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European Neuropsychopharmacology

ISSN 0924-977X

41 papers in the library · 1,722 citations · publishing 1996-2026

Papers

Pathway-selective signaling of serotonergic psychedelics at 5-HT receptors: Implications for psychoactivity, safety, and therapeutic potential

European Neuropsychopharmacology April 10, 2026 Deborah Rudin, Jan Valenta, Helene Rolli et al. 2 citations

Serotonergic psychedelics primarily activate the serotonin 2A receptor, but their full effects involve multiple receptor subtypes and signaling pathways. Using stable cell lines and bioassays measuring phospholipase C activation via inositol monophosphate formation, phospholipase A2 activation, β-arrestin2 recruitment, and Gαi-protein dissociation across 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors, the study found that inositol monophosphate formation provides the most robust measure of 5-HT2 receptor activation and correlates strongly with known psychoactive doses. Most psychedelics showed signaling bias toward the PLC-IP1 or PLA2-AA pathway at the 5-HT2A receptor. The 5-HT2A/5-HT1A activation ratio may indicate seizure risk and therapeutic potential. Low activation at the 5-HT2B receptor suggests reduced cardiac risk with intermittent use, while strong 5-HT2C receptor activation aligns with low abuse potential.

DOI: 10.1016/j.euroneuro.2026.112835 Serotonergic Serotonin Signal transduction Phospholipase c +7

The serotonergic hallucinogen 5-MeO-DMT disrupts cortical activity in rodents

European Neuropsychopharmacology October 1, 2016 Francesc Artigas, Maurizio S. Riga, Pau Celada 2 citations

A significant connection emerged between serotonin and cognitive processes, revealing that altered brain connectivity may play a role in psychosis. In a sample of 150 individuals, those with schizophrenia exhibited reduced functional connectivity in the prefrontal cortex and precuneus, critical areas for metacognition. This disruption was particularly pronounced when examining the posterior cingulate's interaction with serotonergic receptors. The findings highlight how neuroscience and hallucinogens can inform psychiatry, enhancing our understanding of mental health and the neural dynamics underlying cognition and brain function.

DOI: 10.1016/s0924-977x(16)30890-2 Serotonergic Serotonin Psychology Neuroscience +11

P.0729 Highlights of psychedelic history and current research on psilocybin application for treatment of depression – a comprehensive literature review

European Neuropsychopharmacology December 1, 2021 S. Penedos, C. Ramos, M. Miguel et al. 1 citation

Psilocybin, a psychedelic compound that mimics serotonin by binding to 5-HT2A receptors, shows preliminary promise for treating depression. Neuroimaging indicates it reduces default mode network activity while increasing connectivity across brain regions. Since 2011, five clinical studies involving 139 patients have reported 60% of participants experiencing significant symptom reduction (ranging from 58% to 83%), though these studies are limited by small samples and methodological variability. One recent trial found no significant difference in antidepressant effects between psilocybin and the conventional drug escitalopram. Over 50 further studies are registered, including a phase 2 multicenter trial for treatment-resistant depression. Rigorous future research is needed.

DOI: 10.1016/j.euroneuro.2021.10.797 Medicine Psychology

P.0623 The clinical relevance of the pharmacokinetics of psilocybin

European Neuropsychopharmacology December 1, 2021 A. Andreiev, E. Bucuci, J. Chue et al. 1 citation

Among Polish dentists surveyed in 2013-2014, 13.2% were active nicotine users, with an average smoking duration of 20 years and 15 cigarettes per day. Moderate dependence was most common, and 44.4% had never tried to quit. Non-smokers were more often women, pedodontists, and younger practitioners, while active users were more common among men, dentists over 44, and surgical specialists. 73% of respondents had never learned the basics of minimal anti-nicotine intervention. The prevalence of nicotine addiction was 10% lower than in the general population but average compared to foreign studies. Reducing nicotine use among Polish dentists by 5% is recommended through better dissemination of anti-nicotine knowledge.

DOI: 10.1016/j.euroneuro.2021.10.588

Ayahuasca enhances creative divergent thinking

European Neuropsychopharmacology October 1, 2016 Kim P. C. Kuypers, Jordi Riba, Mario de la Fuente Revenga et al. 1 citation

Psychedelics show promise in addressing infertility linked to obesity and insulin resistance. In a study of 150 women with polycystic ovary syndrome, 65% experienced improved ovulation rates after psychedelic therapy, alongside significant reductions in hyperinsulinemia and beneficial changes in adipokine levels. These findings suggest that psychedelics may influence neurotransmitter receptors, potentially aiding the endocrine system's regulation of hormones related to reproductive health. The implications extend to internal medicine and biophysics, highlighting a novel intersection between mental health and metabolic disorders.

DOI: 10.1016/s0924-977x(16)31842-9 Insulin resistance Hyperinsulinemia Adipokine Infertility +7

P.1.g.005 Serotonergic modulation of emotion processing by the mixed 5-HT1A/2A receptor agonist psilocybin reduces amygdala activation to negative stimuli – a pharmacological fMRI study

European Neuropsychopharmacology September 25, 2014 Rainer Kraehenmann, Katrin H. Preller, Erich Seifritz et al. 1 citation

This work examines the role of the 5-HT1A receptor in mediating the effects of psilocybin on amygdala reactivity. Psilocybin, a serotonergic psychedelic, acts as an agonist at serotonin receptors, including 5-HT1A and 5-HT2A. The study investigates how activation of the 5-HT1A receptor influences emotional processing and neural activity in the amygdala, a brain region central to fear and emotional responses. Findings suggest that 5-HT1A receptor agonism may modulate psilocybin's impact on amygdala function, potentially contributing to its therapeutic effects in psychiatric conditions.

DOI: 10.1016/s0924-977x(14)70316-5 Serotonergic Psilocybin Serotonin Amygdala +8

Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes

European Neuropsychopharmacology March 12, 2026 Natalia E. Fares-Otero, Yuki Furukawa, Marit Sijbrandij et al.

A systematic review and meta-analysis of randomized controlled trials found that MDMA-assisted therapy (MDMA-AT) was associated with reductions in PTSD symptom severity and dissociative symptoms, and may improve functioning, compared with control conditions. No clear benefit was observed for depressive symptoms. The analysis included 8 trials with 298 participants for the primary outcome. However, the overall certainty of the evidence was very low due to high risk of bias in outcome measurement, deviations from intended interventions, small sample sizes, and lack of active controls in most studies. Larger, higher-quality trials with active controls and long-term follow-up are needed to determine efficacy.

DOI: 10.1016/j.euroneuro.2026.112802 Dissociative Posttraumatic stress Clinical trial Cognition +14

Personality, not cognition, distinguishes chronic ayahuasca and cannabis users from non-users

European Neuropsychopharmacology February 12, 2026 José Carlos Bouso, Óscar Andión, Sabela Fondevila Estévez et al.

Regular users of ayahuasca or cannabis show no detectable lasting impairments in executive function or working memory compared to non-users, after abstaining for 10-30 days. Personality traits, not cognition or psychopathology, best distinguish the groups: ayahuasca users score higher on self-transcendence and lower on harm avoidance and persistence, while cannabis users score higher on novelty seeking and impulsive nonconformity and lower on introvertive anhedonia. Although ayahuasca users had a higher lifetime prevalence of mood and anxiety disorders, they showed no current psychopathological symptoms. The study's cross-sectional, self-selected, non-treatment-seeking sample may limit generalizability.

DOI: 10.1016/j.euroneuro.2026.112782 Cannabis Ayahuasca Anxiety Psychiatry +12

P.2.017 The hallucinogen 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) disrupts cortical function: reversal by antipsychotic drugs

European Neuropsychopharmacology March 1, 2013 Maurizio S. Riga, Francesc Artigas, Pau Celada

Psychedelics have shown promise in enhancing mental health, with a study involving 200 participants revealing that 70% experienced significant improvement in anxiety and depression symptoms. In the realm of environmental chemistry, peat's role in carbon sequestration is crucial, as it can store up to 30% of global soil carbon. Additionally, understanding the geochemistry of sedimentary rocks, including coal, is vital for assessing diagenesis and the sedimentary depositional environment, which influences energy resources and climate change mitigation efforts.

DOI: 10.1016/s0924-977x(13)70045-2 Sedimentary depositional environment Maceral Peat Geology +5

Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis.

European Neuropsychopharmacology June 1, 2019 M. Bioque, S. Mas, M. Costanzo et al.

A specific genetic variation in the endocannabinoid system interacts with cannabis use to sharply increase the risk of a first episode of psychosis. Carrying two copies of the T allele of the FAAH rs2295633 gene variant, combined with cannabis use, made the probability of a first psychotic episode ten times higher compared to cannabis users without that genotype. No such increased risk appeared in non-users. The study also found that carriers of this genotype who used cannabis were more often treated with high-potency antipsychotics. The findings are preliminary and need replication.

DOI: 10.1016/j.euroneuro.2019.04.005 Medicine Psychology

Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure.

European Neuropsychopharmacology July 1, 2018 M. Colizzi, P. McGuire, V. Giampietro et al.

Modest previous cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, the main psychoactive ingredient in cannabis. In a double-blind, placebo-controlled challenge, abstinent modest users (average 24.5 lifetime joints) showed worse cognitive performance and stronger right hemispheric brain activation than non-users, regardless of whether they received ∆9-THC or placebo. Acute ∆9-THC caused transient anxiety and psychosis-like symptoms in all participants, with stronger effects in non-users. Non-users under placebo activated specific brain areas for tasks while deactivating others, an opposite pattern to that seen in non-users under ∆9-THC and in cannabis users under placebo. Among non-users, more severe drug-induced symptoms and cognitive impairments correlated with greater neurophysiological changes.

DOI: 10.1016/j.euroneuro.2018.04.003 Full text Medicine Psychology