Use our interactive tool to look up scientifically supported answers to key questions on cannabinoids and cannabis-based products.
There are many different types of cannabinoids – some are natural, either found in plants or made endogenously in the human body, and some are synthetic1
Phytocannabinoids are naturally occurring cannabinoids produced by the Cannabis sativa L species of plants.1 There are over 120 different known phytocannabinoids2
Only a few are thought to be present in reasonable quantities2
The two best characterised are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC)3
There are also endocannabinoids: molecules made by the body that bind and interact with the cannabinoid receptors as well as other neurotransmitter systems. The primary endocannabinoids identified to date are anandamide (also known as N-arachidonoylethanolamine [AEA]) and 2-arachidonoylglycerol (2‑AG)4,5
Finally, synthetic cannabinoids are designed to replicate or closely resemble natural cannabinoids and/or to interact with cannabinoid receptors (known as CB1 and CB2)6,7
Refs: 1. Pertwee. Handbook of Cannabis. Series editor Iversen L. Oxford University Press. Oxford, UK. 2014; 2. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 3. Lahda et al. Molecules 2020;25:4042; 4. Cristino et al. Nat Rev Neurol 2020;16:9–29; 5. Hillard. Neuropsychopharmacology 2018;43:155–72; 6. Papaseit et al. Int J Med Sci 2018;15:1286–95; 7. NHS UK Cannabis-based products for medicinal use: frequently asked questions. Available at: https://www.england.nhs.uk/medicines-2/support-for-prescribers/cannabis-based-products-for-medicinal-use/cannabis-based-products-for-medicinal-use-frequently-asked-questions/#what-are-synthetic-cannabinoids-and-are-they-included-in-the-re-scheduling. Accessed January 2021.
There are a number of cannabinoids that have been studied in animals, including, but not limited to, cannabichromene (CBC), cannabidivarin (CBDV), cannabigerol (CBG) and delta-9-tetrahydrocannabivarin (THCV).1,2 Some have even been investigated in humans in early phase studies.3,4 However, these cannabinoids have not yet reached advanced clinical trials in patients
Better understanding of the pharmacology of cannabinoids and their testing through clinical trials will continue to improve our knowledge of their potential medicinal properties
CBC, one of the most abundant cannabinoids in cannabis plants, is the end-product of cannabidiolic acid (CBDA) when it is broken down by heat or UV light.5,6 Some studies in animals have explored its anti-inflammatory and analgesic effects,1,5 though this has not been tested in humans
CBG has been reported to have anti-inflammatory and anxiolytic-like effects in mouse models,1,2 but this has not been studied in human patients
CBDV and THCV (the propyl analogues of CBD and THC, respectively) may have different effects to CBD and THC because of differences in their structure.1,6 Both have been explored in early phase human trials,3,4 but not yet in advanced randomised clinical trials, and more scientific evidence is required to better understand their medicinal potential
Refs: 1. Ligestri et al. Physiol Rev 2016;96:1593–659; 2. Zagzoog et al. Sci Rep 2020;10:20405; 3. Jadoon et al. Diabetes Care 2016;39:1777–86; 4. Morano et al. Neuropsychiatr Dis Treat 2020;16:381–96; 5. Salami et al. Molecules 2020;25:4036; 6. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31.
The legal status of cannabinoids differs depending on the type of cannabinoid, the type of product that contains them, and also by country1–3
There are many known phytocannabinoids,4 and controlled drugs regulations apply to some (e.g. delta-9-tetrahydrocannabinol [THC] and cannabinol [CBN]) but not others (e.g. cannabidiol [CBD]).1,5 This means products that only contain CBD (i.e. CBD-based consumer products) are assessed differently to those containing THC1,5
There are also country-level differences in the regulations and legal status of different cannabis-based products that are important to be aware of:1–3,5
Regulatory approved cannabis-based medicines are subject to strict medicines regulations and are legally available via prescription in those countries for which a licensed indication exists2,5,6
For ‘Medical cannabis’ (non-regulatory approved cannabis-based products), the legal situation varies by country1,3,7
For CBD-containing products and foods (such as oils and supplements), the legal status varies and in some cases is unclear in certain countries3,7–10
The use of cannabis for recreational purposes is illegal in most EU countries3
Refs: 1. UK Government. Drug licensing factsheet: Cannabis, CBD and other cannabinoids. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/825872/factsheet-cannabis-cbd-and-cannabinoids-2019.pdf. Accessed January 2021; 2. European Monitoring Centre for Drugs and Drug Addiction. Medical use of cannabis and cannabinoids: questions and answers for policymaking. December 2018. Available at: https://www.emcdda.europa.eu/system/files/publications/10171/20185584_TD0618186ENN_PDF.pdf. Accessed January 2021; 3. European Monitoring Centre for Drugs and Drug Addiction (2017), Cannabis legislation in Europe: an overview, Publications Office of the European Union, Luxembourg. Available at: https://publications.europa.eu/resource/cellar/c0703c01-0d38-11e7-8a35-01aa75ed71a1.0001.03/DOC_1. Accessed January 2021; 4. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 5. Food and Drug Administration. FDA and Cannabis: Research and Drug Approval Process. Available at: https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process. Accessed January 2021; 6. European Medicines Agency. European regulatory system for medicines: A consistent approach to medicines regulation across the European Union (EMA/716925/2016). 2016. Available at: https://www.scribd.com/document/461348291/european-regulatory-system-medicines-european-medicines-agency-consistent-approach-medicines-en-pdf. Accessed January 2021; 7. Food and Drug Administration. FDA regulation of cannabis and cannabis-derived products, including cannabidiol (CBD). 2020; 8. European Monitoring Centre for Drugs and Drug Addiction. Italy and Sweden: court decisions on low-THC cannabis product. July 2019. Available at: https://www.emcdda.europa.eu/news/2019/italy-and-sweden-court-decisions-low-thc-cannabis-products_en. Accessed January 2021; 9. UK Food Standards Agency. Consumer advice on cannabidiol extracts. 2020. Available at: https://www.food.gov.uk/safety-hygiene/cannabidiol-cbd. Accessed December 2020; 10. Australian Department of Health Therapeutic Goods Administration. Notice of interim decisions to amend (or not amend) the current Poisons Standard. 9 September 2020. Available at: https://www.tga.gov.au/sites/default/files/notice-interim-decisions-proposed-amendments-poisons-standard-acms-and-joint-acms-accs-meetings-june-2020.pdf. Accessed January 2021.
Our understanding of cannabinoids is continuing to grow, but there is a need for additional, high-quality evidence for their use as disease- and symptom-modifying treatments1
Although there are many different cannabinoids, and several of these have been evaluated in a variety of formulations and routes of administration, only a few therapeutic uses have been thoroughly tested in clinical studies in patients2,3
For those cannabinoids that have gained regulatory approval as treatments of disease symptoms, their approved use varies between countries2,5,7
Refs: 1. Lahda et al. Molecules 2020;25:4042; 2. Stasiulewicz et al. Int J Mol Sci 2020;21:2778; 3. Whiting et al. JAMA 2015;313:2456–73; 4. Shi et al. Cureus 2019;11:e3918; 5. European Monitoring Centre for Drugs and Drug Addiction. Medical use of cannabis and cannabinoids: questions and answers for policymaking. December 2018. Available at: https://www.emcdda.europa.eu/system/files/publications/10171/20185584_TD0618186ENN_PDF.pdf. Accessed January 2021; 6. Turner, Agrawal. Marijuana. Treasure Island (FL): StatPearls Publishing. 2020; 7. Food and Drug Administration. FDA regulation of cannabis and cannabis-derived products including cannabidiol (What You Need to Know And What We’re Working to Find Out About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD). Available at: https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis. Accessed January 2021.
Of the 120+ known cannabinoids, only a small number of them are associated with the euphoric 'high' linked with cannabis use1,2
The euphoria is brought about through activation of the CB1 receptor;1 examples of cannabinoids with euphoric effects include delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN).2 The extent of the euphoric effects depends on the dose and route of cannabinoid administration3,4
Other cannabinoids, including cannabidiol (CBD), cannabichromene (CBC) and cannabidivarin (CBDV) do not activate the CB1 receptor and so are not associated with intoxicating or euphoric effects;5 although these may be associated with other effects, e.g. somnolence in the case of CBD6,7
Refs: 1. Pertwee. Handbook of Cannabis. Series editor Iversen L. Oxford University Press. Oxford, UK. 2014; 2. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 3. Heustis. Chem Biodivers 2007;4:1770–804; 4. Spindle et al. JAMA Netw Open 2018;1:e184841; 5. Ligestri et al. Physiol Rev 2016;96:1593–659; 6. Chesney et al. Ther Adv Psychopharmacol 2020;10:1–13; 7. Brown, Winterstein. J Clin Med 2019;8:989.
Cannabis is a generic term for the Cannabis sativa L plant and its products1,2
Marijuana is a term used for cannabis that is used recreationally, most typically through smoking2
‘Medical cannabis’ is a broad term used to describe some cannabis-based products. These are used for medical purposes but are not approved by medicines regulators2,3
Quality of CBD oils can vary, and products may not contain the amount of CBD that their label indicates, because of a lack of standardisation and quality control.8-10 They may also contain contaminants or other cannabinoids, including delta-9-tetrahydrocannabinol (THC), potentially even at levels sufficient to cause THC-associated adverse events11,12
Refs: 1. Pertwee. Handbook of Cannabis. Series editor Iversen L. Oxford University Press. Oxford, UK. 2014; 2. Papaseit et al. Int J Med Sci 2018;15:1286–95; 3. NHS Medical cannabis (and cannabis oils). Available at: https://www.nhs.uk/conditions/medical-cannabis/. Accessed January 2021; 4. VanDolah et al. Mayo Clin Proc 2019;94:1840–51; 5. Hazecamp. Med Cannabis Cannabinoids 2018;1:65–72; 6. European Parliament and the Council. Regulation of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods (EC No 1924/2006). 2006. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32006R1924&from=en. Accessed January 2021; 7. ASA. The CAP code. Medicines, medical devices, health-related products and beauty products. Available at: https://www.asa.org.uk/type/non_broadcast/code_section/12.html. Accessed January 2021; 8. Liebling et al. Cannabis Cannabinoid Res 2020;DOI:10.1089/can.2019.0078; 9. Bonn-Miller et al. JAMA 2017;318:1708–9; 10. FDA. What you need to know (and what we’re working to find out) about products containing cannabis or cannabis-derived compounds, including CBD. 2020. https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis. Accessed January 2021; 11. Chesney et al. Ther Adv Psychopharmacol 2020;10:1–13; 12. Bonomo et al. Br J Clin Pharmacol 2018;84:2495–8.
Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are two of the best characterised phytocannabinoids.1 Although they derive from the same plant and have the same chemical formula (C21H30O2), they differ in their structure and their effects2–5
As with other cannabinoids, such as cannabichromene (CBC), cannabigerol (CBG), and tetrahydrocannabivarin (THCV), THC and CBD derive from the Cannabis sativa L plant4
They have different structures and pharmacology.4 THC is thought to act primarily through CB1 receptors, which are predominantly found in the central nervous system, and it is through CB1 receptor activity that THC is believed to cause the acute, euphoric effects typically associated with recreational cannabis use4,5
In contrast, the key mechanisms underlying the actions of CBD are currently unclear.5 CBD is not intoxicating, and is believed to act primarily at sites other than the cannabinoid receptors4,5
While CBD and THC have different pharmacological actions and medical potential, ongoing scientific and clinical research is key to improving our understanding of their effects1
CBD and THC are made in the plant as acidic forms (cannabidiolic acid [CBDA] and tetrahydrocannabinolic acid [THCA]) and are decarboxylated to their neutral active forms1
Refs: 1. Lahda et al. Molecules 2020;25:4042; 2. National Center for Biotechnology Information. PubChem Compound Summary for CID 644019, Cannabidiol. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Cannabidiol. Accessed January 2021; 3. National Center for Biotechnology Information. PubChem Compound Summary for CID 16078, Dronabinol. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Dronabinol. Accessed January 2021; 4. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 5. Ligresti et al. Physiol Rev 2016;96:1593–659.
Over 120 different plant-based cannabinoids (phytocannabinoids) are produced by the Cannabis sativa L plant species.1,2 They are made as a sticky resin by structures called trichomes, which are most abundant in the flowers and upper leaves of the female cannabis plant1,3
In contrast, synthetic cannabinoids are man-made. They are designed to replicate or closely resemble natural cannabinoids and/or to interact with cannabinoid receptors (known as CB1 and CB2)4,5
Some synthetic cannabinoids have been approved as medicines5
Synthetic cannabinoids can also be made illegally for recreational use e.g. spice and K2.4,6 These tend to be structurally unrelated to phytocannabinoids and often have a higher affinity for cannabinoid receptors than naturally occurring cannabinoids.6 Consequently, there is a risk of detrimental effects4,6
Refs: 1. Pertwee. Handbook of Cannabis. Series editor Iversen L. Oxford University Press. Oxford, UK. 2014; 2. Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 3. Andre et al. Front Plant Sci 2016;7:19; 4. Papaseit et al. Int J Med Sci 2018;15:1286–95; 5. Stasiulewicz et al. Int J Mol Sci 2020;21:2778; 6. Abdulrahim, Bowden-Jones, on behalf of NEPTUNE group. Harms of Synthetic Cannabinoid Receptor Agonists (SCRAs) and Their Management. London: Novel Psychoactive Treatment UK Network (NEPTUNE), 2016. Available at: http://neptune-clinical-guidance.co.uk/wp-content/uploads/2016/07/Synthetic-Cannabinoid-Receptor-Agonists.pdf. Accessed January 2021.
It is important to be aware of the potential adverse events associated with any product containing cannabinoids, so that they can be weighed up against their potential benefits. There are many different types of products that are derived from cannabis or that include cannabinoids, and the associated risks will differ for each one*,†,1–4
*Adverse events or adverse drug reactions must always be reported to the manufacturer and local medicines regulatory body as early as possible.
†In the UK, in addition to reporting adverse events to the manufacturer, they should be reported through the Yellow Card scheme conducted by the MHRA. Further information can be found at https://yellowcard.mhra.gov.uk/ or via the MHRA Yellow Card app.
1. Whiting et al. JAMA 2015;313:2456–73; 2. Pratt et al. Syst Rev 2019;8:320; 3. Ladha et al. Molecules 2020;25:4042; 4. Bonomo et al. Br J Clin Pharmacol 2018;84:2495–8.