How Cannabinoids Work
Cannabinoids produce their health effects primarily through interacting with the body’s endocannabinoid system (ECS). There’s also evidence that many cannabinoids, such as CBD, interact with other, non-cannabinoid receptors in the body as well.
Cannabinoids and the Endocannabinoid System
The ECS is dedicated entirely to interacting with cannabinoids, which is why most of the effects of phytocannabinoids are mediated by this essential system.
Consisting of cannabinoid receptors, endocannabinoids, and metabolic enzymes, the ECS works to maintain homeostasis: a state of balance within the body.
Receptors are protein molecules present on cells that interact with specific substances and produce various effects.
Many cannabinoids can interact directly with the two cannabinoid receptors in the body, CB1 and CB2. They do so by binding to them in a similar manner as our body’s naturally produced endocannabinoids such as anandamide and 2-AG.
These receptors are found in all parts of the body, with CB1 being especially abundant in the brain and CB2 in immune system tissues.
Furthermore, research has shown that cannabinoids can interact with several other receptors that may eventually be considered as part of the ECS, such as GPR119 and GPR55. ²
On top of that, cannabinoids can also have less direct effects on the ECS. One of the best examples of this is CBD. While it doesn’t bind to cannabinoid receptors directly, it can modulate the function of the CB1 receptor and suppresses enzymes that break down endocannabinoids. ³
Other Cannabinoid Mechanisms
Aside from the ECS, cannabinoids have also been shown to interact with many other receptors present throughout the body.
For example, multiple cannabinoids have been shown to activate vanilloid receptor 1 (TRPV1), which is involved in regulating temperature and control the sensations of heat and pain. ⁴
Other targets noted by research studies include the central nervous system receptors for neurotransmitters such as serotonin, glycine, and GABA. These receptors control functions including memory, learning, and mood modulation. ⁵ ⁶
Finally, cannabinoids can have other non-receptor effects, such as blocking transporter proteins. ⁷
How Do Cannabinoids Differ from Each Other?
Although cannabinoids are quite similar in structure, they have some slight differences that account for their varying effects. As a result, distinct cannabinoids can affect your body quite differently. The best example of this is CBD and THC.
THC is widely recognized for its mind-altering psychotropic effects which can include euphoria, impaired memory, and decreased motor skills. It’s most commonly found in the flower of medical marijuana.
Meanwhile, CBD and many other cannabinoids, such as CBN and CBG, are non-psychoactive, which means they don’t alter your mental state.
THC and CBD also have various beneficial health effects some of which are similar, while others are unique to each cannabinoid.
For example, both cannabinoids may treat pain and inflammation, but only THC has shown a positive effect on Tourette’s syndrome, whereas CBD is recognized for its potent anxiety-relieving properties. ⁸ ⁹
Furthermore, cannabinoids can enhance and modify each other’s effects, a phenomenon known as the entourage effect. ¹⁰ For example, both CBD and the minor cannabinoid THCV seem to reduce the psychotropic effects of THC. ¹¹
This may explain why whole-plant cannabis products are more effective and produce fewer side effects than pure THC or CBD on their own. ¹²
Cannabinoids vs Cannabinoid Acids
Another important distinction to be aware of is between cannabinoids and cannabinoid acids.
Cannabis plants don’t directly make THC, CBD, or other cannabinoids. Instead, they produce their acidic forms, such as THCA and CBDA, which are precursors to these cannabinoids.
When heat is applied to these cannabinoid acids, they undergo a process called decarboxylation and lose their acid group, becoming THC, CBD, and so forth. That’s why these resulting cannabinoids are sometimes referred to as “activated.”
Although we’re more familiar with the non-acidic form of cannabinoids, their acidic counterparts can also have beneficial health effects. Besides, all acidic cannabinoids are non-psychotropic, so they won’t get you high.
Unsurprisingly, their levels are highest in raw cannabis and decrease when the plant material is dried or exposed to heat.
There’s no official definition for which cannabinoids count as “major.” However, most references to major cannabinoids typically include CBGA, THCA, CBDA, CBCA, and their non-acidic forms. In turn, these cannabinoids can convert into many more “minor” cannabinoids.
CBGA & CBG
Cannabigerolic acid (CBGA) is widely regarded as the “mother of all cannabinoids.” This means that cannabis plants produce CBGA first before it’s converted into other cannabinoids.
Depending on which enzyme reaction occurs, CBGA can turn into THCA, CBDA, CBCA, or its non-acidic form cannabigerol (CBG). ¹³
CBG is considered the next big thing in the cannabis industry because much like CBD, it’s a non-intoxicating cannabinoid with many potential health benefits. These include:
- Antibacterial properties ¹⁴
- Anti-inflammatory effects in studies of mice with multiple sclerosis and inflammatory bowel disease ¹⁵ ¹⁶
- Neuroprotection against Parkinson’s disease in mice ¹⁷
- Inhibition of colon cancer cell growth ¹⁸
- Appetite stimulation, offering a non-intoxicating alternative to THC for wasting caused by diseases such as cancer and HIV ¹⁹
THC & THCA
Tetrahydrocannabinol (THC) is the best-known cannabinoid because it’s largely responsible for the psychoactive effects of cannabis. These include impaired short-term memory and motor skills, euphoria, and, in some susceptible individuals, anxiety, and paranoia.
However, research has shown that THC also has many beneficial effects and is used to help with many symptoms and disorders, including:
- Pain and inflammation
- Nausea and vomiting
- Wasting and loss of appetite
- Tourette’s syndrome
- Multiple sclerosis
- Opioid withdrawal
Like most cannabinoids, THC starts out in its acidic form — tetrahydrocannabinolic acid (THCA). THCA is a non-intoxicating cannabinoid that’s been shown to have some beneficial effects, including anti-inflammatory, ²⁰ neuroprotective, ²¹ anti-obesity, ²² and anti-cancer qualities. ²³
Raw cannabis plants are high in THCA. This gets converted into THC when exposed to heat.
CBD & CBDA
Cannabidiolic acid (CBDA) is the acid version of cannabidiol (CBD). These non-psychotropic cannabinoids come with a wide variety of health benefits.
CBD is best known as the main active ingredient in CBD oil, which is used by an increasing number of people worldwide to support their overall health and address specific symptoms and conditions.
CBD is one of the most well-studied cannabinoids. Although it’s most recognized for its effectiveness in treatment-resistant epilepsy, research suggests that it may also help with a long list of health issues, including: ²⁴
- Anxiety disorders and depression
- Drug addiction
- Inflammation and pain
- Sleep issues
- Neurodegenerative conditions
CBDA has been studied far less, but the findings suggest that it can help with depression, ²⁵ inflammation, ²⁶ nausea, ²⁷ and other disorders.
It also seems to have much stronger effects on the serotonin receptor than CBD, which means CBDA may be particularly helpful for neurologic issues linked to serotonin dysfunction, such as seizures. ²⁸
Most CBD products lack CBDA because they’re decarboxylated (heated) during production, which converts it all into CBD. However, in raw cannabis plants, 95% of the CBD is present in the CBDA form.
CBCA & CBC
Cannabichomenic acid (CBCA) and cannabichromene (CBC) are another pair of non-intoxicating cannabinoids produced from CBGA.
They haven’t seen too much research, but CBC has been reported to relieve pain, ²⁹ inflammation, ³⁰ act as an antidepressant, ³¹ and even support the functions of neural stem progenitor cells, ³² which are crucial to healthy brain function and have real potential in the treatment of neurodegenerative diseases.
It may also have positive effects on seizures, Huntington’s, and Parkinson’s disease. ³³
Minor cannabinoids get their name from their relatively small concentrations in cannabis plants and the fact that most of them are derived from major cannabinoids.
There are well over 100 minor cannabinoids in cannabis but we will look at the ones that have received the most attention.
Cannabinol (CBN) is a minor, non-intoxicating cannabinoid produced when THC is exposed to oxygen. ³⁴ That’s why CBN concentrations are low in raw cannabis but can reach significant levels in older plants.
Many people believe that CBN is helpful for sleep issues because aged cannabis has stronger sleep-inducing effects.
However, this belief is somewhat misguided. Rather than promoting sleep on its own, research indicates that CBN might enhance the sedating effects of THC. ³⁵
Aside from that, studies of CBN have shown anti-inflammatory, ³⁶ neuroprotective, ³⁷ appetite-stimulating, ³⁸ pain-relieving, ³⁹ and other beneficial properties.
Much like CBG, CBN is predicted to grow in popularity in the near future thanks to the overwhelming interest in CBD.
Tetrahydrocannabivarin (THCV) is an analog of THC, which means it’s structure is very similar. Despite this, THCV does not appear to share its cousin’s intoxicating effects.
This minor cannabinoid has been shown to have several beneficial properties. Most notably, it can reduce appetite and help regulate blood sugar and insulin sensitivity, making it a serious candidate for the treatment of obesity and diabetes. ⁴⁰
It also has neuroprotective properties that can help with Parkinson’s disease and other neurodegenerative disorders ⁴¹ and can promote bone growth. ⁴²
Another study also found that THCV displayed the strongest anti-acne effects out of five studied minor cannabinoids. ⁴³
Cannabicyclol (CBL) is a non-psychotropic cannabinoid produced when CBC degrades from sunlight exposure. Given that it’s only been recently discovered, we don’t know too much about CBL’s effects.
Cannabidavarin (CBDV) is a non-intoxicating minor cannabinoid similar in structure to CBD. Much of the interest in this cannabinoid has revolved around its anti-epileptic effects.
The company GW Pharmaceuticals — which recently released the first CBD-only pharmaceutical drug, Epidiolex — is currently testing CBDV in clinical trials of epilepsy.
Aside from that, CBDV may also help with other conditions and symptoms, including Rett syndrome, ⁴⁴ Duchenne muscular dystrophy, ⁴⁵ nausea, ⁴⁶ and autism. ⁴⁷
Cannabichromevarin (CBCV) is a minor, non-intoxicating cannabinoid first identified in 1975.
Like other cannabinoids ending in “V,” it’s an analog of its close cousin CBC, which means it has a similar structure but with a slight difference.
CBCV hasn’t seen much research so we don’t know too much about its effects.
Cannabigerol monomethyl ether (CBGM) is a minor cannabinoid related to CBG. Like other rare cannabinoids, we don’t know too much about its effects due to a lack of research.
Cannabielsoin (CBE) is a minor cannabinoid metabolite of CBD. So far, studies of mice, guinea pigs, and some other animals have shown that CBD can be metabolized (breaks down) into CBE. ⁴⁸ Presumably, a similar process occurs in humans when we ingest CBD.
Aside from hypothesizing that CBE plays a role in the effects of CBD, there is not much additional research into CBE yet.
Cannabicitran (CBT) is a relatively rare minor cannabinoid. There haven’t been many studies looking at this cannabinoid, so we don’t know much about its health effects.