Previous systematic reviews and meta-analyses have reported impressive antidepressant effects of ketamine in treatment-resistant depression (TRD). While ketamine has been compared with electroconvulsive therapy (ECT), the gold standard treatment, the extent and durability of its antidepressant effects over longer periods remain unclear. To our knowledge, this is the first systematic review...
Background: 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. Methods: This...
3,4-methylenedioxymethamphetamine (MDMA) is being investigated as a new therapy for post-traumatic stress disorder (PTSD). With antidepressants as the first-line pharmacotherapy for PTSD, it is important to understand any drug-drug interactions between antidepressants and MDMA. This study aimed to investigate the association between antidepressant use and MDMA fatality using a drug-death...
The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline,...
BACKGROUND: Current treatments for obsessive-compulsive disorder (OCD), including serotonin reuptake inhibitors and cognitive-behavioral therapy, are often insufficient. Psilocybin, a 5HT2a agonist psychedelic, has shown promise for treating OCD, but rigorous evidence is still needed. AIMS: This randomized clinical trial evaluated safety, tolerability, and benefit of multiple psilocybin doses...
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. This systematic review was conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in...
This meta-analysis and systematic review examined the effects of psychedelic substances on death anxiety, specifically evaluating whether psychedelic experiences are associated with statistically significant reductions in death anxiety. A systematic search identified 8 studies suitable for meta-analysis and 10 additional studies for systematic review. Using a random-effects model, the...
Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways. This study evaluated the effects of THC, CBD, and their...
Background: Schizophrenia is a serious psychiatric disorder that affects over 24 million people worldwide. Current therapies treat positive symptoms but show little efficacy for negative and cognitive symptoms, which can impact quality of life. Development of effective medication for this unmet medical need is imperative. Phytocannabinoids, such as cannabidivarin (CBDV), show promising results...
One of the most robust acute effects of cannabis is impaired memory. Although memory is not a unitary construct, most cannabis research has focused on verbal memory. Less is known about its effects on more ecologically valid domains of memory, such as prospective and temporal order memory. We conducted a randomized, double-blind, placebo-controlled study to map out which aspects of memory are...
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.
Background: Endocannabinoid (eCB) signalling is pivotal for brain programming, including the reward system neurodevelopment. Prenatal exposure to Δ9-tetrahydrocannabinol (THC), cannabis psychoactive component, can perturb eCB tone via CB1 receptor and alter the response to salient stimuli. Aim: We hypothesise that prenatal THC exposure disrupts the eCB-dopamine nexus in the nucleus accumbens...
Background: While ketamine is widely used in anesthesia and pain management, its non-medical use is increasing worldwide. In France, surveillance data indicate a sharp rise in ketamine-related disorders, but comprehensive characterization of affected patients and associated complications remains limited. Aims: To examine trends on ketamine in France from 2019 to 2023, and describe severe...
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...
Classical psychedelics-a broad class of compounds that include psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline-have shown significant promise for the treatment of mental health conditions in recent clinical trials. Organizations such as the National Network of Depression Centers (NNDCs) can play a pivotal role in uniting researchers and clinicians working in this field...
To investigate the reporting of harms in systematic reviews (SRs) focused on hallucinogen use. 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...
Indigenous Peoples have cultivated and protected natural psychoactive medicines through ceremony, kinship, and spiritual responsibility across generations, yet their long-standing contributions have often been marginalized through extractive research, commercialization, and policy exclusion. It is Indigenous communities that have stewarded and gained expertise working with psychoactive...
Background: Changes in well-being, personality, and personal values have been documented post-psilocybin; however, evidence from placebo-controlled trials is limited. Aims: To examine the effects of psilocybin versus placebo on psychiatric symptoms, personality, and personal values in healthy participants. Potential mediators were also explored. Methods: This secondary analysis used data from a...
Lysergic acid diethylamide (LSD) has been considered as a potential treatment for depression for over 75 years, but its therapeutic potential has only recently been considered in mainstream psychiatry. Repeated ingestion of low doses of LSD ("microdoses") is thought to reduce depression, but the neurobiology underlying this effect is unknown. We previously reported that low doses of LSD...
Background: Psilocybin has shown rapid and sustained antidepressant effects in patients with major depressive disorder, yet the neurobiological mechanisms underlying these outcomes remain unclear. Aims: This study aimed to bridge clinical and preclinical findings by investigating the relationships between 5-HT 2A receptor occupancy (RO) achieved after administration of psilocybin and its...
Abuse potential assessment of drugs with central nervous system activity is a critical component of the development of new medications for regulatory filings for approval worldwide. These new drug applications typically include recommendations for scheduling status as a controlled substance, if scheduling is warranted. This commentary focuses on the approach and current issues related to...
Background: Although psychedelics have regained attention as potential treatment tools for various mental disorders, little research has examined their impact on temporal perception. Aims: This double-blinded placebo-controlled study aimed to investigate changes in temporal perception under psilocybin, both through performance during the Temporal Bisection Task (TBT) and through subjective...
This review provides an overview of Roland R. Griffiths' history of research, and his mentoring and collaborating approach to science that contributed to his impact in behavioral and neuropsychopharmacology and psychedelic medicines development. The approach was to summarize studies in his major domains of research, including preclinical and clinical abuse liability assessment science, alcohol,...
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...
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...