The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems (such as the brain)). The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood.
More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes. Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor.
In addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH).
The oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45% (mean 31%). The elimination half-life of CBD is 18–32 hours.
Cannabidiol is metabolized in the liver and intestines by enzymes CYP2C19 and CYP3A4, and UGT1A7, UGT1A9, and UGT2B7 isoforms.
Cannabidiol is currently approved in the United States under the name Epidiolex as a treatment for epilepsy disorders. It should be noted that cannabidiol has been the subject of sensational health claims in the popular media. A 2016 study found that there is only limited high-quality evidence for cannabidiol having any neurological effect in people.
CBD is under preliminary research for its potential antipsychotic effect, possibly mitigating some of the negative, psychosis-like effects of THC.
- Risks with vaped/smoked CBD
According to clinical studies,well-tolerated and shows little to no toxicity.
In a 2011 literature review, CBD was found to not alter physiological parameters such as heart rate, blood pressure, and body temperature. Moreover, psychological and psychomotor functions are not adversely affected. Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans. As a result, it is considered to have a good safety profile. However, this information should be interpreted cautiously as cannabidiol has been subject to relatively few human studies; further research is needed to fully establish its safety profile.
Commonly reported side effects from prescribed cannabidiol use include tiredness, diarrhea, and changes of appetite and weight.
-low abuse potential compared to THC and other recreational substances. Cannabidiol administration does not produce euphoria or other reinforcing effects and there is no evidence that use results in physical or psychological dependence.
Cannabidiol can be an inhibitor of CYP enzymes (including CYP3A4), which are involved in the metabolism of many psychoactive substances. As a result, it has the potential to cause dangerous interactions. Caution is advised when combining cannabidiol with other substances, particularly with higher doses.
Internationally, cannabidiol is not scheduled under the Convention on Psychotropic Substances or any other UN drug treaty.
Australia:** Cannabidiol (in preparations for therapeutic use containing 2 per cent or less of other cannabinoids found in cannabis) was placed in Schedule 4 as a "Prescription Only Medicine OR Prescription Animal Remedy" in 2015. It was previously listed in Schedule 9 as a prohibited substance.
Canada:** Cannabidiol is specifically listed in the Schedule II Controlled Drugs and Substances Act. However, in 2016 Canada’s "Access to Cannabis for Medical Purposes Regulations" came into effect. These regulations improve access to cannabis used for medicinal purposes, including CBD.
Hong Kong: Illegal in Hong Kong since 1st February 2023, punishable by 7 years imprisonment.
New Zealand:** Cannabidiol is a controlled substance in New Zealand. However, by passing the Misuse of Drugs Amendment Regulations 2017 in September 2017, many of the restrictions currently imposed by the regulations are removed since then. The changes will mean that CBD products, where the level of other naturally occurring cannabinoids is less than 2% of the cannabinoid content, will be easier to access for medical use.
Switzerland:** Cannabidiol is not subject to the Narcotics Act in Switzerland because it does not produce a psychoactive effect. It is still subject to standard Swiss legislation.
United Kingdom:** In 2016, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a statement that products containing CBD used for medical purposes are considered as a medicine subject to standard licensing requirements.
United States:** Cannabidiol is legal under the 2018 Farm Bill. The rest of the cannabis plant (anything with more than 0.3% Delta-9-THC) is still under Schedule I of the Controlled Substances Act.
Cannabidiol (Wikipedia)
Cannabidiol (Isomer Design)
Cannabidiol (Drugs-Forum)
Project CBD
Mechoulam, R., Peters, M., Murillo-Rodríguez, E., & Hanuš, L.O. (2007). Cannabidiol--recent advances. Chemistry & Biodiversity, 4 8, 1678-92.
Mechoulam, R., Parker, L. A., & Gallily, R. (2002). Cannabidiol: an overview of some pharmacological aspects. The Journal of Clinical Pharmacology, 42(S1).
Devinsky, O., Cilio, M. R., Cross, H., Fernandez‐Ruiz, J., French, J., Hill, C., ... & Martinez‐Orgado, J. (2014). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802. https://doi.org/0.1111/epi.12631
Cannabidiol can be administered via oral. The route of administration can influence both the onset and intensity of pain relief.