Interações medicamentosas do canabidiol: um guia farmacológico - Bruno José Dumêt Fernandes; Alena Pereira dos Santos (Revista Científica Eletrônica do Conselho Regional de Farmácia da Bahia, 2025)
Devido ao crescente uso de canabidiol (CBD), é provável que ocorra interações quando administrado junto a medicamentos. Produtos de cannabis medicinal contêm uma variedade de fitocanabinoides, incluindo 9-tetrahidrocanabinol (9-THC), que é psicoativo, e o CBD sem efeitos eufóricos. Interações farmacodinâmicas podem ocorrer se a cannabis medicinal for administrada junto a medicamentos depressores do sistema nervoso central. Objetivo: fornecer orientação clínica sobre possíveis interações medicamentosas entre o CBD e outros medicamentos prescritos simultaneamente. Método: Esse estudo é uma revisão narrativa que busca sintetizar e discutir a farmacocinética e as principais enzimas, transportadores e receptores celulares, responsáveis pelos mecanismos das interações medicamentosas do CBD. Conclusão: a interação medicamentosa não é um determinante da resposta clínica e, para cada paciente, o regime de dosagem do CBD, com base nas evidências científicas, deve ser individualizado e acompanhado pelo farmacêutico e pelo médico prescritor. Referências KICMAN, A. & TOCZEK, M. The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease. Int J Mol Sci. 2020; 21: 6740. DOI: 10.3390/ijms21186740 PISANTI, S.; MALFITANO, A.M.; CIAGLIA, E. et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017; 175: 133–150. DOI: 10.1016/j.pharmthera.2017.02.041. BROWN, J.D. & WINTERSTEIN, A.G. Potential adverse drug events and drug–drug interactions with medical and consumer cannabidiol (CBD) use. J Clin Med. 2019; 8: 989. DOI: 10.3390/jcm8070989. LUCAS, C.J.; GALETTIS, P.; SCHNEIDER, J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018; 84: 2477–2482. DOI: 10.1111/bcp.13710. FERREIRA-JUNIOR, N.C.; CAMPOS, A.C.; GUIMARÃES, F.S. et al. Biological bases for a possible effect of cannabidiol in Parkinson’s disease. Braz J Psychiatry. 2020; 42(2): 218-224. DOI: 10.1590/1516-4446-2019-0460. LANDMARK, C.J. & BRANDL, U. Pharmacology and drug interactions of cannabinoids. Epileptic Disord. 2020; 22 (Suppl. 1): S16-S22. DOI: 10.1684/epd.2019.1123. NASRIN, S.; WATSON, C.J.W.; BARDHI, K. et al. Inhibition of udp-glucuronosyltransferase enzymes by major cannabinoids and their metabolites. Drug Metab Dispos. 2021; 49: 1081–1089. DOI: 10.1124/dmd.121.000530. GROTENHERMEN, F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003; 42: 327–360. DOI: 10.2165/00003088-200342040-00003. OHLSSON, A.; LINDGREN, J.E.; ANDERSSON, S. et al. Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration. Biomed Environ Mass Spectrom. 1986; 13: 77–83. DOI: 10.1002/bms.1200130206. GASTON, T.E. & FRIEDMAN, D. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav. 2017; 70 (Pt B): 313–318. DOI: 10.1016/j.yebeh.2016.11.016. HUESTIS, M.A. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007; 4: 1770–1804. DOI: 10.1002/cbdv.200790152. ZHU, H.J.; WANG, J.S.; MARKOWITZ, J.S. et al. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther. 2006; 317: 850–7. DOI: 10.1124/jpet.105.098541. BALACHANDRAN, P.; ELSOHLY, M.; HILL, K.P. Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review. J Gen Intern Med. 2021; 36(7): 2074–2084. DOI: 10.1007/s11606-020-06504-8. US Food and Drug Administration. Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers 2023. Disponível em https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Acesso em 3 jun 2024. FLOCKHART, D.A. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine 2007; Disponível em https://drug-interactions.medicine.iu.edu/MainTable.aspx. Acesso em 3 jun 2024. TURPEINEN, M.; RAUNIO, H.; PELKONEN, O. The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metabol. 2006; 7 (7): 705-714. DOI: 10.2174/138920006778520633. MINERS, J.O. & BIRKETT, D.J. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998;45 (6):525-538. DOI: 10.1046/j.1365-2125.1998.00721.x. Cytochrome P-450 CYP2C9 Inducers. Disponível em https://go.drugbank.com/categories/DBCAT001245. Acesso em 3 jun 2024. VAN BOOVEN, D.; MARSH, S.; MCLEOD, H. et al. Cytochrome P450 2C9-CYP2C9. Pharmacogenet Genomics. 2010; 20 (4): 277-281. DOI: 10.1097/FPC.0b013e3283349e84. DYMOND, A.W.; SO, K.; MARTIN, P. et al. Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from two clinical trials. Eur J Clin Pharmacol. 2017; 73 (2): 175-184. DOI: 10.1007/s00228-016-2153-7. Cytochrome P-450 CYP2C19 Inducers. Disponível em https://go.drugbank.com/categories/DBCAT001246. Acesso em 3 jun 2024. ZANGER, U.M.;·RAIMUNDO, S.;·EICHELBAUM, M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004; 369: 23–37. DOI: 10.1007/s00210-003-0832-2. UpToDate®: Inhibitors and inducers of P-glycoprotein (P-gp) drug efflux pump (P-gp multidrug resistance transporter 2024. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Disponível em https://www.uptodate.com/contents/image?imageKey=DRUG/73326. Acesso em 10 junho 2024. SERA, L. & DUNCAN, N. Medical cannabis: Roles, responsibilities, and challenges for clinical pharmacists. J Am Coll Clin Pharm. 2023; 6:732–741. MacCALLUM, C.A & RUSSO, E.B. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018; 49: 12-19. DOI: 10.1016/j.ejim.2018.01.004. UJVÁRY, I. & HANUŠ, L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis Cannabinoid Res. 2016; 1(1): 90-101. DOI: 10.1089/can.2015.0012. MacCALLUM, C.A; LO L.A.; BOIVIN, M. "Is medical cannabis safe for my patients?" A practical review of cannabis safety considerations. Eur J Intern Med. 2021; 89: 10–8. DOI: /10.1016/j.ejim.2021.05.002.