Psilocybin shows therapeutic promise for several psychiatric disorders, but the acute perceptual and cognitive alterations produced by conventional doses (10-25 mg) require in-clinic supervision, which limits scalability. Whether the therapeutically relevant pharmacology of psilocybin can be separated from its hallucinogenic activity remains unresolved. To address this gap, we conducted a Phase...
A resurgent therapeutic frontier, the contemporary renaissance in psychedelic science has accelerated investigation of classic serotonergic psychedelics (psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline), empathogenic entactogenic agents (3,4-methylenedioxymethamphetamine (MDMA)), and glutamatergic dissociatives (ketamine) as adjuncts to psychotherapy. While...
There is growing interest in psychedelic compounds such as psilocybin, 3,4-metheylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT) given emerging research on potential uses as treatments for a variety of health conditions. The United States Food and Drug Administration (FDA) has granted multiple “Breakthrough Therapy” designations to various...
Archives of ToxicologyJuly 1, 2026Kamil Jurowski, Alicja Krośniak, Damian Kobylarz et al.
Lysergamide analogs such as ALD-52, 1P-LSD, 1B-LSD, 1 V-LSD, and 1cP-LSD have emerged as new psychoactive substances (NPS) with hallucinogenic potential, yet their toxicological profiles remain largely unexplored. In this study, a comprehensive in silico assessment was conducted using multiple platforms (e.g., ADMETlab 3.0, Percepta, STopTox, ProTox 3.0, VEGA, TEST 5.1.2) to predict critical...
In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and...
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...
Preclinical studies suggest that lysergic acid diethylamide (LSD) may induce lasting changes in brain function and learning ability, but evidence in humans is uncertain. Motor learning, in particular, has clinical relevance but has not been investigated in human studies of psychedelics. Forty-five healthy subjects (24 women) participated in this randomized crossover trial comparing 100 µg LSD...
The head-twitch response (HTR) is widely used as a preclinical assay for the hallucinogenic potential of compounds, with its utility based on 5HT 2A R activation. Here, we examine how the polypharmacological agonists lisuride and lysergic acid diethylamide (LSD) influence behavioral and physiological outcomes in mice to test whether the HTR reliably reflects overall psychoactivity. Lisuride...
Attention deficit and hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder (Drechsler et al., 2020). Recently, psychedelics have become of interest regarding developing treatment options for ADHD. The aim of this systematic review is to find all studies from the APA PsychInfo and MEDLINE databases, where psychedelics have been used for ADHD and assess whether further clinical...
Introduction MM120 (lysergide D-tartrate, LSD, CAS 32426-57-6) is under development as a potential treatment for generalized anxiety disorder and major depressive disorder. MM120 may elicit profound lasting psychological changes through interaction with brain 5-HT1A, 1B, 2A, 2C, 6 and 7 receptors, among others, while the complete mechanism is not clear. Objectives The study was performed to...
Introduction MM120 (lysergide D-tartrate, a formulation of LSD) is under development as a potential treatment for generalized anxiety and major depressive disorders. How psychedelic drugs interact at the TrkB receptor, a key target of neuroplasticity, is not reported. Objectives The study evaluated binding and functional activity of known serotonergic psychedelic compounds and SRI fluoxetine at...
Introduction Research on psychedelic compounds has grown quickly in the past decade. Yet molecule-specific, quantitative summaries are scattered, making it hard to see how interest differs by compound or over time. Objectives To quantify PubMed-indexed publications on ketamine, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), psilocybin, and psilocin; to describe annual trends...
The emergence of contemporary psychological stressors, synthetic psychoactive substance abuse, and non-substance behavioral dependency networks presents critical investigative challenges within public healthcare and classical toxicology (Agadatantra), traditionally analyzed through the concepts of Madya (intoxicants), Mada (intoxication), and severe cognitive perversion (Prajñāparādha). This...
Serotonergic psychedelics are known for their profound effects on consciousness and are gaining renewed interest as potential psychiatric treatments. These advances underscore the need to clarify the mechanisms of action of these compounds. This systematic review compiles and critically evaluates 23 in vitro and 26 in vivo electrophysiological studies on psychedelic compounds, with an emphasis...
Little is known about the correlates of repeated non-medical lysergic acid diethylamide (LSD) use. Therefore, we aimed to determine the prevalence and correlates of past-year LSD use among people aged 18 years and older in the United States who first used LSD at least 5 years ago. Using data from the 2015-2019 National Survey on Drug Use and Health, we examined the estimated weighted prevalence...
For English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-mystical factors (visual experience and...
Summary Psychedelic compounds such as lysergic acid diethylamide (LSD) are increasingly studied for their neuroplastic effects and potential relevance to brain aging and neurodegeneration. However, the molecular mechanisms linking psychedelic-induced plasticity to age-associated cognitive decline remain unclear. Brain aging and dementia are characterized by coordinated transcriptional programs...
Psychedelics are seeing renewed interest due to their potential as therapeutic tools; however, despite promising clinical findings, the underlying signaling mechanisms and brain-region specific effects of psychedelics remain unclear. This dissertation first describes a comprehensive study aimed at understanding the on and off-target actions of ~40 diverse psychedelic substances representing...
Brain StimulationMay 21, 2026Lucas Dwiel, Mackenzi L. Prina, Elise Bragg et al.
A leading theory for how psychedelics are able to produce robust clinical improvement and preclinical behavioral changes is that psychedelics act through neuroplastic mechanisms to induce lasting structural and functional alterations in neural circuits. However, psychedelics produce these effects across wide swaths of the brain. Based on our prior work, we hypothesized that engaging a specific...
Psychedelics produce long-lasting effects, but their circuit mechanisms remain unclear. Here we show that, in rats, a single dose of lysergic acid diethylamide (LSD) persistently reduces pain affect. This effect is recapitulated by local administration in the anterior cingulate cortex (ACC), but not primary somatosensory cortex. Neuropixels recordings reveal that LSD suppresses stimulus-evoked...