Chapter 9 - Synthetic Cannabinoids: Synthesis and Biological Activities

Abstract

Abstract Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune, and endocrine systems. Most of these effects have been attributed to the ability of these compounds to interact with the cannabinoid CB1 and CB2 receptors. The FDA approval of Marinol®, a product containing synthetic THC (dronabinol), in 1985 for the control of nausea and vomiting in cancer patients receiving chemotherapy, and in 1992 as an appetite stimulant for AIDS patients, has further intensified the research interest in these compounds. Since 2000, smokable herbal mixtures under the brand name Spice were first sold on the Internet and in various specialized shops. When smoked, the Spice products have effects similar to those of cannabis. Forensic investigations were undertaken by German and Austrian authorities in order to identify the psychoactive ingredients of Spice. A new psychoactive substance JWH-018 has been identified in Spice products. JWH-018 was first synthesized in 1995 and produces effects similar to those THC. Subsequently, the synthetic cannabinoid CP 47,497 was also identified. Since 2009, other synthetic cannabinoids were identified in Europe and the United States. None of the above-mentioned synthetic cannabinoids is internationally controlled as a drug and there is no information on any of them having been authorized as a medicinal product in the European Union. There are no officially published safety data and little is known about their effects in humans. Some of the characteristics of these compounds, for example, volatility and activity in small doses, are likely to present further analytical and toxicological challenges. Responding to potential health concerns, Europe and the United States has taken legal actions to ban or otherwise control Spice products and related compounds.