PsychopharmacologyOctober 28, 2026Samantha N. Melendez, Margy Y. Chen, Claire L. Pince et al.
Cannabis research is advancing rapidly, yet fundamental questions persist regarding the optimal design of human studies to empirically assess the potential harms and benefits of cannabis. There exist central methodological differences between studies that rely on controlled dose paradigms, ensuring internal validity, and those that utilize naturalistic, self-administration approaches which...
Rationale Ketamine has emerged as a rapid-acting antidepressant drug for treatment-resistant depression in adults and is currently evaluated for adolescent depression. However, the long-term effects of ketamine exposure during this period of brain development remain unclear, particularly regarding addiction liability. Objectives To investigate whether repeated ketamine exposure during...
Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, females remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple...
Classical psychedelic drugs such as the tryptamine psilocybin can alter temporal perception. Previously, the phenylethylamine psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-HT2A receptor agonist, altered timing precision and accuracy in mice performing the discrete-trials temporal discrimination task (TDT), a retrospective timing task where subjects differentially respond depending on...
RATIONALE: Regular cannabis use has been associated with alterations in reward-related neural processes, yet findings remain inconsistent and the relationship between neural activity and behavioural performance is not fully understood. OBJECTIVES: The present study aimed to characterise neural and behavioural correlates of reward processing in regular cannabis users (CU) compared with matched...
Psilocybin can produce rapid and sustained antidepressant-like and anxiolytic effects, yet the receptor and circuit mechanisms underlying these behavioral changes remain unclear. While the serotonin 2A receptor mediates psilocybin's acute psychedelic effects, psilocin (the active metabolite of psilocybin) binds many serotonin receptor subtypes. Our prior work has identified the serotonin 1B...
MDMA is increasingly being studied for therapeutic applications, yet the prevalence and characteristics of post-acute negative effects remain debated. We aimed to characterize MDMA's post-acute negative effects, including prevalence and symptom profile among recreational users. Given preclinical work and limited human evidence suggesting that certain supplements and antidepressants may mitigate...
Combining meditation with psychoactive substances is often assumed to be a niche practice centred on classic psychedelics. We sought to broaden this narrative in two cross-sectional studies. Study 1 used a broad naturalistic sample (N = 1,391) to examine the prevalence of substance use, meditation, and their simultaneous combination, as well as associations with subjective happiness. Study 2...
The medical use of cannabis-derived products in children and adolescents has expanded beyond established indications for purified cannabidiol (CBD), with increasing investigation of CBD-rich extracts containing Δ9-tetrahydrocannabinol (THC) for neuropsychiatric conditions. Although preliminary studies suggest potential symptomatic benefits, the evidence remains limited by small samples,...
PsychopharmacologyOctober 13, 2026Marisa J. Savini, Kylie M. King, Lillianna P. Puppel et al.
Abstract: Rationale: Psychedelics are considered to be promising therapeutic agents that could effectively treat several psychological disorders. However, these compounds can exert acute adverse effects that limit their practicality. Objectives: Across three experiments, the present study examined the acute and delayed effects of psilocybin (PSIL) and its putatively non-hallucinogenic analog,...
PsychopharmacologyOctober 5, 2026Jingqi Xu, Adrien Nette, Christina Zakala et al.
Cannabis and tobacco are widely used substances with addiction potential, which have opposing effects on cognition and subjective experience and are often co-used in a single occasion. The purpose of this systematic review was to synthesize evidence of the acute effects of same-occasion co-use of cannabis and tobacco. Databases Embase, Medline, CINAHL, PsycINFO, and Web of Science were searched...
PsychopharmacologySeptember 29, 2026Praneet Suresh, Josie Kins, Lex Levkovskyy et al.
Psychedelics exhibit rapid, durable therapeutic effects across diverse psychiatric conditions, yet their broad-spectrum psychoactivity poses challenges for clinical translation. As a proof-of-concept, we aimed to quantify associations between 19 neurotransmitter receptors and the subjective effects of 21 psychedelic drugs with broadly assayed binding profiles. We used a custom Global Vectors...
RATIONALE An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition. OBJECTIVES In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects...
RATIONALE: Delta-9-tetrahydrocannabinol (Δ9-THC) has been reported to evoke psychedelic-like experiences at high doses in some individuals. However, the doses of Δ9-THC that occasion such effects and the phenomenology of these experiences are poorly understood. OBJECTIVES: This brief report presents preliminary findings from a pilot human laboratory study that directly compared the acute...
PsychopharmacologyAugust 27, 2026Shayan Eghdami, Mahsa Boroon, Amir-Abbas Keshavarz-Akhlaghi et al.
Approximately 40-60% of patients with obsessive-compulsive disorder (OCD) fail to respond to standard serotonergic and behavioral therapies. This systematic review evaluates the efficacy, durability, and safety of ketamine, a glutamate modulator, for moderate to severe OCD. Following PRISMA guidelines, we searched electronic databases through January 2026 for studies treating moderate-to-severe...
RATIONALE Sex differences in the effects of cannabis have been demonstrated in animals, though the human evidence is more equivocal. In particular, more work is needed to better understand interactions between sex and dose in determining acute pharmacological effects of cannabis, especially at higher potencies of Δ9-tetrahydrocannabinol (THC). OBJECTIVES Sex differences were examined following...
RATIONALE: Psilocybin (PSI) microdosing, defined as a repeated administration of sub-perceptual doses, has gained increasing attention as a potential therapeutic strategy for affective and anxiety disorders. However, some molecular mechanisms, particularly regarding epigenetic regulation in the medial prefrontal cortex (mPFC), remain poorly understood. OBJECTIVES: Therefore, the present study...
This paper critiques the use of the term "mysticism" in psychedelic research, arguing its continued use is outdated and misleading. It highlights the confusion stemming from the historical context of "mysticism," particularly through the works of Walter Stace and Walter Pahnke, whose ideas have shaped the psychedelic discourse despite being flawed and largely unexamined. The paper is divided...
Negative self-referential emotions such as embarrassment and shame play a key role in the psychopathology of psychiatric disorders but are often insufficiently addressed by standard treatments. Psychedelics such as ayahuasca - an Amazonian plant decoction containing the psychedelic N,N-dimethyltryptamine (DMT) and harmala alkaloids, have been proposed to positively modulate self-referential...
6-(2-aminopropyl)benzofuran (6-APB) is a recreational drug that is structurally similar to MDMA. Very little is known about the behavioral effects of 6-APB or its dose-effect relationship in vivo. As the popularity of new psychoactive substances (NPS), such as 6-APB, increases due to their unscheduled status and easy availability, it is important to understand the potential benefits and/or...
In humans, researchers can readily query the subjective states elicited by drugs of abuse, but no such introspective readout is currently available in rodents. Rats can convey information relevant to their internal states via ultrasonic vocalizations (USVs). We sought to measure USVs and locomotor behavior as parallel behavioral indices of the effects of drugs and ventral tegmental area...
PsychopharmacologyJuly 1, 2026Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
Interest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid...
RATIONALE: Attention-deficit hyperactivity disorder (ADHD) shows substantial heterogeneity in symptoms and cognitive deficits. According to the Triple Pathway Model, this variability may stem from impairments in three neuropsychological domains: inhibition, motivation, and temporal processing. Repeated low-dose administration of psychedelics is being explored as a treatment for ADHD, but...
RATIONALE: Clinical interest in psilocybin-assisted rehabilitation for motor disorders is growing. However, psilocybin's motor effects are under-researched, and quantifying them is essential for assessing treatment risks and outcomes. OBJECTIVES: This study aims to clarify whether acute effects of psilocybin disrupt established patterns of manual dexterity and coordination. Specifically, we...
BACKGROUND: Alcohol use disorder (AUD) remains a major global health concern, with high morbidity and mortality and limited long-term treatment success. Psychedelic therapy has re-emerged as a potential novel intervention for AUD, yet little is known about how affected individuals perceive such treatments. METHODS: This mixed-method study explored attitudes and perceptions of psychedelic...