Other Medications Changed THC/CBD Spray Exposure in Different Directions

The effect of another medication on THC/CBD exposure depends on the drug and the pathway involved. A human interaction study found lower cannabinoid exposure with rifampicin, higher exposure with ketoconazole, and no significant pharmacokinetic change with omeprazole under the tested conditions.

Three separate crossover comparisons

Stott and colleagues studied 36 healthy volunteers in three groups of 12. Within each group, participants received THC/CBD oromucosal spray alone and in combination with one interacting medication. The study was open-label, and the three medication groups were analyzed separately.

The cannabinoid administration was a single four-spray dose. Plasma THC, CBD and 11-hydroxy-THC were followed over time, with peak concentration and area under the concentration–time curve used to characterize exposure. These measurements did not directly assess driving impairment.

An active metabolite was especially informative

Repeated rifampicin administration reduced exposure to all three measured analytes, including 11-hydroxy-THC. Ketoconazole increased exposure, with a particularly large change in the active metabolite. Mean 11-hydroxy-THC area under the curve to the last measurement rose from 21.78 to 84.34 hour·ng/mL in that comparison.

Omeprazole did not significantly change the pharmacokinetic profile under the study conditions. That is a result for the tested dose and formulation, not evidence that every medication sharing a metabolic pathway is interaction-free.

Exposure findings do not dictate an individual dose adjustment

The small healthy-volunteer groups, substantial between-person variability and single cannabinoid challenge limit generalization to patients using repeated doses. Giving four sprays together also differs from spreading doses across a day. Some interaction analyses included fewer participants because of incomplete data.

The study directly tested what other medications did to cannabinoid exposure. It did not establish the reciprocal effect of CBD on every co-medication, nor a universal method for adjusting treatment. Such changes require the patient’s prescribing clinician and product-specific information.

For interpreting a cannabis toxicology result, concurrent medications can be part of the exposure history rather than an afterthought. Even an interaction-associated concentration change does not provide a measured impairment curve. Our explanation of THC concentration and impairment addresses that separate question.

Primary research

Colin Stott and colleagues. SpringerPlus (2013). A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers.