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Abstract
Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included ‘cannabidiol’, ‘tetrahydrocannabinol’, and ‘cytochrome P450’. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included. Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, cause changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.
Disclosure statement
Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie and Atai Life Sciences. Dr. S. Roger McIntyre is a CEO of Braxia Scientific Corp.
Kayla M. Teopiz has received personal fees from Braxia Scientific Corp.
Dr. Rhee was supported in part by the National Institute on Aging (NIA) (#R21AG070666 and #R21AG078972), National Institute of Mental Health (#R21MH117438), and National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut in the past three years. Dr. Rhee serves as a review committee member for patient-centered outcomes research institute (pcori) and substance abuse and mental health services administration (samhsa) and has received honoraria payments from pcori and samhsa. Dr. Rhee has also served as a stakeholder/consultant for pcori and received consulting fees from pcori. Dr. Rhee serves as an advisory committee member for international alliance of mental health research funders (iamhrf). Dr. Rhee is currently a co-editor-in-chief of mental health science and has received honorarium payments annually from the publisher, john wiley & sons, inc.
Dr. Roger Ho received funding from Institute of Health Innovation and Technology (iHealthtech) National University of Singapore, Operating Expense (A-0001415-09-00).
Data availability statement
All data analyzed in this study are available in the published article.