Abstract Psilocybin acutely alters neurotrophic, neurochemical, and immune markers, but the relationships between these responses and circulating microRNAs (miRNAs), i.e. non-coding RNAs that regulate post-transcriptional gene expression, remain unclear. In a randomized, double-blind, placebo-controlled study of 62 healthy adults who received psilocybin (0.17 mg/kg) or placebo, we previously...
Women experience a disproportionate burden of affective and stress-related disorders, with symptom variability shaped by endocrine transitions across the menstrual cycle, pregnancy, postpartum, and menopause. Although psychedelic-assisted therapies are increasingly investigated for these conditions, hormonal state represents a largely unaccounted determinant of variability in exposure,...
Serotonergic psychedelics are advancing as psychiatric treatments, yet acute responses vary between individuals and the contribution of sex, a fundamental biological variable, remains largely unexamined. We pooled two double-blind, placebo-controlled studies in healthy volunteers (N = 72; 31 male, 41 female) comparing psilocybin 15 mg, 2C-B 20 mg, and LSD 50 μg. Linear mixed models tested sex...
Abstract Despite growing interest in psychedelic-assisted psychotherapy, research investigating the psychotherapeutic components is lacking. This leaves unanswered questions regarding the psychotherapy's necessity and form. This observational study addresses this gap by measuring the outcomes of a psilocybin truffle retreat, followed by the outcomes of two psychotherapy interventions that...
Abstract Background The Pivotal Mental States (PiMS) construct posits that psychedelics and other stress-inducing practices, such as fasting and hypoxia, can evoke transformative mental states through increased serotonin receptor activation in the brain. These states are associated with enhanced cognitive flexibility, accelerated associative learning, and psychological insights that may...
Ayahuasca is a psychoactive brew containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids that induces marked alterations in perception, emotion and self-referential processing. However, the multiscale biological organization linking peripheral metabolism, brain network dynamics, neurochemistry, and subjective experience in humans remains poorly understood. Here, we applied an...
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational...
Abstract Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole‐brain computational...
Abstract Psilocybin induces profound alterations in consciousness, yet prevailing neural models often describe a monolithic change in brain connectivity that may not fully capture the multifaceted nature of the psychedelic state. To test the hypothesis of a composite neural state, this study applied a robust, data-driven framework, Connectome Independent Component Analysis (connICA) with...
Background The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization,...
Background: Preliminary research indicates that psychedelics may hold promise as analgesic agents. This study investigated the potential analgesic effects of lysergic acid diethylamide (LSD) microdosing on pain tolerance and subjective pain perception in healthy participants. Methods: Utilizing a randomised, placebo-controlled design, participants received 15 μg of LSD or placebo over four...
Abstract Background and aims Research on classical psychedelics like ayahuasca is increasingly focused on treating mental disorders and enhancing well-being. Ayahuasca has shown promise in improving cognitive flexibility, emotion regulation, and sleep, though findings are mixed and further research is needed. This study tracked participants over three months, assessing cognitive flexibility,...
Promising results have emerged in the use of psychedelic drugs for treating depression. Despite multiple neural models attempting to elucidate the acute psychedelic experience, and an increased focus on potential mechanisms driving persistent change, the connections between the acute state and the enduring therapeutic outcomes remain elusive. This targeted review aims to bridge this gap by...
3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N =...
Acute intoxication from Δ9-tetrahydrocannabinol (THC, the primary active ingredient of cannabis) can lead to neurocognitive impairment and interference with day-to-day operations, such as driving. Present evaluations of THC-induced impairment in legal settings rely on biological drug tests that solely establish cannabis use, rather than cannabis impairment. The current study evaluated the...
3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or "legal high". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic...
Ayahuasca is an Amazonian brew with 5-HT2A-dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory...
Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an...
5-MeO-DMT is a short-acting psychedelic that is anecdotally reported to induce a radical disruption of the self and a paradoxical quality of aroused, waking awareness that is nevertheless devoid of any specific perceptual contents. Here, we conducted an exploratory observational study of the phenomenological and neuronal effects of this compound. We collected micro-phenomenological interviews,...
A three-item Peak Experience Scale (PES) was developed to rapidly evaluate the strength of the psychoactive experience, and to guide the dosing regimen, of the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; mebufotenin). This paper aims to compare the PES with a range of established questionnaires designed to evaluate the psychedelic experience. Data were gathered from three separate...
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational...
As research on psychedelics (hallucinogenic serotonin receptor 2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent...
The repeated use of small doses of psychedelics (also referred to as "microdosing") to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on...
Psilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state's neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after...