The International Journal of Neuropsychopharmacology
November 22, 2017
André Schmidt, Felix Müller, Patrick C. Dolder et al.
25 citations
Modafinil, but not methylphenidate or MDMA, increased brain activity in a limbic-cortical-striatal-pallidal-thalamic circuit and the amygdala when healthy subjects viewed fearful faces. Activation in frontal brain regions correlated with increased feelings of fearfulness and depressiveness after modafinil. Despite modafinil's cognitive enhancement effects, potential adverse effects on emotion processing should be considered.
Journal of Proteome Research
June 27, 2018
Martina I. Boxler, Gabriel L. Streun, Matthias E. Liechti et al.
23 citations
A single 125 mg dose of MDMA alters dozens of endogenous metabolites in human plasma, including increases in cortisol, pregnenolone sulfate, and several inflammation mediators, alongside a decrease in calcitriol. These changes suggest heightened stress and serotonergic activity, activation of inflammatory pathways, and potential reduction in neuroprotective factors for brain dopamine neurons.
Die Psychotherapie
February 15, 2024
Helena Aicher, Yasmin Schmid, Peter Gasser
20 citations
Since the late 1990s, psychedelics have experienced a renaissance, attracting increasing international attention. Scientific studies increasingly examine the possibilities and risks of psychedelic-assisted therapy (PAT). Since 2014, based on exceptional permits from the Swiss health authority (BAG), LSD, MDMA, and psilocybin have been used therapeutically within limited medical applications on a case-by-case basis. Over the past nine years, more than 1000 exceptional permits have been granted to about 60 therapists, and an estimated 2000 to 3000 treatments with psychedelics have been conducted.
PLoS ONE
June 15, 2016
Andrea E Steuer, Corina Schmidhauser, Eva H Tingelhoff et al.
18 citations
Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
Journal of Proteome Research
July 19, 2017
Martina I. Boxler, Matthias E. Liechti, Yasmin Schmid et al.
17 citations
A single dose of MDMA (ecstasy) alters the plasma metabolome in healthy adults. In a double-blind, placebo-controlled crossover trial with 15 participants, nine metabolites showed significant concentration changes after MDMA compared with placebo. The main changes involved glycerophospholipids, which may indicate increased energy production, and the ratio of methionine-sulfoxide to methionine, a potential marker of oxidative stress. Baseline samples were essential to avoid overestimating effects due to high interday variability among individuals.
Neuroscience Applied
January 1, 2025
Matthias E. Liechti, Peter Gasser, Helena Aicher et al.
16 citations
Switzerland's limited access program for psychedelic/MDMA-assisted therapy, started in 2014 with two physicians, had grown to about 100 physicians by 2024, treating 723 patients (245 with MDMA, 130 with LSD, 348 with psilocybin). Approximately 1660 treatments occurred in 2024, with patients typically receiving 2-4 sessions within 12 months. The program is authorized by the Swiss Federal Office of Public Health for patients with mostly incurable diseases where the substance can alleviate suffering and no alternatives exist or have failed. The article describes the program's history, legal requirements, costs, professional roles, education, patient characteristics, outcomes, and adverse effects, comparing it to similar programs in Canada and Australia.
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.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
February 9, 2024
Yasmin Schmid, Anya K. Bershad
15 citations
MDMA and serotonergic psychedelics both produce prosocial effects, but they do so through different mechanisms that may influence which psychosocial interventions work best with each compound. This narrative overview compares evidence across four categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. MDMA alters self-perception in a way less tied to mystical-type states than serotonergic psychedelics. MDMA enhances responses to social reward, while serotonergic psychedelics may also do so but require more research. Both drug classes dampen reactivity to negative social stimuli and induce social neuroplasticity in preclinical evidence, promoting adaptive rewiring of neural circuits that may aid trauma processing.
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.
British Journal of Pharmacology
September 6, 2013
Cédric M. Hysek, Yasmin Schmid, Anna Rickli et al.
7 citations
A 125 mg dose of MDMA, a common recreational amount, produces only a moderate increase in body temperature in controlled clinical settings where risk factors like high ambient temperature, physical exertion, and dehydration are avoided. Severe hyperthermia, a rare but life-threatening complication of recreational MDMA use, typically requires additional permissive factors such as repeated or high doses, crowded conditions, or hyperthyroidism. The drug carvedilol, which blocks both α- and β-adrenoceptors, reduced MDMA-induced thermogenesis in humans and reversed established hyperthermia in rats, but its utility for treating severe MDMA toxicity in emergency settings remains unknown and requires further evaluation in case reports or series.
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 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.
Swiss Medical Weekly
July 1, 2025
Samuel E Christen, Elias Bekka, Yasmin Schmid et al.
3 citations
Caffeine, nicotine, cannabis, and psilocybin are naturally occurring psychoactive substances that alter perception, consciousness, cognition, and emotions. Their natural origins have led to long histories of human use and cultural significance. Caffeine and nicotine are widely available as everyday stimulants, while psilocybin is strictly regulated and cannabis is legal in some regions. Their pharmacological and toxicological properties are well known, but ongoing research investigates therapeutic use for specific diseases and disorders. This narrative review provides an overview of these four substances, summarizing evidence on therapeutic potential, health benefits, and associated risks.
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.
Neuropharmacology
May 1, 2025
Michael Noback, Johnny A Kenton, Adam K Klein et al.
2 citations
A compound called 2,5-dimethoxy-4-propylamphetamine (DOPR), a psychedelic that activates 5-HT2A receptors, can increase motivation in mice with low baseline motivation without causing hallucinogenic-like effects. In a progressive ratio breakpoint task (PRBT) involving 80 mice, doses as low as 0.0106 mg/kg improved performance only in animals with low initial motivation; high-performing mice were unaffected. The head-twitch response (HTR) assay in 72 mice showed hallucinogenic-like effects only at doses of 0.1 mg/kg or higher. These results suggest that low doses of DOPR might treat amotivated states while avoiding hallucinogenic side effects, warranting further research in rodents with disease-relevant conditions.
Healthcare (Basel)
September 12, 2025
Anna Schuldt, Ian C. Clark, Yasmin Schmid et al.
1 citation
Experts in palliative care, oncology, psychiatry, and psychedelic-assisted therapy identified special considerations for using psychedelics near the end of life. They emphasized a non-medicalized setting, the potential to reduce preparation time, and the importance of addressing anxiety, depression, and spiritual distress. Dosing flexibility was recommended: low-to-medium doses for relational issues, higher doses for transcendental experiences. Therapists need knowledge of mystical states, existential aspects of life-threatening illness, and their own inner work. The findings provide a first step toward specific treatment recommendations for psychedelic-assisted therapy in palliative care.
Clinical toxicology (Philadelphia, Pa.)
March 1, 2025
Joep J. J. Ouwerkerk, David M. Wood, Alison M. Dines et al.
1 citation
When 3,4-methylenedioxymetamfetamine (MDMA) is taken with alcohol, emergency department visits show higher odds of agitation, drowsiness, and vomiting compared to MDMA alone. Co-intoxication with other substances increases odds of bradycardia, psychosis, and coma. Mortality rates remain low across all groups. Female patients report less chest pain but more vomiting, headache, and hypotension than males. These variations suggest that physicians should consider both the type of co-intoxication and patient sex to optimize treatment.
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.
Front Psychiatry
April 23, 2025
Martin L. Williams, Deborah Rudin, Yasmin Schmid et al.
Psilocybin is one of many compounds that act as agonists of serotonin receptors and produce psychedelic effects. Beyond psilocybin, other classic psychedelics such as mescaline, N,N-DMT, and 5-MeO-DMT, along with novel compounds called psychoplastogens, show promise for treating mental health conditions like depression, PTSD, and anxiety in palliative care. This research topic includes seven articles: case reports on ketamine for depression and 5-MeO-DMT for PTSD; a review of clavine alkaloids; Phase 1 trials of an ayahuasca analog and a novel DMT formulation; a preclinical study of psilacetin; and a discussion of psychedelics for end-of-life distress. The field is expanding beyond psilocybin to explore a wider range of compounds.