Chemoinformatic Consideration of Novel Psychoactive Substances: Compilation and Preliminary Analysis of a Categorised Dataset

Abstract

This paper is dedicated to Prof. Paola Gramatica on the occasion of her retirement.Abstract: Recent years have seen the emergence into circulation of a growing array of novel psychoactive substances (NPS). Knowledge of the pharmacological profiles and risk liability of these compounds is typically very scarce. Development of chemoinformatic tools enabling prediction of properties within uncharacterised analogues has potential be of particular use. In order to facilitate this, compilation of a chemical inventory comprising known NPS is a necessity. Sourcing a variety of published governmental and analytical reports, a dataset composed of 690 distinct acknowledged NPS, complete with defined chemical structures, has been constructed. This is supplemented by a complementary series of 155 established psychoactive drugs of abuse (EPDA). Classification was performed in accordance with their key molecular structural features, subjective effect profiles and pharmacological mechanisms of action. In excess of forty chemical groupings, spanning seven subjective effect categories and six broad mechanisms of pharmacological action, were identified. Co-occurrence of NPS and EPDA within specific classes was common, showcasing inherent scope both for chemical read-across and for the derivation of structural alerts.

‘Cannabis’ ontologies I: Conceptual issues with Cannabis and cannabinoids terminology

“…The resulting substances, however, are not phytocannabinoids found in the environment but novel compounds, mimicking their pharmacological effects without being derived from, nor directly relatable to them. Firman et al. (2019) find that out of the ‘223 compounds identified, a mere ten … bear structural relation to THC’.…”

“…Historically, the myriad of new cannabinoid molecules discovered in the last decades (Firman et al., 2019; Shevyrin et al., 2016) have been termed ‘synthetic cannabinoids’ by opposition to ‘phytocannabinoids’, the naturally occurring cannabinoids found in Cannabis plants. While the word ‘phytocannabinoid’ links to an unambiguous and delimited relatum , the expression ‘synthetic cannabinoids’ is given by ostentation rather than by description.…”

“…A compressive arrangement of those ‘synthetic agonists active at cannabinoid CB1 and CB2 receptors’ (Firman et al., 2019) is still to be found. Shevyrin et al.…”

“…A compressive arrangement of those 'synthetic agonists active at cannabinoid CB1 and CB2 receptors' (Firman et al, 2019) is still to be found. Shevyrin et al (2016) made insightful proposals (classifying these substances in six groups: 'classical', 'nonclassical', 'hybrid cannabinoids', 'aminoalkylindoles', 'eicosanoids', and 'other cannabinoids'), and Biernat (2018) proposed three categories ('cannabinoids derived directly from cannabis', 'synthetic versions of cannabinoids found in cannabis', and 'compounds that are similar to cannabinoids found in cannabis'), among others.…”

A Deep Generative Model Enables Automated Structure Elucidation of Novel Psychoactive Substances

“…First is the high degree of structural similarity between candidate NPSs, which are often analogues from the same medicinal chemistry series 11,12 . A second challenge is the rapid rate at which novel compounds emerge onto the grey market, which necessitates the development of new assays for previously unknown substances 13,14 . Assay development requires substantial time and effort, and the inherent novelty of NPSs means that analytical reference materials are rarely available for NPSs that have recently entered the market 15 .…”