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One reason for this is the better thermodynamic stability of Δ 8-THC relative to Δ 9-THC (Hanuš et al., 2016). Subsequent research focused much more on Δ 9-THC, but the effects of Δ 8-THC continued to be characterized throughout the following decades. Δ 9-THC was determined to be the compound, almost entirely, responsible for the intoxicating properties of cannabis, including alterations in mood, perception and cognition. By 1966, it was realized that Δ 8-THC was present in only negligible amounts in cannabis and cannabis-derived products, such as hash (Hively et al., 1966). Δ 8-THC was first derived from the cyclization of cannabidiol (CBD) and it was discovered to be highly psychoactive in human studies (Adams, 1942). We highlight the gaps in our knowledge of Δ 8-THC pharmacology where further studies are needed, particularly in humans.ĭelta-8-tetrahydrocannabinol (Δ 8-THC) is a cannabinoid that is a double bond isomer of the more well-known Δ 9-THC (Figure 1). The reduced potency of Δ 8-THC in clinical studies compared with Δ 9-THC can be explained by weaker cannabinoid CB 1 receptor affinity, although there are other plausible mechanisms that may contribute. Δ 8-THC is a partial agonist of the cannabinoid CB 1 receptor and has cannabimimetic activity in both animals and humans. Overall, the pharmacokinetics and pharmacodynamics of Δ 8-THC and Δ 9-THC are very similar. We give special focus to studies that directly compared Δ 8-THC to its more commonly studied isomer, Δ 9-THC. In this review, we summarize the pharmacological studies of Δ 8-THC, including receptor binding, cell signalling, in vivo cannabimimetic activity, clinical activity and pharmacokinetics. There have been dozens of Δ 8-THC studies dating back over many decades, yet no review articles have comprehensively covered these findings. The use of the intoxicating cannabinoid delta-8-tetrahydrocannabinol (Δ 8-THC) has grown rapidly over the last several years.