HOW DO CANNABINOIDS WORK?
In 1988, researchers first described the endocannabinoid system in humans. The endocannabinoid system is a biological system composed of internally produced cannabinoids called endocannabinoids and cannabinoid receptors. Endocannabinoid receptors are expressed throughout the central nervous system and peripheral nervous system. The most well-understood cannabinoid receptors are the CB1 and CB2 receptors. The CB1 receptor is mostly found in the brain and also found in the digestive tract, muscle and adipose tissue. The CB2 receptor is mostly found in the immune system. Endocannabinoids interact with these receptors to regulate bodily functions and physiological processes. Phytocannabinoids, or cannabinoids produced by the cannabis plant, can stimulate the endogenous cannabinoid receptors. By stimulating cannabinoid receptors, it is believed that cannabinoids affect human health. Interestingly, the cannabis plant also uses cannabinoids to promote its own health and prevent disease. Cannabinoids have antioxidant properties that protect the leaves and flowering structures from ultraviolet radiation. Cannabinoids neutralize the harmful free radicals generated by UV rays, protecting the cells.
THE SIGNIFICANCE OF CANNABINOIDS
Our goal is to help educate patients and help them make better decisions when selecting products. There are six cannabinoids for which INSA currently tests. Understanding the effect of these different cannabinoids may help patients to better select products to meet their needs.
TETRAHYDROCANNABINOL ( THC)
THC is the principal psychoactive constituent of cannabis. The actions of THC result from its partial agonist activity at the CB1 and CB2 receptors. A synthetic form of THC is approved by the FDA as an appetite stimulant for people with AIDS and antiemetic for people receiving chemotherapy. There is also research suggesting its utility in Alzheimer’s disease, autism, cancer, chronic pain, epilepsy, digestive disorders, multiple sclerosis, and schizophrenia.
TETRAHYDROCANNABINOLIC ACID (THCA)
In the cannabis plant, THC occurs mainly in an acidic form as tetrahydrocannabinolic acid. Over time, or when heated, THCa is decarboxylated, producing THC. THCa is non psychoactive. It does not activate CB1 cannabinoid receptors in the brain. It is estimated that more than 95% of the THCa is converted to THC when combusted. Importantly, the research suggests that THCa is therapeutically effective at low doses. Studies have found that THCa may have anti-nausea and anti-emetic effects. Also, CBD:THC preparations could be useful in treating patients with epilepsy. There is also research suggesting that THCa has immune-modulating effects which could prove useful in treating patients with autoimmune disorders. Another recent study also demonstrated THCa’s potential neuro0-protective qualities which could make it useful for patients with neurodegenerative disorders such as Huntington’s disease, Parkinson’s disease and Alzheimer’s disease.
CBD is another non-psychoactive cannabinoid. CBD-based products are approved outside the US and are currently going through regulatory review in the US. Sativex (nabiximols) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC The drug was approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis. In 2017, a double-blinded, randomized, placebo-controlled study of Epidiolex (cannabidiol) on treating Dravet syndrome, a rare and debilitating form of epilepsy, found that CBD significantly reduced the number of seizures patients experienced. A 2015 systematic review of studies on CBD and addiction found that CBD acts on neurotransmitters involved in addiction. Studies showed beneficial effects for tobacco and cannabis dependence. Another study showed a reduction of social anxiety in patients treated with CBD.
CANNABIDIOL ACID (CBDA)
Similar to THCa, CBDa is the precursor compound to CBD. Several studies demonstrate that CBDa is biologically active and could have therapeutic benefits. Preclinical studies show that CBDa could inhibit bacterial growth, reduce inflammation, and reduce nausea/vomiting.
Most of the CBN found in cannabis is due to oxidation of THC into CBN. CBN is either non-psychoactive or very mildly psychoactive. It appears to be the most sedative cannabinoid and is synergistic with both CBD and THC for inducement of sleep. Research also suggests that CBN has an analgesic effect.
CBG is another non-psychoactive cannabinoid. By the time most strains of cannabis reach maturity, most of the CBG has been converted into other cannabinoids, primarily THC or CBD, usually leaving somewhere below 1% CBG in the plant. CBG has potential for alleviating pain. Preclinical research suggests that CBG could be more effective in treating neuropathic pain than CBD. It has been shown to improve inflammatory bowel disease. In other preclinical studies, CBG has demonstrated neuroprotective properties and may prove promising for the treatment of neurodegenerative diseases such as Huntington’s disease. CBG induces production of the body’s natural skin moisturizers, holding promise for dry - skin syndromes and with the potential to treat other skin conditions.
CBC is another non-psychoactive cannabinoid that interacts with many receptors in the brain beyond just the CB1 and CB2 receptors which may result in some of its medicinal properties. Preclinical research suggests that CBC may exhibit anti-
inflammatory and anti-bacterial properties. Research has also demonstrated that CBC has anti-depressant type effects.