Cannabinoid Drug Interactions

Description

In dose-ranging, randomized, controlled trials, serum concentrations of clobazam and its active metabolite (N-CLB) increased beyond the therapeutic range when in combination with high-dose CBD (15-20 mg/kg/day)

N-CLB levels appear to increase at a substantially higher rate than CLB levels. One study of 13 subjects with refractory epilepsy who were taking concomitant CLB and CBD reported elevated CLB and N-CLB levels. The mean increase in CLB was ~60% while the mean increase in N-CLB was ~500%, resulting in a reduction of CLB dosing.

Mechanism

CBD inhibition of CYP 2C19 resulting in decreased metabolism of N-CLB to its inactive metabolite

Evidence

Geffrey et al 2015
Devinsky et al 2018
Gaston et al 2017

Disclaimer

The drug interaction information provided in this section is a compilation of published literature, including clinical trials and case reports and may include interpretation¹ by PCCC.

Additional information regarding theoretical drug interactions is also presented and is based on our evaluation of the potential for harm if such an interaction were to occur.

Criteria considered:

• Hepatic metabolism of the victim drug
• Cytochrome P450 involvement
• Drugs with a narrow therapeutic window
• Dose, frequency, and route of cannabis use