Cumyl‐CBMICA: A new synthetic cannabinoid receptor agonist containing a cyclobutyl methyl side chain

Abstract

Since the beginning of the phenomenon of new psychoactive substances (NPS), synthetic cannabinoid receptor agonists (SCRAs) have been the largest and most prevalent subclass of these drugs in Europe. Many countries implemented specific legislation scheduling classes of substances defined on the basis of their chemical structure to reduce supply. We describe the identification and analytical characterization within the EU project ADEBAR plus of 1-(cyclobutylmethyl)-N-(2-phenylpropan-2-yl)-1Hindole-3-carboxamide which resulted in the formal notification through the Early Warning System of the European Monitoring Centre for Drug and Drug Addiction (EMCDDA). This is the first identification of this new SCRA worldwide and the analytical data was distributed (inter-)nationally right after identification in 2019. First, the substance was isolated from the herbal material using preparative high-performance liquid chromatography (HPLC). Structure elucidation and analytical characterization were performed using gas chromatography-mass spectrometry (GC-MS), gas chromatography-solid state infrared spectroscopy (GC-sIR), liquid chromatographyelectrospray ionization-quadrupole time of flight-mass spectrometry (LC-ESI-qToF-MS), Raman spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The new compound contains a cyclobutyl methyl group as a side chain and has not been described in any patent to our knowledge. Based on the semisystematic nomenclature of SCRAs, we propose Cumyl-CBMICA as a short name for the compound.

A transnational perspective on the evolution of the synthetic cannabinoid receptor agonists market: Comparing prison and general populations

“…Since the enactment of legislation covering NPS (NpSG = Neue‐psychoaktive‐Stoffe‐Gesetz) in November 2016, Germany now implements analog controls for SCRAs as described in detail in previous publications 39,40 . When first enacted, the legislation controlled 86% of the SCRAs monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCCDA), including the most prevalent SCRAs on the market at that time 39 .…”

“…Legislative changes to cover SCRAs with increasingly diverse core structures were enacted via the NpSG in July 2019, and these cover the γ‐carbolinone substances. This may have led to a greater diversification of the tail structures producing, for example, the recently detected Cumyl‐CBMICA, an indole‐3‐carboxamide SCRA with a cyclobutyl methyl tail 40 …”

“…The positive samples in Scotland were exclusively papers, whereas of the Since the enactment of legislation covering NPS (NpSG = Neuepsychoaktive-Stoffe-Gesetz) in November 2016, Germany now implements analog controls for SCRAs as described in detail in previous publications. 39,40 When first enacted, the legislation controlled 86% of the SCRAs monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCCDA), including the most prevalent SCRAs on the market at that time. 39 However, the legislation appears, at least in its early phases, to have driven SCRA diversity in the German domestic market with compounds appearing to be specifically designed to avoid legislative control via the NpSG.…”

“…This may have led to a greater diversification of the tail structures producing, for example, the recently detected Cumyl-CBMICA, an indole-3-carboxamide SCRA with a cyclobutyl methyl tail. 40…”

New synthetic cannabinoids carrying a cyclobutyl methyl side chain: Human Phase I metabolism and data on human cannabinoid receptor 1 binding and activation of Cumyl‐CBMICA and Cumyl‐CBMINACA

“…1H-indole-3-carboxamide) was purified out of seized herbal blends and comprehensively described elsewhere 7. Cumyl-CBMINACA (1-(cyclobutylmethyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) was extracted from herbal blends seized in Germany and purified using flash-chromatography.…”