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Drug Interactions with Cannabinoids

Mar 04, 2020 4:45 pm

Cannbinoids are widely available and used for a variety of indications, but little is known about their safety and their potential for drug interactions. The Canadian Medical Journal has published a review of drug interactions with cannabinoids, many of which are mediated by cytochrome-P450 metabolism.

Tetrahydrocannabinol (THC) and cannabidiol are pharmacologically active cannabinoids in marijuana that are metabolized by cytochrome P450 (CYP)3A4 and by CYP2C9.  These pathways may be affected by other CYP3A4 inhibitors, such as the anti-fungal drug ketoconazole which has been shown to increase THC and cannabidiol concentrations.  Other CYP3A4 inhibitors, including macrolides (clarithromycin) and verapamil may increase the effects of cannabidiol. Other CYP2C9 inhibitors such as cotrimoxazole, fluoxetine and amiodarone could increase THC exposure and effects

Smoked marijuana has been shown to increase the clearance of theophylline by 40% and similar effects can be expected for other drugs metabolized by CYP1A2, such as olanzapine. Increased drug clearance occurs with regular marijuana use (> 2 marijuana cigarettes per week); no effect of occasional use has been reported.

Marijuana may yield additive effects when combined with sympathomimetics (e.g., tachycardia), central nervous system depressants (alcohol and opioids) and anticholinergics (e.g., tachycardia, confusion).

A serious “red flag” interaction may occur when marijuana interacts with warfarin, although more research is needed. 

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