The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides.

Novel psychedelics (NPs) are a growing group of compounds with unknown use profiles and subjective effects. A survey of 1,180 NP users examined usage patterns and adverse events for three structural families: phenethylamines, tryptamines, and lysergamides. Novel phenethylamines were most prevalent (61.5%), followed by tryptamines (43.8%) and lysergamides (42.9%). Compared to phenethylamines, tryptamine and lysergamide users had significantly fewer physical adverse events, but no significant differences in psychological adverse events appeared. A machine-learning classifier distinguished three specific compounds—2C-B, 1P-LSD, and 4-AcO-DMT—with moderate accuracy (AUC 0.79). The findings suggest NP classes may differ in adverse event rates and phenomenology, though subjective experience may blur distinctions.

Study at a glance

Abstract

Novel psychedelics (NPs) are an expanding set of compounds, presenting new challenges for drug policy and opportunities for clinical research. Unlike their classical derivatives, little is known regarding their use profiles or their subjective effects. The purpose of this study was to compile usage patterns and adverse event rates for individual NPs belonging to each of three main psychedelic structural families. Targeting the most widely used representatives for each class, we expanded on their phenomenological distinctions. A two-part survey was employed. We investigated the prevalence of novel phenethylamines, tryptamine and lysergamides in NP users (N = 1180), contrasting the type and incidence of adverse events (AEs) using a set of logistic regressions. Honing in on 2-4-Bromo-2,5-dimethoxyphenyl)ethanamine (2C-B) (48.6%), 1-propionyl-lysergic acid diethylamide (1P-LSD) (34.2%) and 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) (23.1%), we examined their phenomenological separability using a gradient boosting (XGBoost) supervised classifier. Novel phenethylamines had the highest prevalence of use (61.5%) seconded by tryptamines (43.8%) and lysergamides (42.9%). Usage patterns were identified for 32 different compounds, demonstrating variable dosages, durations and a common oral route of administration. Compared to phenethylamines, the odds for tryptamines and lysergamides users were significantly less for overall physical AEs. No significant differences in overall psychological AEs were found. Overall model area under the curve (AUC) stood at 0.79 with sensitivity (50.0%) and specificity (60.0%) for 2C-B ranking lowest. NP classes may hold distinct AE rates and phenomenology, the latter potentially clouded by the subjective nature of these experiences. Further targeted research is warranted.