The cannabis plant contains more than 400 chemical constituents
The cannabis plant and cannabinoids
The cannabis plant contains more than 400 chemical constituents with approximately 100 that are specific to the cannabis plant and referred to as cannabinoids.1,2 Additionally, the plant also contains terpenes, flavonoids and essential fatty acids such as omega-3 and 6 fatty acids.1,2
The different parts of the plant produce these constituents at different concentrations – for example the inflorescence ‘flower’ of the female plant produces the highest concentration and consistency of cannabinoids, whilst the seeds provide the richest source of omega fatty acids.
Cannabinoids are the primary constituents responsible for its physiological and therapeutic effects. The most abundant cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD) but other prominent cannabinoids are also present.1,2 THC and CBD are the most used cannabinoids in medicinal cannabis with varying mechanisms of actions and different effects on the body.
THC was the first cannabinoid to be discovered in the 1960s and is the most well-known cannabinoid. THC is a partial agonist of cannabinoid receptors3 and Its activation of CB1 receptors in the central nervous system is responsible for the psychotropic actions, or “high” associated with the ingestion of cannabis. The acute effects of THC may include relaxation, euphoria, increased sociability, increased appetite and dry mouth. At higher doses THC has been known to induce anxiety or paranoia, increased heart rate, slower reflexes, bloodshot eyes and altered memory.
Isolates of THC or high THC cannabis products are therapeutically used to treat loss of appetite in people with AIDS and to treat severe nausea and vomiting caused by cancer chemotherapy. THC is also used to treat numerous other indications including pain and symptoms associated with multiple sclerosis
Although THC elicits therapeutic benefits, some patients may find THC’s psychotropic effects intoxicating and undesirable.
CBD is the other main cannabinoid responsible for the medicinal benefits of cannabis. Unlike THC, CBD does not elicit any psychotropic effects. In fact, CBD tends to have almost opposing effects to THC. CBD has many modes of action in the body,3,4 including but not limited to:
Due its multimodal action, CBD exhibits an impressive range of actions in the human body, including in the brain. CBD has been shown to be clinically beneficial for epilepsy, pain, Parkinson’s disease, anxiety disorders and symptomatic improvement in schizophrenia.5,6 Moreover, there is growing research being conducted into the benefits of CBD for other indications.
CBD is devoid of the psychotropic effects that are observed with THC, it is well-tolerated and has been established as generally safe with few serious adverse effects.6-8 Furthermore, a report by the World Health Organization also found no adverse health outcomes, no public health risks or abuse potential WHO report.9
However, CBD may interact with other conventional medications, which should be assessed on a case-by-case basis.
There are other structurally-similar cannabinoids found in the plant at lower concentrations, commonly referred to as ‘minor cannabinoids’.1,2 The most commonly found minor cannabinoids include cannabigerol (CBG), cannabidivarin (CBDV) cannabinol (CBN), cannabichromene (CBC) and tetrahydrocannabivarin (THCV)
The chemical structures of the most abundant cannabinoids found in cannabis plants, with the green representing the shared structural components.
We are still learning about the pharmacology of these cannabinoids but they appear to elicit effects different to THC and CBD on the endocannabinoid system, as well as the other physiological systems of the body.3
Terpenes are compounds found in many plants that give plants their flavor, odour and protect them against microbes. Terpenes are widely found in other medicinal and culinary plants and are used in foods and cosmetics for their flavour and scent. Terpenes also have their own significant therapeutic potential, with beta-caryophellyene, alpha pinene and humelene being some of the best-studied terpenes. These terpenes have shown anti-inflammatory, and antioxidant properties, along with protective effects to a range of critical body systems.10 Emerging research indicates terpenes show therapeutic promise for many conditions. Terpenes may also contribute to the entourage effect that is seen in whole plant or full-spectrum extracts.11
The “entourage effect” is the term commonly used to refer to the combined action of the cannabinoids being greater than their individual actions.
Cannabinoid content profiles
As mentioned earlier, medicinal cannabis as term reflects a class of drugs more than an individual drug. There is a range of medicinal cannabis products available the differ in cannabinoid content. Individual cannabinoid isolates are straight forward but the “whole-plant” or “full spectrum” extracts are more complicated as they vary greatly.
The cannabinoid content of a cannabis plant will differ both in type and abundance based on strain, individual plant genetics, growing conditions and when plants are harvested.12 Different cannabinoid profiles will elicit different actions in the body.1
Intensive breeding strategies can yield plants with specific and desired compound profiles, usually higher in one cannabinoid over the others. Pharmaceutical-grade medicinal cannabis are required to provide information on cannabinoid content, which is achieved through analytical chemical analysis.
Furthermore, cannabinoids in combination may elicit greater therapeutic benefit than individual cannabinoids for some indications. There is evidence that cannabis plant extracts, such as ‘full-spectrum’ extracts, have effects that cannot simply be attributed to the individual constituents.11 Moreover, there is some evidence to suggest CBD may minimize some of the negative side effects associated with THC and enhance therapeutic efficacy.13-17
- ElSohly M and Gul W (2014): Constituents of cannabis sativa. Pertwee RG, editor. Handbook of Cannabis. Oxford University Press, pp. 3-22.
- ElSohly M, et al. Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod. 2017; 103: 1-36.
- Morales P, et al. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017; 103: 103-131.
- Ibeas Bih C, et al. Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics. 2015; 12(4): 699-730.
- Larsen C and Shahinas J. Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials. J Clin Med Res, 2020. 12(3): 129-141.
- Pauli C, et al. Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Front Pharmacol. 2020; 11: 63.
- Chesney E, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020.
- Dos Santos R, et al. Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. Expert Opin Drug Metab Toxicol, 2020.
- World Health Organizarion, Cannabidiol Critical Review Report. Expert Committee on Drug Dependence. 4-7 June 2018 https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf
- Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur J Med Chem. 2018; 5(157):198-228.
- Russo E. The case for the entourage effect and conventional breeding of clinical cannabis: no “Strain,” no gain. Front Plant Science. 2018; 9: 1969.
- Grof C. Cannabis, from plant to pill. Br J Clin Pharmacol. 2018; 84(11): 2463-2467.
- Hindocha C, et al. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. Eur Neuropsychopharmacol. 2015; 25: 325–334
- Dalton W, et al. Influence of cannabidiol on delta-9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976; 19: 300–309.
- Morgan C, et al. Cannabidiol attenuates the appetitive effects of Delta(9)-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology. 2010; 35: 1879–1885.
- Martin-Santos R, et al. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012; 18: 4966–4979
- Bhattacharyya S, et al. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010; 35: 764–774.