European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
September 1, 2021
Martin K Madsen, Dea S Stenbæk, Albin Arvidsson et al.
132 citations
Psilocybin, a novel therapeutic, is metabolized to psilocin, which alters brain function by engaging serotonin receptors. In fifteen healthy individuals, a psychoactive dose (0.2-0.3 mg/kg) reduced the integrity and segregation of brain networks, including the default mode network, while increasing connectivity between networks like the executive control and dorsal attention networks. These changes correlated with plasma psilocin levels and subjective drug intensity. The findings link psilocin's time course to shifts in brain functional architecture and subjective experience, offering insight into the neurobiological mechanisms of psychedelic effects and consciousness.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Daure et al.
55 citations
Over the past century, clinical research on psychedelics has evolved from an early focus on safety into a 'psychedelic renaissance' after the 1990s. A scientometric analysis of 31,687 documents from the Web of Science identified major research themes: hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and dissociative substances. The field has shifted from basic science to clinical applications, including phase 2 and 3 trials and evidence synthesis. Recent trends include NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada lead in productivity, reflecting legislative influences. This translational evolution has already led to esketamine approval for depression and may lead to further approvals across mental and physical conditions. Toxicology screening tools for NPS are urgently needed and may follow a similar path.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
January 1, 2023
Lucas Oliveira Maia, Dimitri Daldegan-Bueno, Isabel Wießner et al.
46 citations
Ayahuasca shows therapeutic potential for depression and substance use disorders, with growing preliminary evidence for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses like cancer and chronic conditions. Long-term regular use does not appear detrimental and may benefit individual and collective health. The evidence for depression and substance use disorders is most consistent, while other conditions represent promising targets requiring further rigorous investigation.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 1, 2022
Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi et al.
42 citations
A low dose of LSD (50 μg) produces both beneficial and detrimental cognitive effects 24 hours after administration. Compared to placebo, LSD sub-acutely improved visuospatial memory and phonological verbal fluency but impaired cognitive flexibility, as measured by fewer categories achieved and more perseveration on the Wisconsin Card Sorting Test. The findings suggest that LSD-assisted therapy might be explored for conditions involving memory and language decline, such as brain injury, stroke, or dementia, while also indicating a mixed 'afterglow and hangover' profile.
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.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Roger S McIntyre, Istvan Bitter, Jozefien Buyze et al.
30 citations
In the ESCAPE-TRD trial, esketamine nasal spray caused treatment-emergent adverse events more often than quetiapine extended release (91.9% versus 78.0%), but these events were typically mild or moderate and transient: 92.0% resolved the same day, and only 4.2% of patients discontinued esketamine due to adverse events compared with 11.0% for quetiapine. The median proportion of days with adverse events was lower with esketamine (11.9% versus 21.3%). Along with greater efficacy, esketamine's tolerability profile supports its use for treatment-resistant depression.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2023
Michael James Winkelman, Attila Szabo, Ede Frecska
26 citations
Serotonergic psychedelics show potential for treating Alzheimer's disease by promoting neuroplasticity and counteracting brain atrophy. Classic psychedelics modulate glutamatergic neurotransmission, stimulate synaptic and network remodeling, and up-regulate neurotrophic factors that support neuronal survival. Muscimol reduces Aβ-induced neurotoxicity, and Sigma-1 receptor agonists protect against Aβ toxicity. Psychedelics activate mTOR pathways in brain regions that atrophy in Alzheimer's, induce structural and functional neural plasticity, increase neurogenesis, and rewire pathological neurocircuitry. These effects enhance brain functional connectivity and address multiple degenerative mechanisms, warranting immediate investigation of psychedelics as treatments for Alzheimer's patients.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2024
Marcelo Falchi-Carvalho, Isabel Wießner, Sérgio Ruschi B Silva et al.
25 citations
Inhaled N,N-Dimethyltryptamine (DMT) produces dose-dependent increases in the intensity, positive valence, and perceptual effects of subjective experiences, with only mild, transient, and self-limited increases in blood pressure and heart rate. No changes in safety blood biomarkers or serious adverse events occurred. The acute effects last around 10 minutes, offering a potentially cost- and time-effective alternative to longer-acting oral psychedelics for clinical use in mood disorders. This open-label, single-ascending, fixed-order, dose-response study in 27 healthy volunteers tested five dose pairs (5/20 mg through 15/60 mg) of inhaled DMT (BMND01 candidate).
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
September 1, 2024
Aleksander Kwaśny, Julia Kwaśna, Alina Wilkowska et al.
24 citations
Ketamine, a medication used for depression, may also reduce anhedonia (loss of interest or pleasure). A systematic review of 22 studies (4 randomized-controlled trials and 18 open-label trials) found that all reported alleviation of anhedonia symptoms after ketamine or esketamine administration, regardless of the number of infusions. Neuroimaging studies showed changes in functional connectivity linked to improvement. However, limitations include few placebo-controlled trials. The review suggests a potential anti-anhedonic effect of ketamine in depressed patients, likely through neuroplastic changes.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
April 1, 2025
Eduard Vieta, Nahida Ahmed, Celso Arango et al.
12 citations
Patients with treatment-resistant depression who received esketamine nasal spray experienced 43.2% more weeks with functional remission over 32 weeks compared to those taking quetiapine extended release, a difference of 2.0 weeks. Esketamine also led to an 11.9% reduction in productivity loss due to absenteeism and a 14.2% reduction in overall work productivity loss. Both treatments were taken alongside an ongoing SSRI or SNRI. The findings suggest that esketamine provides greater improvements in daily functioning and workplace productivity for this patient group.
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.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 17, 2025
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
7 citations
Inhaled vaporized DMT (60 mg) produces profound altered states of consciousness and is safe and well-tolerated in healthy adults. In a randomized, double-blind, placebo-controlled crossover trial with 25 participants, DMT significantly increased subjective intensity and most measures on the 5D-ASC, HRS, and MEQ questionnaires compared to an active placebo (0.6 mg DMT). Physiological parameters such as blood pressure and heart rate rose transiently within safe limits. Adverse events were predominantly mild and temporary. Biochemical changes were not clinically relevant. Physiological increases correlated with subjective experiences, suggesting a link between bodily responses and the psychedelic state.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Óscar Soto-Angona, Adriana Fortea, Lydia Fortea et al.
7 citations
A scoping review of 16 human and 11 animal studies suggests that classic psychedelics may not increase seizure risk in healthy individuals or animals when used alone, but concomitant use of other substances like kambo or lithium could raise that risk. The evidence is heterogeneous and lacks sufficient external validity, so conclusions should be interpreted cautiously. The review also outlines possible neurobiological mechanisms and future research directions.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2023
Isabel Wießner, Marcelo Falchi, Dimitri Daldegan-Bueno et al.
6 citations
Low to moderate doses of LSD alter language structure, semantics, and vocabulary over time. In a double-blind, placebo-controlled crossover study, 24 healthy volunteers (age 35±11, 33% women) received 50 μg LSD or placebo. LSD reduced verbosity, lexicon, and connectivity in speech networks from 1.5 to 4 hours, decreased semantic distances between words from 2 to 24 hours, and shifted vocabulary related to grammar, persons, time, space, and biological processes from 1.5 to 24 hours. Simpler, disconnected structure and increased semantic similarity may reflect cognitive impairments, while vocabulary changes may indicate subjective perceptual shifts. Automated language analysis could offer unconstrained insights into psychedelic cognition.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Zeus Tipado, Kim P C Kuypers, Bettina Sorger et al.
5 citations
Psychedelics like LSD and psilocybin alter perception by activating serotonin receptors in cortical and subcortical brain regions, often causing visual disturbances or hallucinations. While current theories focus on disrupted communication between these brain areas, rare conditions like Charles Bonnet syndrome suggest the retinofugal pathway may also play a key role. Interneurons in the retina called amacrine cells could be the first site of psychedelic modulation, disrupting how visual information is hierarchically processed. This paper presents a new theory of psychedelic modulation in the retinofugal pathway, drawing parallels with clinical conditions to explain visual perceptual changes.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 1, 2024
Víctor De la Peña-arteaga, Marta Cano, Daniel Porta-Casteràs et al.
5 citations
In patients with obsessive-compulsive disorder (OCD) undergoing a 3-month mindfulness-based cognitive therapy (MBCT) programme, distinct baseline brain connectivity patterns were associated with four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Key brain nodes—the precuneus and frontopolar cortex—within the ventral default mode network and frontostriatal network showed predictive and response associations with clinical changes. MBCT may modulate connectivity in these networks, potentially reducing symptoms across domains. These network-based biomarkers could help personalize treatment and identify patients most likely to benefit from MBCT.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 1, 2026
A Reif, Yağcıoğlu Ae Anıl, I Bitter et al.
3 citations
A 2-year extension of a clinical trial followed 183 adults with treatment-resistant depression who had been using esketamine nasal spray alongside an antidepressant. Over 136 weeks, 96.7% reported side effects, but 98.3% of those occurring on dosing days resolved the same day, and only 3.3% stopped treatment due to side effects. Among patients who achieved remission during the earlier phase, 79.2% did not relapse or discontinue treatment throughout the extension; the overall relapse rate for those reaching remission across both studies was 6.9%. No new safety concerns emerged, and the safety profile matched that seen in shorter-term studies.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
January 16, 2026
Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko et al.
1 citation
Psilocybin-assisted therapies are being tested for major depressive disorder and treatment-resistant depression, but rigorous research requires not only measuring the drug's effects but also consistently reporting non-pharmacological factors—such as the physical and social environment (set and setting)—that can influence outcomes. To address this, the ReSPCT guidelines were developed as a 30-item framework for standardized reporting. This review evaluated 13 clinical trial protocols (11 Phase II and 2 Phase III) from ClinicalTrials.gov and the EU Clinical Trials Information System. Using the ReSPCT checklist, only 15.6% of 390 item-level assessments showed full compliance; 64.6% had partial compliance, and 19.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 23, 2025
Jessica Henry, Bruna Giribaldi, David J Nutt et al.
1 citation
In patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in all three domains of dysfunctional attitudes (achievement, dependency, self-control) at six weeks, while a six-week daily course of escitalopram improved only the achievement domain and did not change optimism. Psilocybin also made patients more optimistic about desirable life events, whereas escitalopram reduced pessimism about negative life events. The findings suggest psilocybin therapy is superior to escitalopram for remediating negative cognitive biases in depression.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 28, 2026
L Belinger, N M Rieser, E J E Engeli et al.
In a double-blind randomized trial with 120 healthy volunteers who received psilocybin, MDMA, or methylphenidate (active placebo), overall blinding was insufficient. Psilocybin had the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological effects. Prior substance experiences did not influence accuracy of forced-choice guesses. These findings offer empirical guidance for designing and reporting blinding procedures in psychedelic trials.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2026
Isabel Werle, Francisco S Guimarães, Rafael G Dos Santos et al.
Ayahuasca, a brew containing the psychedelic DMT, helps rodents overcome persistent and generalized fear memories by boosting brain-derived neurotrophic factor (BDNF) signaling in the infralimbic (IL) region of the medial prefrontal cortex. In rats exposed to stress or high-intensity fear conditioning, repeated ayahuasca (0.3 mg/kg DMT) enhanced extinction learning and its retention, and reduced fear generalization. These effects were blocked by infusing an anti-BDNF antibody or a TrkB receptor antagonist into the IL cortex. The reduction in fear generalization depended on BDNF in females but not males. The findings suggest psychedelics may aid in treating difficult-to-extinguish trauma memories, such as those in PTSD.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2025
Danica E Johnson, Nelson B Rodrigues, Sydney Weisz et al.
Depression with co-occurring posttraumatic stress disorder (PTSD) leads to more severe symptoms and poorer response to standard treatments. In a retrospective analysis of 134 patients with treatment-resistant depression, four ketamine infusions (0.5-0.75 mg/kg) reduced depressive symptoms equally in those with and without comorbid PTSD; no significant group-by-time interaction was found. PTSD symptoms also significantly improved across all symptom clusters, with moderate to large effect sizes. Ketamine shows promise as an effective intervention for this hard-to-treat population, though future randomized trials should explore factors driving improvement and long-term outcomes.