Social Cognitive and Affective Neuroscience
October 4, 2013
Cédric M. Hysek, Yasmin Schmid, Linda D. Simmler et al.
356 citations
MDMA (ecstasy) enhances emotional empathy and prosocial behavior in men but impairs recognition of negative emotions like fear, anger, and sadness, especially in women. In a placebo-controlled, double-blind crossover trial with 32 healthy volunteers, MDMA increased explicit and implicit emotional empathy on the Multifaceted Empathy Test and boosted prosocial choices on the Social Value Orientation test in men. It did not affect cognitive empathy but worsened identification of negative facial expressions on the Face Emotion Recognition Task, particularly in women. MDMA also raised plasma cortisol, prolactin, and oxytocin levels, markers linked to social behavior. These effects may explain MDMA's recreational sociability and its potential therapeutic use in psychotherapy for social dysfunction or PTSD.
Neuropsychopharmacology
September 28, 2011
Boris B. Quednow, Michael Kometer, Mark A. Geyer et al.
241 citations
The hallucinogen psilocybin disrupts automatic and controlled inhibition processes in healthy humans by stimulating the serotonin-2A receptor (5-HT(2A)R). In a double-blind, randomized study with 16 participants, psilocybin (260 μg/kg) reduced prepulse inhibition of the acoustic startle response at short lead intervals, increased scores on the altered states of consciousness questionnaire, and increased errors and response latencies in the interference condition of the Stroop Test. These effects were attenuated by pretreatment with the 5-HT(2A/2C)R antagonist ketanserin (40 mg), which alone had no significant effects. The findings indicate that sensorimotor gating and attentional control deficits in schizophrenia may involve changes in the 5-HT(2A)R system.
Neuropsychopharmacology
February 14, 2007
Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al.
194 citations
Psilocybin, a hallucinogenic 5-HT(2A) receptor agonist, produces opposite effects on prepulse inhibition (PPI) of the startle response depending on the time interval between the prepulse and the startle stimulus. In healthy humans, psilocybin dose-dependently reduced PPI at short intervals (30 ms) and increased PPI at long intervals (120-2000 ms), with no effect at medium intervals (60 ms). The reduction in PPI at short intervals correlated with impaired sustained attention, consistent with PPI deficits seen in schizophrenia. Psilocybin also impaired attention and increased altered states of consciousness scores.
Journal of Psychopharmacology
July 22, 2014
Yasmin Schmid, Cédric M. Hysek, Linda D. Simmler et al.
154 citations
A low dose of MDMA (75 mg) enhanced emotional empathy for positive emotional situations and reduced recognition of sad faces, but did not affect cognitive empathy, social cognitive inferences, or moral judgment. Methylphenidate (40 mg) had no effects on emotional processing, empathy, or mental perspective-taking. MDMA increased subjective feelings of closeness, openness, and trust, along with plasma oxytocin and prolactin levels. These social-cognitive effects likely contribute to MDMA's popularity as a party drug.
Journal of Psychopharmacology
March 30, 2006
Boris B. Quednow, Frank Jessen, Kai‐uwe Kühn et al.
105 citations
Chronic MDMA (ecstasy) use is linked to long-term serotonin depletion and memory deficits. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users, and 19 male drug-naive controls took a German version of the Rey Auditory Verbal Learning Test. MDMA users showed widespread verbal memory deficits—in learning, consolidation, recall, and recognition—compared to both cannabis users and controls, while cannabis users performed similarly to controls. MDMA users also had worse recall consistency and strong retroactive interference, measures tied to frontal lobe function. Memory performance correlated with the amount of MDMA taken. The findings suggest MDMA-related memory deficits involve frontal cortex dysfunction, not just temporal or hippocampal damage.
Frontiers in Psychiatry
August 18, 2017
Zurina Hassan, Oliver G. Bosch, Darshan Singh et al.
62 citations
Human culture involves learning to consume natural or synthetic psychoactive compounds that alter mental states and behavior. After a novel psychoactive substance (NPS) emerges and is experimentally used, its benefits and harms can be estimated, leading to legal classifications ranging from medical use to complete bans. However, banned drugs often continue to be used, allowing better understanding of their properties, and views on a drug can shift from harmful to medically useful. This review summarizes recent neuropharmacological progress on several NPS, including mitragynine, synthetic cannabinoids, dimethyltryptamine, novel serotonergic hallucinogens, cathinones, ketamine, novel dissociatives, gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol, highlighting both emerging harm potentials and potential medical applications.
British Journal of Clinical Pharmacology
December 11, 2015
Matthias E. Liechti, Boris B. Quednow, Evangelia Liakoni et al.
57 citations
Gamma-hydroxybutyrate (GHB) produced mixed stimulant-sedative effects in healthy men, with higher doses causing more sedation and dizziness but no changes in heart rate or blood pressure. Plasma exposure to GHB rose disproportionately with dose—a 40% greater increase than expected from dose alone—indicating nonlinear pharmacokinetics. The psychotropic effects were closely tied to plasma concentrations, and no acute tolerance developed over time.
Molecules
April 22, 2021
Paul Cumming, Milan Scheidegger, Dario Dornbierer et al.
45 citations
Hallucinogens such as LSD, psilocybin, and mescaline are being re-evaluated for their psychotherapeutic potential. This narrative review covers in vitro and ex vivo binding studies and molecular imaging using PET or SPECT. Early PET work with [11C]-MBL showed that most specific binding is to serotonin 5-HT2A receptors, but interactions with 5-HT1A receptors and other pathways may contribute to the unique experiences. Other important factors include blood-brain barrier permeability, metabolism, and active metabolites. Only a few PET or SPECT studies of radiolabeled hallucinogens exist, most recently using [11C]Cimbi-36. Hybrid imaging combining PET with fMRI is expected to advance future research.
Psychoneuroendocrinology
July 17, 2015
Oliver G. Bosch, Christoph Eisenegger, Jürg Gertsch et al.
42 citations
Gamma-hydroxybutyrate (GHB), a GHB-/GABAB-receptor agonist, produces euphoric, disinhibiting, and vitality-enhancing effects in healthy men. In a randomized, placebo-controlled crossover trial with 16 males, a single 20 mg/kg dose increased charitable donations and prosocial money distributions among participants who initially showed low prosociality. However, GHB did not alter emotion recognition, empathy, theory-of-mind, or basic cognitive functions. The drug raised plasma progesterone levels but left oxytocin, testosterone, cortisol, aldosterone, DHEA, and ACTH unchanged. These findings suggest that GHB's mood and prosocial effects may involve GHB-/GABAB-receptors and progesterone rather than typical social hormones like oxytocin or testosterone.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
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.
PLoS One
April 9, 2013
Oliver G. Bosch, Michael Wagner, Frank Jessen et al.
34 citations
Recreational users of MDMA show verbal learning and recall deficits that are linked to reduced glucose metabolism in the prefrontal and parietal cortex, and word recognition difficulties are additionally associated with reduced metabolism in the mediotemporal region. These findings indicate that memory problems in MDMA users result from combined dysfunction across frontal, parietal, and mediotemporal brain areas.
European Neuropsychopharmacology
March 8, 2017
Oliver G. Bosch, Michael M. Havranek, A Baumberger et al.
22 citations
Gamma-hydroxybutyrate (GHB), a drug used for narcolepsy and abused recreationally, has prosexual effects in healthy men. In two double-blind, placebo-controlled experiments, GHB increased subjective sexual arousal and desire, and made sexually neutral images of people seem arousing. Brain scans showed that GHB boosted activity in reward regions like the nucleus accumbens when viewing erotic pictures, and increased connectivity between the nucleus accumbens and the ventromedial prefrontal cortex. The findings indicate GHB enhances hedonic sexual functioning and lowers the threshold for perceiving erotic cues by sensitizing mesolimbic reward pathways.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
Neuropsychopharmacology
March 3, 2021
Nora Penzel, Linda A. Antonucci, Linda T. Betz et al.
18 citations
Earlier cannabis initiation among people with recent-onset psychosis is associated with more severe positive symptoms and greater gray matter volume in a cerebellar network previously linked to schizophrenia. This cerebellar volume increase correlates with lower volume in an insula-temporal-frontal network also implicated in schizophrenia. The findings suggest that early cannabis use may alter the developmental trajectory of specific brain networks, increasing later psychosis risk.
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.
NeuroImage: Clinical
September 19, 2022
Josua Zimmermann, Nicole Friedli, Francesco Bavato et al.
14 citations
Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.
The International Journal of Neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena Aicher, Dario 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.
Brain
October 19, 2025
Rebecca C Coray, Vincent Beliveau, Josua Zimmermann et al.
1 citation
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.