The Dark Side of Cannabidiol: The Unanticipated Social and Clinical Implications of Synthetic Δ8-THC.

Introduction: The explosive growth of the cannabis industry in the United States over the past decade has spurred a multitude of products derived from phytocannabinoids produced by Cannabis sativa L. Decades of cannabis prohibition coupled with the more recent 2018 Farm Bill have lead to several unanticipated consequences and the widespread availability of synthetic cannabinoids derived from hemp CBD, including Δ8-THC, Δ10-THC and HHC. Methods: Herein, we review the available literature of the complexity of the chemistry of its current manufacture, namely, the acid-catalyzed ring closure of cannabidiol (ACRCC), the myriad of issues involving the unsolved technical problems with quality control of ACRCC-Δ8-THC and the multitude of isomerized byproducts, and the lack of consistent regulation regarding consumer safety and labeling. Results: We provide what we believe is the first comprehensive listing of all the documented ACRCC-Δ8-THC byproducts. Perhaps, most importantly, we highlight the growing concern that, other than Δ8-THC itself, the compounds in ACRCC-Δ8-THC product mixtures have not been subjected to any human toxicological evaluation. This is especially troubling as ACRCC-Δ8-THC products relate to vaping, and their contribution to a growing and lethal epidemic of electronic cigarette, or vaping, product use-associated lung injury (EVALI). Conclusions: Quality control is totally inadequate in the newly emerging Δ8-THC industry. American consumers are ingesting products that are mislabeled with many compounds that have never received any toxicological testing. EVALI cases continue to be reported with a fatality rate approaching 2% (in California).