Dino Luethi - The Consciousness Library

Acute dose-dependent effects of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) compared with 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin in a double-blind, placebo-controlled study in healthy participants.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 1, 2026 Denis Arikci, Joran Borgulya, Isabelle Straumann et al. 1 citation

Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin...

DOI: 10.1038/s41386-026-02428-9 Full text

Comparison of acute effects of 3,4-methylenedioxymethamphetamine (MDMA) with and without a supplemental booster dose in healthy participants: a double-blind, randomized, placebo-controlled, crossover study

Translational Psychiatry June 4, 2026 Mélusine Humbert‐droz, Anna M Becker, Jan Valenta et al.

3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AT) is being investigated as a treatment for several psychiatric disorders, particularly posttraumatic stress disorder. Phase 2 and 3 trials typically administered a first dose of MDMA followed by a second "booster" dose 1.5-2.5 h later, to extend the acute effect duration. However, the risks and benefits of the booster dose...

DOI: 10.1038/s41398-026-04148-6 Full text MDMA Ecstasy Placebo Adverse effect +6

5‐HT 2A receptor agonism by tert ‐leucinamide and valinamide synthetic cannabinoids: In vitro and in vivo evidence

British Journal of Pharmacology May 5, 2026 Giorgia Corli, Deborah Rudin, Dino Luethi et al.

Abstract Background and Purpose New synthetic cannabinoid receptor agonists (SCRAs) are associated with severe adverse effects, including unexpected psychiatric symptoms. These compounds are mainly active through their potent agonism on the cannabinoid receptors CB 1 and CB 2 . Recently, evidence of the direct interaction of some SCRAs with the serotonergic 5‐HT receptors has emerged....

DOI: 10.1111/bph.70457 Serotonergic In vivo In vitro Agonism +6

Pathway-selective signaling of serotonergic psychedelics at 5-HT receptors: Implications for psychoactivity, safety, and therapeutic potential

European Neuropsychopharmacology April 10, 2026 Deborah Rudin, Jan Valenta, Helene Rolli et al. 2 citations

Serotonergic psychedelics primarily exert their effects through activation of the serotonin (5-HT) 2A receptor (5-HT 2A R). However, the full pharmacological profiles of these substances involve multiple serotonin receptor subtypes and intracellular signaling pathways. This study characterized the signaling behavior of a panel of serotonergic psychedelics using stable cell lines and a series of...

DOI: 10.1016/j.euroneuro.2026.112835 Serotonergic Serotonin Signal transduction Phospholipase c +4

Dose-dependent pharmacokinetics and acute effects of intravenous bolus N,N-dimethyltryptamine: double-blind, randomized versus open-label dose-escalation administration study in healthy participants

Translational Psychiatry March 27, 2026 Livio Erne, Lorenz Mueller, Isabelle Straumann et al.

N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that produces short-lived peak effects when administered intravenously as a bolus dose. Initial trials suggested therapeutic effects of DMT in depressive disorders. However, systematic data on dose-dependent pharmacokinetics and acute effects of intravenous bolus DMT administration are currently lacking. We used a double-blind,...

DOI: 10.1038/s41398-026-03987-7 Full text Tolerability Pharmacokinetics Crossover study Placebo +7

Acute effects of MDMA, MDA, lysine-MDMA, and lysine-MDA in a randomized, double-blind, placebo-controlled, crossover trial in healthy participants.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2026 Isabelle Straumann, Patrick Vizeli, Isidora Avedisian et al. 5 citations

3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally, as a research tool, and in MDMA-assisted therapy in patients with posttraumatic stress disorder. 3,4-Methylenedioxyamphetamine (MDA) is a psychoactive metabolite of MDMA. Acute effects of MDMA and MDA have never been directly compared in humans. Lysine-conjugated amphetamines slowly release active amphetamine once absorbed,...

DOI: 10.1038/s41386-025-02248-3 Full text

Behavioral effects of psychedelic and non-psychedelic serotonin 2A receptor agonist drugs in pigs

Neuroscience Applied 2026 CA Madsen, M. Navarro, E. Kolesnik et al.

Background: Serotonergic psychedelics induce their psychoactive effects by stimulating the brain’s serotonin 2A receptor (5-HT2AR). In humans, a cerebral 5-HT2AR occupancy of ≥60% is required to elicit a profound psychedelic experience with psilocybin [1] and for pigs, a dose corresponding to ∼65% 5-HT2AR occupancy elicits headshakes [2]. We posit that in order to assess biochemical and...

DOI: 10.1016/j.nsa.2025.106824 Serotonin Receptor Drug Action physics +3

Receptor interaction profiles of 4-alkoxy-2,6-dimethoxyphenethylamines (Ψ derivatives) and related amphetamines

Frontiers in Pharmacology November 20, 2025 Karolina E. Kolaczynska, Daniel Trachsel, Marius C. Hoener et al. 1 citation

Background 4-substituted 2,6-dimethoxyphenethylamines and the corresponding amphetamines (so-called pseudo [Ψ] derivatives) are a hitherto mostly unexplored group of psychedelics. Still, preliminary investigations indicate that these derivatives are promising and potent psychedelics in humans. In this study, we examined the monoamine receptor and transporter interaction properties of several...

DOI: 10.3389/fphar.2025.1703480 Receptor Cricetulus Structure–activity relationship Hek 293 cells +7

The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects

Molecular Psychiatry November 5, 2025 Dino Luethi, Grant C. Glatfelter, Eline Pottie et al. 1 citation

Abstract Various ring-substituted α-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT 2A ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various...

DOI: 10.1038/s41380-025-03325-1 Full text Serotonin In vivo Potency In vitro +10

Development and Validation of a Rapid LC-MS/MS Method for Plasma Analysis of Ketamine, Norketamine, Dehydronorketamine, and Hydroxynorketamine.

Biomedical chromatography : BMC September 1, 2025 Jan Thomann, Selina Kraus, Livio Erne et al. 1 citation

Ketamine, a well-established dissociative anesthetic, has recently gained significant attention for its rapid-acting antidepressant effects, particularly in treatment-resistant depression. In this study, we developed and validated a state-of-the-art liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the bioanalysis of ketamine and its metabolites, norketamine,...

DOI: 10.1002/bmc.70171 Full text Bioanalysis Clinical study Liquid chromatography Mass spectrometry +5

Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants.

Clinical Pharmacokinetics July 14, 2025 Lorenz Mueller, Aaron Klaiber, Laura Ley et al. 4 citations

Mescaline is a classic serotonergic psychedelic with a long history of human use. The present study analyzed the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and urinary recovery of oral mescaline hydrochloride. Data from 105 single-dose administrations (100-800 mg) in 49 participants from two phase I trials were analyzed with compartmental pharmacokinetics and...

DOI: 10.1007/s40262-025-01544-x Full text Mescaline Compound Substance Pharmacokinetics +22

Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial.

JAMA Psychiatry June 1, 2025 Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid et al. 14 citations

Microdosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, LSD's efficacy in reducing ADHD symptoms remains unknown. To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo. This...

DOI: 10.1001/jamapsychiatry.2025.0044 Full text Medical research Clinical trials Psychedelics Mental health +1

Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study.

Clinical pharmacology and therapeutics May 26, 2025 Denis Arikci, Friederike Holze, Lorenz Mueller et al. 6 citations

Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders. Different LSD formulations (base or tartrate, oral or intravenous) are being used. Unclear is whether LSD base and tartrate pharmacokinetics are equivalent. Additionally, LSD's absolute oral bioavailability is unknown. Therefore, we tested the bioequivalence of...

DOI: 10.1002/cpt.3726 Full text Psychedelics Pharmacology Drug absorption Medical research +1

Liquid chromatography-tandem mass spectrometry-based pharmacokinetic and metabolic analysis of 4-bromo-2,5-dimethoxyphenethylamine and its metabolites in human plasma.

Drug metabolism and disposition: the biological fate of chemicals April 28, 2025 Jan Thomann, Deborah Rudin, Selina Kraus et al. 4 citations

4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is widely used recreationally and has recently gained interest as a treatment for mental health disorders. In this study, a liquid chromatography-tandem mass spectrometry method to quantify 2C-B and its metabolites 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) and 4-bromo-2-hydroxy-5-methoxyphenylacetic acid (B-2-HMPAA) in human plasma was developed...

DOI: 10.1016/j.dmd.2025.100086 Full text Bioanalytical chemistry Bioanalysis Method validation Pharmacokinetics +4

Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre‐Administration in a Randomized, Double‐Blind, Cross‐Over Phase I Trial

Clinical Pharmacology & Therapeutics February 28, 2025 Lorenz Mueller, Alen Jelusic, Avram Tolev et al. 15 citations

Psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), are being investigated for the treatment of depressive and anxiety disorders, for which concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) is prevalent. The present study investigated the acute response to single doses of LSD (100 μg) after daily administration of paroxetine (10 mg for 7 days,...

DOI: 10.1002/cpt.3618 Pharmacokinetics Placebo Double blind Pharmacology +5

Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants

Neuropsychopharmacology December 19, 2024 Livio Erne, Severin B Vogt, Lorenz Müller et al. 14 citations

Abstract N,N -dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We...

DOI: 10.1038/s41386-024-02041-8 Full text Psychedelic medicine DMT Research Controlled substance trials Psychopharmacology +1

Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology December 1, 2024 Isabelle Straumann, Isidora Avedisian, Aaron Klaiber et al. 20 citations

Racemic 3,4-methylenedioxymethamphetamine (MDMA) acutely increases mood, feelings of empathy, trust, and closeness to others and is investigated to assist psychotherapy. Preclinical research indicates that S-MDMA releases monoamines and oxytocin more potently than R-MDMA, whereas R-MDMA more potently stimulates serotonin 5-hydroxytryptamine-2A receptors. S-MDMA may have more stimulant...

DOI: 10.1038/s41386-024-01972-6 Full text MDMA Research Psychopharmacology Clinical trials Drug metabolism

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects.

Translational Psychiatry September 30, 2024 Aaron Klaiber, Yasmin Schmid, Anna M Becker et al. 27 citations

Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lacking. Additionally, its mechanism of action has not been investigated in humans. We used a randomized, double-blind, placebo-controlled, crossover design in 16 healthy subjects (8 women) who...

DOI: 10.1038/s41398-024-03116-2 Full text Mescaline Psychedelics Pharmacology Serotonin receptors +1

Derivatization-free determination of chiral plasma pharmacokinetics of MDMA and its enantiomers.

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

3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography-tandem mass spectrometry method for the quantification of MDMA and...

DOI: 10.1016/j.jchromb.2024.124123 Full text Bioanalysis Enantioselective Pharmacokinetics Enantiomers +2

Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology October 1, 2023 Laura Ley, Friederike Holze, Denis Arikci et al. 127 citations

Mescaline, lysergic acid diethylamide (LSD), and psilocybin are classic serotonergic psychedelics. A valid, direct comparison of the effects of these substances is lacking. The main goal of the present study was to investigate potential pharmacological, physiological and phenomenological differences at psychoactive-equivalent doses of mescaline, LSD, and psilocybin. The present study used a...

DOI: 10.1038/s41386-023-01607-2 Full text Psychedelics Hallucinogens Comparative drug research Pharmacology

Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants.

Translational Psychiatry May 23, 2023 Severin B Vogt, Laura Ley, Livio Erne et al. 85 citations

N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test...

DOI: 10.1038/s41398-023-02477-4 Full text Psychedelic medicine DMT Research Clinical trials Intravenous drug administration +1

Editorial: Old and new psychoactive substances: Pharmacology and potential applications

Frontiers in Psychiatry January 4, 2023 Felix P. Mayer, Dino Luethi, Lorena B. Areal et al. 1 citation

The consumption of psychoactive substances is inextricably linked with human history. Longstanding evidence supports the consumption of psychoactive substances that are found in plants and fungi (e.g. cathinone and muscimol, which are present in Catha edulis and Amanita muscaria, respectively) and alcoholic beverages. With the advent of more refined chemical approaches, isolated (e.g. cocaine)...

DOI: 10.3389/fpsyt.2022.1087005 Psychopharmacology

Liquid chromatography-tandem mass spectrometry method for the bioanalysis of N,N-dimethyltryptamine (DMT) and its metabolites DMT-N-oxide and indole-3-acetic acid in human plasma.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences December 15, 2022 Dino Luethi, Karolina E. Kolaczynska, Severin B Vogt et al. 24 citations

The indole alkaloid N,N-dimethyltryptamine (DMT) induces psychedelic effects in humans. In addition to ceremonial and recreational use, DMT is subject to clinical investigations. Sensitive bioanalytical methods are required to assess the pharmacokinetics of DMT and its metabolites in human plasma. Here, a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the...

DOI: 10.1016/j.jchromb.2022.123534 Full text Ayahuasca DMT Hplc Pharmacokinetics +6

Use of the head-twitch response to investigate the structure–activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines

Psychopharmacology December 7, 2022 Adam L. Halberstadt, Dino Luethi, Marius C. Hoener et al. 7 citations

Abstract Rationale 4-Thio-substituted phenylalkylamines such as 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4- n -propylthiophenethylamine (2C-T-7) produce psychedelic effects in humans and have been distributed as recreational drugs. Objectives The present studies were conducted to examine the structure–activity relationships (SAR) of a series of 4-thio-substituted...

DOI: 10.1007/s00213-022-06279-2 Full text Thio- Head geology Pharmacology Stereochemistry

Structure‐activity Relation of Halogenated 2,5‐Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues

The FASEB Journal May 1, 2022 Deborah Rudin, Dino Luethi, Marius C. Hoener et al.

Objective and hypothesis 4‐Substituted derivatives of 2,5‐dimethoxyamphetamine (referred to as DOX derivatives) exhibit psychedelic and euphoria‐inducing effects, mainly mediated by 5‐HT 2A receptor activation; for this reason, they are used recreationally but also bear therapeutic potential. Studies in humans and animals revealed that 4‐substitution with halogens results in high clinical...

DOI: 10.1096/fasebj.2022.36.s1.r2121 Desmethyl Relation database Biochemistry Data mining

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