Search Results (32)

Clinical trials and naturalistic studies describe psychedelics under markedly different exposure conditions. This narrative review searched PubMed/MEDLINE, the Cochrane Library, ClinicalTrials.gov, and regulatory sources through 15 July 2026, and examined safety and outcomes across four dimensions of exposure: dose, frequency, person, and context. In screened adults receiving one to three supervised doses, transient headache, nausea, anxiety, and cardiovascular activation are common; serious reactions are uncommon but include persistent anxiety, suicidality signals, and a recent case of hallucinogen persisting perception disorder. Evidence supports MDMA (3,4-Methylenedioxymethamphetamine) -assisted therapy for post-traumatic stress disorder and psilocybin-based interventions for depression, although functional unblinding, selected samples, inconsistent comparators, and a recent negative primary trial constrain certainty. Naturalistic studies suggest that vulnerability and context modify outcomes, but frequency is inconsistently measured and rarely linked to cumulative exposure or long-term health. Short-term microdosing trials show limited benefit, whereas long-term cardiac and psychiatric safety remains unresolved. Exposure-defined cohorts, prospective registries, echocardiographic surveillance, and blinding-aware comparative trials are priorities. Full article

New psychoactive substances (NPS) are a heterogeneous group of recreational drugs that mimic the actions and psychoactive effects of existing pharmaceutical products or recreational drugs. As NPS can be highly potent, even exceeding their template compound’s potency, there are frequent reports of non-fatal and fatal intoxications. One principal target for hallucinogenic and psychedelic drugs, including NPS, is the 5-hydroxytryptamine receptor 2A (5-HT_2A). Since NPS are designed to evade legal restrictions, this drug market is quickly evolving, and researchers are playing catch-up, investigating these novel compounds for their toxicological and pharmacological properties. Receptor binding affinity (Ki) is an important property describing ligand–receptor interactions and is a prerequisite for receptor activation. Competitive in vitro assays can be used to assess Ki; this is a resource-intensive process. We used publicly available Ki data for the 5-HT_2A, calculated molecular descriptors and fingerprints, and trained five classification machine learning models. The predictive performance of the models had precisions and recalls up to 93% and 92%, respectively. We used explainable artificial intelligence, i.e., SHAP values and similarity maps, for model interpretation. The results are in line with previous experiments and support its suitability to predict the binding affinities of possible 5-HT_2A ligands. Full article

This article provides a critical analysis of the term “entheogen” as a name for certain psychoactive drugs, arguing that it functions more as a theological construct than a neutral designation. The article analyzes how entheogenic discourses present claims about the historicity of their use, their supposed spiritual or religious meaning, and their ultimate significance for individual and social transformation as descriptive, when they are, in fact, normative. Particular attention is given to the creation of the term “entheogen” as an alternative to other designations, how advocates understand the alleged exceptional nature of entheogens and what they do, appeals to shamanism as a legitimating discourse, and the eschatological hopes invested in these substances as agents of social, cultural, and religious renewal. Rather than adjudicating the truth of these claims or creating an alternative designation, the article interrogates the theological interests and commitments at work, and the rhetorical strategies that sustain them. In doing so, the article argues that entheogenic discourses often blur the boundaries between description and prescription, or advocacy. The article suggests the need for a more reflexive, contextual approach to how we understand the use of these substances. Full article

The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or “psychoplastogens,” for psychiatric disorders. However, the widespread application of classical psychedelics—such as psilocybin and LSD—and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of ibogaine, life-threatening cardiotoxicity. Addressing these limitations, Tabernanthalog (TBG) has emerged as a frontrunner in the field. This non-hallucinogenic analog of ibogaine was rationally designed to eliminate interactions with the human ether-à-go-go-related gene (hERG, KCNH2) potassium channel, thereby mitigating cardiotoxic risks. While initially characterized for its anti-addictive and antidepressant-like properties, recent data from 2024–2025 have significantly expanded its therapeutic horizon. TBG demonstrates robust efficacy in preclinical models of neuropathic and visceral pain, as well as in the rescue of cognitive deficits associated with cancer-related cognitive impairment (CRCI). TBG has shown efficacy in reversing cognitive impairments induced directly by the presence of a tumor in preclinical models, rather than by chemotherapy-specific neurotoxicity. Crucially, emerging evidence suggests that TBG’s mechanism extends beyond simple 5-HT2A receptor agonism. New findings point to a multi-target profile involving the inhibition of nicotinic acetylcholine receptors (nAChRs), positive modulation of NMDA receptors, and functional crosstalk with mGlu2 receptors. Furthermore, TBG appears to induce structural neuroplasticity without the widespread induction of immediate early genes (IEGs) seen with classical hallucinogens, suggesting a decoupling of therapeutic rewiring from the subjective psychedelic experience. This review synthesizes current preclinical evidence to discuss TBG as a promising chemical scaffold for next-generation neurotherapeutics targeting the intersection of psychiatry and neurology. Full article

This study assessed the correlates of cannabis and psychedelic use and legalization support among young adults in the United States (US). Using 2025 data among adults ages 18–34 (n = 3227), we assessed cannabis and psychedelic message exposure and perceptions, mental health symptoms (Patient Health Questionnaire-4 [PHQ-4]), and adverse childhood experiences (ACEs) in relation to past-6-month cannabis use (40.5%), past-year psychedelic use (11.9%), and legalization support. Relative to cannabis, psychedelics showed less legalization support, promotional and risk-message exposure, and social acceptability and higher perceived addictiveness and harm (p’s < 0.001). Factors associated with cannabis use and greater legalization support included: lower perceived addictiveness (aOR = 0.88, CI = 0.83–0.93; B = −0.04, SE = 0.01) and harm (aOR = 0.75, CI = 0.71–0.80; B = −0.16, SE = 0.01), higher social acceptability (aOR = 1.25, CI = 1.19–1.33; B = 0.19, SE = 0.01), and higher PHQ-4 (aOR = 1.04, CI = 1.01–1.07); more ACEs (aOR = 1.10, CI = 1.06–1.14) and more promotional (aOR = 1.08, CI = 1.01–1.17) and risk-message exposure (aOR = 1.27, CI = 1.17–1.39) were associated with use. Factors associated with psychedelic use and greater legalization support included: more promotional-message exposure (aOR = 1.61, CI = 1.36–1.91; B = 0.09, SE = 0.04), lower addictiveness (aOR = 0.87, CI = 0.78–0.97; B = −0.03, SE = 0.02) and harm (aOR = 0.74, CI = 0.66–0.82; B = −0.19, SE = 0.02), higher acceptability (aOR = 1.59, CI = 1.47–1.73; B = 0.15, SE = 0.01), and higher PHQ-4 (aOR = 1.06, CI = 1.02–1.11; B = 0.02, SE = 0.01); more risk-message exposure (aOR = 1.29, CI = 1.08–1.54) and ACEs (aOR = 1.15, CI = 1.09–1.21) were associated with use. Perceptions and mental health may influence cannabis and psychedelic use and legalization support, and message exposure may be particularly relevant in shaping psychedelic use and legalization support. Thus, information is crucial to ensure population understanding of the risks, benefits, and overall population impacts of cannabis and psychedelic use and legalization. Full article

Interest in psychoactive substances, including psychedelics, is rapidly expanding in medical, academic, and other popular fields. Despite the classifications established within the psychopharmacological scientific community, certain plants, animals, and fungi, as well as the substances obtained from them, have been misclassified by both the media and academic circles. This opinion piece aims to present arguments to answer the following question: Is CBD a non-psychoactive phytocannabinoid? Hundreds of robust scientific studies published in recent years involving CBD have strengthened its clinical use in the treatment of seizures, anxiety, psychosis, schizophrenia, post-traumatic stress disorder, and addiction. As part of the arguments to answer the question posed, this text provides a historical overview of the classifications of psychoactive substances available to date, and offers reflections on these terminologies and a proposed classification of psychedelics. Full article

Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedelic compounds (PSYs), via 5-HT2A activation, can fill a critical therapeutic gap: the need for agents that simultaneously suppress neuroinflammation and promote regeneration. We dissect the evidence suggesting PSYs can reprogram the neuroimmune milieu by downregulating key pro-inflammatory cytokines (e.g., TNF-α, IL-6) in glial cells while concurrently upregulating crucial neurotrophic factors (e.g., BDNF) that promote synaptic plasticity and oligodendrocyte support. However, we argue that the current evidence, largely derived from non-specific inflammation models, is insufficient to predict clinical efficacy in an autoimmune disease like MS. We critically analyze the significant translational barriers—from cardiovascular and psychiatric risks to profound legal and ethical challenges—that temper the immediate clinical promise. Finally, we propose a forward-looking perspective, suggesting that the true value of PSYs may lie not in their direct clinical use, but in uncovering novel therapeutic pathways. The emergence of non-hallucinogenic, functionally selective 5-HT2A agonists, inspired by psychedelic pharmacology, represents a more viable strategy to harness these mechanisms for MS therapy, demanding rigorous preclinical validation in disease-relevant models. Full article

Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin. Current evidence supports a higher prevalence of affective disorders in females, and a growing awareness of sex-based differences in response to drug therapy. Estrogen’s influence on serotonin physiology is an aspect that must be accounted for when planning a treatment regimen that includes a psychoactive drug such as psilocybin. A review of the current literature was conducted, and an analysis of how the fluid hormonal states in females across their different reproductive phases may impact serotonin dynamics, synaptic plasticity, and therapeutic timing of psilocybin use is discussed. Future research should focus on the influence of sex hormones on psychedelic-assisted therapy in the effort to further personalize treatment plans for these pathologies. Full article

Background: Substance use disorders (SUDs) are highly prevalent, affecting over 48.5 million Americans. Available treatments for SUD remain insufficient, and many patients do not respond to existing interventions despite adequate adherence to treatments. While novel therapies for SUD are urgently needed, the use of psychedelic drugs for the treatment of SUDs has shown promise. Objectives: This overview of systematic reviews summarizes existing evidence on hallucinogens—serotonergic psychedelics and ketamine—for the treatment of SUD. Methods: A comprehensive search of the literature was conducted to identify relevant evidence for using serotonergic and non-serotonergic psychedelics for the treatment of SUDs. After initial screening (n = 468 studies), 62 studies were retrieved and assessed for eligibility, and a total of 16 systematic reviews were included. Conclusions: Although preliminary, evidence suggests that the use of serotonergic and non-serotonergic psychedelics for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances. Research with these drugs has faced significant challenges, though, and caution when interpreting results is warranted, given high risk of bias and several other methodological limitations from the studies to date. Furthermore, risks associated with these drugs are not negligible. For now, the use of psychedelic drugs for the treatment of SUDs remains experimental, and existing evidence is insufficient to support its use in clinical practice. Full article

Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article

Gas chromatography with mass spectrometry (GC-MS) is a common analytical technique used for identifying and quantifying drugs of abuse, as well as their metabolites, extracted from biological samples. Depending on the properties of the analyzed compounds, particularly in the case of metabolites, derivatization is often necessary. In this article, we will address the definition, properties, sample preparation, and GC-MS analysis of the most common drugs of abuse in their native (seized) form and their metabolites in biological samples (urine, blood, hair, and tissue). Drugs that will be described are: amphetamines and their derivatives, cannabinoids, cocaine, opioids, lysergide (LSD), benzodiazepines, gamma-hydroxybutyric acid (GHB), phencyclidine (PCP), mescaline, psilocin, and psilocybin. The literature review showed that the analysis of the drugs of abuse requires a simple extraction procedure and analysis with or without derivatization. However, the analysis of the metabolites requires removing the interferences from the matrix (proteins, other compounds, water, and other species that may interfere with the analysis or contaminate the GC-MS). This review article will provide insights into the available procedures for sample preparation and analytical methods, helping authors gain the necessary information and select the desired procedure for analysis. Full article

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions and long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved in emotional processing and cognition. It has also shown promise in psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD’s pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and the potential for hallucinogen-persisting perception disorder (HPPD). Challenges such as small sample sizes, variable dosing protocols, and regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, and personalized treatment strategies to ensure its safe and effective integration into clinical practice. Full article

Several authors have advanced the idea that psychedelics such as psilocybin might be effective means for achieving moral bioenhancement (MBE). Here, I discuss some reservations on this assertion from both neuropharmacological and bioethical perspectives, and surmised that there is little, if any, good justification for such a claim. The indication of psychedelics for MBE is undermined by their hallucinogenic properties and the risk of adverse psychosis. There is also a lack of sound bioethical basis for using psychedelics to enhance morality. Based on our current understanding, the use of psychedelics specifically for MBE in healthy individuals would violate the ethical principle of non-maleficence. Unless there is unequivocal demonstration that psychedelics could enhance morality, or that new non-hallucinogenic derivatives become available, an indication for psychedelics in MBE would be untenable. Full article

Psychoactive drugs are compounds that alter the function of the central nervous system, resulting in changes in perception, mood, cognition, and behavior. A subclass of psychoactive drugs, psychedelics, are hallucinogenic drugs that can trigger psychedelic experiences and possible changes in mental perception. The potential use of psychedelics as a therapeutic has led to an increase in clinical research focusing on the treatment of mental disorders including anxiety and depression. There are numerous species belonging to Psychotria and Banisteriopsis which have been reported to contain psychedelic and psychoactive compounds; however, there is a lack of validated analytical methods for raw plant material, which is crucial if these plants are to be commercially cultivated for medicines. This study provides a fully validated method using ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) for the following six compounds: tryptamine, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), tetrahydroharmine (THH), harmaline, and harmine. The validated method was used to determine the psychoactive concentrations in Psychotria viridis, Psychotria carthagenensis, Banisteriopsis caapi, and Alicia anisopetala. Validation parameters were established; linearity (R² = 0.988–0.999), limit of detection (LOD) (0.06–0.11 ng/mL), limit of quantitation (LOQ) (0.18–0.34 ng/mL), accuracy, precision, extraction efficiency (>98%), recovery (74.1–111.6%), and matrix effect (70.6–109%) were all evaluated. All six compounds eluted within nine minutes, with a total analysis time of 20 min including column equilibration. This method establishes a high-throughput method for the robust analysis of psychedelics which may see future use in agricultural research and industry. Full article

Accurate and generalizable classification of brain states is essential for understanding their neural underpinnings and improving clinical diagnostics. Traditionally, functional connectivity patterns and graph-theoretic metrics have been utilized. However, cortical gradient features, which reflect global brain organization, offer a complementary approach. We hypothesized that a machine learning model integrating these three feature sets would effectively discriminate between baseline and atypical brain states across a wide spectrum of conditions, even though the underlying neural mechanisms vary. To test this, we extracted features from brain states associated with three meta-conditions including unconsciousness (NREM2 sleep, propofol deep sedation, and propofol general anesthesia), psychedelic states induced by hallucinogens (subanesthetic ketamine, lysergic acid diethylamide, and nitrous oxide), and neuropsychiatric disorders (attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia). We used support vector machine with nested cross-validation to construct our models. The soft voting ensemble model marked the average balanced accuracy (average of specificity and sensitivity) of 79% (62–98% across all conditions), outperforming individual base models (70–76%). Notably, our models exhibited varying degrees of transferability across different datasets, with performance being dependent on the specific brain states and feature sets used. Feature importance analysis across meta-conditions suggests that the underlying neural mechanisms vary significantly, necessitating tailored approaches for accurate classification of specific brain states. This finding underscores the value of our feature-integrated ensemble models, which leverage the strengths of multiple feature types to achieve robust performance across a broader range of brain states. While our approach offers valuable insights into the neural signatures of different brain states, future work is needed to develop and validate even more generalizable models that can accurately classify brain states across a wider array of conditions. Full article