European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
October 1, 2017
Michael D Wunderli, Matthias Vonmoos, Marina Fürst et al.
37 citations
Chronic MDMA use is linked to memory and thinking problems, but past research often failed to separate effects of MDMA from those of other drugs like stimulants. In this study, 26 MDMA users who avoided stimulants, 25 MDMA users who also used stimulants, and 56 non-users completed cognitive tests. Hair analysis confirmed drug use patterns. MDMA-only users showed strong, specific impairments in declarative memory (effect size d=0.90), while stimulant-using MDMA users had broader, larger deficits across memory, working memory, executive functions, and attention (d=0.70 to 1.21). The findings suggest that pure MDMA use mainly harms declarative memory, whereas additional cognitive deficits stem from stimulant co-use.
Frontiers in pharmacology
January 1, 2023
Klemens Egger, Frederik Gudmundsen, Naja Støckel Jessen et al.
17 citations
Co-administration of harmine with DMT in rats increased brain DMT levels by inhibiting its metabolism to indole-3-acetic acid, yet no significant occupancy of serotonin 5-HT2A receptors by DMT was detected, even at brain DMT concentrations up to 11.3 µM. Low doses of DMT and/or harmine did not significantly alter brain glucose metabolism as measured by [18F]FDG-PET. These preliminary findings suggest that the role of MAO-A inhibition in potentiating DMT's psychedelic effects may be more complex than previously assumed, and further dose-response studies are needed.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
March 1, 2025
Klemens Egger, Javier Jareño Redondo, Jovin Müller et al.
14 citations
Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.
The international journal of neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena D Aicher, Dario A Dornbierer et al.
10 citations
A new pharmaceutical formulation combining pure DMT and harmine produced ayahuasca-like psychological effects lasting 2-3 hours in 31 healthy male volunteers, with consistent drug levels and no serious adverse events. DMT reached peak plasma concentrations of 22.1 ng/mL, while buccal harmine reached 32.5 ng/mL in a sustained-release profile but caused no distinguishable subjective effects on its own. All drug conditions were safe and well tolerated, suggesting the formulation could reduce risks and improve therapeutic outcomes for mental health disorders.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 1, 2024
Amelie Zacher, Josua Zimmermann, David M Cole et al.
10 citations
Chronic methamphetamine users show diminished cognitive and emotional empathy toward positive stimuli, elevated punitive social behavior regardless of provocation, and heightened self-reported trait anger compared to non-users. Chronic MDMA users differ from controls only by displaying increased punitive behavior when provoked. Higher hair concentrations of both drugs may be linked to reduced cognitive empathy, and greater lifetime MDMA use correlates with more punitive behavior among MDMA users. The dopaminergic mechanism of methamphetamine may underlie social-cognitive deficits.
Der Nervenarzt
September 1, 2024
Johannes Jungwirth, Francesco Bavato, Boris B Quednow
6 citations
A review article examines the risks and methodological weaknesses of studies on psychedelic and dissociative agents for mental health treatment. While ketamine, esketamine, LSD, and psilocybin show promising results for conditions like treatment-resistant depression, leading to approvals of esketamine in the US, EU, and Switzerland, and psilocybin for compassionate use in Australia, Canada, and Switzerland, the authors caution that excessive expectations and insufficient risk-benefit estimation can harm patients and physician reputation. The article focuses specifically on treatment risks and study quality issues, emphasizing that careful assessment of challenges is crucial despite hopes for a paradigm shift in psychiatry.
Child and adolescent psychiatry and mental health
September 16, 2023
Florian Vock, Lydia Johnson-Ferguson, Laura Bechtiger et al.
3 citations
Sexual minority youth (SMY) and heterosexual youth differ in substance use rates, with SMY-females showing higher use of cannabis, ecstasy/MDMA, and hallucinogens at age 17, and also tobacco and stimulants by age 20. SMY-males reported lower tobacco and cannabis use at age 17 but higher ecstasy/MDMA and hallucinogen use at age 20. Psychosocial factors such as internalizing symptoms, self-control, and peer influences partly explain these differences. The findings highlight the need for targeted prevention, especially for SMY-females early in life.
Psychological medicine
August 26, 2025
Lydia Johnson-Ferguson, Michelle Loher, Laura Bechtiger et al.
2 citations
Frequent cannabis use in young adulthood predicts increases in psychotic-like experiences, internalizing symptoms, aggression, problematic substance use, and higher odds of not being in employment, education, or training, along with decreased general well-being from ages 20 to 24. These associations held whether cannabis exposure was measured by self-reported frequency or by hair THC concentrations, and effect sizes were small. Composite measures combining self-reports and hair data were no more informative than either source alone. The findings come from a community sample of 863 young adults, with 150 reporting weekly-to-daily use and 110 having detectable cannabis in hair at age 20.
NeuroImage. Clinical
January 1, 2024
Antje Opitz, Josua Zimmermann, David M Cole et al.
2 citations
Chronic users of methamphetamine and MDMA show similar deficits in conflict control and emotional processing, rather than substance-specific differences. In an emotional face-word Stroop task with anger and happy faces, both user groups exhibited smaller behavioral effects of cognitive-emotional conflict and selective impairments in processing anger, compared to amphetamine-naïve controls. These deficits were accompanied by stronger P3 event-related potential modulations, indicating altered stimulus-response mapping and decision-making. The findings suggest that chronic use of substituted amphetamines may affect noradrenergic systems, which could underlie the observed similarities. Understanding noradrenaline's role in these processes is an important direction for future research.
Psychopharmacology
July 14, 2026
Helena D Aicher, Joëlle Dornbierer, Luzia Caflisch et al.
A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
June 1, 2026
Klemens Egger, Robert Bozsak, Helena D Aicher et al.
A psychedelic dose of DMT combined with harmine (mimicking ayahuasca) globally increased cerebral glucose metabolism by 12.5% in 14 healthy males, as measured by FDG-PET scans during peak drug effects. Widespread cortical increases appeared in higher-order brain networks. Global glucose metabolism correlated positively with harmine plasma levels but not with DMT levels or subjective intensity. This recapitulates a classic finding for psilocybin, suggesting a potential metabolic signature of the psychedelic state.
Translational psychiatry
May 21, 2026
Francesco Bavato, Andrea Steuer, Anna M Jacobsen et al.
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
Neuroscience and biobehavioral reviews
April 1, 2026
Yanfang Xia, Boris B Quednow, Dominik R Bach
A systematic review of 100 publications found that 36 pharmacological compounds have been tested for their effects on aversive memory in healthy humans. The most studied drugs were hydrocortisone, propranolol, and D-cycloserine. Solid evidence supports propranolol's impact on memory reconsolidation, while weak evidence suggests effects of several compounds on memory encoding, consolidation, or extinction. Fifteen compounds showed significant effects in single studies without replication. The review highlights the need for greater comparability across studies.