Neuropsychopharmacology
February 25, 2022
Friederike Holze, Laura Ley, Felix Müller et al.
223 citations
In healthy volunteers, 100 and 200 micrograms of LSD and 30 milligrams of psilocybin produce comparable subjective effects, including alterations of mind that are qualitatively and quantitatively very similar. The 15 milligram psilocybin dose produces clearly weaker subjective effects. The 200 microgram dose of LSD induces higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 microgram dose. LSD at both doses has clearly longer effect durations than psilocybin. Psilocybin increases blood pressure more than LSD, whereas LSD increases heart rate more than psilocybin, though both show comparable overall cardiostimulant properties. Any differences between LSD and psilocybin appear dose-dependent rather than substance-dependent, except for the differential effects on heart rate and blood pressure.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2023
Laura Ley, Friederike Holze, Denis Arikci et al.
127 citations
At equally strong doses, the classic psychedelics mescaline, LSD, and psilocybin produce comparable subjective experiences, with no evidence of qualitative differences in altered states of consciousness. Autonomic effects were moderate; psilocybin increased diastolic blood pressure more than LSD, while LSD showed a trend toward higher heart rate than psilocybin. Mescaline had the longest effect duration (mean 11.1 hours), followed by LSD (8.2 hours) and psilocybin (4.9 hours). Mescaline and LSD, but not psilocybin, raised circulating oxytocin. None altered brain-derived neurotrophic factor. Tolerability was similar, though mescaline caused slightly more subacute adverse effects 12–24 hours later.
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
July 13, 2022
Patrick Vizeli, Isabelle Straumann, Urs Duthaler et al.
43 citations
A single 125 mg dose of MDMA, given to 30 healthy men after fear conditioning and two hours before extinction learning, reduced skin conductance responses to a conditioned fear cue during both extinction learning and its recall the next day, compared with placebo. The drug did not affect fear-potentiated startle responses. Subjective feelings of trust and openness during extinction learning were linked to poorer discrimination between danger and safety cues during recall. MDMA raised oxytocin levels fourfold, but this increase did not correlate with fear extinction outcomes. The findings suggest MDMA can accelerate fear extinction learning and retention, at least for some physiological measures of fear, which may help explain its therapeutic benefit in PTSD.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2023
Isabelle Straumann, Laura Ley, Friederike Holze et al.
41 citations
Co-administering MDMA (100 mg) with LSD (100 µg) does not improve the quality of the acute subjective effects compared with LSD alone in healthy adults. The combination prolongs the duration of subjective effects and increases blood pressure, heart rate, and pupil size more than LSD alone. Oxytocin levels rise more with MDMA alone or the combination than with LSD alone. The findings suggest that combining MDMA with LSD offers no relevant benefits over LSD alone for psychedelic-assisted therapy.
Translational psychiatry
September 30, 2024
Aaron Klaiber, Yasmin Schmid, Anna M Becker et al.
27 citations
Mescaline produces dose-dependent subjective and physiological effects in healthy people, with doses above 100 mg increasing blood pressure and heart rate. Subjective effects lasted from 6.4 hours at 100 mg to 14 hours at 800 mg, and the drug reached peak concentration in blood after about 2 hours with a half-life of 3.5 hours. Nausea and vomiting were common at the highest dose. Blocking serotonin 5-HT2A receptors with ketanserin reduced the effects of 800 mg mescaline to levels similar to lower doses, indicating that mescaline's acute effects are primarily mediated by these receptors.
Neuroscience Applied
January 1, 2024
Isabelle Straumann, Friederike Holze, Laura Ley et al.
24 citations
A pooled analysis of three randomized crossover studies with 85 healthy participants and 113 single-dose administrations of psilocybin (15, 20, 25, and 30 mg) examined safety. The 20, 25, and 30 mg doses produced stronger subjective effects than 15 mg, and all doses induced higher 'good drug effects' than 'bad drug effects.' Only 25 and 30 mg increased anxiety. Autonomic effects were moderate: tachycardia occurred with 7% of administrations, and body temperature above 38°C rose with dose, reaching 32% at 30 mg. Kidney and liver function remained unchanged. Five participants (6%) reported transient flashbacks, and no serious adverse reactions occurred. The findings indicate that a single psilocybin dose is safe regarding acute psychological and physical harm in healthy participants under controlled conditions.
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.
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelušić, Avram Tolev et al.
15 citations
In a double-blind, placebo-controlled crossover study with 23 healthy participants, daily paroxetine (an SSRI antidepressant) did not reduce the pleasant subjective effects of a single 100 μg dose of LSD, but it significantly lessened negative effects such as 'bad drug effect,' anxiety, and nausea. Paroxetine increased LSD's peak concentration and total exposure by 40% and 50%, respectively, by inhibiting the CYP2D6 enzyme, indicating this enzyme is involved in LSD metabolism. The interaction was strongest in normal CYP2D6 metabolizers and weakest in poor metabolizers. The findings suggest LSD can be safely added to SSRI treatment without dose adjustment when the SSRI inhibits CYP2D6, but no definitive recommendation can be made for other SSRIs.
JAMA network open
November 4, 2024
Cihan Atila, Isabelle Straumann, Patrick Vizeli et al.
15 citations
A single dose of MDMA (ecstasy) caused acute hyponatremia (low blood sodium) in 31% of 96 healthy participants across four placebo-controlled trials. Hyponatremia occurred in 37% of those with unrestricted fluid intake but in none of the 15 participants whose fluid intake was restricted, suggesting fluid restriction may prevent this complication. The drop in sodium levels correlated with a sharp rise in oxytocin (433% increase) but not with copeptin, a marker of vasopressin. This challenges the long-held belief that MDMA-induced hyponatremia is caused by vasopressin release and instead points to oxytocin mimicking vasopressin's water-retaining effect in the kidneys due to structural similarity.
Translational psychiatry
September 4, 2024
Patrick Vizeli, Erich Studerus, Friederike Holze et al.
15 citations
LSD dose is the strongest predictor of the drug's subjective and autonomic effects, but non-pharmacological factors also play a significant role. Pre-drug mood states—such as well-being, emotional excitability, and anxiety—predict subjective effects, heart rate, and body temperature. The personality trait openness to experiences correlates with stronger mystical-type effects and oceanic boundlessness. Prior hallucinogen use is linked to less anxious ego dissolution and a less intense overall altered state. Acute anxiety relates negatively to the functionality of the Cytochrome 2D6 enzyme. Sex and body weight do not significantly influence the drug experience.
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.
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.
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.
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.
Religion Brain & Behavior
March 31, 2026
Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.
After administration of LSD, psilocybin, mescaline, or DMT, mystical oneness—the core of mystical experience—showed dose-sensitive strong correlations with luminous light and renewal, and a moderate-to-strong correlation with ego disintegration. These findings from 386 healthy participants across 15 studies support a broader, dynamic model of mystical experience, where mystical oneness unfolds with ego disintegration, renewal, and luminous light. The results offer insights for psychedelic-assisted therapy.
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.