Journal of Psychopharmacology最新文献

{"title":"Efficacy of N, N-dimethyltryptamine (DMT) psychedelic therapy for substance misuse: A systematic review and meta-analysis.","authors":"Lisa M Wallace, Andrea Bujor, Gustavo Sudre, Mark Kennedy, Diana-Elena Bahnareanu, Khushi Mittal","doi":"10.1177/02698811261430518","DOIUrl":"10.1177/02698811261430518","url":null,"abstract":"<p><strong>Background: </strong>Conventional psychological and pharmacological substance abuse treatments are limited to moderate effect sizes and fail to magnify outcomes when combined. Analog psychedelic agents N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) show therapeutic potential for treatment-resistant psychiatric disorders including substance addictions.</p><p><strong>Methods: </strong>This systematic review and meta-analysis synthesized DMT intervention studies (1960-2024) across PubMed, PsycINFO, Web of Science, and EBSCO databases, calculating pooled effects for substance use reduction. Subgroup sensitivity analyses examined the impacts of psychotherapy, population type, and treatment design on outcomes.</p><p><strong>Results: </strong>DMT yielded a large overall effect size for substance abuse reduction (<i>g</i> = 0.94, 95% CI: 0.56-1.31, <i>p</i> < 0.0001), with superior efficacy for drug use (<i>g =</i> 1.35, 95% CI: 0.63-2.07, <i>p</i> < 0.0001) compared to alcohol use (<i>g</i> = 0.65, 95% CI: 0.31-0.99, <i>p</i> < 0.0001). Studies incorporating psychotherapy showed significantly greater effects (<i>g</i> = 1.38, 95% CI: 1.06-1.71, <i>p</i> < 0.0001) than those without (<i>g</i> = 0.60, 95% CI: 0.09-1.12, <i>p</i> < 0.0001), with significant subgroup difference (<i>p</i> = 0.0121). High risk of bias and high heterogeneity were observed (<i>I</i>² = 96.9%), with effects varying by substance type and treatment context. No publication bias was detected.</p><p><strong>Conclusion: </strong>When combined, available studies demonstrate DMT's potentially substantial post-treatment efficacy for substance misuse, particularly with psychotherapy. Effect magnitudes vary by abused substances. Included studies had substantial methodological limitations and high risk of bias. Reported effects should therefore be interpreted as preliminary rather than indicative of established efficacy. Furthermore, the use of exploratory subgroup analyses in this review can only conclude that DMT efficacy for treating alcohol and substance abuse disorders is highly heterogeneous, depending on study and treatment design. If sustained positive results are clearly demonstrated in future research, it might position DMT-assisted psychotherapy as an effective, economical alternative to conventional treatments.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1224-1246"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classic psychedelics and personality: An updated systematic review.","authors":"Anna Beatriz Vicentini, Caio César de Paula, José Augusto Silva Reis, José Carlos Bouso, Jaime E C Hallak, Rafael G Dos Santos","doi":"10.1177/02698811261449386","DOIUrl":"10.1177/02698811261449386","url":null,"abstract":"<p><strong>Background: </strong>The impact of classic psychedelics (5-HT2A receptor agonists) on personality traits has been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are linked to agonism at cortical serotonergic 5-HT_2A receptors. However, research results are contradictory. Therefore, the present paper aims to systematically evaluate the effects of psychedelics on personality, updating (2016-2024) a previous systematic review by Bouso and collaborators (2018). The International Prospective Register of Systematic Reviews ID for this study is CRD42024582704.</p><p><strong>Method: </strong>Systematic review using four databases (PubMed, LILACS, PsycINFO, and SciELO) including randomized controlled trials, open-label, and observational studies. Interventions included the consumption of any classic psychedelic (lysergic acid diethylamide, psilocybin, ayahuasca/dimethyltryptamine, mescaline), and the studies were required to use some instrument for personality assessment. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct the data collection.</p><p><strong>Results: </strong>Out of 6043 references screened, 48 studies were included: 14 experimental and 34 observational. The most consistent findings were increases in <i>Openness</i> and reductions in <i>Neuroticism</i>, especially with psilocybin and ayahuasca. Changes in other traits, such as <i>Extraversion</i>, <i>Agreeableness</i>, and <i>Conscientiousness</i>, were more variable. Microdosing was associated with modest reductions in <i>Neuroticism</i> and higher <i>Absorption</i>. Most studies used instruments based on the Five-Factor Model, reflecting its growing dominance.</p><p><strong>Conclusions: </strong>Classic psychedelics seem to promote lasting personality changes, most consistently increasing <i>Openness</i> and reducing <i>Neuroticism</i>. Future research would benefit from combining experimental and naturalistic designs, using longer follow-up periods and more diverse personality models to better understand the interplay between psychedelics and personality, thus providing a more accurate guide for clinical use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1187-1212"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101679","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":"Ayahuasca-inspired DMT/harmine formulation alters creative thinking dynamics during artistic creation.","authors":"Dila Suay, Helena D Aicher, Berit Singer, Michael J Mueller, Alen Jelusic, Lionel Calzaferri, Paul Springfeld, Dario A Dornbierer, Milan Scheidegger","doi":"10.1177/02698811251353256","DOIUrl":"10.1177/02698811251353256","url":null,"abstract":"<p><strong>Background: </strong>While psychedelics are often claimed to enhance creativity, their precise effects on distinct stages of creative cognition remain poorly understood. This study investigated the acute effects of an ayahuasca-inspired formulation combining N,N-dimethyltryptamine (DMT) and harmine (DMT/HAR), as well as harmine alone (HAR), on micro-level (divergent/convergent thinking) and macro-level (creative process dynamics) creativity.</p><p><strong>Methods: </strong>In a double-blind, placebo-controlled, within-subject design, 30 healthy male participants completed three sessions (DMT/HAR, HAR, placebo). Micro-level creativity was assessed using the picture concept task (convergent thinking) and alternative uses task (divergent thinking). Macro-level dynamics were examined through a real-world painting task using the creative process report diary, which captured dynamic stage transitions. Subjective experiences were also recorded to explore their predictive value for creativity.</p><p><strong>Results: </strong>DMT/HAR significantly impaired convergent thinking, particularly in individuals with higher baseline reasoning. Divergent thinking showed no overall effect but revealed trend-level reductions in fluency and elaboration under DMT/HAR. At the macro-level, both DMT/HAR and HAR reduced incubation-related transitions, while DMT/HAR uniquely decreased transitions from incubation to illumination, suggesting altered pathways to insight. Subjective experiences such as altered meaning perception and increased insightfulness selectively predicted divergent, but not convergent, thinking outcomes.</p><p><strong>Conclusions: </strong>This study demonstrates that the effects of DMT/HAR on creativity are not uniform. By capturing real-world creative behavior through an ecologically valid painting task, this study offers the first evidence that psychedelics influence not only creative cognition but also the dynamic processes that give rise to it. These findings highlight the importance of integrating cognitive, phenomenological and process-level perspectives to better understand creative thinking under altered states. Future research should further investigate how individual differences in subjective experience and cognitive style modulate the unfolding of creative processes under psychedelics.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1292-1304"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862312","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":"Speech markers of psychological change following a psychedelic 5-MeO-DMT retreat.","authors":"Joanna Kuc, Rosalind G McAlpine, Amelia Sellers, George Blackburne, Daniel R Lametti, Jeremy I Skipper","doi":"10.1177/02698811261443690","DOIUrl":"10.1177/02698811261443690","url":null,"abstract":"<p><strong>Background: </strong>5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent, short-acting psychedelic, induces profound shifts in cognition, affect, and self-awareness. Because language explicitly expresses these domains and voice implicitly conveys them, both may serve as potential 'biomarkers' of behavioural change.</p><p><strong>Aim: </strong>This study introduces a novel framework for analysing baseline language and vocal features, pre- to post-psychedelic changes, and assessing their potential to predict subjective experiences and psychological outcomes.</p><p><strong>Methods: </strong>Daily voice journals from 29 participants were collected via \"RetreatBot\" for 2 weeks before and after 5-MeO-DMT (1 × 12 mg). Transcripts were analysed using natural language processing (bag-of-words for vocabulary; transformer model for textual affect), and acoustic features (e.g. pitch, jitter, shimmer) were extracted to assess vocal dynamics.</p><p><strong>Results: </strong>Following 5-MeO-DMT, speech markers revealed increased cognitive language, decreased social words, and altered voice quality (increased jitter/shimmer). Baseline speech patterns predicted psychedelic preparedness, emotional breakthrough, and post-experience well-being.</p><p><strong>Conclusion: </strong>This first longitudinal analysis of speech markers surrounding a psychedelic retreat reveals a shift from external focus to introspection. Speech markers predicted and tracked psychological transformation surrounding the 5-MeO-DMT retreat experience, establishing vocal journaling as a valuable framework for monitoring changes during the \"preparation\" and \"integration\" periods.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1321-1340"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing mindfulness and compassion through an ayahuasca-inspired formulation containing N,N-DMT and harmine: A randomized controlled trial in healthy subjects.","authors":"Helena D Aicher, Ilhui A Wicki, Daniel Meling, Michael J Mueller, Dario A Dornbierer, Milan Scheidegger","doi":"10.1177/02698811251344689","DOIUrl":"10.1177/02698811251344689","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness and compassion are therapeutically relevant and can be increased through different forms of meditation practices. However, meditation practice needs time and commitment. These resources are often limited in patients with mood disorders. Therefore, efficacious remedies that increase mindfulness and compassion could provide therapeutic options. This study aimed to investigate the relationship between psychedelic experiences induced by an ayahuasca-inspired N,N-dimethyltryptamine (DMT)/harmine formulation on mindfulness and compassion in healthy subjects.</p><p><strong>Methods: </strong>This study applies a randomized, double-blind, placebo-controlled within-subjects design in a laboratory setting with 31 healthy participants. Each subject received a formulation comprising DMT + harmine, harmine + placebo, and placebo only on three different study days. Primary outcomes were mindfulness (MINDSENS) and compassion (SOCS).</p><p><strong>Results: </strong>A significant effect of the drug on mindfulness (<i>p</i> < 0.05, <i>F</i> = 3.41), self-compassion (SOCS-S; <i>p</i> < 0.01, <i>F</i> = 7.53), and compassion with others (SOCS-O; <i>p</i> < 0.05, <i>F</i> = 3.37) 1 day post-treatment was found. Significant differences between the high- and low-sensitivity groups were found for mindfulness (<i>p</i> < 0.05, <i>F</i> = 6.54), self-compassion (<i>p</i> < 0.05, <i>F</i> = 4.21), and compassion with others (<i>p</i> < 0.05, <i>F</i> = 4.42).</p><p><strong>Conclusions: </strong>In line with previous studies on traditional botanical ayahuasca, our findings support the notion that the DMT/harmine formulation might have therapeutic potential through its ability to acutely enhance mindfulness and compassion. Continuing studies in therapeutic settings are needed to further elucidate the mechanisms of action of ayahuasca-inspired formulations.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1281-1291"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ayahuasca on neuropsychological performance and social cognition: A systematic review.","authors":"Caio César de Paula, Anna Beatriz Vicentini, Lorena Terene Lopes Guerra, José Carlos Bouso, Jaime E C Hallak, Rafael G Dos Santos","doi":"10.1177/02698811261424212","DOIUrl":"10.1177/02698811261424212","url":null,"abstract":"<p><strong>Background: </strong>Ayahuasca has aroused increasing interest due to its therapeutic effects. However, its effects on cognition are poorly understood. Hence, a systematic review evaluating the cognitive effects of ayahuasca was conducted.</p><p><strong>Method: </strong>This systematic review was conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in PubMed, Web of Science, PsycINFO, SciELO, and LILACS using terms related to ayahuasca, neuropsychology, and social cognition, encompassing all studies published up to March 25, 2025. Human observational, experimental, and clinical studies assessing neuropsychological performance or social cognition following ayahuasca administration were included. Titles, abstracts, and full texts were independently screened by two reviewers, with disagreements resolved with a third reviewer.</p><p><strong>Results: </strong>A total of 16 articles were selected, including observational (<i>n</i> = 11) and experimental (<i>n</i> = 5) studies. The results indicated distinct effects of ayahuasca on cognition. In the short term, improvements in functions such as working memory and cognitive flexibility were observed and attributed to neurochemical modulation of cortical networks. Regarding social cognition, observational studies have reported an increase in empathy and emotion recognition, while experimental studies have only observed reduction in reaction times. Long-term studies in general did not observe neuropsychological deficits, with some studies reporting improved memory and executive function.</p><p><strong>Conclusions: </strong>Although these findings are promising, there are methodological limitations, such as small sample sizes, diverse administration protocols, the observational nature of several studies, and possible learning effects. Further controlled, randomized studies are needed to elucidate the underlying mechanisms and consolidate the evidence. The PROSPERO ID for this study is CRD42024559125.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1151-1165"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377916","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 systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects.","authors":"Elliot Hampsey, Kirsty Martin, Michail Kalfas, Louis Benson, Sirid Wihlborg, Luke Jelen, Allan H Young, James Rucker","doi":"10.1177/02698811261453938","DOIUrl":"10.1177/02698811261453938","url":null,"abstract":"<p><strong>Introduction: </strong>Despite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood.</p><p><strong>Methods: </strong>This systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy-<i>N,N</i>-dimethyltryptamine (5-MEO-DMT).</p><p><strong>Results: </strong>We identified 32 eligible trials. LSD was the most studied compound, followed by DMT, split between intravenous (IV) and oral formulations. Psilocybin was also frequently studied. Mescaline was reported in two trials, with IV LSD, IV psilocybin, inhalation 5-MEO-DMT, and intranasal 5-MEO-DMT reported in single studies. Key findings include dose proportional <i>C</i>_max values for LSD and psilocybin, alongside differences between oral and IV formulations of DMT that may be clinically significant.</p><p><strong>Discussion: </strong>This systematic review highlights key variations in absorption, distribution, and elimination between the studied compounds that may have important implications in both clinical and research settings.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1213-1223"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of LSD, DMT and psilocybin on cognitive and psychological functions: A systematic review of the literature.","authors":"Marten Kase, Karl Kristjan Kaup, Jaan Aru","doi":"10.1177/02698811251412012","DOIUrl":"10.1177/02698811251412012","url":null,"abstract":"<p><p>We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies examining the influence of psychedelics on empathy, reaction time, attention, inhibition, emotional processing, memory, cognitive flexibility, and related cognitive functions using experimental methods. Additional searches were done in Google Scholar. The systematic review included 32 studies. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Psychedelics impaired, enhanced or had no effect on memory depending on the task and timing of the assessment. Dose-dependent impairments were seen in many of the reaction time, attention, and inhibition tasks, although some studies found no effects. Some studies found impaired recognition of negative stimuli under the acute effects of psychedelics. The findings regarding cognitive flexibility were mixed. Many studies had small samples, and it is hard to find a reliable placebo due to psychedelics' unique subjective effects. Future studies should use bigger samples and also study more longitudinal effects of psychedelics on cognitive and psychological functions.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1166-1186"},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of aripiprazole in modulating putamen and thalamus functional connectivity in early psychosis patients.","authors":"Chi Chen, I-Fei Chen, Wan-Chen Chang, Chen-Chung Liu, Ming H Hsieh, Tzung-Jeng Hwang, Hai-Gwo Hwu, Yi-Ting Lin, Pei-Chi Tu, Chih-Min Liu","doi":"10.1177/02698811261464518","DOIUrl":"https://doi.org/10.1177/02698811261464518","url":null,"abstract":"<p><strong>Background: </strong>Early psychosis is marked by cortico-striatal and thalamocortical dysconnectivity, yet how aripiprazole modulates these circuits remains unclear.</p><p><strong>Methods: </strong>We examined putamen and thalamus functional connectivity (FC) in 30 early psychosis patients (ultra-high-risk, first-episode psychosis, schizophreniform disorder, or first-episode schizophrenia) and 30 matched healthy controls. At baseline, patients were naïve to dopamine receptor-targeting medication or minimally exposed (<12 weeks). All patients received flexible-dose aripiprazole, and symptoms were assessed using the Positive and Negative Syndrome Scale at baseline, days 14 and 28. Baseline resting-state functional MRI was acquired for patients and controls, and follow-up scans for patients after 41.6 ± 13.9 days of treatment.</p><p><strong>Results: </strong>Compared with controls, patients showed hypoconnectivity within/between bilateral putamen, between putamen and thalamus, and between thalamus and salience network (SN) nodes. In contrast, hyperconnectivity was observed between the putamen and both sensorimotor (SM) and default mode network (DMN) nodes, as well as between the thalamus and SM nodes. After treatment with aripiprazole, FC increased within/between bilateral putamen, between putamen and SN nodes, and between thalamus and SN nodes, and decreased between thalamus and SM nodes and between putamen and SM nodes. At the uncorrected level (<i>p</i> < 0.05), increases in FC between the right ventral rostral putamen and bilateral putamen correlated with improvement in positive symptoms.</p><p><strong>Conclusion: </strong>Findings suggest aripiprazole partially normalizes aberrant striatal-thalamic coupling early in psychosis, and putaminal FC changes may relate to clinical response. Aripiprazole may achieve therapeutic benefits by restoring integration within striatal hubs and their crosstalk with large-scale networks implicated in psychotic symptom expression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261464518"},"PeriodicalIF":5.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604357","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":"Mediators of treatment response in a clinical trial of naltrexone and bupropion for methamphetamine use disorder: A longitudinal mediation analysis.","authors":"Ramin Mojtabai, Ryoko Susukida, Mehdi Farokhnia, Trang Quynh Nguyen, Lorenzo Leggio, Cecilia Bergeria, Smita Prasad, Kelly E Dunn, Masoumeh Amin-Esmaeili","doi":"10.1177/02698811261464533","DOIUrl":"10.1177/02698811261464533","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying pharmacological treatments for stimulant use disorders are poorly understood. This study examined whether changes in craving, depressive symptoms, and/or impulsivity mediate treatment effect in pharmacotherapy with combined naltrexone and bupropion for methamphetamine use disorder (MUD).</p><p><strong>Methods: </strong>The study was based on secondary analysis of data from the Accelerated Development of Additive Pharmacotherapy Treatment for methamphetamine disorder (ADAPT-2) trial which randomized adults with MUD to combined treatment with injectable naltrexone (380 mg every 3 weeks) plus oral bupropion (450 mg daily) versus placebo. A total of 403 adults with MUD participated in the first stage; 225 of first stage participants in the placebo arm who did not respond to treatment were re-randomized in the second stage. Mediation effects were examined using longitudinal multi-level structural equation modeling.</p><p><strong>Results: </strong>Naltrexone-bupropion treatment was associated with decreases in drug use, craving, depressive symptoms, and impulsivity. The indirect effect of treatment through change in craving was significant (self-reported use = -0.21, 95% credible interval (CrI) = -0.35, -0.09; drug screen-ascertained use = -0.36, 95% CrI = -0.63, -0.16). Change in craving mediated 56% of the treatment effect on self-reported drug use and 45% of the effect on drug screen-ascertained use. Estimates for mediated effects for depressive symptoms and impulsivity were smaller in magnitude and nonsignificant.</p><p><strong>Conclusion: </strong>Reduction in craving mediates the effect of naltrexone-bupropion pharmacotherapy in MUD. Craving may serve as a surrogate measure of treatment efficacy in short-term trials and help identify promising candidate medications to be tested in larger and longer-term trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov number: NCT03078075.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261464533"},"PeriodicalIF":5.3,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592424","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}