The use of the intoxicating cannabinoid delta-8-tetrahydrocannabinol (Δ 8 -THC) has grown rapidly over the last several years. There have been dozens of Δ 8 -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 Δ 8 -THC, including receptor binding, cell signalling, in vivo cannabimimetic activity, clinical activity and pharmacokinetics. We give special focus to studies that directly compared Δ 8 -THC to its more commonly studied isomer, Δ 9 -THC. Overall, the pharmacokinetics and pharmacodynamics of Δ 8 -THC and Δ 9 -THC are very similar. Δ 8 -THC is a partial agonist of the cannabinoid CB 1 receptor and has cannabimimetic activity in both animals and humans. 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. We highlight the gaps in our knowledge of Δ 8 -THC pharmacology where further studies are needed, particularly in humans.delta-8-THC, pharmacodynamics, pharmacokinetics, Δ 8 -THC | INTRODUCTIONDelta-8-tetrahydrocannabinol (Δ 8 -THC) is a cannabinoid that is a double bond isomer of the more well-known Δ 9 -THC (Figure 1). 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).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 9 -THC was determined to be the compound, almost entirely, responsible for the intoxicating properties of cannabis, including alterations in mood, perception and cognition. Subsequent research focused much more on Δ 9 -THC, but the effects of Δ 8 -THC continued to be characterized throughout the following decades. One reason for this is the better thermodynamic stability of Δ 8 -THC relative to Δ 9 -THC (Hanuš et al., 2016). Note that early studies referred to Δ 8 -THC as Δ 6 or Δ 1(6) and Δ 9 -THC as Δ 1 . This review will follow the modern ring numbering system even when the original publication used the old numbering.There is currently debate about the regulatory status of Δ 8 -THC in the United States (e.g. Koski, 2021). The Agriculture Improvement Act of 2018 (informally called the 'Farm Bill') removed hemp and hemp products containing less than 0.3% Δ 9 -THC from the legal definition of marijuana in the Federal Controlled Substances Act (Agriculture Improvement Act of 2018, 2018). Importantly for Δ 8 -THC, hemp was defined as including 'all derivatives, extracts, cannabinoids, isomers, acids, salts and salts of isomers'. Because Δ 8 -THC is both an isomer of CBD and a derivative of CBD when obtained from the cyclization Abbreviations: C max , maximal concentration; CYP, cytochrome P450; P-gp, P-glycoprotein; Tmax, time to maximal concentration; Δ 8 -THC, delta-8-tetrahydrocannabinol.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.