Review of delta‐8‐tetrahydrocannabinol (Δ8‐THC): Comparative pharmacology with Δ9‐THC

Delta-8-THC, an intoxicating cannabinoid, has rapidly grown in use. This review summarizes decades of pharmacological studies on delta-8-THC, including receptor binding, cell signaling, animal and human activity, and pharmacokinetics, with special focus on comparisons to delta-9-THC. The pharmacokinetics and pharmacodynamics of the two isomers are very similar. Delta-8-THC is a partial agonist of the CB1 receptor and has cannabimimetic activity in both animals and humans. Its reduced potency in clinical studies compared to delta-9-THC can be explained by weaker CB1 receptor affinity, though other mechanisms may contribute. Gaps in knowledge, particularly in human studies, are highlighted.

Study at a glance

Abstract

The use of the intoxicating cannabinoid delta‐8‐tetrahydrocannabinol (Δ8‐THC) has grown rapidly over the last several years. There have been dozens of Δ8‐THC studies dating back over many decades, yet no review articles have comprehensively covered these findings. In this review, we summarize the pharmacological studies of Δ8‐THC, including receptor binding, cell signalling, in vivo cannabimimetic activity, clinical activity and pharmacokinetics. We give special focus to studies that directly compared Δ8‐THC to its more commonly studied isomer, Δ9‐THC. Overall, the pharmacokinetics and pharmacodynamics of Δ8‐THC and Δ9‐THC are very similar. Δ8‐THC is a partial agonist of the cannabinoid CB1 receptor and has cannabimimetic activity in both animals and humans. The reduced potency of Δ8‐THC in clinical studies compared with Δ9‐THC can be explained by weaker cannabinoid CB1 receptor affinity, although there are other plausible mechanisms that may contribute. We highlight the gaps in our knowledge of Δ8‐THC pharmacology where further studies are needed, particularly in humans.