Journal of Psychopharmacology最新文献

{"title":"The occurrence and potential role of mystical experiences in MDMA-assisted therapy for PTSD: A secondary analysis.","authors":"Tijmen P L Bostoen, Erwin Krediet, Annette M van Schagen, Nic J A van der Wee, Erik J Giltay","doi":"10.1177/02698811261464502","DOIUrl":"https://doi.org/10.1177/02698811261464502","url":null,"abstract":"<p><strong>Background: </strong>The potential safety and efficacy of the psychedelic 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has been researched in phase 2 and phase 3 clinical trials. We examined the occurrence and role of mystical experiences in MDMA-AT.</p><p><strong>Methods: </strong>Data were sourced from two phase 2 randomized trials of MDMA-AT for chronic PTSD, in which participants received two sessions with either MDMA or active placebo, in conjunction with psychotherapy. The Mystical Experience Questionnaire 30-item version (MEQ30) was administered after each MDMA session. The association of mystical experiences and PTSD symptom severity (Clinician Administered PTSD Scale for DSM-IV (CAPS-IV)) was analyzed using multilevel regression and mediation analyses.</p><p><strong>Results: </strong>Fifty-three participants with chronic PTSD were included. Standard doses of MDMA (<i>n</i> = 39) were associated with significantly higher mean MEQ30 scores (M = 63.1, SE = 4.9; 42.1% of maximum) compared to active placebo (M = 24.7, SE = 5.5; 16.4%), <i>t</i>-test <i>p</i> < 0.001. Mediation analysis revealed a significant indirect effect of the MEQ30 Positive Mood subscale on symptom reduction (<i>b</i> = -0.170, 95% CI (-0.353, -0.007)), while the MEQ total score and other subscales showed smaller, non-significant indirect effects on CAPS-IV scores.</p><p><strong>Conclusions: </strong>MEQ30 scores were significantly higher for MDMA sessions than for active placebo sessions in patients undergoing MDMA-assisted therapy for chronic PTSD. Among mystical-type experiences, the positive mood subscale, rather than full mystical-type states, appeared to contribute most to the mitigation of PTSD symptoms. These findings should be interpreted with caution due to the limited sample size and secondary nature of the analysis.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261464502"},"PeriodicalIF":5.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium toxicity from angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker co-prescription: A population-based cohort study.","authors":"Fatemeh Ahmadi, Flory Tsobo Muanda, Eric McArthur, Matthew Weir, Amit X Garg","doi":"10.1177/02698811261473401","DOIUrl":"https://doi.org/10.1177/02698811261473401","url":null,"abstract":"<p><strong>Rationale: </strong>Initiating an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) in patients taking lithium may increase the concentration of serum lithium and the risk of lithium toxicity.</p><p><strong>Objective: </strong>In patients taking lithium, to compare the 90-day risk of lithium toxicity following a new co-prescription of an ACEi or ARB versus a new co-prescription of a beta-blocker.</p><p><strong>Methods: </strong>Population-based cohort study in Ontario, Canada, from 2002 to 2024. Patients 50 years of age and older taking lithium who were co-prescribed an oral ACEi or ARB (<i>n</i> = 2267) or a beta-blocker (<i>n</i> = 2110). Outcomes were assessed within 90 days of initiating the drug co-prescription. The primary outcome was a hospital admission with lithium toxicity. Secondary outcomes were all-cause mortality and all-cause hospitalization. Overlap weighting using propensity scores was used to balance groups on indicators of baseline health. Risk ratios (RR) were obtained using weighted log-binomial regression, and risk differences (RD) were obtained using weighted binomial regression.</p><p><strong>Results: </strong>In lithium users, co-prescription of an ACEi or ARB versus a beta-blocker was not associated with a higher risk of hospital admission with lithium toxicity (47/2267 patients co-prescribed an ACEi or ARB (2.1%) versus 54/2110 patients co-prescribed a beta-blocker (2.6%); weighted RR 0.72 (95% CI, 0.47 to 1.11); weighted RD -0.75% (95% CI, -1.74% to 0.25%). In lithium users, co-prescription of an ACEi or ARB versus a beta-blocker was not associated with a higher risk of all-cause mortality or all-cause hospitalization.</p><p><strong>Conclusion: </strong>The findings of this study suggest that the higher risk of lithium toxicity in patients co-prescribed an ACEi or ARB observed in some prior studies may be overstated.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261473401"},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CB1 receptor-enriched functional connectivity analysis revealed target-specific modulation by cannabidiol in early psychosis.","authors":"Giada Lombardi, Ekaterina Shatalina, Aisling O'Neill, Robin Wilson, Mitul Mehta, Sagnik Bhattacharyya","doi":"10.1177/02698811261470456","DOIUrl":"https://doi.org/10.1177/02698811261470456","url":null,"abstract":"<p><strong>Background: </strong>Cannabidiol (CBD) has emerged as a potential antipsychotic treatment, acting as a negative allosteric modulator of cannabinoid type-1 (CB1) receptors within the endocannabinoid system. Although previous neuroimaging studies have shown that CBD induces changes in aberrant brain activity and functional connectivity (FC) in psychosis, they have not directly integrated information about the spatial distribution of the molecular targets through which CBD may act.</p><p><strong>Aim: </strong>In this study, we aimed to investigate whether a single dose of CBD may acutely modulate CB1 receptor-enriched FC in patients with early psychosis and to compare these effects with healthy controls (HC).</p><p><strong>Methods: </strong>Thirteen patients with early psychosis (PSY) and 14 age- and sex-matched HC underwent resting-state functional magnetic resonance imaging (fMRI). Patients participated in a randomised, double-blind, placebo-controlled crossover study receiving 600 mg CBD (PSY-CBD) or matched placebo (PSY-PLB). CB1 receptor-enriched FC was computed using Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), integrating Positron Emission Tomography (PET)-derived CB1 receptor maps with fMRI data.</p><p><strong>Results: </strong>Three main findings emerged: (i) PSY-PLB showed increased CB1 receptor-enriched FC across multiple regions compared to HC; (ii) a single dose of CBD significantly reduced CB1 receptor-enriched FC of the right insular cortex relative to PLB; (iii) no differences were observed when CB1 receptor-enriched FC maps of PSY-CBD were compared with those of HC.</p><p><strong>Conclusion: </strong>Our findings support the potential of CBD to regulate CB1 receptor-enriched FC in early psychosis, providing mechanistic insight into its antipsychotic effects and highlighting REACT as a valuable tool for integrating molecular and functional imaging in psychiatric research.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261470456"},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pharmacometric framework for norepinephrine transporter occupancy and dose equivalence across psychotropic medications.","authors":"Mohammed Aboukaoud, Bosmat Hoch, Revital Amiaz","doi":"10.1177/02698811261470450","DOIUrl":"https://doi.org/10.1177/02698811261470450","url":null,"abstract":"<p><strong>Background: </strong>Norepinephrine transporter (NET) inhibition is a relevant mechanism across psychotropic medications, although prescribing classifications are largely based on drug class rather than quantitative target engagement.</p><p><strong>Aims: </strong>To facilitate cross-drug comparisons of noradrenergic activity, we developed a pharmacometric model to estimate NET occupancy for 26 psychotropic agents and their active metabolites.</p><p><strong>Methods: </strong>NET occupancy was estimated using National Institute of Mental Health Psychoactive Drug Screening Program Ki data, protein-binding-corrected plasma concentrations, a standard receptor occupancy model, and logit-derived ED50 values, and was compared with published positron emission tomography (PET) estimates.</p><p><strong>Results: </strong>After protein-binding correction, desipramine, milnacipran, and maprotiline showed very high NET occupancy (⩾90%), nortriptyline, doxepin, and norquetiapine showed high occupancy (70%-90%), and hydroxybupropion and duloxetine showed moderate occupancy (50%-70%). Clomipramine, atomoxetine, and reboxetine demonstrated moderate-low occupancy (30%-50%), whereas venlafaxine showed low occupancy (~28%). Hydroxybupropion exhibited substantially greater NET engagement (~68%) than bupropion (~2%), and most Selective serotonin reuptake inhibitors showed minimal occupancy (<10%). Estimated ED50 values ranged from 6.6 mg (desipramine) to ⩾63 mg (duloxetine), and predicted occupancies correlated moderately with PET data (<i>r</i> = 0.76, <i>p</i> = 0.028, R² = 0.58).</p><p><strong>Conclusions: </strong>These findings suggest that variability in NET engagement across psychotropic medications may not be fully captured by conventional class-based classifications. The proposed framework offers a mechanism-informed approach to comparative pharmacological analysis and introduces a conceptual noradrenergic activity index. This approach may be useful for hypothesis generation in future studies integrating pharmacokinetic-pharmacodynamic modeling with in vivo imaging and clinical outcomes.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261470450"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Where is the sweet spot for psychedelic-enhanced fear extinction? An integrative quantitative synthesis of dose-effect patterns in rodent models.","authors":"Isabel Werle, Maria Eduarda Cardoso Probst, Leandro Jose Bertoglio","doi":"10.1177/02698811261464979","DOIUrl":"https://doi.org/10.1177/02698811261464979","url":null,"abstract":"<p><strong>Background: </strong>Individuals with anxiety and stress-related disorders frequently demonstrate impaired threat extinction. Although psilocybin, lysergic acid diethylamide (LSD), <i>N,N</i>-dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), and ketamine can facilitate fear extinction in rodent models, comprehensive integrative analyses remain limited.</p><p><strong>Methods: </strong>Regression-based approaches were employed to estimate cross-study trends to assess whether the dose-effect relationships of these compounds are linear, bell-shaped, or follow alternative patterns. The potential moderating effects of specific biological or procedural factors on extinction learning and recall were also assessed. Effect sizes from 177 experiments in mice and rats were analyzed by compound and pooled across classical psychedelics, with doses normalized using allometric scaling and serotonin 5-HT2A or 5-HT1A receptor-adjusted relative potency.</p><p><strong>Results: </strong>The available data for LSD were insufficient for evaluating the hypothesized relationships. For the other psychedelics, linear models provided the best relative fit for extinction learning and recall. Within the tested ranges, lower doses, except for MDMA, were frequently associated with larger positive effect sizes. Pooled analyses indicated that the interval between treatment administration and extinction recall testing may influence the effects of classical psychedelics on fear extinction. In contrast, sex, age, preconditioning stress/high-intensity conditioning, and the treatment-extinction learning interval did not affect the observed dose-effect relationships. These pooled associations were sensitive to high-leverage observations.</p><p><strong>Conclusion: </strong>Psychedelics appear to enhance fear extinction across a broad range of doses. The timing of administration relative to memory extinction retrieval may contribute to variability in these effects. Evidence supporting nonlinear dose-effect relationships remains limited.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261464979"},"PeriodicalIF":5.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarifying age filtering in a TriNetX-based study on pediatric antidepressant use and treatment-emergent mania.","authors":"Kuo-Wang Tsai, Joshua Wang","doi":"10.1177/02698811261473407","DOIUrl":"https://doi.org/10.1177/02698811261473407","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261473407"},"PeriodicalIF":5.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression.","authors":"Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros, Sophie Laborde, Daniel Amorim, Marcelo Falchi-Carvalho, Nicole Galvão-Coelho, Isabel Wießner, Draulio B Araujo","doi":"10.1177/02698811261465005","DOIUrl":"10.1177/02698811261465005","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have demonstrated rapid antidepressant effects of inhaled <i>N,N</i>-dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations.</p><p><strong>Aims: </strong>Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD).</p><p><strong>Methods: </strong>In 2 open-label clinical trials, 27 healthy individuals and 14 patients with TRD, respectively, received inhaled DMT in a supportive clinical setting. Repeated assessments were conducted from baseline up to 12 months (only patients), including state anxiety (State-Trait Anxiety Inventory State, STAI-S), life satisfaction (Satisfaction with Life Scale, SWL), and quality of life (World Health Organization Quality of Life Instrument - Abbreviated Version, WHOQOL-BREF, and Spirituality, Religion and Personal Beliefs Module, WHOQOL-SRPB).</p><p><strong>Results: </strong>All volunteers showed reduced state anxiety after inhalation up to 1 day afterward. Healthy volunteers reported increased life satisfaction up to 14 days post-administration. Beyond symptom reduction, patients reported increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including Physical Health, Psychological Health, Social Relationships, and Environment (WHOQOL-BREF), and partially Inner Peace and Hope & Optimism (WHOQOL-SRPB).</p><p><strong>Conclusion: </strong>These findings suggest that inhaled DMT, combined with psychological support, is associated with recovery of daily functioning and health domains in patients with depression. Although limited by open-label design, lacking placebo control, and modest sample size, this exploratory study highlights the value of incorporating multidimensional outcomes in psychedelic research and DMT's potential relevance in both clinical and public health contexts.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1270-1280"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5-HT_1A receptor blockade potentiates the subjective effects of DMT.","authors":"Zarmeen Zahid, Rick J Strassman, Clifford R Qualls, Sandeep M Nayak","doi":"10.1177/02698811261443696","DOIUrl":"10.1177/02698811261443696","url":null,"abstract":"<p><strong>Introduction: </strong>Serotonergic psychedelics are being investigated in the treatment of various disorders and in the improvement of well-being. Evidence suggests that their subjective effects may play a role in long-term behavioral outcomes. The subjective effects are mediated by 5-HT_2A receptor agonism, but the 5-HT_1A receptor may also play a role in the subjective effects. This study elucidates the effects of 5-HT_1A receptor blockade using pindolol pre-treatment on the subjective effects induced by <i>N,N</i>-dimethyltryptamine (DMT).</p><p><strong>Methods: </strong>In a double-blind, randomized, placebo-controlled within-subjects design, 12 (10 males, 2 females) experienced hallucinogen-using participants received a sub-hallucinogenic dose of intravenous DMT fumarate, 0.1 mg/kg, after pre-treatment with 30 mg oral racemic pindolol. Subjective effects were measured using the Hallucinogen Rating Scale.</p><p><strong>Results: </strong>Pindolol pre-treatment increased DMT-induced subjective effects with a moderate effect size (<i>M</i> = 0.514). Blood pressure and mean arterial pressure also increased with pindolol pre-treatment at 2 minutes following DMT administration, but heart rate was not affected.</p><p><strong>Conclusions: </strong>5-HT_1A receptor blockade results in a global intensification of DMT-induced subjective effects, suggesting a functional role of 5-HT_1A receptor action in the mechanism of psychedelic-induced subjective effects.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1261-1269"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-<i>N,N</i>-dimethyltryptamine) in patients with treatment-resistant depression.","authors":"Claire Roberts, Mathieu Seynaeve, Anna O Ermakova, Fiona Dunbar, Hattie Wells, Adeep Puri, Catherine Bird, James J Rucker","doi":"10.1177/02698811261420087","DOIUrl":"10.1177/02698811261420087","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the safety and effect on clinical outcomes of depression of Beckley Psytech Ltd (BPL)-003, an intranasal formulation of 5-methoxy-<i>N,N</i>-dimethyltryptamine, in patients with moderate-to-severe major depressive disorder (MDD) with treatment-resistant depression (TRD).</p><p><strong>Methods: </strong>Twelve participants with TRD were enrolled in a 12-week, open-label, phase 2a trial. Safety of a single intranasal dose of 10 mg BPL-003 was assessed through clinical evaluations, treatment-emergent adverse events (TEAEs) and Readiness for Discharge Questionnaire (RDQ). Key depression-related assessments were Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline, percentage of responders, and participants in remission on Days 2, 8, 29, 57 and 85 post-dose.</p><p><strong>Results: </strong>All participants completed the trial; 2 females, 10 males, aged 31-55 years. Nine (75.0%) participants had 18 treatment-related TEAEs; 8 mild, 9 moderate and 1 severe (increased blood pressure, which returned to baseline within the observation period), with nausea and nasal discomfort the most frequently reported. Ten participants were ready after their first RDQ (nominal time 90 minutes post-dose). Median time from dosing to discharge readiness was 98 minutes (range 95-167). There was a mean decrease in MADRS total score from baseline of 12.2-13.0 points across all timepoints between Days 2 and 85; most participants (10/11) were responders, and 7 were in remission at ⩾1 post-dose timepoint.</p><p><strong>Conclusion: </strong>Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1247-1260"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting and exploring ayahuasca effects: Perception, mind-wandering, and EEG oscillations.","authors":"Natan Silva-Costa, Jéssica Andrade Pessoa, Kátia Cristina Andrade, Sérgio Mota-Rolim, Fernanda Palhano-Fontes, Draulio B Araujo, Isabel Wießner","doi":"10.1177/02698811251389563","DOIUrl":"10.1177/02698811251389563","url":null,"abstract":"<p><strong>Background: </strong>Psychedelics induce profound changes in perception and thinking; however, little is known about the neural mechanisms and prediction of these effects.</p><p><strong>Aims: </strong>Investigating ayahuasca-induced experiences, mind-wandering, and electroencephalogram (EEG) oscillations, beyond the prediction of subjective experiences by baseline EEG.</p><p><strong>Methods: </strong>In a randomised, double-blind, placebo-controlled, parallel-arm design, 50 healthy volunteers received 1 mL/kg of ayahuasca or placebo. We measured subjective psychedelic experiences (Hallucinogen Rating Scale (HRS), Mystical Experience Questionnaire (MEQ)) and mind-wandering (Amsterdam Resting-State Questionnaire (ARSQ)). EEG signals were assessed before administration (+0h), and 2 hours (+2h) and 4 hours (+4h) post-administration. Relationships between subjective and EEG effects were examined.</p><p><strong>Results: </strong>Ayahuasca, compared to placebo, induced subjective experiences, including changed perception, cognition, emotion (HRS), mystical experiences (MEQ), and visual, discontinuous, and content-laden thinking (ARSQ). Ayahuasca, compared to placebo, changed EEG oscillations, including decreased global alpha as well as increased frontomedial delta and right posterior theta and beta. Under ayahuasca, lower theta correlated with higher mystical experiences (MEQ) and higher alpha correlated with lower Thoughts about Nothing (ARSQ). Baseline global EEG oscillations predicted ayahuasca-induced experiences, with lower theta linked to higher interoception (HRS Heart Beat, HRS Rush, ARSQ Somatic Awareness) and lower beta linked to higher positive emotionality (HRS Happy).</p><p><strong>Conclusion: </strong>Ayahuasca induced consciousness alterations, visual, bodily, emotional, and mystical experiences, chaotic and meaningful mind-wandering, and decreased especially alpha. While acute theta seems inversely related to mystical experiences, baseline theta and beta seem to inversely predict interoception and emotionality.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1305-1320"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}