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DOI: 10.1055/a-2593-6351
Evidence of Potential Drug Interactions Between Cannabidiol and Other Drugs: A Scoping Review to Guide Pharmaceutical Care
Supported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Abstract
Cannabidiol (CBD), a non-psychoactive cannabinoid with therapeutic potential, is increasingly used in combination with other drugs, raising concerns about potential interactions and their impact on safety and efficacy. This scoping review aimed to map the current evidence on CBD interactions across different drug classes and assess their clinical significance. The study followed the Joanna Briggs Institute guidelines, utilizing a structured protocol based on the population, concept, and context (PCC) framework. Five databases were searched, and preclinical and clinical studies on CBD pharmacokinetic and pharmacodynamic interactions were included, with publications in English, Portuguese, or Spanish. Out of 136 studies analyzed, 91.91% were published after 2011, reflecting a sharp rise in interest in this area. A total of 271 interactions were identified, with 203 related to pharmacokinetics, primarily involving metabolism mediated by cytochrome P450 (CYP) enzymes, and 68 linked to pharmacodynamics, including additive effects such as sedation. Among the most relevant findings, CBD was shown to inhibit CYP enzymes like CYP3A4 and CYP2C19, potentially increasing plasma levels of co-administered drugs. However, only 5.15% of studies evaluated the clinical relevance of these interactions, indicating a substantial gap in knowledge regarding their safety implications. This review highlights the urgent need for rigorous clinical research to determine the clinical significance of CBD-drug interactions, particularly in patients undergoing polypharmacy. Understanding these interactions is crucial for optimizing therapeutic outcomes, minimizing adverse effects, and enabling safer clinical use of CBD in diverse treatment regimens.
Supporting Information
- Supporting Information
Supplementary materials include the PRISMA-ScR checklist, a table of study exclusions, summaries of pharmacokinetic and pharmacodynamic interactions, and the list of included studies.
Publication History
Received: 19 September 2024
Accepted after revision: 23 April 2025
Accepted Manuscript online:
23 April 2025
Article published online:
08 May 2025
© 2025. Thieme. All rights reserved.
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References
- 1 Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definition. BMC Geriatr 2017; 17 (01) 230-239
- 2 Bhagavathula AS, Tesfaye W, Vidyasagar K, Fialova D. Polypharmacy and hyperpolypharmacy in older individuals with parkinsonʼs disease: A systematic review and meta-analysis. Gerontology 2022; 68 (10) 1081-1090
- 3 Kujawska MT, Górska J, Droździk T, Barski J. Cannabis in Parkinsonʼs disease: the patientsʼ view. Front Neurol 2021; 12: 664586
- 4 McInnes GT, Brodie MJ. Drug interactions that matter. A critical reappraisal. Drugs 1988; 36 (01) 83-110
- 5 Tornio A, Filppula AM, Niemi M, Backman JT. Clinical studies on drug-drug interactions involving metabolism and transport: Methodology, pitfalls, and interpretation. Clin Pharmacol Ther 2019; 105 (06) 1345-1361
- 6 Brunton L, Knollmann B. Goodman and Gilmanʼs. The Pharmacological Basis of Therapeutics, 14th ed. New York, NY: McGraw Hill; 2022
- 7 Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, Mastinu A. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol 2018; 227: 300-315
- 8 Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012; 133 (01) 79-97
- 9 Caicedo DA, Pérez-Mañá C, Farré M, Papaseit E. An overview of the potential for pharmacokinetic interactions between drugs and cannabis products in humans. Pharmaceutics 2025; 17: 319
- 10 Gilmartin CGS, Dowd Z, Parker APJ, Harijan P. Interaction of cannabidiol with other antiseizure medications: A narrative review. Seizure 2021; 86: 189-196
- 11 Mechoulam R, Shvo Y. Hashish. I. The structure of cannabidiol. Tetrahedron 1963; 19 (12) 2073-2078
- 12 Russo E, Agredano PM, Flachenecker P, Lawthom C, Munro D, Hindocha C, Bagul M, Trinka E. The attitudes, knowledge and confidence of healthcare professionals about cannabis-based products. J Cannabis Res 2024; 6 (01) 32-45
- 13 Bansal S, Zamarripa CA, Spindle TR, Weerts EM, Thummel KE, Vandrey R, Paine MF, Unadkat JD. Evaluation of cytochrome P450-mediated cannabinoid-drug interactions in healthy adult participants. Clin Pharmacol Ther 2023; 114 (03) 693-703
- 14 Alsherbiny MA, Li CG. Medicinal cannabis-potential drug interactions. Medicines (Basel) 2018; 6 (01) 3-12
- 15 Nader FD. Pharmacokinetic and pharmacodynamic interactions between cannabidiol and other drugs: A systematic scoping review [protocol]. OSF; 2021. Available from: https://doi.org/10.17605/OSF.IO/GH45N
- 16 Graham M, Martin JH, Lucas CJ, Murnion B, Schneider J. Cannabidiol drug interaction considerations for prescribers and pharmacists. Expert Rev Clin Pharmacol 2022; 15 (12) 1383-1397
- 17 Hossain KR, Alghalayini A, Valenzuela SM. Current challenges and opportunities for improved cannabidiol solubility. Int J Mol Sci 2023; 24: 14514
- 18 Dale T, Downs J, Olson H, Bergin AM, Smith S, Leonard H. Cannabis for refractory epilepsy in children: A review focusing on CDKL5 Deficiency Disorder. Epilepsy Res 2019; 151: 31-39
- 19 Abu-Sawwa R, Scutt B, Park Y. Emerging use of epidiolex (Cannabidiol) in epilepsy. J Pediatr Pharmacol Ther 2020; 25 (06) 485-499
- 20 Zhu HJ, Wang JS, Markowitz JS, Donovan JL, Gibson BB, Gefroh HA, Devane CL. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther 2006; 317 (02) 850-857
- 21 Brown JD, Winterstein AG. Potential adverse drug events and drug-drug interactions with medical and consumer cannabidiol (CBD) use. J Clin Med 2019; 8 (07) 989
- 22 Nelson KM, Bisson J, Singh G, Graham JG, Chen SN, Friesen JB, Dahlin JL, Niemitz M, Walters MA, Pauli GF. The essential medicinal chemistry of cannabidiol (CBD). J Med Chem 2020; 63 (21) 12137-12155
- 23 Qian L, Beers JL, Jackson KD, Zhou Z. CBD and THC in special populations: Pharmacokinetics and drug-drug interactions. Pharmaceutics 2024; 16 (04) 484
- 24 Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid metabolites as inhibitors of major hepatic CYP450 enzymes, with implications for cannabis-drug interactions. Drug Metab Dispos 2021; 49 (12) 1070-1080
- 25 Smith RT, Gruber SA. Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions. Front Psychiatry 2023; 13: 1055481
- 26 Wei Y, Tang C, Sant V, Li S, Poloyac SM, Xie W. A molecular aspect in the regulation of drug metabolism: Does PXR-induced enzyme expression always lead to functional changes in drug metabolism?. Curr Pharmacol Rep 2016; 2 (04) 187-192
- 27 VanLandingham KE, Crockett J, Taylor L, Morrison G. A phase 2, double-blind, placebo-controlled trial to investigate potential drug-drug interactions between cannabidiol and clobazam. J Clin Pharmacol 2020; 60 (10) 1304-1313
- 28 Schaiquevich P, Riva N, Maldonado C, Vázquez M, Cáceres-Guido P. Clinical pharmacology of cannabidiol in refractory epilepsy. Farm Hosp 2020; 44 (05) 222-229
- 29 Bergmann KR, Broekhuizen K, Groeneveld GJ. Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency. Br J Clin Pharmacol 2020; 86 (02) 380-385
- 30 Devinsky O, Thiele EA, Wright S, Checketts D, Morrison G, Dunayevich E, Knappertz V. Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials. Acta Neurol Scand 2020; 142 (06) 531-540
- 31 Klein P, Tolbert D, Gidal BE. Drug-drug interactions and pharmacodynamics of concomitant clobazam and cannabidiol or stiripentol in refractory seizures. Epilepsy Behav 2019; 99: 106459
- 32 Bardhi K, Coates S, Watson CJW, Lazarus P. Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy. Expert Rev Clin Pharmacol 2022; 15 (12) 1443-1460
- 33 Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: A systematic review. Drug Metab Rev 2014; 46 (01) 86-95
- 34 Vázquez M, Guevara N, Maldonado C, Guido PC, Schaiquevich P. Potential pharmacokinetic drug-drug interactions between cannabinoids and drugs used for chronic pain. Biomed Res Int 2020; 2020: 3902740
- 35 Sales AJ, Crestani CC, Guimarães FS, Joca SRL. Antidepressant-like effect induced by cannabidiol is dependent on brain serotonin levels. Prog Neuropsychopharmacol Biol Psychiatry 2018; 86: 255-261
- 36 Fraguas-Sánchez AI, Fernández-Carballido A, Simancas-Herbada R, Martin-Sabroso C, Torres-Suárez AI. CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer. Int J Pharm 2020; 574: 118916
- 37 Jesus CHA, Ferreira MV, Gasparin AT, Rosa ES, Genaro K, Crippa JAS, Chichorro JG, Cunha JMD. Cannabidiol enhances the antinociceptive effects of morphine and attenuates opioid-induced tolerance in the chronic constriction injury model. Behav Brain Res 2022; 435: 114076
- 38 Olivas-Aguirre M, Torres-López L, Villatoro-Gómez K, Perez-Tapia SM, Pottosin I, Dobrovinskaya O. Cannabidiol on the path from the lab to the cancer patient: Opportunities and challenges. Pharmaceuticals (Basel) 2022; 15 (03) 366
- 39 Land MH, MacNair L, Thomas BF, Peters EN, Bonn-Miller MO. Letter to the Editor: Possible Drug-Drug Interactions Between Cannabinoids and Candidate COVID-19 Drugs. Cannabis Cannabinoid Res 2020; 5 (04) 340-343
- 40 Anderson LL, Absalom NL, Abelev SV, Low IK, Doohan PT, Martin LJ, Chebib M, McGregor IS, Arnold JC. Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions. Epilepsia 2019; 60 (11) 2224-2234
- 41 Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP. UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia 2017; 58 (09) 1586-1592
- 42 Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol 2018; 18 (01) 143
- 43 Martinez Naya N, Kelly J, Corna G, Golino M, Polizio AH, Abbate A, Toldo S, Mezzaroma E. An overview of cannabidiol as a multifunctional drug: Pharmacokinetics and cellular effects. Molecules 2024; 29 (02) 473
- 44 Ho JJY, Goh C, Leong CSA, Ng KY, Bakhtiar A. Evaluation of potential drug-drug interactions with medical cannabis. Clin Transl Sci 2024; 17 (05) e13812
- 45 Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ 2020; 192 (09) E206
- 46 Tricco AC, Lillie E, Zarin W, OʼBrien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169 (07) 467-473
- 47 World Health Organization. Anatomical Therapeutic Chemical (ATC) Classification [Internet]. 2021. Accessed January 17, 2023 at: https://www.who.int/tools/atc-ddd-toolkit/atc-classification