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Urs Duthaler

20 papers in the library · 1,540 citations · publishing 2019-2024

Papers

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Ketanserin exhibits dose- and concentration-proportional serotonin 2A receptor occupancy in healthy individuals: Relevance for psychedelic research

European Neuropsychopharmacology August 9, 2024 Friederike Holze, M. Madsen, Claus Svarer et al. 16 citations

The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants...

Inter-individual variability in neural response to low doses of LSD.

Translational Psychiatry July 15, 2024 Nadia R. P. W. Hutten, Conny W E M Quaedflieg, Natasha L. Mason et al. 16 citations

The repeated use of small doses of psychedelics (also referred to as "microdosing") to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on...

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...

In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin

Frontiers in Pharmacology April 29, 2024 Jan Thomann, Oliver V Stoeckmann, Deborah Rudin et al. 52 citations

In vivo , psilocybin is rapidly dephosphorylated to psilocin which induces psychedelic effects by interacting with the 5-HT 2A receptor. Psilocin primarily undergoes glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). Herein, we investigated psilocybin’s metabolic pathways in vitro and in vivo , conducting a thorough analysis of the enzymes involved. Metabolism studies were...

Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide administration in healthy participants.

British Journal of Clinical Pharmacology 2024 Friederike Holze, Livio Erne, Urs Duthaler et al. 12 citations

Lysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic-pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing. The present study characterized the pharmacokinetics,...

Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology December 1, 2023 Isabelle Straumann, Laura Ley, Friederike Holze et al. 41 citations

There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly positive, negative subjective effects, including anxiety, may occur. The induction of overall positive acute subjective effects is desired in psychedelic-assisted therapy because positive acute experiences are associated with greater...

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...

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...

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...

Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants

Clinical Pharmacology & Therapeutics December 12, 2022 Friederike Holze, Urs Duthaler, Anna M Becker et al. 116 citations

Psilocybin is being investigated as a potential treatment for psychiatric and neurological disorders. Only a few studies have evaluated the pharmacokinetics (PKs) of psilocybin and have used body weight‐adjusted dosing. Data on PKs and the PK‐pharmacodynamic (PD) relationship of fixed doses that are commonly used are unavailable. The present study characterized the PKs and PK‐PD relationship of...

Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants

The International Journal of Neuropsychopharmacology November 4, 2022 Aaron Klaiber, Friederike Holze, Ioanna Istampoulouoglou et al. 100 citations

Abstract Background Lysergic acid diethylamide (LSD) is currently being investigated in psychedelic-assisted therapy. LSD has a long duration of acute action of 8–11 hours. It produces its acute psychedelic effects via stimulation of the serotonin 5-hydroxytryptamine-2A (HT2A) receptor. Administration of the 5-HT2A antagonist ketanserin before LSD almost fully blocks the acute subjective...

Development and validation of an LC-MS/MS method for the quantification of mescaline and major metabolites in human plasma

Journal of Pharmaceutical and Biomedical Analysis August 1, 2022 Jan Thomann, Laura Ley, Aaron Klaiber et al. 23 citations

Mescaline is a psychedelic phenethylamine found in different species of cacti. Currently, mescaline's acute subjective effects and pharmacokinetics are investigated in several modern clinical studies. Therefore, we developed a bioanalytical method for the rapid quantification of mescaline and its metabolites in human plasma. Mescaline and its metabolites 3,4,5-trimethoxyphenylacetic acid...

Effects of 3,4-Methylenedioxymethamphetamine on Conditioned Fear Extinction and Retention in a Crossover Study in Healthy Subjects

Frontiers in Pharmacology July 13, 2022 Patrick Vizeli, Isabelle Straumann, Urs Duthaler et al. 43 citations

Background: 3,4-Methylenedioxymethamphetamine (MDMA) has shown initial promise as an adjunct in psychotherapy to treat posttraumatic stress disorder (PTSD). Its efficacy and safety have been demonstrated across phase I–III studies. However, the mechanism underlying the potential utility of MDMA to treat PTSD in humans has not yet been thoroughly investigated. Preliminary evidence suggests that...

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects

Neuropsychopharmacology February 25, 2022 Friederike Holze, Laura Ley, Felix Müller et al. 223 citations

Abstract Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women,...

Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects

Clinical Pharmacology & Therapeutics November 7, 2021 Anna M Becker, Friederike Holze, Tanja Grandinetti et al. 177 citations

The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double‐blind, placebo‐controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo....

Development and validation of an LC-MS/MS method for the bioanalysis of psilocybin’s main metabolites, psilocin and 4-hydroxyindole-3-acetic acid, in human plasma

Journal of Chromatography B December 7, 2020 Karolina E. Kolaczynska, Matthias E. Liechti, Urs Duthaler 55 citations

Psilocin is the active metabolite of psilocybin, a serotonergic psychedelic substance. It is used recreationally and investigated in substance-assisted psychotherapy. The pharmacokinetic properties of psilocin are only partially characterized. Therefore, we developed and validated a rapid LC-MS/MS method to quantify psilocin and its metabolite 4-hydroxyindole-3-acetic acid (4-HIAA) in human...

Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects

Neuropsychopharmacology October 15, 2020 Friederike Holze, Patrick Vizeli, Laura Ley et al. 243 citations

Abstract Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25...

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Clinical Pharmacology & Therapeutics September 25, 2020 Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten et al. 63 citations

“Microdoses” of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic‐pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double‐blind, randomized, placebo‐controlled...

Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use.

Biochemical Pharmacology June 1, 2019 Dino Luethi, Marius C. Hoener, Stephan Krähenbühl et al. 46 citations

In recent years, experimental research on lysergic acid diethylamide (LSD) in humans has gained new momentum. In humans, LSD is metabolized rapidly into several metabolites but knowledge of the involved metabolizing enzymes is limited. The aim of the current study was to identify the cytochrome P450 (CYP) isoforms involved in the metabolism of LSD to 6-norlysergic acid diethylamide (nor-LSD)...

Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects

British Journal of Clinical Pharmacology March 19, 2019 Friederike Holze, Urs Duthaler, Patrick Vizeli et al. 72 citations

Aims The aim of the present study was to characterize the pharmacokinetics and exposure–subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients. Method LSD (100 μg) was administered in 27 healthy subjects using a placebo‐controlled, double‐blind, cross‐over design. Plasma levels of LSD, nor‐LSD,...