Fourth Generation of Synthetic Cannabinoid Receptor Agonists A Review on the Latest Insights.
Over the past few years, an emerging number of new psychoactive substances (NPSs) entered the illicit market. NPSs are designed to resemble the effects of classical drugs of abuse, reinforcing their effects and duration. Among the most abused NPS, synthetic cannabinoids are cannabinoid receptor agonists (SCRAs) that mimic the effect of the main psychotropic phytocannabinoid Δ9-tetrahydrocannabinol (THC). We herein reviewed the international literature to provide available information on the newest SCRAs generation. Compared to the previous SCRAs generations, the structures of the last generation result in increased affinity for and efficacy at cannabinoid CB From November 2017 to February 2021, at least 20 new fourth-generation SCRAs were formally reported to international drug agencies. Our understanding of the neurotoxicity of these compounds is still limited due to the lack of global data, but their potency and their toxicity are likely higher than those of the previous generations.