Pharmacologic Similarities and Differences Among Hallucinogens

Abstract

Hallucinogens constitute a unique class of substances that cause changes in the user's thoughts, perceptions, and mood through various mechanisms of action. Although the serotonergic hallucinogens such as lysergic acid diethylamide, psilocybin, and N,N‐dimethyltryptamine have been termed the classical hallucinogens, many hallucinogens elicit their actions through other mechanisms such as N‐methyl‐D‐aspartate receptor antagonism, opioid receptor agonism, or inhibition of the reuptake of monoamines including serotonin, norepinephrine, and dopamine. The aim of this article is to compare the pharmacologic similarities and differences among substances within the hallucinogen class and their impact on physical and psychiatric effects. Potential toxicities, including life‐threatening and long‐term effects, will be reviewed.

Interpol Review of Drug Analysis 2019-2022

“…2019 SERS method for screening spiked beverages for various hypnotics [ 849 ]; 2021 survey of socio-demographics, preferences, experiences and attitudes associated with hallucinogen use in Slovakia [ 850 ]; review of different hallucinogens [ 851 ].…”

RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine

“…Classical serotonergic psychedelic compounds (e.g., psilocybin, dimethyltryptamine, lysergic acid diethylamide) have reemerged as novel approaches for the treatment of mental health disorders, including depressive disorders . Serotonergic psychedelic compounds may overcome some of the limitations of existing antidepressants, including the slow onset of therapeutic response, poor response rates, adverse effects, withdrawal symptoms, and a requirement for long-term administration to prevent relapse. − The antidepressant effects of serotonergic psychedelics are believed to be mediated primarily through agonism of the 5-hydroxytryptamine 2A (5-HT2A) receptor. ,− Numerous psychoactive tryptamines activate the 5-HT2A receptor and elicit hallucinogenic effects in humans, − including psilocin (4-hydroxy- N , N -dimethyltryptamine) and the synthetic tryptamine analog, 4-hydroxy- N , N -diisopropyltryptamine (4-OH-DiPT), which, anecdotally, is reported to produce a hallucinogenic effect of 2–3 h in humans. ,− Psilocin is delivered in the form of a 4- O -phosphate prodrug, with the phosphate being cleaved efficiently in vivo to form the active species.…”

“…2 − 6 The antidepressant effects of serotonergic psychedelics are believed to be mediated primarily through agonism of the 5-hydroxytryptamine 2A (5-HT2A) receptor. 1 , 7 − 9 Numerous psychoactive tryptamines activate the 5-HT2A receptor and elicit hallucinogenic effects in humans, 10 − 12 including psilocin (4-hydroxy- N , N -dimethyltryptamine) and the synthetic tryptamine analog, 4-hydroxy- N , N -diisopropyltryptamine (4-OH-DiPT), which, anecdotally, is reported to produce a hallucinogenic effect of 2–3 h in humans. 10 , 13 − 16 Psilocin is delivered in the form of a 4- O -phosphate prodrug, with the phosphate being cleaved efficiently in vivo to form the active species.…”