A systematic review found that THC and CBD are processed by specific liver enzymes (CYP2C9, CYP3A4, CYP2C19) and generally pose a low risk of clinically significant drug interactions at typical doses.
Read this if you use cannabis alongside prescription medications and want to understand interaction risk.
THC metabolized by CYP2C9 and CYP3A4; low overall drug interaction risk at typical doses
What the researchers found
The review identified the specific cytochrome P-450 (CYP-450) enzymes responsible for metabolizing major cannabinoids. THC is primarily metabolized by CYP2C9 and CYP3A4. CBD is metabolized by CYP2C19 and CYP3A4. CBN uses CYP2C9 and CYP3A4. Synthetic cannabinoids JWH-018 and AM2201 use CYP1A2 and CYP2C9.
Clinical pharmacogenetic data confirmed CYP2C9 as important for THC metabolism, and a drug interaction study with ketoconazole (a CYP3A4 inhibitor) confirmed CYP3A4's role for both THC and CBD. However, a study with omeprazole suggested CYP2C19 may play a less significant role in CBD metabolism than in vitro data predicted.
Overall, studies of THC, CBD, and CBN inhibition and induction of major CYP-450 enzymes suggested a low risk of clinically significant drug interactions with most use, though the authors noted that specific human data were lacking. Smoked cannabis appeared to induce CYP1A2, which metabolizes theophylline.
Why it matters
As cannabis use becomes more common alongside prescription medications, understanding drug interaction potential is essential for patient safety. This review provides the pharmacokinetic foundation for predicting which drug combinations could be problematic.
The numbers in context
THC: CYP2C9, CYP3A4. CBD: CYP2C19, CYP3A4. CBN: CYP2C9, CYP3A4. JWH-018: CYP1A2, CYP2C9. AM2201: CYP1A2, CYP2C9. Overall drug interaction risk rated as low for most clinical use.
How the study worked
This was a systematic review of published data on cannabinoid drug metabolism, including in vitro studies of enzyme substrates, inhibitors, and inducers, pharmacogenetic studies, and clinical pharmacokinetic interaction studies. The review covered both natural cannabinoids (THC, CBD, CBN) and synthetic cannabinoids (JWH-018, AM2201).
What this study cannot tell us
Most data came from in vitro studies, which may not fully predict in vivo interactions. The low interaction risk assessment was based on limited human data. Cannabinoid doses used in in vitro studies may not reflect clinical concentrations. The review predated the widespread use of high-dose CBD products, which may pose greater interaction risks.
How to read the evidence
This is a systematic review of pharmacokinetic data. While comprehensive, much of the evidence is from in vitro studies with limited clinical confirmation.
When this study was published
Published in 2014. Since then, FDA-approved CBD (Epidiolex) has revealed clinically significant CYP interactions at high doses, particularly with clobazam.
The bigger picture
Drug interactions are a critical safety consideration for any new therapeutic agent. This review establishes the metabolic profile of major cannabinoids, providing a framework that physicians and pharmacists can use to evaluate potential interactions with patients' existing medications.
Questions still open
- Do high-dose CBD products (like Epidiolex) have greater drug interaction potential? How do genetic variations in CYP enzymes affect individual responses to cannabinoids? Should patients on certain medications be advised to avoid cannabis?
Common questions
Can cannabis interact with my medications?
Why does smoked cannabis affect theophylline?
Read the original research
Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.
Drug metabolism reviews, 46(1), 86-95
Citation
Stout, Stephen M; Cimino, Nina M. (2014). Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.. Drug metabolism reviews, 46(1), 86-95. https://doi.org/10.3109/03602532.2013.849268
Explore the wider topic
- CBD Oil Quality Guide: How to Avoid Snake Oil
- Anxiety After Quitting Weed: When to Consider Medication
- Cannabis for Chemotherapy Nausea: What the Evidence Actually Shows
- Cannabis for Chronic Pain: What the Research Actually Supports
- Cannabis and Epilepsy: The Epidiolex Story and What It Means
- Does CBD Actually Work for Anxiety? What the Evidence Shows
- Does CBD Help with Weed Withdrawal? What Studies Show
- CBD vs THC: The Differences That Actually Matter
- The Proven Medical Benefits of Cannabis: What Research Supports
- Quitting Weed Before Surgery
- Weed and Medications: What Changes When You Quit
- Quitting Weed During Pregnancy: What You Need to Know
- Quitting Weed While Pregnant: What You Need to Know
- Cannabis and Older Adults: Risks Seniors Should Know
- Cannabis and Breastfeeding: THC in Breast Milk