Translational psychiatry
May 23, 2023
Severin B Vogt, Laura Ley, Livio Erne et al.
85 citations
Intravenous DMT can produce a psychedelic state that is short-lasting and controllable. A double-blind, placebo-controlled crossover trial with 27 healthy participants tested five DMT regimens: low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus plus low infusion (15 mg + 0.6 mg/min), and high bolus plus high infusion (25 mg + 1 mg/min). Bolus doses induced very intense effects within 2 minutes, with more negative feelings and anxiety than infusions. Infusions produced slowly increasing, dose-dependent effects that plateaued after 30 minutes. All effects subsided within 15 minutes of stopping the infusion. Acute tolerance developed, with stable subjective effects from 30 to 90 minutes despite rising plasma concentrations. Intravenous DMT infusion is a promising tool for tailored psychedelic therapy.
Frontiers in Pharmacology
April 29, 2024
Jan Thomann, Oliver V Stoeckmann, Deborah Rudin et al.
52 citations
Psilocybin is rapidly converted to psilocin in the body, which causes psychedelic effects by binding to the 5-HT2A receptor. Psilocin is mainly broken down by glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). In laboratory experiments with human liver microsomes, about 29% of psilocin was metabolized, while specific enzymes CYP2D6 and CYP3A4 metabolized nearly 100% and 40%, respectively. Monoamine oxidase A produced small amounts of 4-HIAA and 4-hydroxytryptophol (4-HTP), but 4-HTP appeared only in lab tests and neither metabolite showed activity at serotonin receptors. Two new potential metabolites were found: norpsilocin in mice and an oxidized form in humans, though CYP2D6 genotype did not affect psilocin levels in people. These findings help understand drug interactions and psilocybin's therapeutic use.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2024
Isabelle Straumann, Isidora Avedisian, Aaron Klaiber et al.
20 citations
The two mirror-image forms of MDMA, S-MDMA and R-MDMA, produce different acute effects in humans. S-MDMA (125 mg) caused stronger feelings of stimulation, happiness, and openness, and larger increases in blood pressure than R-MDMA (125 or 250 mg) or racemic MDMA (125 mg). R-MDMA did not produce more psychedelic-like effects than S-MDMA. S-MDMA also increased plasma prolactin, cortisol, and oxytocin more than the other forms. The body eliminated S-MDMA faster (half-life 4.1 hours) than R-MDMA (half-life 12-14 hours). The findings suggest that S-MDMA's stronger stimulant effects are due to its higher potency rather than a qualitative difference, and that equivalent effects may occur at doses of 100 mg S-MDMA, 125 mg racemic MDMA, and 300 mg R-MDMA.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2022
Deborah Rudin, John D McCorvy, Grant C Glatfelter et al.
18 citations
Derivatives of (2-aminopropyl)indole and (2-aminopropyl)benzofuran are new psychoactive substances with stimulant effects. This study characterized six isomers of the sulfur-based analog (2-aminopropyl)benzo[β]thiophene (APBT) in vitro and three isomers in vivo. APBTs inhibited monoamine reuptake and induced transporter-mediated substrate release, similar to MDMA, but did not stimulate locomotion in mice. Instead, they acted as full agonists at 5-HT2 receptor subtypes and induced head-twitch responses, indicating psychedelic-like activity. Replacing oxygen with sulfur enhanced serotonin transporter release potency and 5-HT2 receptor activity, shifting the profile toward psychedelic and entactogenic effects with minimal psychomotor stimulation, suggesting potential for drug-assisted psychotherapy.
Neuropsychopharmacology
December 19, 2024
Livio Erne, Severin B Vogt, Lorenz Müller et al.
14 citations
Continuous intravenous infusions of DMT produce dose-dependent subjective effects that plateau after 30 minutes, with a ceiling effect for good drug effect at 1.8 mg/min. The highest dose tested (2.4 mg/min) caused greater anxious ego dissolution and significant anxiety compared to placebo. DMT showed dose-proportional pharmacokinetics and moderate acute tolerance. When participants could self-titrate their dose, they chose moderate to strong psychedelic effects comparable to the 1.8 mg/min rate. These findings can guide dose selection in future DMT research and show that subjective effects can be rapidly adjusted through dose titration.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 17, 2024
Hugo R. Arias, L. Micheli, Deborah Rudin et al.
14 citations
New non-hallucinogenic iboga alkaloid derivatives, called ibogalogs (TBG, IBG, and DM506), reduce pain hypersensitivity in mouse models of neuropathic and visceral pain. IBG provided the longest pain relief at a lower dose, while DM506 acted fastest. The pain-relieving effect was blocked by the 5-HT2A receptor antagonist ketanserin, indicating that activation of the 5-HT2A receptor, not its inhibition, mediates this activity. Ibogalogs activate 5-HT2A and 5-HT6 receptors and act as inverse agonists (except TBG) at the 5-HT7 receptor. Based on prior work, 5-HT6 inhibition and 5-HT7 activation relieve pain, so these receptors are not involved. The anti-hypersensitivity activity of ibogalogs in mice is mediated by 5-HT2A receptor activation.
European journal of pharmacology
March 5, 2024
Hugo R Arias, Deborah Rudin, Dustin J Hines et al.
12 citations
A non-hallucinogenic compound derived from ibogamine, DM506, produces anxiolytic- and sedative-like effects in mice without causing hallucinogenic head-twitch responses. At 15 mg/kg, DM506 induces both acute and long-lasting anxiety-reducing behavior in naive and stressed mice. Repeated 5 mg/kg doses show no cumulative effects or side effects. Higher doses (40 mg/kg) cause sedation that is blocked by the 5-HT2A receptor antagonist volinanserin. DM506 binds to human 5-HT2A (Ki = 24 nM) and 5-HT2B (Ki = 16 nM) receptors, activating them with EC50 values of 9 nM and 3 nM, respectively, acting as a partial agonist compared to the full agonist DOI. Electroencephalography shows increased transition from alert to deep-sleep brain wave activity.
Frontiers in psychiatry
January 1, 2023
Deborah Rudin, Alexander Areesanan, Matthias E Liechti et al.
9 citations
Classic psychedelics LSD, psilocin, DMT, and mescaline do not directly alter the proliferation or cytokine release of primary human T lymphocytes, nor do they stimulate NF-κB induction in monocytes. These findings indicate no relevant direct immune-modulatory effects of these substances on the tested human immune cells in vitro. The results support the safety of using classic psychedelics in assisted psychotherapy for patients with life-threatening conditions where immune suppression would be harmful.
Clinical pharmacology and therapeutics
May 26, 2025
Denis Arikci, Friederike Holze, Lorenz Mueller et al.
6 citations
LSD base and tartrate formulations taken orally are bioequivalent, meaning they produce the same drug levels in the body. The absolute oral bioavailability of LSD is 80%, and all tested oral forms—ethanolic base solution, watery tartrate solution, and rapid-dissolving tablet—show similar pharmacokinetics. Intravenous LSD causes stronger subjective effects like ego dissolution and anxiety compared to oral forms. These findings support interchangeable oral dosing in research and clinical use.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
May 1, 2024
Dino Luethi, Deborah Rudin, Isabelle Straumann et al.
6 citations
Two bioanalytical methods—achiral and enantioselective—were developed and validated to measure MDMA and its metabolite MDA in human plasma. Both methods met regulatory guidelines for accuracy, precision, selectivity, and sensitivity over calibration ranges of 0.5–500 ng/mL (achiral) and 0.5–1,000 ng/mL (chiral). The enantioselective method reliably quantified individual enantiomers in racemic samples, and racemic calibrations accurately measured single-enantiomer samples. Pharmacokinetic parameters from clinical participants treated with racemic MDMA or a single enantiomer were comparable between methods. Because MDMA and MDA do not undergo chiral inversion, enantioselective separation is unnecessary when only one enantiomer is administered.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
January 1, 2026
Isabelle Straumann, Patrick Vizeli, Isidora Avedisian et al.
5 citations
In a double-blind, placebo-controlled crossover trial with 23 healthy adults, the acute effects of MDMA, its metabolite MDA, and two lysine-conjugated prodrugs were compared. MDA produced stronger and longer-lasting subjective drug effects (6.1 vs. 4.1 hours), greater stimulant effects, more negative effects, fear, and visual alterations than MDMA at equimolar doses. The lysine-conjugated prodrug of MDA (Lys-MDA) delayed the onset and peak of effects but otherwise acted similarly to MDA. Lys-MDMA did not release MDMA into the blood and produced no effects, indicating it is not a functional prodrug. The findings suggest MDA has a less favorable therapeutic profile than MDMA, and lysine conjugation can modulate the timing but not necessarily improve tolerability of effects.
Drug metabolism and disposition: the biological fate of chemicals
April 28, 2025
Jan Thomann, Deborah Rudin, Selina Kraus et al.
4 citations
A liquid chromatography-tandem mass spectrometry method was developed and validated to measure the recreational psychedelic 2C-B and two of its metabolites (BDMPAA and B-2-HMPAA) in human plasma. The method achieved linear ranges of 0.5–100 ng/mL for 2C-B, 2.5–1000 ng/mL for BDMPAA, and 0.5–1000 ng/mL for B-2-HMPAA with high accuracy and precision. Pharmacokinetic analysis used samples from clinical participants who received 30 mg of 2C-B. Key metabolic enzymes included MAO-A, MAO-B, cytosolic enzymes, and CYP2D6. Unlike 2C-B, the metabolites did not activate the serotonin 2A receptor, indicating they do not contribute to the psychedelic effect. The method provides a reliable tool for future clinical studies.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
July 1, 2026
Denis Arikci, Joran Borgulya, Isabelle Straumann et al.
1 citation
In a double-blind, randomized, placebo-controlled crossover trial, 24 healthy adults received three doses of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin. The 30 mg dose of 2C-B produced subjective effects comparable to MDMA but weaker than psilocybin, and increased emotional empathy similarly to MDMA. Only psilocybin caused bad drug effects and anxiety. MDMA produced the greatest cardiovascular stimulation, followed by psilocybin and then 2C-B. Only MDMA raised plasma oxytocin and neurophysin I. The average subjective effect duration of 30 mg 2C-B was 4.9 hours, similar to MDMA (4.8 h) and shorter than psilocybin (6.1 h). 2C-B had a plasma elimination half-life of about 1.3 hours.
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.
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.