Brazilian Journal of Pain
Brazilian Journal of Pain
Review Article

Genetic testing for cannabinoid use

Testes genéticos para uso de canabinoides

Ciro Dresch Martinhago; Rafael Moraes de Albuquerque Pessoa

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BACKGROUND AND OBJECTIVES: Cannabis is the most popular and consumed illicit drug in the world, it has about 540 bioactive phytocannabinoids, including tetrahydrocarbinol (THC) and cannabidiol (CBD). The therapeutic potential of phytocannabinoids has been the subject of many studies in recent decades for many medical situations, including the management of chronic pain. The advent of pharmacogenetics currently allows the indication of the Cannabis dose to be evaluated individually. The objective of this work was to carry out a survey of the literature on the medicinal use of Cannabis and the application of pharmacogenetics in this therapy.
CONTENTS: THC and CBD phytocannabinoids are the most abundant and researched. In the endocannabinoid system there are compounds similar to phytocannabinoids, cell receptors and metabolism enzymes. All these molecules are secreted from genes, which may have individual genetic polymorphisms that determine the modulation of the endocannabinoid system, and consequently impact the patients’ therapeutic response.
CONCLUSION: The existence of genetic tests for the prior assessment of the patients genetic profile in order to avoid side effects and to have more assertiveness in the indication of the cannabis product is an important tool to increase adherence to cannabis treatment.


Cannabis, Genetic variation, Medical marijuana, Pharmacogenetics, Polymorphism, Single nucleotide


JUSTIFICATIVA E OBJETIVOS: A cannabis é a droga ilícita mais popular e consumida no mundo, possuindo cerca de 540 fitocanabinoides bioativos, entre eles o tetra-hidrocarbinol (THC) e o canabidiol (CBD). O potencial terapêutico dos fitocanabinoides tem sido alvo de muitos estudos nas últimas décadas para muitas situações médicas, incluindo o manejo da dor crônica. O advento da farmacogenética permite que atualmente a indicação da dose de cannabis seja avaliada individualmente. O objetivo deste estudo foi realizar um levantamento da literatura sobre o uso medicinal da cannabis e a aplicação da farmacogenética nessa terapia.
CONTEÚDO: Os fitocanabinoides THC e CBD são os mais abundantes e pesquisados. No sistema endocanabinoide, existem compostos similares aos fitocanabinoides, receptores celulares e enzimas de metabolismo. Todas essas moléculas são secretadas a partir de genes que podem possuir polimorfismos genéticos individuais determinantes para a modulação do sistema endocanabinoide e, consequentemente, impactam a resposta terapêutica do paciente.
CONCLUSÃO: A existência de testes genéticos para avaliação prévia do perfil genético do paciente a fim de evitar efeitos colaterais e ter mais assertividade na indicação do produto de cannabis é uma importante ferramenta para aumentar a aderência ao tratamento com cannabis.


Cannabis, Farmacogenética, Maconha medicinal, Nucleotídeo único, Polimorfismo, Variação genética


1 Horpe HHA, Talhat MA, Khokhar JY. High genes: genetic underpinnings of cannabis use phenotypes. Prog Neuropsychopharmacol Biol Psychiatry. 2021;106:110164.

2 Urits I, Charipova K, Gress K, Li N, Berger AA, Cornett EM, et al. Adverse Effects of Recreational and medical Cannabis. Psychopharmacol Bull. 2021;51(1):94-109.

3 Grieco M. Cannabis Medicinal: baseado em fatos. Rio de Janeiro: Agir; 2021. 400p.

4 Romero P, Peris A, Vergara K, Matus JT. Comprehending and improving cannabis specialized metabolism in the systems biology era. Plant Sci. 2020;298:110571.

5 Ahmed S, Roth RM, Stanciu CN, Brunette MF. The Impact of THC and CBD in schizophrenia: a systematic review. Front Psychiatry. 2021;12:694394.

6 Bialas P, Fitzcharles MA, Klose P, Hauser W. Long-term observational studies with cannabis-based medicines for chronic non-cancer pain: a systematic review and meta-analysis of effectiveness and safety. Eur J Pain. 2022;26(6):1221-33.

7 Bonaccorso S, Ricciardi A, Zangani C, Chiappini S, Schifano F. Cannabidiol (CBD) use in psychiatric disorders: A systematic review. Neurotoxicology. 2019;74:282-98.

8 Bousman CA, Bengesser SA, Aitchison KJ, Amare AT, Aschauer H, Baune BT, Asl BB, Bishop JR, Burmeister M, Chaumette B, Chen LS, Cordner ZA, Deckert J, Degenhardt F, DeLisi LE, Folkersen L, Kennedy JL, Klein TE, McClay JL, McMahon FJ, Musil R, Saccone NL, Sangkuhl K, Stowe RM, Tan EC, Tiwari AK, Zai CC, Zai G, Zhang J, Gaedigk A, Müller DJ. Review and Consensus on Pharmacogenomic Testing in Psychiatry. Pharmacopsychiatry. 2021;54(1):5-17.

9 Filippini G, Minozzi S, Borrelli F, Cinquini M, Dwan K. Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis. Cochrane Database Syst Rev. 2022;5:CD013444.

10 Kuhns L, Kroon E, Colyer-Patel K, Cousijn J. Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence. Psychopharmacology (Berl). 2022;239(5):1231-49.

11 Wang L, Hong PJ, May C, Rehman Y, Oparin Y, Hong CJ, Hong BY, AminiLari M, Gallo L, Kaushal A, Craigie S, Couban RJ, Kum E, Shanthanna H, Price I, Upadhye S, Ware MA, Campbell F, Buchbinder R, Agoritsas T, Busse JW. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ. 2021;374:n1034.

12 Demers CH, Bogdan R, Agrawal A. The genetics, neurogenetics and pharmacogenetics of addiction. Curr Behav Neurosci Rep. 2014;1(1):33-44.

13 Hryhorowicz S, Walczak M, Zakerska-Banaszak O, Slomski R, Skrzypczak-Zielinska M. Pharmacogenetics of cannabinoids. Eur J Drug Metab Pharmacokinet. 2018;43(1):1-12.

14 Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92(4):414-7.

15 Lowe H, Toyang N, Steele B, Bryant J, Ngwa W. The endocannabinoid system: a potential target for the treatment of various diseases. Int J Mol Sci. 2021;22(17):9472.

16 Crist RC, Clarke TK, Berrettini WH. Pharmacogenetics of opioid use disorder treatment. CNS Drugs. 2018;32(4):305-20.

17 Gilron I, Blyth FM, Degenhardt L, Di Forti M, Eccleston C, Haroutounian S, Moore A, Rice ASC, Wallace M. Risks of harm with cannabinoids, cannabis, and cannabis-based medicine for pain management relevant to patients receiving pain treatment: protocol for an overview of systematic reviews. Pain Rep. 2019;4(3):e742.

18 Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147 Suppl 1:S163-71.

19 Freeman TP, Craft S, Wilson J, Stylianou S, ElSohly M, Di Forti M, Lynskey MT. Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta-analysis. Addiction. 2021;116(5):1000-10.

20 Arnold JC, Hone P, Holland ML, Allen JD. CB2 and TRPV1 receptors mediate cannabinoid actions on MDR1 expression in multidrug resistant cells. Pharmacol Rep. 2012;64(3):751-7.

21 Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J. 2006;8(2):E298-306.

22 Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092-101.

23 Velazquez MNR, Parween S, Udhane SS, Pandey AV. Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 activities caused by genetic variations in cytochrome P450 oxidoreductase. Biochem Biophys Res Commun. 2019;515(1):133-8.

24 Nasrin S, Watson CJW, Bardhi K, Fort G, Chen G, Lazarus P. Inhibition of UDP-Glucuronosyltransferase Enzymes by Major Cannabinoids and Their Metabolites. Drug Metab Dispos. 2021;49(12):1081-9.

25 Hu DG, Mackenzie PI, Hulin JA, McKinnon RA, Meech R. Regulation of human UDP-glycosyltransferase (UGT) genes by miRNAs. Drug Metab Rev. 2022;54(2):120-40.

26 Omura K, Motoki K, Kobashi S, Miyata K, Yamano K, Iwanaga T. Identification of human UDP-glucuronosyltransferase and sulfotransferase as responsible for the metabolism of dotinurad, a novel selective urate reabsorption inhibitor. Drug Metab Dispos. 2021;49(11):1016-24.

27 Rambaran KA, Chu M, Johnson TB, Alzghari SK. The current landscape of marijuana and pharmacogenetics. Cureus. 2017;9(7):e1525.

28 Murphy T, Matheson J, Mann RE, Brands B, Wickens CM, Tiwari AK, Zai CC, Kennedy J, Le Foll B. Influence of cannabinoid receptor 1 genetic variants on the subjective effects of smoked cannabis. Int J Mol Sci. 2021;22(14):7388.

29 Bourgault Z, Matheson J, Mann RE, Brands B, Wickens CM, Tiwari AK, Zai CC, Kennedy J, Le Foll B. Mu opioid receptor gene variant modulates subjective response to smoked cannabis. Am J Transl Res. 2022;14(1):623-32.

30 Kebir O, Lafaye G, Blecha L, Chaumette B, Mouaffak F, Laqueille X, Benyamina A. ABCB1 C3435T polymorphism is associated with tetrahydrocannabinol blood levels in heavy cannabis users. Psychiatry Res. 2018;262:357-8.

31 Bosia M, Buonocore M, Bechi M, Stere LM, Silvestri MP, Inguscio E, Spangaro M, Cocchi F, Bianchi L, Guglielmino C, Cavallaro R. Schizophrenia, cannabis use and Catechol-O-Methyltransferase (COMT): Modeling the interplay on cognition. Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:363-8.

32 Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57(10):1117-27.

33 Gasse A, Vennemann M, Kohler H, Schurenkamp J. Toxicogenetic analysis of Delta9-THC-metabolizing enzymes. Int J Legal Med. 2020;134(6):2095-103.

34 Maeda H, Hazama S, Shavkat A, Okamoto K, Oba K, Sakamoto J, et al. Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and Japanese populations. Mol Diagn Ther. 2014;18(3):333-42.

35 Schneider JS, Gasse A, Schurenkamp M, Sibbing U, Banken S, Pfeiffer H, et al. Multiplex analysis of genetic polymorphisms within UGT1A9, a gene involved in phase II of Delta(9)-THC metabolism. Int J Legal Med. 2019;133(2):365-72.

36 Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, et al. A large-scale genome-wide association study meta-analysis of cannabis use disorder. Lancet Psychiatry. 2020;7(12):1032-45.

37 Sideli L, Quigley H, La Cascia C, Murray RM. Cannabis Use and the Risk for Psychosis and Affective Disorders. J Dual Diagn. 2020;16(1):22-42.

38 Karlsson Linner R, Biroli P, Kong E, Meddens SFW, Wedow R, Fontana MA, et al. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nat Genet. 2019;51(2):245-57.

39 Carvalho C, Vieira-Coelho MA. Cannabis induced psychosis: A systematic review on the role of genetic polymorphisms. Pharmacol Res. 2022;181:106258.

40 Cosker E, Schwitzer T, Ramoz N, Ligier F, Lalanne L, Gorwood P, et al. The effect of interactions between genetics and cannabis use on neurocognition. A review. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:95-106.

41 Misiak B, Stramecki F, Gaweda L, Prochwicz K, Sasiadek MM, Moustafa AA, et al. Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review. Mol Neurobiol. 2018;55(6):5075-100.

42 Volkow ND, Swanson JM, Evins AE, DeLisi LE, Meier MH, Gonzalez R, et al. Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review. JAMA Psychiatry. 2016;73(3):292-7.

43 Zwicker A, LeBlanc MA, Pavlova B, Alda M, Denovan-Wright EM, Uher R, et al. Genetic counselling for the prevention of mental health consequences of cannabis use: A randomized controlled trial-within-cohort. Early Interv Psychiatry. 2021;15(5):1306-14.

44 Byrne EM, Gehrman PR, Medland SE, Nyholt DR, Heath AC, Madden PA, et al. A genome-wide association study of sleep habits and insomnia. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(5):439-51.

45 Lima WAG, Taylor AP. Fenótipo da gordura, fatores associados e o polimorfismo rs9939609 do gene FTO. Rev Bras Cineantropom Desempenho Hum. 2010;12(2):164-72.

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