Delta-8-Tetrahydrocannabinol, an emerging NPS and other structurally related cannabinoids

Abstract

The aim of this presentation is to find answers why delta-8 THC is an emerging NPS and why structurally related analogs like delta-10 THC, tetrahydrocannabivarin and THC-O-acetate are also of concern? From a regulatory point of view, banning delta-8 THC, as has been done with delta-9 THC, will attract people to become interested in other isomers and structurally related analogues. So how to deal with this? We screened the available scientific literature dealing with the biological and chemical synthesis methods of cannabinoids, including their precursors, conversion reactions, types of extractions, relevant by-products and known pharmacological data. Delta-8 THC, differing in the location of a double bond between two carbons from delta-9 THC, is present in very low concentrations in cannabis plants. Like delta-9 THC, it can provoke psychoactive effects such as euphoria, visual and time distortion, relaxation, difficulty in thinking, speaking and reading, and a dream-like state. The dose required to achieve these clinical effects is unclear, as controlled dose-response studies of delta-8 THC in humans are scarce. Delta-8 THC is known to be less potent than delta-9 THC, but a standard human dose has not been set. Several countries have banned or restricted delta-8 THC products, but elsewhere it remains legal and available for sale to individuals of all ages. Where the sale is not restricted, delta-8 THC is often available at tobacco shops and convenience stores in various formulations, such as vape cartridges, dried plants, or candy gummies. Furthermore, as the awareness and popularity of delta-8 THC expands, it is predictable that medical caregivers will encounter increasing numbers of patients who are under the influence of delta-8 THC. Toxicology screening assays for delta-8 THC are also not readily available in most medical facilities and certainly not for law enforcement. Most importantly, a worrying interest is noticed based on the information available on the internet and social media, that deals with the question « How to make delta-8 THC? CBD to delta-8 THC step-by-step ». Given the fact that CBD is legal, not psychoactive, but that it can be used as precursor in the process for converting CBD to delta-8 THC, being psychoactive, is frightening. Even more since the conversion isn’t alchemy or magic; in fact, it's much less complicated than one might expect. The basic process for converting CBD to delta-8 THC simply is: “CBD + acid + time = delta-8 THC”. One by-product commonly found in delta-8 THC products is olivetol, a precursor for the synthesis of THC in the chemical laboratory or manufacturing plant. The Swiss Federal Customs Administration seized a total of 260 kg of olivetol and 260 kg of p-mentha-2,8-dien-1-ol in 2019, an indication that some of the delta-8 THC on the market may be synthetically produced. Another molecule of particular concern is the cannabinoid called THC-O-acetate (the acetyl ester of THC), which seems to be popping up in gummies and vapes. It is basically acetylated THC, which does not occur naturally in cannabis plants and can be called a New Psychoactive Substance (NPS). Interestingly, also heroin was created by acetylating morphine over 100 years ago. No human studies on the effects of acetylated THC are available, illustrating the danger. Many cannabinoids can be obtained from ingredients extracted from hemp and by means of biotechnological processes. We therefore need to inform the public in saying that just because the starting material is legal, it does not make the resulting product(s) legal or safe. We recommend regulatory oversight, uniformity of delta-8 THC's status and its analogues, wide-scale scientific dissemination for law enforcement and the general public, together with sufficient laboratory testing know how and capacity.