Journal of Psychopharmacology最新文献

Rationale: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication difficulties and restricted, repetitive behaviors. Although several pharmacological agents have been trialed, treatments for core features remain limited. Propranolol, a non-selective β₁/β₂-adrenoceptor antagonist (β-blocker, NbN), has shown potential effects across multiple ASD-related domains.

Methods: A narrative review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses principles. Systematic searches in PubMed, Scopus, ScienceDirect, and ProQuest identified 22 studies, of which 15 were included, comprising randomized controlled trials, single-dose psychopharmacological challenge studies, and reviews.

Results: Evidence suggests that propranolol may improve social anxiety, verbal problem-solving, cognitive flexibility, emotional regulation, and behavioral dysregulation. Benefits of facial scanning and verbal fluency have also been described. The drug may attenuate adrenergic hyperarousal and promote parasympathetic dominance. However, most positive findings derive from small samples or single-dose studies, while sustained double-blind trials are scarce. Polypharmacy contexts remain underexplored.

Discussion: Propranolol may serve as an adjunctive therapy in selected ASD cases, particularly when other strategies are insufficient. Its central nervous system penetration and anxiolytic profile support potential clinical use. Emerging evidence suggests that autonomic biomarkers and pharmacogenetic factors (e.g., CYP2D6, ADRB1/2 polymorphisms) could inform patient selection.

Conclusions: Propranolol shows promise in modulating adrenergic activity relevant to several ASD symptom domains. The most consistent evidence supports anxiolytic effects under sustained dosing, whereas cognitive and behavioral findings remain preliminary. Larger, placebo-controlled trials with biomarker integration are needed to clarify efficacy, long-term safety, and clinical positioning. Until then, its use should remain cautious and highly individualized.

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the associations of anti-saccade error rate with stimulus type (cocaine, neutral) and with BDI-II total score. Penalized regression then modeled the error rate among the entire set of BDI-II items to select the most relevant symptom correlates.

Results: Anti-saccade error rates were higher on cocaine relative to neutral trials (p < 0.001), confirming attentional bias. Error rates were positively associated with BDI-II total scores, controlling for demographic and recent cocaine use variables (p < 0.001); this association did not differ by stimulus content (p = 0.742). Among BDI-II items, Loss of Pleasure, Crying, Agitation, Changes in Sleeping Pattern, Concentration Difficulty, Tiredness, and Loss of Interest in Sex were retained by the penalized regression of error rates.

Conclusions: Attentional bias was drug-specific, and overall error rates were strongly related to somatic factors underlying depression in CUD. The association between inhibitory control and depression in CUD may be driven by physiological symptomatology, including sleep impairment and fatigue.

Clinicaltrials: gov:NCT02896712.

Background: The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the 3D-ASC remains widely used for summarizing broader experiential domains.

Aims: We wanted to provide an updated, psychometrically revalidated version of the ASC. We tested whether the 42-item 11-ASC could be integrated into a coherent three-dimensional framework. We further hypothesized that this revised model would outperform the original 66-item 3D-ASC while preserving its conceptual clarity.

Methods: Data from 901 5D-ASC questionnaires from 398 healthy participants across 16 randomized, mostly placebo-controlled psychedelic (lysergic acid diethylamide, psilocybin, mescaline, and N,N-dimethyltryptamine) studies were split for exploratory and confirmatory factor analysis. We compared the 3D-ASC and 11-ASC in terms of reliability and model fit, and tested whether the 11-ASC could be summarized within a three-dimensional model.

Results: Ten of the 11 subscales formed three higher-order dimensions-Positive (PosE), Distressing (DisE), and Perceptual (PerE) effects-mirroring the 3D-ASC but with improved fit. We propose this as the 3D-ASCr scale. The Anxiety subscale could not be integrated due to consistent floor effects (low anxiety in the sample), but given its clinical relevance, it is retained within 3D-ASCr (as part of DisE or a standalone subscale).

Conclusion: The 3D-ASCr is an updated version of the ASC and is recommended for use with classic serotonergic psychedelics in both clinical practice and research.

Objective: To investigate the reporting of harms in systematic reviews (SRs) focused on hallucinogen use.

Methods: A search was conducted in May 2022 using MEDLINE, Embase, Epistemonikos, and Cochrane databases to retrieve SRs focused on the use of hallucinogens. Investigators screened the titles and abstracts from the search for study inclusion in a masked, triplicate fashion. Investigators analyzed the included SRs for reported harms linked to hallucinogen use via a pre-established harms reporting assessment. Methodological quality of SRs was graded using the A MeaSurement Tool to Assess Systematic Reviews-2 (AMSTAR-2) in a masked, duplicate manner. Study characteristics for each review were extracted in duplicate. The corrected covered area was measured for SR dyads.

Results: Our search returned 908 articles, and 32 SRs met eligibility criteria for final harms reporting analysis. Of the included reviews, 28 SRs (56.2%) indicated harms as a primary or secondary outcome, 2 SRs (6.3%) reported predetermined methods to grade, collect harms data, or statistically analyze harms. A significant relationship was found between completeness of harm reporting and whether harms were listed as a primary or secondary outcome.

Conclusion: Harms were largely underreported in scientific literature regarding hallucinogen use, despite many studies designating them as a primary or secondary outcome. Inadequate reporting is unlikely to provide credible evidence used to evaluate the benefit-harm trade-off. Therefore, steps should be taken to improve the reporting of harms in studies concerning hallucinogen use.

Psychedelics are gaining attention as putative treatments for a range of psychiatric conditions, and evidence suggests that they produce sustained behavioural and clinical change. Enhanced learning is an emerging candidate mechanism mediating these sustained effects. This narrative review synthesises evidence across behavioural, neural and computational levels to examine the current evidence base for how psychedelics may alter learning mechanisms. We propose that viewing psychedelic mechanisms through the lens of learning unifies context-dependent outcomes, increased environmental sensitivity and neuroplastic change. We discuss how persistent changes in top-down and bottom-up information processing at a systems-level may account for both the therapeutic and adverse effects of psychedelics, and highlight a mechanistic convergence between such systems-level changes and the recently identified psychedelic-mediated reopening of critical learning periods. This systems-level framework may explain why psychedelic outcomes vary widely and hinge critically on the context: it is the learning environment, including psychological support and therapeutic insights, which shapes the lasting effect. If the post-psychedelic period is characterised by a vulnerable neuroplastic state in combination with increased environmental sensitivity, usually observed uniquely during childhood, this would offer a window of opportunity for revision of entrenched beliefs. Understanding these mechanisms has important translational relevance for the design and implementation of psychedelic-assisted psychotherapy.

Background: Major depressive disorder (MDD) is a globally prevalent psychiatric condition associated with significant morbidity and often suboptimal treatment outcomes. Probiotics have emerged as a promising adjunctive therapy targeting the gut-brain axis in MDD.

Aims: This systematic review aimed to critically evaluate the efficacy of probiotics in the treatment of clinically diagnosed MDD, assess methodological quality and therapeutic readiness, and identify research gaps relevant to clinical application.

Methods: A systematic search of MEDLINE, Web of Science, and PubMed was conducted in June 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Double-blind, placebo-controlled, randomised controlled trials (RCTs) involving adults with MDD were included. Risk of bias was assessed using the Cochrane Risk of Bias tool.

Results: Thirteen RCTs involving 437 adults aged 18-75 years with MDD were included. Most trials reported improvements in depressive symptoms, particularly in outpatients with mild-to-moderate MDD treated with multi-strain formulations containing Lactobacillus and Bifidobacterium over 4-8 weeks. Secondary outcomes across metabolic, inflammatory, cognitive, neurotrophic, and gastrointestinal domains showed variable improvements. Probiotic benefits were most consistent in Iranian outpatients, more modest in European inpatients, and positive but variable in East Asian outpatients. Risk of bias was predominantly low, though attrition, selective reporting, and methodological heterogeneity remained sources of bias.

Conclusions: Probiotics appear safe and well-tolerated, with modest adjunctive benefit in MDD, most evident for multi-strain formulations in younger, outpatient populations with mild-to-moderate symptoms, supporting an individualised, context-dependent approach. Future trials should stratify patients, extend intervention durations, and integrate mechanistic endpoints to refine patient-tailored recommendations.

Rationale: Ketamine, known for its rapid-acting antidepressant effects, is often coadministered with other psychoactive drugs, including opioids and cannabinoids, in both clinical and recreational settings. We investigated whether ketamine (R-, S-, or racemic R, S-) isoforms alter the subjective effects of morphine or Δ⁹-tetrahydrocannabinol (THC) and whether the interoceptive effects of ketamine overlap with these drugs.

Objectives: Rats were trained to discriminate morphine (6.4 mg/kg) or THC (3 mg/kg) from their respective vehicle controls. Subsequently, different ketamine isoforms were administered at doses of 5, 10, or 30 mg/kg either prior to or instead of the training drug.

Results: In drug interaction tests, naltrexone (0.1 mg/kg) fully antagonized morphine's effects, and rimonabant (0.32, 1, and 3.2 mg/kg) partially inhibited THC cue. However, ketamine isoforms did not fully block the discriminative stimulus effects of morphine or THC. In generalization tests, as expected, fentanyl (0.1 mg/kg) fully substituted for the morphine cue, and cannabidiol did not substitute (10 mg/kg) or partially substituted (3 and 50 mg/kg) for the THC cue. However, none of the ketamine isoforms fully substituted for the morphine or THC cue. Ketamine isoforms did not alter response rates in the morphine experiment, but suppressed responding in the THC experiment.

Conclusions: These findings indicate that ketamine isoforms do not produce opioid- or cannabis-like subjective effects and are unlikely to fully mask the interoceptive effects of morphine or THC. However, their coadministration with cannabinoids may lead to pronounced sedative-like suppression. This warrants further investigation into the safety and interaction profiles of such drug combinations, particularly in therapeutic settings.

Background: Treatment acceptability impacts patient preference, adherence and clinical outcomes and is recognised as important in developing new treatments.

Aims: To evaluate factors associated with the acceptability of home-based transcranial direct current stimulation as a potential treatment for major depressive disorder (MDD).

Methods: We conducted exploratory factor analysis using principal component analysis with varimax rotation and parallel analysis to identify underlying factors and calculated Cronbach's alpha for both questionnaires. One questionnaire was investigated in a general population sample and another in a double-blind, randomised, sham-controlled clinical trial in MDD.

Results: The general population cohort consisted of 879 participants (628 women), and the clinical trial cohort included 151 MDD participants (104 women). The clinical trial questionnaire was assessed at baseline and after the 10-week randomised treatment. In the general population, two factors emerged: expected benefits and safety, and potential burdens (eigenvalues 4.27 and 1.22). In the clinical trial, one factor was evident at each time point. At baseline, all items were highly correlated and loaded onto a single factor (eigenvalue 1.52, explaining 30.45% of variance). At week 10, all components except side effects loaded onto a single factor (eigenvalue 1.84, explaining 36.71%). No differences were found between active and sham treatment arms. Acceptability components were well-related: two distinct factors (expected benefits and burdens) were found in the general population, while a single factor of general acceptability was observed in the MDD cohort.

Conclusions: These findings highlight the dynamic nature of acceptability and the importance of assessing it in treatment development.

Introduction: Schizophrenia is a severe mental disorder that impacts thoughts, emotions, and behavior, affecting 0.32% of the global population. While antipsychotic medications are crucial for managing symptoms, nearly half of individuals with schizophrenia experience weight gain, leading to treatment non-compliance and further health complications. Our systematic review and network meta-analysis aim to provide comprehensive evidence on the safety and efficacy of pharmacological and non-pharmacological interventions for antipsychotic-induced weight gain.

Methods: We conducted this study in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, following our protocol (CRD42024599597). We searched PubMed, Scopus, Web of Science, and Cochrane Library until July 2025. Only randomized placebo-controlled trials were included. We focused on anthropometric measurements and safety profiles. The primary outcome was weight change, while the secondary outcomes included waist-hip ratio, waist circumference, and hip circumference.

Result: Fifty-five studies were included in the meta-analysis, with a total of 2977 individuals. Regarding the weight change, the highest three interventions hold the highest probability of being the most effective therapy in weight loss compared to the Usual care group were Semagultide (MD: -13.5 [-17.3, -9.57], followed by Metformin + NutriEx (MD: -6.34, [-9.85, -2.9]), then Nizatidine (MD: -5.46 [-7.77, -2.76]). According to non-pharmacological interventions, all interventions showed significant reductions in weight (p-value < 0.05).

Conclusion: We found that Semaglutide has the highest probability of being the most effective therapy in the reduction of weight gain and BMI. Liraglutide was associated with mild adverse effects. Additional trials focusing on non-pharmacological approaches are essential.