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

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.