JAMA psychiatry
June 1, 2025
Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid et al.
14 citations
Repeated low doses of LSD (20 μg twice weekly for six weeks) did not reduce ADHD symptoms more than placebo in adults with moderate-to-severe ADHD. In a double-blind randomized trial with 53 participants, the LSD group showed an average 7.1-point improvement on the ADHD symptom scale, while the placebo group improved by 8.9 points—a difference that was not statistically significant. The treatment was physically safe and psychologically well tolerated. The findings suggest that microdosing LSD, despite popular interest, offers no advantage over placebo for ADHD symptom relief.
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.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
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.
British journal of clinical pharmacology
January 1, 2024
Friederike Holze, Livio Erne, Urs Duthaler et al.
12 citations
After oral doses of 85 and 170 μg, LSD reaches peak blood concentrations of 1.8 and 3.4 ng/mL at about 1.7 hours, with elimination half-lives of 3.7 and 4.0 hours. Only 1% of the dose is excreted unchanged in urine within 24 hours, while 16% is eliminated as the metabolite 2-oxo-3-hydroxy-LSD. Subjective drug effects last 9.3 to 11 hours, with maximal intensity reaching 77% to 87%. LSD shows dose-proportional pharmacokinetics and first-order elimination, and its effects are dose-dependent. The findings confirm earlier work on LSD's metabolism and time course.
European journal of endocrinology
March 27, 2025
Cihan Atila, Andi Nikaj, Svenja Leibnitz et al.
9 citations
Neurophysin I (NP-I), a stable byproduct of the oxytocin precursor, can serve as a reliable biomarker for oxytocin secretion when stimulated by MDMA. In a double-blind, placebo-controlled crossover study, 15 patients with hypothalamic-posterior-pituitary dysfunction and 15 matched healthy controls received a single 100 mg dose of MDMA or placebo. In healthy controls, MDMA caused an 8-fold increase in oxytocin (peak: 624 pM) and a 20-fold increase in NP-I (peak: 1508 pM). Patients showed no notable oxytocin increase (peak: 92 pM) and only a mild NP-I rise (peak: 263 pM). The difference in NP-I area under the curve between groups was significant (2340 pM·5 h; 95% CI, 1462-3218). NP-I measurement offers a way to assess oxytocin secretion, aiding research into conditions like autism, anxiety, and depression.
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.
British journal of clinical pharmacology
November 25, 2024
Aaron Klaiber, Mélusine Humbert-Droz, Laura Ley et al.
6 citations
Mescaline doses up to 800 mg appear safe in controlled clinical settings for healthy individuals. In two double-blind, placebo-controlled studies with 48 participants and 96 administrations, positive subjective effects increased with dose and consistently outweighed negative effects. Autonomic effects rose moderately: systolic blood pressure exceeded 180 mmHg in 6% of administrations, heart rate above 100 beats/min occurred in 3%, and body temperature above 38 °C in 5%. Nausea limited higher doses. Kidney and liver function and blood cell counts remained normal. Flashbacks followed 2% of administrations. Adverse effects totaled 51 at 100 mg and 180 at 800 mg.
Drug testing and analysis
September 1, 2024
Verena Angerer, Yasmin Schmid, Florian Franz et al.
6 citations
In six healthy volunteers, the new psychoactive substance MDAI at 3.0 mg/kg produced subjective effects comparable to 125 mg of MDMA, including increased blood pressure, but did not raise heart rate or body temperature. MDAI increased cortisol and prolactin levels, appeared in serum about 20 minutes after ingestion, and remained detectable for at least 4 days in serum and 6 days in urine. The drug was well tolerated. Further research is needed to evaluate whether MDAI might have medicinal applications.
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.
Journal of psychopharmacology (Oxford, England)
December 26, 2025
Kurt Stocker, Matthias Hartmann, Yasmin Schmid et al.
5 citations
A psychometric revalidation of the Altered States of Consciousness Scale (ASC) using data from 901 questionnaires across 16 psychedelic studies (with LSD, psilocybin, mescaline, and DMT) shows that ten of the eleven subscales can be grouped into three higher-order dimensions—Positive Effects, Distressing Effects, and Perceptual Effects—mirroring the original three-dimensional model but with improved statistical fit. The Anxiety subscale could not be integrated due to floor effects (low anxiety in the sample) but is retained for clinical relevance. The revised scale, 3D-ASCr, is recommended for use with classic serotonergic psychedelics.
Clinical pharmacokinetics
July 14, 2025
Lorenz Mueller, Aaron Klaiber, Laura Ley et al.
4 citations
Mescaline, a classic psychedelic, shows dose-proportional increases in blood concentration and effects after oral administration. Peak levels occur within about 2 hours, with a half-life of 3.5 hours. Effects begin around 1 hour after dosing, with intensity and duration increasing from 13% and 2.8 hours at 100 mg to 89% and 15 hours at 800 mg. About 53% of the dose is excreted unchanged in urine, and 31% as a main metabolite. Oral bioavailability is at least 53%, limited by first-pass metabolism, with renal elimination as the primary clearance route.
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.
Psychopharmacology
March 26, 2025
Laura Ley, Matthias E Liechti, Anna M Becker et al.
3 citations
Healthy volunteers enroll in psychedelic trials primarily out of interest in the substances and the appeal of the study setting, hoping for personal development and transformative experiences. In a series of six double-blind, placebo-controlled trials involving 151 participants, positive experiences were promoted by music, access to nature, and a trusting relationship with the investigator. A sterile hospital environment, lack of investigator support, and investigator-induced discomfort were criticized. Most volunteers felt their expectations were exceeded and would take the substances again, ideally in a natural setting with friends. Four key factors for positive study experiences are a secure interpersonal relationship, an aesthetically pleasing environment, access to nature, and music.
Endocrine connections
June 1, 2025
Cihan Atila, Sara-Jessica Camerin, Matthias E Liechti et al.
2 citations
A single oral dose of MDMA (100 mg) strongly activates the hypothalamic-pituitary-adrenal (HPA) axis in healthy adults. Plasma ACTH increased from 12 ng/L to 38 ng/L and cortisol from 347 nmol/L to 566 nmol/L within 120 minutes. Prolactin showed a mild, non-significant change. MDMA did not affect other anterior pituitary hormones (TSH, LH, GH) or their peripheral hormones (fT4, testosterone, estradiol). The findings suggest MDMA may serve as a novel stimulation test for simultaneously assessing the HPA axis and oxytocin systems, but further validation in larger populations is needed.
Frontiers in psychiatry
January 1, 2025
Peter Gasser, Matthias E Liechti, Friederike Holze
2 citations
A 64-year-old man with traumatic life experiences and neuropathic pain from chemotherapy was treated with LSD and MDMA. Initial 200 µg LSD doses produced no acute effects, but 400 µg doses led to subjective effects and lasting therapeutic benefits. Switching to MDMA—both high doses (150-175 mg) and repeated low doses (12.5-25 mg)—resulted in marked improvements in neuropathic pain that persisted after treatment stopped. MDMA mini/microdosing has not been widely studied; this case documents benefits of low-dose MDMA for pain disorders, though further research is needed.
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.
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.
International review of neurobiology
January 1, 2025
Severin B Vogt, Matthias E Liechti
1 citation
Serotonergic psychedelics such as psilocybin, LSD, mescaline, DMT, and 5-MeO-DMT produce comparable acute subjective and somatic effects primarily through interactions with 5-HT2A receptors, but their exact therapeutic mechanisms remain unclear. These classic psychedelics differ substantially in pharmacokinetics and metabolism, leading to different durations of action that may influence their suitability for specific therapeutic uses. MDMA has a distinct psychopharmacological profile with stimulant-like and empathogenic effects. Acute effects of psychedelics mirror their plasma-concentration-time curves, whereas MDMA's acute effects are shorter-lasting than its presence in the body, and MDMA exhibits marked acute pharmacological tolerance.
International journal of methods in psychiatric research
June 1, 2026
Kurt Stocker, Matthias Hartmann, Frederick S Barrett et al.
The eight-factor structure of the Psychedelic Experience Scale (PES48), which includes the Mystical Experience Questionnaire (MEQ30) and additional factors for paradoxicality, connectedness, visual experience, and distressing experience, is valid for use in English. Analysis of 280 measurements from 145 healthy participants in four placebo-controlled psilocybin studies found that six subscales have high internal consistency, one good, and one acceptable. Both the MEQ30 and MEQ40 models show acceptable to good model fits, with better fits in English than in German. All six MEQ40 scale means were higher in English data, suggesting that the PES48 provides a broader conceptualization of mystical and non-mystical psychedelic experiences, and that setting may influence mystical experience.
BMJ open
May 11, 2026
Julia Colcott, Alexandre A Guerin, Olivia Carter et al.
A new tool, the MDMA-Assisted Psychotherapy Side Effects Tool (M-SET), was developed to systematically capture side effects during MDMA-assisted psychotherapy. Experts in MDMA-AP and neuropsychopharmacology participated in a two-round online Delphi process to refine a list of 165 items across four questionnaires covering screening, baseline, medication session days, and follow-up. The tool aims to improve safety monitoring and build a more robust evidence base on the tolerability of MDMA-AP for research and clinical use.
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.