Stress is a major determinant of psychopathology, with coping and cognitive impairment arising from abnormal glucocorticoid activity and brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity in the hippocampus. The endocannabinoid system modulates stress and hippocampal functioning since early development, thus its early-life disruption may program vulnerability to stress-related...
Minor cannabinoids and semisynthetic cannabis constituents, such as derivatives of tetrahydrocannabinol (THC) and hexahydrocannabinol (HHC), are increasingly encountered in consumer products, yet their signaling profiles at cannabinoid receptors remain incompletely characterized. Here, we describe how structural modifications of THC and HHC, including variations in alkyl side-chain length...
Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for brain development, with ω-3 species supporting neuronal membrane architecture, synaptogenesis and cognitive maturation, and ω-6 species linking lipid metabolism to neuronal signalling via the endocannabinoid system (ECS), the network of receptors, lipid mediators, and enzymatic pathways that orchestrate neurodevelopmental...
RATIONALE: Social withdrawal in the sub-chronic phencyclidine (PCP) rat model—a behavioral correlate of schizophrenia’s negative symptoms—is well characterized, yet the psychological mechanisms underlying this deficit remain unclear. OBJECTIVES: Despite the complexity of social behavior, assessments often rely on a single metric (e.g., total interaction time) that has limited explanatory power,...
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on...
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...
Social withdrawal is a core negative symptom of schizophrenia and remains poorly understood at the molecular level. Dysregulation of the endocannabinoid system has been implicated in social behavior, yet its downstream signaling mechanisms are not fully characterized. In this context, this study examined the effects of the fatty acid amide hydrolase (FAAH) inhibitor, URB597, on CREB expression...
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...
Powder DiffractionDecember 1, 2025Analio Dugarte-Dugarte, Jacco van de Streek, Graciela Dı́az de Delgado et al.
Abstract The crystal structures of two arylcyclohexylamine derivatives – methoxmetamine·HCl (2-(3-methoxyphenyl)-2-(methylamino)cyclohexan-1-one hydrochloride, MMXE·HCl) and methoxetamine·HCl (2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one hydrochloride, MXE·HCl) – have been determined using laboratory X-ray powder diffraction data contained in the Powder Diffraction File ™ . MMXE·HCl and...
BackgroundTaking very small doses of psychedelics (LSD, truffles) over an extended period became prevalent in Western societies for its alleged cognitive benefit, including enhanced creativity. However, in the absence of robust, double-blind-controlled quantitative studies, such claims remain anecdotal.MethodsHere we present results from 3 double-blind placebo-controlled longitudinal trials...
ObjectiveMicrodosing psychedelics has been widely reported to enhance focus and problem-solving, sparking interest in its potential to treat attentional disorders such as ADHD. However, existing studies largely rely on anecdotal evidence and lack adequate placebo control.MethodsThis study contributes to the literature by examining the longitudinal effects of microdosing psilocybin truffles in...
Psychedelics, particularly psilocin, are increasingly being studied for their mind-altering effects and potential therapeutic applications in psychiatry. Visual hallucinations, especially the illusion of motion in static images, are a hallmark of their action. Despite growing interest, the underlying mechanisms remain poorly understood, as their systematic evaluation in both humans and animals...
Hexahydrocannabinol (HHC) is a new psychoactive substance known for its mind-altering effects and temporary legal status. It is widely used in parts of the Europe and United Kingdom as a legal alternative to ∆9-tetrahydrocannabinol, yet little research has explored its effects and safety. This study examined how HHC is processed in the body, its toxicity, and its impact on behavior in male...
Baeocystin is a naturally occurring tryptamine-based compound found in various psychoactive mushrooms, including in several species of Psilocybe genus. Due to its structural similarity to psilocybin, which has shown a therapeutic potential in treatment of psychiatric disorders, there is a growing interest in investigating whether baeocystin exhibits comparable effects. This study investigated...
Recent studies intensively explore psilocybin's antidepressant potential, but variables like previous experience, repeated use, setting, and sex remain underexplored. This study examines acute and long-term effects of psilocybin in healthy individuals. A double-blind, placebo-controlled, cross-over study included 40 healthy participants (20 females, mean age 38). Each received two doses of...
Mitochondria are central to cellular energy metabolism, contributing to synaptic transmission and plasticity. The mitochondrial membranes present the cannabinoid type-1 receptor (mito-CB1R), which has been functionally linked to neuronal energy supply and cognitive processing. Prenatal exposure to Δ9-tetrahydrocannabinol (pTHC) has been associated with cognitive impairments associated with...
Recent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear. This study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) on synaptogenesis...
In animal models, ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, induces schizophrenia-like symptoms, such as positive and negative symptoms, as well as cognitive deficits. In the present study, we evaluated the behavioral responses and the number of EODs (electric organ discharges) of the weakly electric fish Gnathonemus petersii using the novel object recognition task...
Scientific ReportsMarch 24, 2025Lisa Höfert, Benjamin Franz, Cedric Groß et al.2 citations
The semi-synthetic cannabinoid hexahydrocannabinol (HHC) has become a highly discussed topic in forensic toxicology since 2022 due to its legal availability at this time and its psychoactive effects. This study aimed to investigate the pharmacokinetics, effects, and immunological detectability of HHC after oral (25 mg HHC fruit gum) and inhalative (three puffs from HHC vape) consumption with...
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration:...
Abstract Background Methoxphenidine (MXP) is a new psychoactive substance that belongs to the group of arylethylamines. Even though MXP has a different pharmacophore than ketamine, both of these substances belong to the dissociatives. To date, MXP has been associated with several intoxications and despite it being banned in most countries it is still available over the internet.1 Aims &...
Abstract Synthetic psilocybin (PSB), but also the PSB-containing mushrooms are used for psychedelic therapy and microdosing. It is necessary to know alkaloids variability and stability in wild-grown mushrooms. Concentrations of other psychotropic (or potentially psychotropic) tryptamines such as psilocin (PS), baeocystin (BA), norbaeocystin (NB), and aeruginascin (AE) are also relevant. This...
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,...
Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse....
The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored...