Eur Neuropsychopharmacol
May 20, 2016
Anna Rickli, Olivier D. Moning, Marius C. Hoener et al.
374 citations
Novel psychoactive tryptamines (DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT) interact with serotonin 5-HT2A receptors as partial or full agonists, but with lower binding affinity than LSD. Their binding affinity correlates with reported psychoactive doses in humans. Several of these tryptamines, like psilocin and DMT, also interact with the serotonin transporter and partially with the norepinephrine transporter, similar to MDMA, whereas LSD does not. LSD, but not the tryptamines, interacts with adrenergic and dopaminergic receptors. The receptor interaction profiles suggest these tryptamines produce hallucinogenic effects similar to classic serotonergic hallucinogens along with MDMA-like psychoactive properties.
Neuropharmacology
December 1, 2015
Anna Rickli, Dino Luethi, Julian Reinisch et al.
216 citations
NBOMe drugs, a class of novel psychoactive substances, bind strongly to serotonin receptors (5-HT2A, 5-HT2B, 5-HT2C) and rat trace amine-associated receptor-1, with most affinities and potencies below 1 μM, similar to LSD. Unlike LSD, NBOMe drugs also interact with α1 receptors, suggesting they may produce hallucinogenic effects comparable to LSD but with additional stimulant properties. The study characterized the receptor binding profiles of twelve 2C drugs, their NBOMe analogs, and LSD in human cells expressing human receptors or transporters, except for TAAR1 where rat/mouse receptors were used.
British Journal of Pharmacology
March 13, 2015
Anna Rickli, Simone Kopf, Marius C. Hoener et al.
115 citations
Benzofurans, a class of newly used psychoactive substances, inhibit norepinephrine and serotonin uptake more than dopamine uptake, similar to MDMA and unlike methamphetamine. They also release monoamines and interact with trace amine-associated receptor 1, like classic amphetamines. Most benzofurans are partial 5-HT2A receptor agonists, similar to MDMA, but also activate 5-HT2B receptors, which is associated with heart valve fibrosis, unlike MDMA and methamphetamine. The benzodifuran 2C-B-FLY potently interacts with 5-HT2 receptors and binds to TA1 receptors, indicating predominant hallucinogenic properties and a risk for vasoconstriction.
British Journal of Pharmacology
March 8, 2012
C.m. Hysek, Yasmin Schmid, Anna Rickli et al.
81 citations
The α₁- and β-adrenoceptor antagonist carvedilol reduced MDMA-induced increases in blood pressure, heart rate, and body temperature in healthy subjects, but did not affect the subjective or psychotropic effects of MDMA, such as drug liking, high, or stimulation. Carvedilol also did not alter plasma exposure to MDMA. These findings suggest that α₁- and β-adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychological effects, indicating carvedilol could be useful for treating cardiovascular and hyperthermic complications associated with ecstasy use.
PLoS ONE
June 15, 2016
Andrea E Steuer, Corina Schmidhauser, Eva H Tingelhoff et al.
18 citations
Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
British Journal of Pharmacology
September 6, 2013
Cédric M. Hysek, Yasmin Schmid, Anna Rickli et al.
7 citations
A 125 mg dose of MDMA, a common recreational amount, produces only a moderate increase in body temperature in controlled clinical settings where risk factors like high ambient temperature, physical exertion, and dehydration are avoided. Severe hyperthermia, a rare but life-threatening complication of recreational MDMA use, typically requires additional permissive factors such as repeated or high doses, crowded conditions, or hyperthyroidism. The drug carvedilol, which blocks both α- and β-adrenoceptors, reduced MDMA-induced thermogenesis in humans and reversed established hyperthermia in rats, but its utility for treating severe MDMA toxicity in emergency settings remains unknown and requires further evaluation in case reports or series.
edoc (University of Basel)
January 1, 2016
Anna Rickli
1 citation
Dopamine release does not appear to contribute to the mood-elevating effects of MDMA (ecstasy) in healthy people. In a double-blind, placebo-controlled crossover study with 16 participants, blocking dopamine release with bupropion did not reduce MDMA's subjective effects but instead prolonged them, while reducing MDMA-induced increases in norepinephrine and heart rate. This suggests norepinephrine, not dopamine, mediates MDMA's cardiostimulant effects, with serotonin and norepinephrine likely driving its psychotropic effects. The work also characterized the pharmacological profiles of many novel psychoactive substances, finding that para-halogenated amphetamines are more serotonergic than their non-halogenated counterparts, pyrovalerone cathinones are potent dopamine transporter inhibitors with high abuse potential, and NBOMe derivatives show high 5-HT2A receptor affinity and selectivity, indicating strong hallucinogenic potential.