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.