Beyond Pharmacokinetics: Gaps for Rational Use of Medicinal Cannabis
TL;DR
Standardized recording of product provenance in future clinical trials, through a structured reporting checklist, would help close the first gap, and confirmation of administered dose, such as biochemical verification of intake or electronic dose-monitoring devices, would help address the second.
Abstract
A recent letter highlights important gaps in translating population pharmacokinetic (popPK) models of (cid:2) 9-tetrahydrocannabinol (THC) into clinically appropriate dosing, raising two considerations: exposure provenance and the unclear exposure– response relationship for psychiatric outcomes. The nominal THC dose does not necessarily reflect the actual dose received. This discrepancy can arise from the product itself, given documented discordance between labeled and measured cannabinoid content, 1 batch-to-batch inconsistency, and variation in regulatory source. Most of the published THC population PK studies reported only limited information on product-level details. 2 Also, it can arise from the patient, since adherence to the intended dosing regimen is rarely assessed and is a practical challenge in real-world settings. Both factors can contribute to the known large variability in THC pharmacokinetics, partly reflected in the wide between-subject variability in bioavailability identified across the reviewed models. Standardized recording of product provenance in future clinical trials, through a structured reporting checklist, would help close the first gap. Confirmation of administered dose, such as biochemical verification of intake or electronic dose-monitoring devices, would help address the second.