Synthetic Cannabinoids: A Pharmacological and Toxicological Overview

Abstract

Synthetic cannabinoids (SCs) are a chemically diverse group of new psychoactive substances (NPSs) that target the endocannabinoid system, triggering a plethora of actions (e.g., elevated mood sensation, relaxation, appetite stimulation) that resemble, but are more intense than, those induced by cannabis. Although some of these effects have been explored for therapeutic applications, anticipated stronger psychoactive effects than cannabis and reduced risk perception have increased the recreational use of SCs, which have dominated the NPS market in the United States and Europe over the past decade. However, rising SC-related intoxications and deaths represent a major public health concern and embody a major challenge for policy makers. Here, we review the pharmacology and toxicology of SCs. A thorough characterization of SCs’ pharmacodynamics and toxicodynamics is important to better understand the main mechanisms underlying acute and chronic effects of SCs, interpret the clinical/pathological findings related to SC use, and improve SC risk awareness. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 63 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Fluorinated‐Squaramide Covalent Organic Frameworks for High‐Performance and Interference‐Free Extraction of Synthetic Cannabinoids

“…Because various functional groups were integrated into the framework, solid-state 13 C cross-polarization magic-angle spinning (CP/MAS) nuclear magnetic resonance (NMR) was applied to validate the functional groups in the FSQ-Xs skeleton. For FSQ-4, a broad peak (≈183.2 ppm) confirmed the presence of the…”

“…[10][11][12] Analyzing SCs is challenging considering their low background level, and the complex matrix (such as proteins, organic acids, carbohydrates, and humic acid) in real-world samples further hinders sensitive detection. At present, the detection of SCs has been dominated by tandem and high-resolution mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), [13] and different sample pre-treatment techniques have been reported for SCs enrichment. However, they are either time-or labor-consuming and only suitable for several kinds of SCs.…”

In vitro cannabinoid activity profiling of generic ban‐evading brominated synthetic cannabinoid receptor agonists and their analogs

“…3 For instance, in Europe, over 230 SCRAs have been detected since 2008, and their number still increases. 4,5 These substances initially appeared on the market as legal alternatives to cannabis, in an attempt to produce compounds with effects similar to those of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), its predominant psychotropic component. 6 The main target of SCRAs is the cannabinoid 1 receptor (CB 1 ), through which they exert their desired psychoactive effects such as euphoria, relaxation, and mood elevation, although most also interact with the cannabinoid 2 receptor (CB 2 ), present on cells associated with the immune system.…”

“…6 The main target of SCRAs is the cannabinoid 1 receptor (CB 1 ), through which they exert their desired psychoactive effects such as euphoria, relaxation, and mood elevation, although most also interact with the cannabinoid 2 receptor (CB 2 ), present on cells associated with the immune system. [6][7][8][9] Whereas these compounds aim to mimic the psychoactive effects of Δ 9 -THC, they are often very potent substances, 10,11 exemplified by effects such as psychosis, agitation, respiratory depression, cardiovascular and renal toxicity, stroke, and coma, with fatalities and mass intoxications having been associated with SCRA use. [12][13][14] Whereas SCRAs containing an indole or indazole flooded the market since the initial identification of JWH-018 as the psychoactive component in "Spice" in 2008, 15,16 more recently, a diverse array of substances carrying atypical structural features have emerged, as a response to the changing legislation in several countries.…”

“…These substances initially appeared on the market as legal alternatives to cannabis, in an attempt to produce compounds with effects similar to those of Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC), its predominant psychotropic component 6 . The main target of SCRAs is the cannabinoid 1 receptor (CB 1 ), through which they exert their desired psychoactive effects such as euphoria, relaxation, and mood elevation, although most also interact with the cannabinoid 2 receptor (CB 2 ), present on cells associated with the immune system 6–9 . Whereas these compounds aim to mimic the psychoactive effects of Δ 9 ‐THC, they are often very potent substances, 10,11 exemplified by effects such as psychosis, agitation, respiratory depression, cardiovascular and renal toxicity, stroke, and coma, with fatalities and mass intoxications having been associated with SCRA use 12–14 …”