Population Survey Data Informing the Therapeutic Potential of Classic and Novel Phenethylamine, Tryptamine, and Lysergamide Psychedelics

Abstract

Introduction: The majority of contemporary psychedelic research has focused on ayahuasca, lysergic acid diethylamide, and psilocybin, though there are hundreds of novel psychedelic compounds that may have clinical utility. The purpose of the present study was to evaluate the therapeutic potential of classic and novel phenethylamine, tryptamine, and lysergamide psychedelics via a large, nationally representative population-based survey. Methods: We tested the unique associations of lifetime classic and novel phenethylamine, tryptamine, and lysergamide psychedelics with past month psychological distress and past year suicidality among respondents pooled from years 2008-2017 of the National Survey on Drug Use and Health (weighted N = 260,964,827). Results: Lifetime classic tryptamine use was associated with a decreased odds of past month psychological distress [aOR = 0.76; (0.69-0.83)] and past year suicidal thinking [aOR = 0.79; (0.72-0.87)]. Lifetime novel phenethylamine use, on the other hand, was associated with an increased odds of past year suicidal thinking [aOR = 1.44; (1.06-1.95)] and past year suicidal planning [aOR = 1.60; (1.06-2.41)]. No other significant associations were found. Discussion and Conclusions: These findings, which may be driven by differences in pharmacodynamics, suggest that classic tryptamines may hold the greatest therapeutic potential of the psychedelics, whereas novel phenethylamines may pose risk for harm. The present findings thus support continued research on the clinical application of classic tryptamines. Though the current results caution against the clinical utility of novel phenethylamines, further study of these and other novel psychedelic substances is nonetheless warranted to better understand their potential application.

Psychedelics use predicts more positive emotional reactivity and diminished outward-focused self-consciousness: the mediating role of ego dissolution and mystical experiences

“…We thus provide evidence, in line with previous cross-sectional studies, that not only clinical or researchbased, but also naturalistic use of psychedelics might be related to generally positive psychological effects (Bouso et al, 2012;Galvão-Coelho et al, 2021;Krebs and Johansen, 2013;Lawn et al, 2017). This is supported by the observations that at the population level psychedelics do not constitute a risk factor for mental health problems (Krebs and Johansen, 2013;Sexton, Nichols and Hendricks, 2019). What is more, many users themselves consider using classic psychedelics as rather psychologically beneficial (Mason and Kuypers, 2018;Kettner, Mason and Kuypers, 2019) and related to fewer harmful effects than other substances (Carhart-Harris and Nutt, 2010).…”

Associations between lifetime classic psychedelic use and markers of physical health

“…The three main classes of classic psychedelics (tryptamines, lysergamides and phenethylamines) are distinguished by unique chemical structures and neurochemical mechanisms ( Szabo, 2015 ). Most notably, they include N,N-dimethyltryptamine (DMT), the DMT-containing admixture ayahuasca, psilocybin, lysergic acid diethylamide (LSD), mescaline, and the mescaline-containing cacti peyote and San Pedro ( Sexton et al, 2019a ).…”

Association Between Lifetime Classic Psychedelic Use and Hypertension in the Past Year

“…Based on the evidence to date, we hypothesized that lifetime classic psychedelic use would be associated with lower odds of hypertension in the past year. Further, in light of recent evidence from a recent population study, 22 we also hypothesized that lifetime tryptamine use would have the strongest association with hypertension in the past year among the main classes of classic psychedelics.…”