How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future

Abstract

New synthetic cannabinoids appear regularly in the illicit drug market, often in response to legal restrictions. These compounds are characterized by increasing binding affinities (Ki) to CB1 and CB2 receptors. Increasing affinity to CB receptors can occur by substitution of a halogen on the terminal position of the pentyl chain of the classical synthetic cannabinoids. Fluorination of the aliphatic side chain of established cannabinoid agonists is a popular pathway of modifying existing active drugs and synthesizing novel drugs to increase potency. Biological impacts of these compounds that have been reported include seizures, body temperature losses that may lead to cardiac distress, as well as cases reporting delirium and severe neural incapacities. These symptoms have been reported in case reports with evidence that like their cannabinoid counterparts, these compounds distribute post-mortem into a variety of tissues, especially adipose tissue. Researchers have detected and identified certain synthetic cannabinoid compounds on botanicals using a variety of separation and detection systems such as GC-FID and GC-MS, as well as LC-MS/MS and NMR. Researchers have utilized a variety of chromatographic methods including LC MS/MS, to identify the parent compounds, their metabolites and structural analogs in biological samples such as urine and blood. The aim of this review is to spotlight the newer generations of synthetic cannabinoids with a more powerful affinity towards the cannabinoid receptors to continue to help researchers and clinicians further predict symptoms as well as future compounds and treatments.