Fast facts on WHAT ARE THE RISKS ASSOCIATED WITH CANNABINOIDS?

What are cannabinoids?

Phytocannabinoids are derived from the are made in laboratories sativa L plant1 • Structurally similar to natural cannabinoids • Most abundant in the and/or interact with female plant, in the flowers 2 and upper leaves1 receptors • Made as a resin by mushroom-shaped structures called Endocannabinoids trichomes1 are made by the body3,4

• Bind and activate the cannabinoid receptors3 • AEA and 2-AG are the most well-studied endocannabinoids1,4

THC and CBD are the best characterised5,7

Some others have also been Only a small number are investigated to evaluate their site of action and potential effects7 present in reasonable quantities in cannabis plants5

THC CBD The proportions of different phytocannabinoids vary between C. sativa strains and THCV with environmental conditions6

∆8 CBC CBV THC CBG CBN

CBDV What are the risks associated with cannabinoids?

For consumer products marketed as containing CBD, the risks are largely unknown • These products are not marketed as medicines (and cannot make medical claims)8 • The label may not reflect true contents of the product, such as: 9,10 CBD-containing • Inconsistent CBD levels consumer/food • Potential inadvertent inclusion of THC10,11 products • Unknown contaminants and impurities10

Recreational cannabis use has potential for harm12 • Short-term risks include psychotic-like experiences, anxiety, and memory impairment12–15 • Longer-term risks are less clear – smoking cannabis may be associated with Recreational respiratory, cardiovascular and psychiatric conditions12,13 cannabis

We know very little about the potential risks of non-regulatory approved cannabis-based products • ‘’ products lack robust clinical trial evidence regarding their safety16,17 Non-regulatory approved cannabis-based products Regulatory approved cannabis-based medicines have been studied for their safety profile • Cannabis-based medicines are not without risk,18 and data on adverse events must be known and published to gain regulatory approval19 • The safety profile is different for each medicine; known adverse events may include dizziness, dry mouth, nausea, somnolence, and euphoria18 Regulatory approved • Safety data are continuously monitored20 cannabis-based medicines

• The young and the elderly • May be at particular risk of adverse effects12 • Pregnant or breast-feeding mothers • Evidence of transfer across the placenta and into breast milk12 • Fetal exposure risks effects on neurological development12,21 • Individuals taking other medicines • Potential for cannabinoids to interact with medicines12

Cannabinoids are not risk free. Ongoing research is key to improving our understanding of the risks associated with different types of cannabis-based products17 Clinical evidence should be at the heart of how cannabinoids are used, to ensure they are effective and well-tolerated22–24

2-AG, 2-arachidonoylglycerol; AEA, ; CBC, ; CBD, ; CBDV, ; CBG, ; CBN, ; CBV, cannabivarin; ∆8THC, delta-8-; THC, delta-9-tetrahydrocannabinol; THCV, delta-9-

1Pertwee. Handbook of Cannabis. Oxford University Press. 2014; 2Morales et al. Prog Chem Org Nat Prod 2017;103:103–31; 3Muralidhar Reddy et al. Curr Pharmacol Rep 2019;5:1–13; 4Cristino et al. Nat Rev Neurol 2020;16:9–29; 5Hillard. Neuropsychopharmacology 2018;43:155–72; 6Potter. Drug Test Anal 2014;6:31–8; 7Ligresti et al. Physiol Rev 2016;96:1593–659; 8European 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; 9Bonn-Miller et al. JAMA 2017;318:1708–9; 10Chesney et al. Ther Adv Psychopharmacol 2020;10:1–13; 11Lachenmeier et al. F1000Res 2019;8:1394; 12Bonomo et al. Br J Clin Pharmacol 2018;84:2495–8; 13WHO. The health and social effects of nonmedical cannabis use, 2016. Available at: https://www.who.int/substance_abuse/publications/msbcannabis.pdf. Accessed December 2020; 14Hindley et al. Lancet Psychiatr 2020;7:344–53; 15Mustonen et al. Br J Psychiatr 2018;212:227–33; 16Pratt et al. Syst Rev 2019;8:320; 17Ladha et al. Molecules 2020;25:4042; 18Whiting et al. JAMA 2015;313:2456–73; 19EMA. From laboratory to patient: the journey of a medicine assessed by EMA. 2019. Available at: https://www.ema.europa.eu/en/documents/other/laboratory-patient-journey-centrally-authorised-medicine_en.pdf. Accessed January 2021; 20European Medicines Agency. European regulatory system for medicines: A consistent approach to medicines regulation across the European Union (EMA/716925/2016). 2016; 21Corsi et al. Nat Med 2020;26:1536–40; 22Royal College of Psychiatrists. Position statement PS05/19. 2019; 23NICE. Cannabis-based medicinal products. NICE guideline 144. 2019; 24Faculty of Pain Medicine position statement on the medicinal use of cannabinoids in pain medicine. December 2019. Available at: https://fpm.ac.uk/sites/fpm/files/documents/2019-12/FPM-Cannabis-statement-2019-final_0.pdf. Accessed December 2020

This information is intended for HCPs. VV-MED-17778; Date of preparation: January 2021