Frontiers in Pharmacology
November 20, 2025
Karolina E. Kolaczynska, Daniel Trachsel, Marius C. Hoener et al.
1 citation
A class of psychedelic compounds called 4-substituted 2,6-dimethoxyphenethylamines and their amphetamine counterparts (Ψ derivatives) were tested for their interactions with monoamine receptors and transporters. These derivatives showed moderate to high affinity and activity at the human 5-HT2A receptor, the primary target for psychedelics, with binding affinities ranging from 8 to 1,600 nM and activation potencies from 32 to 3,400 nM. They acted as partial agonists at this receptor. The phenethylamine derivatives also bound to 5-HT1A and 5-HT2C receptors with moderate affinity, while amphetamine derivatives had weaker affinities. Some Ψ derivatives interacted with TAAR1 and adrenergic receptors. Compared to 2,4,5-trisubstituted derivatives, the 2,4,6-trisubstituted Ψ derivatives were generally less potent at the 5-HT2A receptor but more potent than 3,4,5-trisubstituted derivatives.
Molecular Psychiatry
November 5, 2025
Dino Luethi, Grant C. Glatfelter, Eline Pottie et al.
1 citation
Psychedelic-like effects of ring-substituted amphetamines are primarily mediated by 5-HT 2A receptors. Small lipophilic substituents at the 4-position of 2,5-dimethoxyamphetamine enhance clinical potency. This study examined 4-alkylated 2,5-dimethoxyamphetamines (methyl, ethyl, propyl, butyl, amyl) for in vitro receptor activity and in vivo effects in mice using the head-twitch response (HTR) assay. Increasing 4-alkyl chain length raised affinity at 5-HT 2A receptors. The 4-propyl analog showed the highest potencies for 5-HT 2A receptor activation (1–9 nM) in vitro; other chain lengths ranged from 2–56 nM. In mice, maximal HTR counts varied from 23 to 119, with potencies from 0.42 to 2.76 mg/kg.
Biomedical chromatography : BMC
September 1, 2025
Jan Thomann, Selina Kraus, Livio Erne et al.
1 citation
A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method accurately measures ketamine and its metabolites norketamine, dehydronorketamine (DHNK), and (2R,6R)-hydroxynorketamine (HNK) in human plasma. The method uses a small sample volume, a simple protein precipitation step, and a fast run time. Linear quantification ranges were 1-1,000 ng/mL for ketamine and norketamine, 0.25-100 ng/mL for DHNK, and 2.5-1,000 ng/mL for (2R,6R)-HNK. The method showed high accuracy, precision, selectivity, and sensitivity, with consistent matrix effects and efficient extraction recovery. It was successfully applied to assess pharmacokinetics in six clinical trial participants, offering a robust approach for clinical studies, drug monitoring, and forensic investigations.
Frontiers in Psychiatry
January 4, 2023
Felix P. Mayer, Dino Luethi, Lorena B. Areal et al.
1 citation
Psychoactive substances have been consumed throughout human history, first from plants and fungi, then isolated compounds like cocaine, and later synthetic drugs such as LSD. Many recreational drugs also have clinical uses, e.g., amphetamines for ADHD. New psychoactive substances (NPS) have expanded the drug market and improved understanding of structure-activity relationships. Recent clinical trials are reevaluating psychedelics like psilocybin and MDMA for conditions such as depression and PTSD. This special issue includes studies on synthetic opioids, NBOMe derivatives, psilocybin's anxiolytic effects in healthy volunteers, psilocybin reducing body weight in obese rats, and reviews linking mystical experiences to symptom reduction. The collection highlights both risks and therapeutic potential of psychoactive compounds.
Translational Psychiatry
June 4, 2026
Mélusine Humbert‐droz, Anna M. Becker, Jan Valenta et al.
A booster dose of MDMA prolongs the acute subjective drug effects compared with a single dose, without increasing peak effects. In a double-blind, randomized, placebo-controlled crossover study with 23 healthy volunteers, a 120 mg dose of MDMA followed by a 60 mg booster after 2 hours extended the duration of subjective effects to an average of 5.6 hours, versus 4.6 hours with a single dose. Adverse effects were more common after both MDMA conditions than placebo. Whether the prolonged effect translates into clinical benefit for MDMA-assisted psychotherapy remains unknown.
Translational Psychiatry
March 27, 2026
Livio Erne, Lorenz Mueller, Isabelle Straumann et al.
Bolus injections of DMT produce very strong subjective effects that peak within 2 minutes and subside completely within 12–30 minutes, consistent with a short elimination half-life of about 6–7 minutes. A ceiling effect for peak subjective effects occurred at the 15 mg dose, and no tolerance developed to the acute effects. Tolerability markedly improved when doses were escalated openly rather than given double-blind, and at equivalent doses the subjective effects were rated as less intense. These results indicate that blinding and expectancy influence the subjective experience and that individual dose-escalation may improve tolerability and guide dose selection in future DMT studies.
The International Journal of Neuropsychopharmacology
May 24, 2018
Dino Luethi, Matthias E Liechti
Rapidly measuring the in vitro pharmacological activity of new psychoactive substances can help predict their psychoactive doses and effects in humans, aiding in the appropriate legal scheduling of these substances.