NeuroImage: Clinical
March 7, 2018
F. Müller, P. Dolder, A. Schmidt et al.
187 citations
LSD alters brain network connectivity. In a double-blind, randomized, crossover study, 20 healthy participants received 100 μg LSD or placebo, and resting-state brain activity was measured with fMRI. LSD decreased functional connectivity within visual, sensorimotor, auditory, and default mode networks, while increasing connectivity between networks and subcortical (thalamus, striatum) and cortical (precuneus, anterior cingulate cortex) hub structures. These hub changes resemble patterns seen in psychosis and may relate to therapeutic effects of hallucinogens.
Psychopharmacology
March 15, 2014
M. Kirkpatrick, M. Baggott, J. Mendelson et al.
78 citations
Across three independent laboratories in Basel, San Francisco, and Chicago, 220 healthy volunteers received either placebo or MDMA (1.5 mg/kg or a 125-mg fixed dose) under double-blind conditions. Despite differences in study methods and participants' prior drug use, MDMA produced very similar cardiovascular and subjective effects at all sites. Prior MDMA use was inversely related to feeling "Any Drug Effect" only at sites testing more experienced users. The pharmacological effects of MDMA are robust and highly reproducible across settings, with modest evidence for tolerance in regular users.
Biochemical Pharmacology
June 1, 2019
D. Luethi, M. Hoener, S. Krähenbühl et al.
46 citations
LSD is metabolized in the human liver into two main metabolites, nor-LSD and O-H-LSD, but only in small amounts—less than 1% of the parent compound was converted over four hours in laboratory experiments using human liver microsomes. Several cytochrome P450 enzymes contribute to this metabolism: CYP2D6, 2E1, and 3A4 for nor-LSD, and CYP1A2, 2C9, 2E1, and 3A4 for O-H-LSD. Enzyme induction by rifampicin increased metabolite formation, while omeprazole had a minor effect on nor-LSD. LSD and nor-LSD both activate serotonin receptors (5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C), with nor-LSD showing lower affinity at the 5-HT2C receptor. O-H-LSD had much weaker receptor activity, suggesting it is inactive. Genetic variations or drug interactions affecting these enzymes could alter LSD's effects.
European Journal of Pharmacology
July 1, 2019
D. Luethi, R. Widmer, D. Trachsel et al.
18 citations
Certain ring-substituted phenethylamines produce psychedelic effects mainly through serotonin 5-HT2A receptors. 2C-BI derivatives, a class of 4'-aryl substituted 2,5-dimethoxyphenethylamines, were tested for binding and activity at monoamine receptors and transporters. Several 2C-BI compounds bound strongly to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations, while only 2C-BI-1 and 2C-BI-7 activated human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted weakly with monoamine transporters. The high affinities at the 5-HT2A receptor suggest a sterically tolerant binding pocket, and potent partial activation by 2C-BI-8 and 2C-BI-12 indicates potential psychedelic effects similar to other 2C compounds.