ability to slow tumor growth while CBD had no effect. However, in more recent studies, CBD has been shown to have anti-tumor effects in other types of cancers. In mice transplanted with human glioma cells – a kind of brain cancer – CBD at a dose of between 15-20 mg/kg administered over 18-28 days was effective in reducing tumor size and prolonging the animals’ survival.16 A similar anti-cancer effect was seen in mice transplanted with other cancer types as well. In mouse models transplanted with human breast cancer, CBD administered at 10mg/kg blocked tumor growth and prevented metastasis – a process where cancer cells can move from one organ to colonize a different one.17 In mice injected with lung cancer cells, treating them with 5mg/kg CBD prevented the cancer cells from colonizing the lungs by 84%.18 While these early animal studies have been promising, no work has yet been completed to evaluate the use of CBD for treating cancer in human patients. According to the U.S. National Library of Medicine, the Hadassah Medical Organization in Jerusalem, Israel, is looking to recruit 60 participants into a clinical trial to assess the use of pure CBD in treating solid tumor cancers. Recruitment has not yet begun. Similarly, a Spanish neurological oncology research group, GEINO, is looking to test a 1:1 THC and CBD combination drug to treat glioblastoma, a type of brain tumor with a median survival time of only approximately 12 months. THC and CBD will be used alongside the chemotherapy drug temozolomide and radiotherapy. Doctors hope to see if hemp's properties will be complementary medications not only for preventing the growth of cancer cells but also in treating side effects of chemotherapy, such as neuropathic pain. Recruitment has not yet begun. Trying CBD for Cancer While initial laboratory and animal research surrounding the use of CBD and other cannabinoids in cancer treatment has been promising, there isn’t enough evidence that they can be effective for treating cancer in humans. As such, health organizations including the American Cancer Society caution against relying on cannabinoids alone as a treatment for cancer while avoiding or delaying conventional medical care. Even with using CBD to treat cancer-related pain, nausea, or vomiting, users should seek out the advice and support of the medical professionals treating their cancer first. It is also important to keep in mind that while CBD is generally safe and well-tolerated, it can also cause a wide range of side effects.19 Some of these can include:20 Tiredness Drowsiness Diarrhea Nausea Dry mouth Low blood pressure Light-headedness Changes in appetite or weight Conclusion Significant foundational research has already been done in both cell culture and animal studies indicating an anti-cancer effect for CBD. But without human trials, it’s not clear if it's effective to use CBD for cancer in human trials. Nonetheless, it’s clear that the link between cancer development and the ECS makes CBD a promising avenue for cancer therapy research. References 1 Greenhalgh, D. G. “The role of growth factors in wound healing.” Journal of Trauma. 41 (1996): 159-67. 2 Pomerantz, M. M. and Matthew L. Freedman. “The genetics of cancer risk.” Cancer. 17 (2011):416-422. 3 Parsa, N. “Environmental factors inducing human cancers.” Iranian Journal of Public Health. 41 (2012): 1-9. 4 Boffetta, P. and Mia Hashibe. “Alcohol and cancer.” The Lancet Oncology. 7 (2006): 149-156. 5 Pertwee, Roger G. “Emerging strategies for exploiting cannabinoid receptor agonists as medicines.” British Journal of Pharmacology. 156 (2009): 397-411. 6 Van Sickle, M. D., et al. “Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret.” Gastroenterology. 121 (2001): 767-774. 7 Duran, M., et al. “Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.” British Journal of Pharmacology. 70 (2010): 656-663. 8 Whiting, Penny F. et al. “Cannabinoids for medical use a systematic review and meta-analysis.” JAMA. 313 (2015): 2456-2473. 9 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 (2010): 167-179. 10 Daris, Barbara, Mojca Tancer Verboten, Zeljko Knez, and Polonca Ferk. “Cannabinoids in cancer treatment: Therapeutic potential and legislation.” Journal of the Association of Basic Medical Sciences. 19 (2019): 14-23. 11 Velasco, Guillermo, Christina Sanchez, and Manuel Guzman. “Endocannabinoids and cancer.” Handbook of Experimental Pharmacology. 231 (2015): 449-472. 12 Wang, D. et al. “Loss of cannabinoid receptor 1 accelerates intestinal tumor growth.” Cancer Research. 68 (2008): 6468-6476. 13 Kovalchuk, Olga, and Igor Kovalchuk. “Cannabinoids as anticancer therapeutic agents.” Cell Cycle. 19 (2020): 961-989. 14 Solinas, M. et al. “Cannabidiol inhibits angiogenesis by multiple mechanisms.” British Journal of Pharmacology. 167 (2012): 1218-1232. 15 Munson, A. E., L. S. Harris, M. A. Friedman, W. L. Dewey, and R. A. Carchman. “Antineopalstic activity of cannabinoids.” Journal of the National Cancer Institute. 55 (1975): 597-602. 16 Massi, P. et al. “Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.” Journal of Pharmacology and Experimental Therapeutics. 308 (2004): 839-845. 17 Elbaz, M. et al. “Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of cannabidiol in breast cancer.” Molecular Oncology. 9 (2015): 906-919. 18 Ramer, R. et al. “Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1.” Biochemical Pharmacology. 79 (2010): 955-966. 19 Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. “Safety and side effects of cannabidiol, a Cannabis sativa constituent.” Current Drug Safety. 6 (2011): 237-249. 20 Huestis, Marilyn A. et al. “Cannabidiol adverse effects and toxicity.” Current Neuropharmacology. 17 (2019): 974-989.
CBD for Nausea
Scientific Confidence Grade Effect Size Rating Editorial Note B *** Cannabis has been used by humans for over 5,000 years in treating nausea and vomiting. Both laboratory studies and controlled trials indicate that cannabinoids (CBD and THC) can be used to prevent nausea and vomiting, particularly in serious cases (e.g., chemotherapy-induced nausea and vomiting). Large-scale randomized controlled trials have only been performed on synthetic THCs and 1:1 CBD and THC formulas. The efficacy of CBD on its own is supported by preliminary studies but is not yet confirmed in controlled trials. In over 30 human trials performed to date, cannabinoids (including THC, synthetic THCs, and 1:1 CBD and THC formulas) always outperform placebo and other anti-nausea medication in preventing nausea and vomiting. Using CBD to Treat Nausea (March 2021) Cannabidiol (CBD) can stimulate the body’s endocannabinoid system, a neuromodulatory system that plays a role in regulating parts of the brain involved in triggering nausea and vomiting. This means CBD oil could be a powerful tool for treating nausea. Cannabis contains a variety of compounds that can stimulate or act on the body’s central nervous system — including the areas of the brain that control nausea and vomiting reflexes.1 In fact, the cannabis plant is one of the oldest known natural pharmacological remedies for treating nausea and vomiting, and has been used for over 5,000 years.2,3 Medical research has since shown that CBD can achieve this effect by stimulating the endocannabinoid system, a neuromodulatory system in the human body influencing various physiological processes — including nausea and vomiting.1 Many anti-nausea drugs currently on the market are based on cannabinoids, such as THC and CBD.4 So, what’s the science behind using CBD for nausea, and will it work for everyone? Nausea Overview The feeling of nausea is a commonly encountered symptom with a wide range of possible biological and psychological causes:5 Infectious (e.g., food poisoning or gastroenteritis) Medication-related (e.g., from chemotherapy or antibiotics) Central Nervous System (e.g., from migraines, meningitis, or seizures) Psychiatric (e.g., anxiety, depression, eating disorders) Labyrinthine (e.g., motion sickness or vertigo) Endocrinological or metabolic (e.g., pregnancy, hormonal imbalances) Gastrointestinal (e.g., from a bowel obstruction, ulcer, or pancreatic diseases) While the feeling of nausea symptoms typically leads to eventual vomiting, this doesn’t always have to be the case. In fact, most people report that nausea is more common and disabling than vomiting because the feeling can last for an extended period of time.6 In a population study based on 62,651 individuals, 12.5% reported nausea being a “minor or major complaint” in the last 12 months.7 Evolutionary biologists believe nausea may have evolved as a natural protective mechanism and this reflex can be found in many different animal species.8 Nausea and vomiting can trigger the expulsion of any ingested toxins (e.g., drugs, alcohol) or contaminated food items containing toxic levels of certain bacteria, poisons, or viruses.9 By emptying the contents of the stomach and upper intestinal tract, the body may be able to prevent or divert the possible dangers stemming from these toxins. However, not all cases of nausea are warranted, and nausea can be inadvertently triggered by a variety of unrelated conditions. For instance, a sensory disconnect between what we see and what we feel — commonly referred to as motion sickness — can trigger unnecessary nausea. Likewise, unrelated conditions such as migraines and anxiety can also be a trigger. Sometimes, nausea can also occur as a side-effect of certain medications such as chemotherapy for cancer treatment. This often makes managing an existing condition even more difficult. Nausea and the Brain Researchers are continuing to shed light on the complex mechanisms that underlie how nausea and the brain are related. What they do know is that the mechanisms encompass our psychological state, central nervous system, autonomic nervous system, endocrine system, and gastric dysrhythmias (conditions that affect normal stomach contraction and digestion).5 Stimuli giving rise to nausea and vomiting originate from various areas including the gut, our sense of balance, and the chemoreceptor trigger zone – an area of the brain (part of the medulla oblongata) that receives inputs from blood-borne drugs or hormones which ultimately initiate vomiting. In addition to the chemoreceptor trigger zone, the medulla oblongata is an area of the brain that is particularly important for other reasons. Many of the signals generated that seem to lead to nausea (e.g., from emotional responses, toxin-related, motion-induced) are relayed to the nucleus tractus solitaries, which is also part of the medulla oblongata. From here, the signals are then passed on to other areas such as the autonomic nervous system (i.e., where involuntary processes are regulated like breathing, heart rate, and digestion), and ultimately give rise to that uncomfortable feeling. 5 Importantly, researchers propose that each individual has a threshold for nausea that changes minute by minute, calling it a “dynamic threshold”. They say that the threshold depends on the interaction between an individual’s inherent factors and some more changeable factors like psychological states of anxiety, anticipation, expectation, and adaptation. The combination of all these factors is what they propose explains the variability of nausea between individuals and for a single individual over time. Cannabis and the Endocannabinoid System A major signaling network involved is the endocannabinoid system (ECS).1 “Endocannabinoids” are naturally produced chemicals in the human body that play a role in regulating a variety of biological responses — including shutting down feelings of nausea and vomiting. Cannabinoids such as THC and CBD can mimic these natural “endocannabinoids” and similarly reduce nausea. THC, or ?9-tetrahydrocannabinol is the principal psychoactive component of cannabis and when consumed can cause the feelings of “euphoria” or “high” that is typically associated with cannabis.10 CBD, or cannabidiol, is non-psychoactive and does not lead to those same sensations. Both THC and CBD can interact with two different types of cell receptors that are part of the ECS: CB1 and CB2. How Cannabinoids Block Nausea and Vomiting Researchers have found CB1 receptors distributed across multiple parts of the brain including areas that regulate nausea and vomiting.11 There’s also evidence that CB1 receptors may be present in the gut where nausea and vomiting may be triggered upon detecting possible contaminants or toxins.12 To date, most studies have examined both nausea and vomiting together. This is largely because nausea is a subjective condition and it can be difficult to measure just how nauseous a patient is compared to another. Distinguishing the two is even harder in animals because it’s not always obvious whether an animal is or isn’t nauseous. While most studies focus on vomiting as an indicator for nausea, it’s important to note that nausea can occur without the need to vomit and there are likely different mechanisms that control nausea that researchers haven’t yet identified. But based on animal studies so far, nausea and vomiting from food poisoning may be signaled by the release of the serotonin hormone in the small intestines. This signaling occurs after the animals have ingested the “bad bacteria” that commonly lead to digestion issues. The researchers then found that this serotonin signal from the gut and the follow-up vomiting could be reduced by activating the CB1 receptors.12 Other animal studies have similar findings, showing that THC can bind CB1 receptors directly and may block nausea and vomiting through this effect.13 CBD can also prevent the breakdown of natural endocannabinoids — such as anandamide — which can help the body maintain stimulation of the CB1 receptors for longer and reduce nausea and vomiting. To further understand CB1’s important role, researchers conducted studies on humans and found that some individuals may have a naturally less responsive ECS when experiencing nausea and vomiting from motion sickness. For instance, a 2010 study of 21 human volunteers found that those who were more likely to experience motion sickness tend to have less CB1 receptor activity.16 In test-tube cell studies, researchers found that THC and anandamide are capable of blocking serotonin signaling directly by binding certain serotonin receptors14 and that CBD can also directly bind to other serotonin receptors to affect serotonin signaling.15 These studies show the possibility that cannabinoids could additionally be reducing nausea and vomiting through signaling pathways outside of CB1 receptor binding. Cannabinoids for Treating Nausea There are three cannabinoids currently approved by the FDA for the pharmaceutical market, two of which – Dronabinol and Nabilone – can be used to treat serious cases of nausea and vomiting (e.g., chemotherapy-induced nausea and vomiting). Both drugs are synthetic versions of THC and are administered in pill form. There are no concrete guidelines for dosing, but both are typically prescribed at doses between 10 mg to 50 mg daily. THC has been used for treating nausea since 1985 and its efficacy has been validated by over a dozen clinical studies and controlled double-blind trials beginning in the 1970s.1,4 In one of the first randomized, double-blind, and placebo-controlled studies — a gold standard in clinical research — 40 out of 55 patients experiencing “severe nausea” reported THC eliminating their nausea and vomiting completely (7mg of THC per square meter of the body surface, taken every four hours for four doses).17 By contrast, only 5 patients in the placebo group reported any reduction in their nausea and vomiting. A 2001 review of 30 different randomized and controlled human trials with a total of 1,366 patients found that across all clinical studies, THC or a synthetic THC alternative was always more effective than placebos and other anti-vomiting medication in treating nausea and vomiting from chemotherapy.18 A more recent 2007 double-blind placebo-controlled study with 61 cancer patients further found that synthetic THC was just as effective in preventing nausea and vomiting as Ondansetron (also known as Zofran) — a commonly used anti-nausea prescription medication.19 Unfortunately, the use of CBD alone has not yet been investigated to the same degree for nausea relief. The only completed clinical trials involving CBD examines a blend of 1:1 THC and CBD. In a 2010 randomized, double-blind, and placebo-controlled pilot study in Spain, 16 participants experiencing chemotherapy-induced nausea and vomiting were given either a THC and CBD nasal spray or a placebo spray.20 These patients could use the spray as needed for up to 4 days after their chemotherapy appointment. Participants inhaled an average of 12.9 mg THC and 12 mg CBD per day. For patients using the THC and CBD spray, 57% reported no nausea and 71% reported no vomiting as compared to just 22% in both categories for patients using the placebo. Only one participant had to be removed from the study after using the spray and experiencing increased anxiety. Currently, the New South Wales government is funding the “largest, most definitive” clinical trial to further evaluate the use of CBD and THC in preventing chemotherapy-induced nausea and vomiting. In the phase II crossover randomized controlled trial, 81 participants were given either placebo capsules or oral capsules containing both THC and CBD (2.5mg each) to be taken three times a day.21,22 Although 31% of participants experienced some side-effects including sedation and dizziness, 83% of participants still preferred using the cannabis extract over a placebo. Potential Side Effects While clinical trials are still lacking when it comes to CBD for nausea, THC has already been well documented as a potent treatment option for nausea, and laboratory studies suggest that CBD may achieve a similar effect. CBD is also remarkably safe when used properly, however, there are several common possible side effects to be aware of:23 Dry mouth Dry or itchy eyes Headaches or light-headedness Increased anxiety or paranoia Sleepiness or lethargy Diarrhea Changes in appetite or weight Both THC and CBD can also interfere with certain prescription drugs. It is best to consult with a physician if you plan on trying a cannabinoid alongside other medication. Heavy chronic use of cannabis, especially in young people, has also be observed to cause recurrent nausea and vomiting in a condition called “cannabinoid hyperemesis syndrome.” The exact cause is unclear, but this condition has only been observed in a very small number of individuals after almost-daily long-term use of cannabis.24 Trying CBD to Treat Nausea Overall, cannabinoids have shown to offer a comparable benefit to alleviating nausea and vomiting similar to pharmaceutical anti-nausea medications. Although THC remains the best studied in controlled trials, CBD and hemp oil can likely impart similar anti-nausea benefits through interfering with the breakdown of natural endocannabinoids and by blocking serotonin receptors. Full-spectrum hemp extract will likely work best thanks to the entourage effect. When trying CBD for nausea, it’s best to follow the dosage recommendations on the CBD product — typically starting at between 10-15 mg a day. Your body weight, genetics, and the type of CBD product you use can all affect how you respond to CBD and the dosage required to treat your nausea or vomiting.25,26 While some studies indicate that even doses up to 1,500 mg a day can be well-tolerated, depending on your body weight general recommendations fall between 30-75 mg for people between 100 to 250 lbs.27 Because higher doses of CBD will inevitably increase the likelihood of side effects. It’s best to begin with a low dose and try going up slowly until you settle on an amount that helps relieve your symptoms. References 1 Parker, Linda A., Erin M. Rock, and Cheryl L. Limbeer. “Regulation of nausea and vomiting by cannabinoids.” British Journal of Pharmacology. 163 (2011): 1411-1422. 2 Kalant, H. “Medicinal use of cannabis: history and current status.” Pain Research and Management. 6 (2001): 80-91. 3 Iversen, Leslie L. The science of marijuana. Oxford UP, 2008. 4 Pertwee, Roger G. “Emerging strategies for exploiting cannabinoid receptor agonists as medicines.” British Journal of Pharmacology. 156 (2009): 397-411. 5 Singh, Prashant, Sonia S. Yoon, and Braden Kuo. “Nausea: a review of pathophysiology and therapeutics.” Therapeutic Advances in Gastroenterology. 9 (2016): 98-112. 6 Stern, R. M., Kenneth L. Koch, and Paul Andrews. Nausea: Mechanisms and Management. Oxford UP, 2011. 7 Haug, Tone T., Arnstein Mylkletun, and Alv A. Dahl. “The prevalence of nausea in the community: psychological, social, and somatic factors.” General Hospital Psychiatry. 24 (2002): 81-86. 8 Borison, H. L., Rosaline Borison, and Lawrence E. McCarthy. “Phylogeneic and neurological aspects of the vomiting process.” The Journal of Clinical Pharmacology. 21 (1981): 23S-29S. 9 Balaban, Carey D. and Bill J. Yates. “What is nausea? A historical analysis of changing views.” Autonomic Neuroscience: Basic and Clinical. 202 (2017): 5-17. 10 Atakan, Zerrin. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic Advances in Psychopharmacology. 2 (2016): 214-254. 11 Sharkey, Keith A. and John W. Wiley. “The role of the endocannabinoid system in the brain-gut axis.” Gastroenterology. 151 (2016): 252-266. 12 Hu, Dong-Liang, et al. “Staphylococcal enterotoxin induces emesis through increasing serotonin release in intestine and it is downregulated by cannabinoid receptor 1.” Cellular Microbiology. 9 (2007): 2267-2277. 13 Van Sickle, M. D., et al. “Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret.” Gastroenterology. 121 (2001): 767-774. 14 Barann, M.. et al. “Direct inhibition by cannabinoids of the human 5-HT3A receptors: probably involvement of an allosteric modulatory site.” British Journal of Pharmacology. 137 (2002): 589-596. 15 Russo, Ethan B., Andrea Burnett, Brian Hall, and Keith K. Parker. “Agonistic properties of cannabidiol at 5-HT1a receptors.” Neurochemical Research. 30 (2005): 1037-1043. 16 Chouker, Alexander, et al. “Motion sickness, stress and the endocannabinoid system.” PLoS One. 21 (2010): e10752. 17 Orr, Leo E., Joseph F. McKernan, and Berit Bloome. “Antiemetic effect of tetrahydrocannabinol compared with pacebo and prochlorperazine in chemotherapy-associated nausea and emesis.” JAMA Internal Medicine. 140 (1980):1431-1433. 18 Tramer, Martin R., et al. “Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.” BMJ. 323 (2001): 16. 19 Meiri, Eyal, et al. “Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.” Current Medical Research and Opinion. 23 (2007): 533.43. 20 Duran, M., et al. “Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.” British Journal of Pharmacology. 70 (2010): 656-663. 21 Grimison, P., et al. “Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.” Annals of Oncology. 7534 (2020): 39996-39998. 22 Grimison, P., et al. “Results of crossover phase II component of randomized placebo-controlled trial evaluating oral THC/cannabis extract for refractory chemotherapy-induced nausea and vomiting (CNIV).” Journal of Clinical Oncology. 38 (2020): 12008-12008. 23 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 (2017): 139-154. 24 Simonetto, Douglas A., Amy S. Oxentenko, Margot L. Herman, and Jason H. Szostek. “Cannabinoid hyperemesis: a case series of 98 patients.” Mayo Clinic Proceedings. 87 (2012): 114-119. 25 Pan, Sheng-dong, et al. “Weight-based dosing in medication use: what should we know?” Patient preference and adherence. 10 (2016): 549. 26 Wang, Leiwei, Howard L. McLeod, and Richard M. Weinshilboum. “Genomics and drug response.” New England Journal of Medicine. 364 (2012): 1144-1153. 27 Bergamaschi, Mateus Machado, et al. “Safety and side effects of cannabidiol, a Cannabis sativa constituent.” Current Drug and safety. 6 (2011): 237-249.
CBD May Help with Cocaine Withdrawal Management, Study Finds
New Study Reveals CBD May Help with Cocaine Withdrawal According to a new study done in mice, CBD can help improve the motor, behavioral, and neurological symptoms caused by chronic and relapsing cocaine use. The study was led by researcher Jorge Manzanares from the Universidad Miguel Hernández de Elche and published in the journal, Neurotherapeutics. According to the report, the research indicates a “potential for [CBD in] the management of cocaine withdrawal.” Cannabidiol (CBD) is one of over a hundred different compounds naturally found in hemp and cannabis. But unlike other common cannabinoids such as THC, CBD has garnered both popular and medical attention due to its non-intoxicating health effects. In recent years, CBD has been investigated for use in treating numerous substance use disorders, including alleviating withdrawal effects from opioids, tobacco, alcohol, and other stimulants. “This is probably because of [CBD’s] anxiolytic, antidepressant, antipsychotic, and neuroprotective actions,” the researchers explained in the study. Cocaine Use on the Rise Cocaine use disorder affects an estimated 20 million users globally, making it the most predominantly used psychostimulant in the world. It is also the leading cause of death among adults using illicit substances. According to the Manzanares’ study, “up to 5 to 6% of cocaine users will develop cocaine dependence within the first year of use.” Dependence typically involves a cycle of intoxication, bingeing, withdrawal, and cravings. Currently, no regulatory agencies have approved specific drugs for use in treating cocaine withdrawal. However, preclinical studies have shown that CBD may be a promising tool due to its ability to block anxiety and psychosis-like symptoms. CBD Alleviates Both Behavioral and Neurological Symptoms In the study, mice were given increasing doses of cocaine across a 12-day period 3 times a day. Cocaine withdrawal symptoms were measured 6 hours after the final dose. Researchers found that mice undergoing cocaine withdrawal were significantly more restless, spending more time running, digging, and rubbing. They also and experienced more “anxiety-like” behavior such as spending less time grooming and exploring. But the “administration of CBD significantly regulated [these] behavioural and [neurological] alterations,” Manzanares’ team explained. Even at low doses, CBD improved motor and anxiety-like symptoms, normalizing the amount of time the mice spent rubbing and grooming. At higher doses, time spent on activities such as running, exploring, and digging also returned to levels to animals without a cocaine addiction. CBD also alleviated neurological changes caused by cocaine withdrawal as well. Mice undergoing sudden cocaine withdrawal showed increased DAT and TH levels, and reduced CNR2 levels in their brain tissue. This was reversed in cocaine-addicted animals given CBD. DAT and TH are both proteins involved in the synthesis and transport of dopamine – a hormone that triggers feelings of happiness and pleasure. The brain’s dopamine signals become dysregulated upon cocaine addiction and withdrawal. CNR2 is a brain protein involved in preventing anxiety and depression. Higher CNR2 levels have been shown to reduce cocaine use in mice with cocaine addictions. CBD Studies for Treating Cocaine Addiction Underway in Humans While most research continues to focus on animal models, similar studies are currently being performed with human patients. The Centre hospitalier de l’Université de Montréal is currently leading a study investigating the effect of 92 days use of CBD in alleviating cocaine craving in cocaine-dependent individuals. The study on 79 participants has since been completed, but results have not yet been published. While additional research is still needed to evaluate the use of CBD in treating cocaine addiction in humans, Manzanares’ team described their work in mice as “unequivocal evidence” that CBD can improve anxiety-like behaviors and motor activities caused by cocaine withdrawal.
Does CBD Impair Driving?
First-Ever Study Shows CBD Does Not Impair Driving A landmark study suggests that CBD-only cannabis and hemp products do not impact driving ability – a finding with implications for drug-driving laws internationally. Using a real-world road test, researchers from the University of Sydney in Australia and the Maastricht University in the Netherlands found that unlike tetrahydrocannabinol (THC), cannabidiol (CBD) does not cause driving impairment. Both THC and CBD are major components of cannabis and are being extensively researched and used for a wide range of health benefits. However, CBD specifically has garnered significant medical attention because unlike THC, using CBD does not result in euphoria or intoxication. Research has since shown that CBD has anti-inflammation, pain-management, and anti-anxiety effects. While CBD is known to be non-intoxicating, no study had yet confirmed whether it would influence a person’s ability to drive. Results from the clinical study showed “no significant differences [in driving performance] between CBD-dominant cannabis and placebo.” “These findings indicate for the first time that CBD, when given without THC, does not affect a subject’s ability to drive,” said study lead author, Thomas Arkell. “That’s great news for those using or considering treatment using CBD-based products.” Tests Done Under Real-Road Conditions Double-blind and randomized driving tests were done on a 100 km stretch of public highway with a certified driving instructor to mimic, as closely as possible, real-world driving conditions. “Road safety is a primary concern,” Arkell said. “These results should allow for evidence-based laws and regulation for people receiving medical cannabis.” Participants were invited to vaporize either THC, CBD, or a THC/CBD blend and researchers compared their driving to participants who took a placebo. Researchers used a THC or CBD dose of 13.75 mg, which was enough to cause strong feelings of intoxication. To measure whether their driving was impaired, the team calculated the car’s standard deviation of vehicle Position (SDLP) – a measurement of the drivers’ overall lane weaving, swerving, and overcorrecting. When individuals are under the influence of alcohol or psychoactive drugs, their SDLP will increase. While CBD had no significant impact on the participants driving ability, those who took THC or the CBD/THC blend had scores comparable to a driver with a blood alcohol concentration of 0.05% – just below the legal limit in the U.S. and Canada. However, the effects of THC use on driving ability subsided after approximately 4 hours, as drivers’ SDLP scores returned to placebo levels. This indicated that the mild driving impairment caused by THC is fairly short-lived. “This is the first study to illustrate the lack of CBD effects on driving,” said study co-author Iain McGregor. “[It also provides] a clear indication of the duration of THC impairment.” Possible Impact on International Drug-Driving Laws While CBD has been legalized in both the U.S. and Canada, whether someone can be charged for impaired driving after using CBD products remain legally ambiguous. In both countries, drivers may be subjected to a standard field sobriety test or other testing procedures if suspected of driving under the influence of alcohol or drugs. “With cannabis laws changing globally, jurisdictions are grappling with the issue of cannabis-impaired driving,” Arkell said. “These results provide much-needed insights into the magnitude and duration of impairment caused by different types of cannabis.” “[This] can help guide road-safety policy not just in Australia but around the world.”
CBD for Anxiety
Scientific Confidence Grade Effect Size Rating Editorial Note A *** The anti-anxiety effect of CBD is well supported within the scientific literature. With research interest growing rapidly, many more clinical studies are on the way investigating the use of CBD in anxiety-disorders and beyond. There has been over 4 decades of scientific research on the anti-anxiety effects of CBD – including both animal studies and human clinical trials. Both animal research and human clinical studies have shown that CBD can significantly reduce anxiety for those with certain anxiety disorders and for individuals in the general population. CBD for Anxiety (March 2021) Can you use CBD for anxiety? Decades of research have been done investigating the anxiolytic or anxiety-reducing effects of CBD. From scientific surveys to clinical studies, here’s the science behind all of it. Cannabidiol (CBD) is growing in popularity as a natural option for treating a wide range of ailments – including anxiety. As a naturally occurring cannabinoid found within the cannabis plant, many have turned to CBD in hopes it will help with a number of health conditions, from stress to pain. Research into the use of CBD for anxiety treatment extends back to as early as the 1970s with great strides still being made today. Anxiety Overview Anxiety is generally defined as a feeling of unease – including those of worry, fear, and apprehension – and can be triggered by a wide variety of events and scenarios. These can be as simple as writing an exam or meeting new people. Stress occurs when we encounter these threatening or unfamiliar situations (these can be both real or perceived), and anxiety is the natural reaction to that stress.1 Anxiety symptoms can vary drastically from person to person, but typical physical symptoms can include: General restlessness Feelings of fear and worry Nausea, dizziness, and/or headaches Trouble concentrating Rapid breathing and/or chest pains Increased heart rate Excessive sweating Fatigue Difficulty falling asleep Everyone experiences feelings of mild anxiety at some point in their lives. Typically, these feelings will fade once the stressful situation triggering them is resolved. But when these feelings become constant, too hard to control or begin affecting your daily life, it can indicate an anxiety disorder. Different Types of Anxiety Disorders Anxiety can be the main symptom of many different complex disorders and can be caused by a combination of varying conditions: Medications Substance abuse Trauma Childhood experiences Panic disorders Genetics The most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) – which serves as the principal authority for psychiatric diagnoses in many parts of the world – lists 7 different anxiety disorders. Anxiety can, however, exist as a major symptom of many other disorders as well, such as obsessive-compulsive disorders and trauma and stressor-related disorders. The 7 anxiety disorders include:2 Generalized Anxiety Disorder (GAD) Individuals with GAD experience excessive anxiety surrounding multiple things within their personal health, everyday life, work, or social environment. This occurs on most days for at least 6 months. Separation Anxiety Disorder People with separation anxiety disorder experience extreme anxiety and fears about being separated from the people they are attached to. Selective Mutism A fairly rare disorder, selective mutism occurs when someone fails to speak in certain social situations even though they have normal language skills. Sometimes this inability to speak may be tied to extreme shyness, fears of social embarrassment, or compulsive traits. Specific Phobia Also called “simple phobias,” people with specific phobias develop intense anxiety or fear of certain objects, animals, or situations. This includes the fear of heights, blood, needles, spiders, etc. Agoraphobia Broadly, agoraphobia is defined as a fear of places and situations where help may not be available if things go wrong, causing the individual to panic, feel trapped and/or helpless. People diagnosed with agoraphobia have an intense fear of 2 or more of the following situations: Using public transportation Being in open spaces Being in enclosed spaces Standing in line or being in a crowd Being outside of the home alone Social Anxiety Disorder Individuals with social anxiety disorder have an intense fear of performative situations where they may be judged or evaluated by others. This can manifest in the workplace, school, or even personal environments. Panic Disorder People with panic disorder have reoccurring panic attacks. These are periods of intense fear that come on quickly and often without warning. They may be triggered by certain situations or objects. Apart from feeling intense anxiety during a panic attack, these individuals often experience anxiety and worry surrounding when the next attack might happen. They may feel the need to avoid certain places, objects, or situations that can trigger an attack which can greatly interfere with their everyday life. What Do We Know About the Types of Anxiety Disorder? Not only are various forms and causes of anxiety complex, but the biology behind anxiety disorders is also not well understood. Most research indicates that extreme anxiety likely arises due to changes in brain chemistry, particularly in areas of the brain that process emotions and fear. These changes affect how the brain controls the production and release of neurotransmitters – the chemical messengers that help neurons communicate with each other.3 A person’s brain chemistry is influenced by their innate genetics as well as their general experiences throughout life, marked significantly by physical and psychological trauma. Currently, most anxiety-related disorders are treated using psychological therapies (e.g. cognitive behavioral therapy) and/or medications (e.g. serotonin reuptake inhibitors such as Prozac and Zoloft). Can CBD Help? Regardless of the cause or severity of your anxiety, CBD may be a good option for easing some of those symptoms. CBD products can influence our body’s endocannabinoid system (ECS) – a neuromodulatory system that plays a role in regulating a wide variety of physical and mental health processes such as memory, learning, mood, pain management, and inflammation.4,5 Our bodies naturally produce endocannabinoids which interact with endocannabinoid receptors on different cells including neurons. The most abundant receptor, CB1, can be found across the central nervous system which includes parts of the brain that control emotions and anxiety – such as the prefrontal cortex.3,6 The second major endocannabinoid receptor, CB2, can also be found in the central nervous system but is primarily found in the immune system. Endocannabinoids can also interact with several other receptors including the serotonin receptor (5-HT1A receptor) and the TRPV1 receptor.7 Cannabinoids from cannabis plants (such as marijuana and hemp), including CBD, can naturally mimic certain endocannabinoids and can modulate the way various endocannabinoid receptors work. While the details are yet to be fully understood, researchers have gathered some insight into how CBD could be influencing each receptor and what could potentially be happening. Specifically, CBD has been shown to decrease and/or change the activity of both CB1 and CB2 receptors.8,9 CBD has also been shown to stimulate the serotonin receptor (5-HT1A) at low concentrations and promote the activity of TRPV1 at higher concentrations. Both of these mechanisms are thought to be anxiolytic and may be contributing to CBD’s anti-anxiety effects.10,11 Furthermore, CBD has also been shown to prevent enzymes from breaking down anandamide, the natural endocannabinoid, which is an important activator of the CB1 receptor.12 What Does the Research Say – Preclinical Studies A lot of the initial research on the anti-anxiety effects of CBD were done in animal models using behavioral tests. In a landmark 1990 study, researchers tested whether 2.5, 5, 10, or 20 mg/kg doses of CBD affected how rats would perform in an elevated plus-maze.13 Elevated plus mazes are commonly used by researchers to study anxiety-related disorders such as PTSD. These mazes contain different open and closed sections. Anxious animals typically spend less time in open sections and more time in closed or protected sections where they are less likely to be attacked by potential predators. At low doses (2.5, 5, and 10 mg/kg), the rats appeared more exploratory and were more likely to enter open spaces in the maze – indicating reduced anxiety. These effects were similar to a 2 mg/kg dose of diazepam – also marketed as Valium – a well-known drug used to create calming effects and treat anxiety in humans. Since then, the anti-anxiety effects of CBD have been broadly confirmed in 30 other animal studies using a variety of behavioral tests. All of them have shown that while high doses (~ 100 mg/kg) were ineffective, lower doses (~ 10 mg/kg) had anti-anxiety effects.7,14 Some animal studies also indicated that CBD has similar effects in reducing stress, fight-or-flight, and compulsive behaviors. Because of this, CBD is also being investigated for use in treating certain phobias and PTSD.15 What Does the Research Say – Clinical Studies The anti-anxiety effects of CBD seen in animals have served as a guide for human research and many clinical studies have since been completed. In as early as the 70s and 80s, researchers have found in double-blind studies that CBD can be used to reduce the anxiety-triggering effects of THC – a major cannabinoid in cannabis that has psychoactive effects.15,16 More recent studies have further examined the use of CBD in treating various forms of anxiety. In a 1993 study, where a double-blind, placebo-controlled, simulated public speaking test was conducted, researchers found that participants who took 300 mg CBD prior to a 4-minute public speaking challenge reported feeling less anxious afterward – as compared to the placebo group. This effect was comparable to known anti-anxiety medications used in the study (e.g., 10 mg of diazepam, 5 mg of ipsapirone).17 Another double-blind placebo-controlled public speaking study in 2019 further confirmed the anti-anxiety effects of CBD in everyday individuals. Participants were asked to take either a placebo, 150, 300, or 600 mg of CBD before taking a simulated public speaking test.18 Those in the placebo group reported significantly higher anxiety both during the speech and after the speech. Participants who took 300 mg of CBD reported significantly lower anxiety. However, at 150 and 600 mg doses of CBD, researchers found no significant difference from placebo. This suggests that finding a moderate dosage may be important for achieving anti-anxiety effects. Anxiety and Sleep A 2019 open-label study on 72 patients with a diagnosis of anxiety or sleep disorders, provided the participants with a range of 25 to 175 mg of CBD per day across a 3-month time frame.19 After just 1 month, the majority of patients (79.2%) reported reduced anxiety. Only a few adverse effects were reported by 3 participants such as dry eyes, mild sedation, and fatigue. Pediatric Anxiety and PTSD A case study from the University of Colorado’s School of Medicine found that CBD was useful in reducing anxiety caused by PTSD for a 10-year-old girl.20 After rounds of ineffective pharmacotherapy and adverse effects from medication, the patient was administered CBD instead. Starting with 25 mg of CBD a day for 4 months, and then moving to a CBD spray (~6-12 mg per spray) as needed after month 4. Using a standardized screen for child anxiety-related disorders, the medical team found that CBD reduced the patient's score from 34 to 18. A score of 25 or higher typically indicates a childhood anxiety disorder. Social Anxiety Disorder In a 2011 double-blind, placebo-controlled, simulated public speaking study, patients with social anxiety disorder were provided with either a placebo or 600 mg of CBD 1.5 hours before completing a 4-minute public speaking challenge.21 Those who took the CBD reported significantly less anxiety, cognitive impairment, and discomfort during their speech performance. In a separate 2019 study, researchers used a similar double-blind placebo-controlled model to study how useful CBD could be in treating social anxiety outside the laboratory. Teenagers with social anxiety disorder took either a placebo or 300 mg of CBD oil for 4 weeks. Questionnaires administered before and after the treatment showed that the CBD group had significantly reduced feelings of anxiety whereas the placebo group showed no significant changes.22 Furthermore, no participants reported any significant health complaints from using the CBD oil in a follow-up meeting. Ongoing Clinical Trials Apart from completed studies, there are also many ongoing trials that hope to further investigate the use of CBD as a treatment for anxiety disorders. A study in the Netherlands is currently looking at whether a weekly dose of 300 mg of CBD administered orally for 8 weeks could help individuals with phobia-related anxiety disorders.23 An ongoing phase 3 clinical trial in Canada is working to determine the possible use of CBD oil capsules (containing 200-800 mg of CBD) to treat generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia. In the U.S., an open-label phase 2 clinical trial is taking place to examine whether a dose of 30 mg a day of CBD taken under the tongue for 4 weeks could help with anxiety and sleep. Trying CBD for Anxiety Decades of animal studies and clinical trials support the use of CBD for anxiety – particularly when used at a moderate dosage. Many studies have indicated that the anti-anxiety effects of CBD tend to decline at higher concentrations. As with using CBD for any health reasons, it’s best to begin with a low dosage and only move up as needed. Studies done to date on the use of CBD in treating anxiety-like responses have all found CBD to be safe and generally well-tolerated with little to no differences from taking a placebo in terms of unwanted anxiety, sedation, positive psychotic symptoms, or intoxication.24 However, at higher concentrations, it can also cause a wide range of side effects. Some of these can include:25 Tiredness Drowsiness Diarrhea Nausea Dry mouth Low blood pressure Light-headedness Changes in appetite or weight Furthermore, there are additional considerations to make when CBD is taken alongside other medications. CBD can interfere with how other drugs are metabolized and processed within the body, possibly causing adverse drug reactions.24 CBD has been reported to interfere with antiretrovirals, antidepressants, antipsychotics, and opioids. Conclusion Significant research has already been done in both animal studies and human clinical trials indicating the benefits of using CBD for anxiety. With further research on the way, it’s clear that CBD will play a large role in how various anxiety disorders may be treated in the future. Likewise, CBD’s strong safety profile also makes it a great option for anxiety treatment. However, as noted, CBD can interfere with certain antipsychotics and antidepressants commonly prescribed for anxiety, making it best to consult a medical practitioner before incorporating CBD into your treatment regimen. Not to mention, different consumption methods have been found to be more effective for anxiety than others. For example, smoking or vaping CBD allows the cannabinoid to enter the bloodstream quicker rather than CBD gummies or oils. So, if you're finding CBD oils aren't effective for your anxiety, it may be worth checking other consumption methods out. References 1 Daviu, Nuria, et al. “Neurobiological links between stress and anxiety.” Neurobiology of Stress. 11 (2019): 100191. 2 Regier, Darrel A., Emily A. Kuhl, and David J. Kupfer. “The DSM-5: Classification and criteria changes.” World Psychiatry. 2 (2012): 92-98. 3 Martin, Elizabeth I. et al. “The neurobiology of anxiety disorders: Brain imaging, genetics, and psychoneuroendocrinology.” Psychiatric Clinics of North America. 32.5 (2009): 549-575. 4 Kruk-Slomka, Marta, et al. “Endocannabinoid system: The direct and indirect involvement in the memory and learning processes – a short review.” Molecular Neurobiology. 54.10 (2017): 8332-8347. 5 Guindon, Josée, and Andrea G. Hobmann. “The endocannabinoid system and pain.” CNS & Neurological Disorders Drug Targets. 8.6 (2009): 403-421. 6 Ashton, C. H. and P. B. Moore. “Endocannabinoid system dysfunction in mood and related disorders.” Acta Psychiatrica Scandinavica. 123.4 (2011): 250-261. 7 Wright, Madison, Patricia D. Ciano, and Bruna Brands. “Use of cannabidiol for the treatment of anxiety: A short synthesis of pre-clinical and clinical evidence.” 5.3 (2020): 191-196. 8 Laprairie, R. B. et al. “Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor.” British Journal of Pharmacology. 172.20 (2015): 4790-4805. 9 Thomas, A. et al. “Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro.” British Journal of Pharmacology. 150.5 (2007): 613-623. 10 Campos, Alline Cristina, and Francisco Silveira Guimarães. “Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats.” Psychopharmacology. 199.2 (2008): 223-230. 11 Lee, Jonathan L. C. et al. “Cannabidiol regulation of emotion and emotional memory processing: Relevance for treating anxiety-related and substance abuse disorders.” British Journal of Pharmacology. 174.9 (2017): 3242-3256. 12 Bisogno, T. et al. “Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide.” British Journal of Pharmacology. 134.4 (2001): 845-852. 13 Guimarães, F. S. et al. “Antianxiety effect of cannabidiol in the elevated plus-maze.” Psychopharmacology. 100.4 (1990): 558-559. 14 Blessing, Esther M. et al. “Cannabidiol as a potential treatment for anxiety disorders.” Neurotherapeutics. 12.4 (2015): 825-836. 15 Papagianni, Eleni P. and Carl W. Stevenson. “Cannabinoid regulation of fear and anxiety: An update.” Current Psychiatry Reports. 21.6 (2019): 28. 15 Karniol, I. G. et al. “Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man.” European Journal of Pharmacology. 28.1 (1974): 172-177. 16 Zuardi, A. W. et al. “Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects.” Psychopharmacology. 76.3 (1982): 245-250. 17 Zuardi, A. W. et al. “Effects of ipsapirone and cannabidiol on human expdrimental anxiety.” Journal of Psychopharmacology. 7 (1993): 82-88. 18 Linares, Ila M. et al. “Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.” Brazilian Journal of Pschiatry. 41.1 (2019): 9-14. 19 Shannon, Scott, et al. “Cannabidiol in anxiety and sleep: A large case series.” The Permanente Journal. 23 (2019): 18-041. 20 Shannon, Scott, and Janet Opila-Lehman. “Effectiveness of cananbidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: A case report.” The Permanente Journal. 20 (2016): 16-005. 21 Zuardi, Antonio Waldo, and José Alexandre S. Crippa. “Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.” Neuropsychopharmacology. 36.6 (2011): 1219-1226. 22 Masataka, Nobuo. “Anxiolytic effects of repeated cannabidiol treatment in teenagers with social anxiety disorders.” Frontiers in Psychology. 10 (2019): 2466. 23 Van der Flier, Febe E. et al. “Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: Study protocol of a randomized controlled trial.” BMC Psychiatry. 19.1 (2019): 69. 24 Skelley, Jessica W. et al. “Use of cannabidiol in anxiety and anxiety-related disorders.” Journal of the American Pharmacists Association. 06.1 (2019): 253-261. 25 Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. “Safety and side effects of cannabidiol, a Cannabis sativa constituent.” Current Drug Safety. 6 (2011): 237-249.
Can CBD Be Used as an Antibiotic?
CBD has Antibiotic Properties Against Wide Range of Disease-Causing Bacteria, Study Finds For the first time, cannabidiol (CBD), has been shown to kill several strains of bacteria that can cause gonorrhea, meningitis, and legionnaires disease. The research conducted in collaboration between the University of Queensland and Botanix Pharmaceuticals Limited complements several other reports in recent years demonstrating the antibiotic potential of CBD. The research team believes CBD may provide the foundation for the development of a new class of antibiotics. The study found CBD effective against a diverse range of over 20 different types of bacteria including several drug-resistant strains, and the sometimes difficult-to-treat family of Gram-negative bacteria. Gram-negative bacteria are more likely to become resistant to antibiotics due to the presence of an extra outer membrane. This acts as “an additional line of defense” by blocking drugs from penetrating into the cell. The bacteria that cause gonorrhea, meningitis, and legionnaires disease all fall within this category. “This is the first-time CBD has been shown to kill some types of Gram-negative bacteria,” said study co-author Mark Blaskovich. “This [finding] is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s,” Blaskovich added. “And we can now consider designing new analogs of CBD with improved properties.” Blaskovich explained that CBD was also particularly useful in breaking down biofilms – the slimy buildup of bacteria and other microorganisms. Common biofilms include dental plaque and pond scum. The thick consistency of biofilms can make it difficult for antibiotics to fully penetrate, which helps bacteria better survive antibiotic treatments. CBD also effective against certain drug-resistant “superbugs” Part of Blaskovich’s study also focused on testing whether CBD could kill a variety of multiple drug-resistant strains of bacteria commonly referred to as “superbugs.” According to the U.S. Centers for Disease Control and Prevention (CDC), widespread overuse of antibiotics has led to a number of disease-causing bacteria developing resistance to conventional antibiotics. In the U.S., “superbugs” infect more than 2.8 million people and kill at least 35,000 every year. As part of the study, CBD was tested against several strains of drug-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and Neisseria gonorrhoeae. These bacteria can cause staph infections, respiratory illnesses, and gonorrhea, respectively. These drug-resistant strains account for an estimated 14,200 deaths in the U.S. yearly and are flagged by the Centers for Disease Control and Prevention (CDC) as “serious threats.” In the study, CBD killed off multiple Australian and American clinical strains of these drug-resistant bacteria, in many cases working just as effectively as it did on non-drug resistant strains. In fact, CBD worked at a similar concentration as vancomycin, the current first-line therapy for severe drug-resistant MRSA staph infections. Even more surprisingly, CBD was also able to kill vancomycin-resistant MRSA as well. To further their study, the research team also created a model to test whether bacteria could mutate and become resistant to CBD’s antibiotic properties over time. “Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during treatment,” Blaskovich said. In the test, MRSA bacteria were more likely to become resistant to the traditional antibiotic, daptomycin, than CBD over a 20-day period. Part of that may be due to how CBD can breakdown the bacteria’s protective membranes, causing them to tear open. “We think cannabidiol kills bacteria by bursting their outer cell membranes, but we don’t know yet exactly how it does that and need to do further research,” Blaskovich explained. CBD clinical trials for drug-resistant bacteria in progress Collaborative efforts between the University of Queensland and Botanix Pharmaceuticals are now focused on clinical trials for a topical CBD formula that can be used to treat MRSA. Early results from their clinical trial found that CBD could eradicate up to 76.2% of MRSA from affected areas after just 7 days of treatment. MRSA is one of the leading causes of post-operation surgical site infections but growing resistance towards conventional antibiotics has made certain strains difficult to treat. “We hope that this will pave the way for treatments for gonorrhea, meningitis, and legionnaires disease,” Blaskovich said. “We are looking at [cannabidiol’s] mode of action, improving its activity, and finding other similar molecules to open up the way for a new class of antibiotics.”
CBD for Seizures
Scientific Confidence Grade Effect Size Rating Editorial Note A ** Additional research is needed to investigate the effectiveness of CBD in treating broad categories of seizures and epilepsy, as well as when used alone or paired with other types of anti-seizure medication. Multiple randomized and placebo controlled studies has shown that CBD can be a useful treatment option for seizures and epilepsy. However, research has only focused on rare and treatment-resistant epilepsies and have not yet confirmed its use outside of certain conditions. Multiple human clinical studies have confirmed that CBD can reduce seizure frequency and severity in patients with certain types of epilepsy. CBD for Seizures (March 2021) CBD products have been extensively studied for their anti-seizure effects. While prescription CBD has been approved by the FDA for treating certain kinds of epilepsy, additional research is still needed to extend its use more generally. Cannabidiol (CBD) is growing in popularity as a natural option for treating a wide range of conditions – from anxiety to seizures. In fact, the first prescription of CBD was approved by the FDA in 2018 to treat specific forms of rare childhood-onset epilepsy. However, clinical research is still ongoing and with varying reports, it’s difficult to dissect just how effective CBD oil might be in treating different types of seizures and epilepsies, or when used alone versus with other types of medication. Here’s a summary of what clinical studies have uncovered so far and what additional research is being done on CBD for seizures. Seizure Overview To control the body, the brain’s billions of neurons use electrical signals to communicate and coordinate our movements. During a seizure, neurons release a burst of disorganized electrical activity in the brain-altering muscle movements (such as stiffness, twitching, spasms), speech, behaviors, sensations, moods, thoughts, and even consciousness.1 Not all seizures are alike and they can be caused by a wide range of triggers such as: Medications, alcohol, or drugs Withdrawal syndromes (from alcohol, benzodiazepines, or others) Heart conditions or a stroke Infections and sepsis Brain injuries or brain disease Fevers Sleep deprivation Genetics Apart from the wide variety of possible causes, there are also many different types of seizures. The three major groups include focal or partial-onset, generalized onset, and unknown onset. Focal (or Partial) Onset Focal onset seizures take place when the abnormal electrical signals occur in just one side – or one hemisphere – of the brain. Depending on how much of the brain becomes involved, symptoms can vary from mild to severe.2 Because only one half of the brain is affected, the individual experiencing the seizure may often notice minor symptoms before it spreads. This is referred to as an “aura” or a premonition. This can manifest as altered feelings (such as déjà vu, fear, euphoria) and/or physical symptoms (such as changes to vision, hearing, or sense of smell). As the seizure spreads across the brain, eventually more symptoms will appear. Focal seizures can also be further divided into two subtypes based on how much of the brain hemisphere becomes involved: Focal impaired awareness occurs when the activity is limited to a smaller single region of the brain. In these instances, only certain symptoms are experienced. For example, if the activity is limited to the occipital lobe of the brain – an area that is involved with vision – sight can become altered. Typically, consciousness is not lost and the person is aware of what is happening. Complex focal seizures happen when a large area of the brain is affected. The person may lose awareness and experience multiple complex symptoms including altered muscle movements and behaviors. It’s important to note that seizures can begin focally – in one side of the brain – but eventually spread to both sides and become generalized. Generalized Seizures Unlike focal seizures which only affect one half of the brain, generalized seizures affect both halves more or less at the same time. Because of this, a loss of consciousness can occur.3 Generalized seizures can be further subdivided into categories: Absence seizures also referred to as “petit mal seizures” are usually short (no longer than about 30 seconds) and can cause rapid blinking or face twitches. Absence seizures can occur in childhood and sometimes be outgrown. Tonic, clonic, and tonic-clonic seizures are also referred to as “grand mal seizures.” Tonic refers to the presence of muscle stiffening while clonic refers to periods of shaking or jerking. One or both of these conditions can happen during a seizure. Atonic seizures (also called drop seizures) involve the sudden loss of body tone when muscles relax which can result in the person collapsing. Before an atonic seizure, people can also experience brief tonic episodes where the muscles stiffen first. Myoclonic seizures involve sudden body or limb jerks. This can include sudden arm, leg, neck, or head movements. To categorize the type of seizure, physicians and other medical professionals typically use detailed patient histories, electroencephalogram (EEG) findings, magnetic resonance imaging (MRI), computed tomography scans (CT or CAT scans), blood tests, and other information. Unknown Onset Sometimes, it can also be difficult to determine the seizure’s onset, and in those situations, the seizure is often referred to as having an unknown onset. This can happen, for instance, if no one was present to witness the seizure and/or if the tests done afterward are inconclusive. Difference Between Seizures and Epilepsy While a seizure is usually a single occurrence, two or more unprovoked seizures may indicate epilepsy – a neurological condition.3 4 With epilepsy, the brain becomes more susceptible to having seizures. This may be due to genetic reasons (such as metabolic problems), developmental issues, or head trauma and brain infections. Epilepsy is one of the most common neurological conditions and affects an estimated 2.2 million Americans. This disorder can significantly impair an individual’s quality of life, lead to cognitive or psychiatric disorders, or contribute to accidental fatalities such as drowning. Treatments will vary depending on age, overall health, types of seizures, possible causes, and frequency. Most treatment options involve medication, surgery, dietary therapies, or vagus nerve stimulation (where an electrical device is implanted in the chest to stimulate the vagus nerve). Despite the growing number of treatment options, research suggests that approximately one-third of epilepsy patients do not respond well to conventional anti-epileptic drugs, making it a major motivation for continued research into anti-seizure medications.5 Can CBD Help? CBD has been known to influence the body’s central nervous system through the endocannabinoid system (ECS) – a neural network that helps regulate a wide variety of physical and mental processes such as memory, learning, mood, pain management, and inflammation.6,7 The importance of the endocannabinoid systems has led to its investigation as a possible target for new anti-epileptic drugs. Many anecdotal reports beginning in the 1900s have indicated some success in using CBD to treat epilepsy – motivating additional research. As part of the endocannabinoid system, our bodies naturally produce endocannabinoids which interact with endocannabinoid receptors on different cells and neurons. Cannabinoids from the cannabis plants, including CBD, can naturally mimic certain endocannabinoids and can modulate the way various endocannabinoid receptors work. The most abundant receptors include CB1 and CB2. Tetrahydrocannabinol (THC) – the primary psychoactive component of cannabis – has been shown to interact heavily with both receptors which allow it to produce anticonvulsant effects.8,9 However, CBD interacts much less with CB1 and CB2, and the exact mechanism by which CBD triggers an anti-seizure effect remains incompletely solved. Nonetheless, multiple animal studies have shown that CBD can have anti-epileptic properties. In mice, CBD has been shown to protect against artificial seizures induced using electrical shocks, or drugs such as pentylenetetrazol, penicillin, and pilocarpine.10,11 CBD reduced the number of severe tonic-clonic seizures the animals experienced and decreased mortality rates. Instead of CB1 and CB2, CBD has instead been suggested to drive its anti-epileptic effects through interacting with many other receptors. This includes the serotonin receptor (5-HT1A receptor), GABA receptors, TRPV1 channels, NMDA receptors, and adenosine signaling.9,12 What Does the Research Say – Survey-Based Studies Despite strong evidence in animal models that CBD can be anti-epileptic, studies in humans have been somewhat mixed – particularly with survey-based studies. In 2001, information interviews with over 215 patients with active epilepsy who also used cannabis products found that 90% of participants reported not seeing any beneficial effects of cannabis in seizure control. Only 7% felt their condition improved and 3% reported their seizures were worse.13 In a separate 2017 Australian study, 976 patients with epilepsy were surveyed and 15% reported using cannabis – regardless of their physician’s knowledge – to control their multi-drug resistant seizures. The majority of them reported an improvement in their condition.14 A significantly different finding from the 2001 study. It’s important to note that many of these survey-based studies are unable to account for dosage, frequency of use, method of administration, and other factors that may influence the effectiveness. For instance, many of these survey participants smoked whole cannabis or used both CBD and THC simultaneously alongside other drugs. What Does the Research Say – Clinical Studies Some clinical studies have also had mixed results while testing the efficacy of CBD in treating epilepsy. However, most are from early studies looking only at short durations (approximately 3-4 months) with a small number of human volunteers (approximately 15). The smaller sample size makes the results less reliable and more variable.15 In one double-blind 1980 study, researchers found that out of 8 participants who took 200-300 mg CBD, 4 of the 8 subjects remained almost free of convulsive crises during the experiment. Whereas 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient.16 In another 1990, small-scale, placebo-controlled study with 12 patients, researchers found no changes in seizure frequency between when patients were given 300 mg of CBD or a placebo.17 Larger scale studies have only just begun in the last decade and most have only investigated the use of CBD in conjunction with other anti-epileptic drugs and in patients with treatment-resistant forms of epilepsy. These are patients with very limited treatment options. Furthermore, most patients tend to be children, and adult patients are underrepresented in most CBD trials. The first randomized, controlled, double-blinded, and multi-center study was done in 2015 and specifically tested the use of 20 mg per kg dose of CBD in addition to conventional anti-epileptic drugs for treating Lennox-Gastaut syndrome – a treatment-resistant and childhood-onset form of epilepsy.18 Of 86 patients aged 2-55 who were in the CBD group, 43.9% reported a reduction in the number of drop seizures while only 21.8% of patients in the placebo group reported an improvement. A similar randomized, double-blind, and placebo-controlled study in 2017 looked at the use of CBD as an add-on option to treat Dravet syndrome – another rare and treatment-resistant childhood-onset epilepsy.19 61 patients aged 2 to 18 were given 20 mg per kg CBD per day. 43% of patients experienced at least a 50% reduction in convulsive-seizures after a 14-week treatment period. Out of the 52 patients that completed the treatment period, 3 patients taking CBD became completely seizure-free. A third randomized, double-blind, placebo-controlled trial was published in 2018 again using CBD as an add-on option to treat patients with Lennox-Gastaut syndrome. 76 patients aged 2 to 55 were given 20 mg per kg CBD, 73 were given 10 mg per kg CBD, and 76 were given a placebo.20 During the 28-day period, the 20 mg per kg CBD group had a 41.9% decrease in drop seizures and the 10 mg per kg group had a 37.2% decrease. The placebo group only experienced a 17.2% decrease in seizure numbers. In all three randomized, double-blind, and placebo-controlled trials, patients taking 20 mg per kg CBD experienced reduced seizure frequencies as compared to those who took a placebo indicating that CBD can be a useful and effective treatment option.21 Furthermore, a 2017 review of 6 different randomized controlled trials and 30 observational studies found that CBD when used in combination with other anti-epileptic drugs at 20 mg per kg a day was more effective than placebo at reducing seizure frequencies.22 Current FDA-Approved Prescription CBD Currently, one CBD-based drug – Epidiolex – has been approved by the Food and Drug Administration (FDA) for treatment of Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis (a genetic disease that can cause seizures). However, similar to other research n CBD, the mechanism by which Epidiolex triggers anticonvulsant effects is unknown. The Epidiolex prescribing information reports that CBD does not appear to exert its anticonvulsant effects through interactions with the cannabinoid receptors. A recent 2020 report proposed that Epidiolex – like other non-prescription CBD – may trigger anti-epileptic effects through targeting other brain receptors such as TRPV1, GPR55, and ENT-1.23 Trying CBD for Seizures Recent clinical reports have shown that CBD can be an effective treatment option for epilepsy – specifically for patients with rare forms of epilepsy, such as Dravet and Lennox-Gastaut syndromes. But CBD is almost always used alongside other anti-epileptic drugs to achieve a consistent anti-epileptic effect – primarily clobazam.21 It’s best to consult with a physician before attempting to use CBD to treat seizures or epilepsy at home. Your doctor may have you on a pharmaceutical that negatively interacts with CBD (or a product that might contain THC). And as with using CBD for any health reasons, it’s best to begin with a low dosage and only move up as needed. However, while CBD is generally safe and well-tolerated, at higher concentrations, it can also cause a wide range of side effects. Some of these can include:24 Tiredness Drowsiness Diarrhea Nausea Dry mouth Low blood pressure Light-headedness Changes in appetite or weight In studies specifically examining the use of CBD in treating epilepsy, the major side effects typically observed include somnolence, diarrhea, and decreased appetite.15 For instance, in the study performed with Lennox-Gastaut patients using CBD, 86% of participants reported at least one or a combination of those side-effects.15 Furthermore, there are additional considerations to make when CBD is taken alongside other medications. CBD can interfere with how other drugs are metabolized and processed within the body possibly causing adverse drug reactions.25 For instance, the efficacy of clobazam – a commonly used benzodiazepine used to treat epilepsy – has been observed to be influenced by CBD. In a systematic review of 4 different randomized, placebo-controlled clinical trials, researchers found that patients who took both CBD and clobazam were more likely to experience a reduction in seizure frequency.26 This is thought to be caused by CBD blocking the breakdown of clobazam. This may help clobazam remain active in the body for longer and exerting increased beneficial effects, but this also increases the risk of adverse reactions.27 Likewise, research has only just begun to investigate whether certain forms of CBD may be more beneficial than others. In a recent 2018 analysis comparing the use of CBD-rich cannabis or purified CBD, researchers found that CBD-rich extracts seem to present a better therapeutic profile than CBD in patients with refractory or drug-resistant epilepsy.28 This may be due to the entourage effect – a synergistic effect of CBD when it works alongside other phytocompounds in cannabis. Although this remains to confirmed in controlled clinical studies. Conclusion Significant research has occurred in the past century from initial small-scale reports to large-scale clinical studies validating the use of CBD for seizures and certain forms of epilepsy. However, studies conducted to date primarily focus on rare and drug-resistant forms of childhood-onset epilepsy – specifically Dravet and Lennox-Gastaut syndrome. Most studies have also only focused on children and have not thoroughly investigated whether patient age, drug tolerance, or long-term risks could be at play. Much more research is still needed to test its use in other forms of seizures and epilepsy. References 1 Stafstrom, Carl E. and Lionel Carmant. “Seizures and epilepsy: An overview for neuroscientists.” Cold Spring Harbor Perspectives in Medicine 5.6 (2015): a022426. 2 Anwar, Haleema, et al. “Epileptic seizures.” Discoveries (Craiova) 8.2 (2020): e110. 3 Sirven, Joseph I. “Epilepsy: A spectrum disorder.” Cold Spring Harbor Perspectives in Medicine 5.9 (2015): a022848. 4 Devinsky, Orrin et al. “Epilepsy.” Nature Review Disease Primers 3.4 (2018): 18024. 6 Guindon, Josée, and Andrea G. Hobmann. “The endocannabinoid system and pain.” CNS & Neurological Disorders Drug Targets. 8.6 (2009): 403-421. 8 Devinsky, O. et al. “Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial.” Lancet Neurology 15.30 (2016): 270-278. 7 Ashton, C. H. and P. B. Moore. “Endocannabinoid system dysfunction in mood and related disorders.” Acta Psychiatrica Scandinavica 123.4 (2011): 250-261. 8 Wallace, Melisa J. et al. “Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects.” European Journal of Pharmacology 29 (2001): 51-57. 9 Szaflarski, Jerzy P. and E. Martina Bebin. “Cannabis, cannabidiol, and epilepsy – From receptors to clinical response.” Epilepsy and Behavior 41 (2014): 277-282. 10 Shirazi-zand, Zahra, et al. “The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice.” Epilepsy and Behavior 21 (2013): 1-7. 11 Jones, Nicholas A. et al. “Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.” Seizure 21 (2012): 344-352. 12 Gaston, Tyler E. and Daniel Friedman. “Pharmacology of cannabinoids in the treatment of epilepsy.” Epilepsy and Behavior 70 (2017): 313-318. 13 Gordon, E. and O. Devinsky. “Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy.” Epilepsia 41 (2001): 1266-1272. 14 Suraev, A. D. et al. “An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.” Epilepsy and Behavior 70 (2017): 334-340. 15 Zaheer, Sidra, et al. “Epilepsy and cannabis: A literature review.” Cureus 10.9 (2018): e3278. 16 Cunha, J. M. et al. “Chronic administration of cannabidiol to healthy volunteers and epileptic patients.” Pharmacology 21.3 (1980): 175-185. 17 Gloss, David, and Barbara Vickrey. “Cannabinoids for epilepsy.” Cochrane Database of Systematic Reviews 3 (2014): CD009270. 18 Thiele, E. A. et al. “Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomized, double-blind, placebo-controlled phase 3 trial.” Lancet 391 (2018): 1085-1096. 19 Devinsky, Orrin, et al. “Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome.” New England Journal of Medicine 376 (2017): 2011-2020. 20 Devinsky, Orrin, et al. “Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome.” New England Journal of Medicine 378 (2018): 1888-1897. 21 Silva, Guilherme Diogo, et al. “Cannabidiol in the treatment of epilepsy: A focused review of evidence and gaps.” Frontiers in Neurology 11 (2020): 531939. 22 Stockings, Emily, et al. “Evidence for cannabis and cannabinoids for epilepsy: A systematic review of controlled and observational evidence.” Journal of Neurology, Neurosurgery and Psychiatry 89 (2017): 741-753. 23 Gray, Royston A. and Benjamin J. Whalley. “The proposed mechanisms of action of CBD in epilepsy.” Epileptic Disorders 22 (2020): 10-15. 24 Bergamaschi, M. M., R. H. Queiroz, and A. W. Zuardi. “Safety and side effects of cannabidiol, a Cannabis sativa constituent.” Current Drug Safety 6 (2011): 237-249. 25 Perucca, Emilio. “Cannabinoids in the treatment of epilepsy: Hard evidence at last?” Journal of Epilepsy Research 7 (2017): 61-76. 26 Lattanzi, Simona, et al. “Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis.” Epilepsia 61 (2020): 1090-1098. 27 Morano, Alessandra, et al. “Cannabinoids in the treatment of epilepsy: Current status and future prospects.” Neuropsychiatric Disease and Treatment 16 (2019): 381-396. 28 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 in Neurology 12 (2018): 759.