NeuropharmacologyOctober 19, 2026U S Drozd, V V Bulygina, G T Shishkina et al.
Exposure to acute, inescapable stress triggers a coordinated neural and endocrine response across corticolimbic and brainstem circuits. Although subanesthetic ketamine has rapid antidepressant effects, it is unclear whether its modulation of the stress-response network depends on the presence of an acute stressor. In this study, naïve rats received subanesthetic ketamine (15 mg/kg) or a...
NeuropharmacologySeptember 18, 2026Yuanlong Li, Xiangyun Dai, Junmei Hu et al.
Ketamine abuse is associated with persistent cognitive deficits and neurotoxicity, though the underlying mechanisms remain incompletely understood. While mitochondrial dysfunction and ferroptosis have been separately implicated, their causal relationship and the key molecular link in ketamine-induced hippocampal damage are unclear. Using a mouse model of ketamine-induced cognitive impairment...
NeuropharmacologySeptember 11, 2026Laura Rullo, Loredana Maria Losapio, Hela Mrizak et al.
Alcohol use disorder (AUD) represents a major public health challenge, with current pharmacological and psychotherapeutic treatments showing limited efficacy. Recent clinical evidence suggests that MDMA-assisted psychotherapy may be effective for AUD, although concerns remain regarding its safety and potential for recreational use. This study investigated the effects of MDMA administration on...
NeuropharmacologyAugust 1, 2026G. S. Marcotto, M. Borghetti, J. Bitraj et al.
Electrical stimulation (ES) is emerging as a non-pharmacological neuromodulation strategy, but its direct impact on human dopaminergic neurons and its relationship to rapid-acting antidepressant mechanisms remain unclear. This study aimed to investigate whether brief biphasic low-frequency low-intensity (LF-LI) ES can induce structural and molecular plasticity in human induced pluripotent stem...
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
NeuropharmacologyJune 11, 2026Vincenzo Crunelli, Tatiana P Morais, William M Connelly et al.
Renewed interest in psychedelic therapeutics has brought serotonin 5-HT2A receptors (5-HT2ARs) back into focus. Given the role of the thalamus in sensory integration and network synchronization, we examined the expression, developmental regulation, and functional impact of thalamic 5-HT2ARs, with particular emphasis on their interaction with extrasynaptic GABAA receptors and the generation of...
Ketamine, a non-competitive N-Methyl-D-Aspartate receptor antagonist, was approved for use with Treatment-Resistant Depression (TRD) and is currently in clinical trials for treating substance use disorder (SUD), and Post Traumatic Stress Disorder. However, ketamine is an addictive drug, and thus we need to better understand ketamine's mechanism of action in addiction to reliably assess the...
NeuropharmacologyJune 1, 2026Nehal G. Fahmy, Nada M. Kamel, Mahmoud M. Khattab et al.
Doxorubicin (DOX), a widely utilized chemotherapeutic agent, is associated with significant adverse effects, including cognitive dysfunction (chemobrain) and depression. Ketamine (KET), the anesthetic, was off-label used as antidepressant and got FDA approval in 2019 for treatment-resistant depression management. Hence, this study investigated the therapeutic efficacy of single [KET(S)] versus...
NeuropharmacologyJune 1, 2026L. Lagojda, Leah MacGregor, Mahfuza Maisha et al.
Dysfunction of the cerebellum is increasingly recognised as a contributor to schizophrenia. As one of the most ubiquitous voltage-gated potassium channels in the brain, the expression and function of Kv2.1 remains underexplored in the cerebellum, and its potential involvement in cerebellar pathophysiology in schizophrenia is unknown. Here, we characterised the expression pattern of Kv2.1 in the...
NeuropharmacologyJune 1, 2026Evan C Smith, Christos Iliopoulos-Tsoutsouvas, Markos-Orestis Georgiadis et al.
Despite being the most prevalently abused illicit drug class, the neurochemical effects of cannabinoids (CBs) in key reward-related brain regions are not fully understood. Here, we used in vivo microdialysis combined with liquid chromatograph mass spectrometry to delineate how single, intraperitoneal injections of delta-9-tetrahydrocannabinol (Δ9-THC), and synthetic partial (AM11101) and full...
NeuropharmacologyMay 6, 2026Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wróbel et al.
Ketamine produces rapid antidepressant effects accompanied by marked changes in fast brain rhythms. High-frequency oscillations (HFO; 130-180 Hz) are an increasingly recognized signature of ketamine across species. However, their relationship to classical gamma activity and their circuit-level organization remain unclear. Using simultaneous multiregion recordings in freely moving male Wistar...
NeuropharmacologyMay 1, 2026Jairo S Acosta-Vargas, Natalia De Las Heras-Martínez, Alberto Marcos et al.
Cannabis use during adolescence is common and may predispose individuals to substance use disorders. Animal studies have explored the gateway hypothesis, but data on ethanol consumption are limited. This study aimed to investigate the potential link between adolescent cannabis exposure and ethanol self-administration, as well as the relationship between predisposing behavioural traits and...
Inhalational anesthetics are currently believed to cause unconsciousness by acting on multiple molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins. Inhalational anesthetics including isoflurane bind to cytoskeletal microtubules (MTs), potentially contributing to causing unconsciousness. This possibility is supported by our...
Cocaine and methamphetamine use disorders pose public health concerns due to the high propensity for relapse driven by persistent drug-associated memories. Output from the medial prefrontal cortex (mPFC) regulates relapse and is controlled by parvalbumin (PV) interneurons, which are surrounded by perineuronal nets (PNNs) that support precise PV neuron firing. We previously showed that removal...
To our knowledge, this is the first fMRI characterization of 5-MeO-DMT in any species, and it reveals a previously unreported sex difference in psychedelic response. The rapid onset and brief duration of peak effects align with 5-MeO-DMT's unique pharmacological profile and clinical reports.
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with serotonin (5-HT). We tested the joint hypotheses. We tested the joint hypotheses that endogenous DMT would accumulate in rat brain after inhibiting monoamine oxidase with pargyline, whereas its acidic metabolite 3-indoleacetic acid (3-IAA) would...
In the last years, Synthetic Cannabinoids (SCBs) have established themselves as one of the largest and most popular groups of Novel Psychoactive Substances (NPS), being frequently detected in biological samples of patients involved in intoxication and death cases. To date, compelling evidence on the potential interaction between SCBs and non-cannabinoid neurotransmission systems has emerged,...
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily for recreational purposes, the molecular mechanisms underlying its actions remain incompletely understood. Here, we examined the acute effects of psilocin, the active metabolite of psilocybin, on excitatory neurotransmission in the prefrontal cortex...
While microdosing psychedelics is increasingly popular for enhancing well-being, its effects on health behavior change (HBC) remain poorly understood. This study investigated self-reported health-related behavior changes and putative underlying psychological mechanisms associated with psychedelic microdosing in a naturalistic setting. A retrospective mixed-method survey was conducted with 365...
Expectations can impact antidepressant treatment and psychedelic therapy, often enhancing placebo effects and influencing outcomes. However, research in this context is lacking. Our study explored the expectations of participants with major depressive disorder (MDD) before microdosing lysergic acid diethylamide (LSD) in an open-label trial. Twenty-three individuals with MDD completed a...
Psilocybin, a psychedelic compound in "magic" mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of...
Major depressive disorder (MDD) affects approximately 5 % of the global population. Classic psychedelics have shown promise in treating various mental health disorders. This study evaluated the feasibility and tolerability of an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label phase 2A trial (LSDDEP1). Nineteen...
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...
Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, is associated with chronic abuse leading to schizophrenia-like cognitive deficits. The gut-brain axis may play a role in mediating substance-induced neurotoxicity; however, its involvement in ketamine-induced cognitive impairment remains poorly understood. Here, chronic ketamine exposure was administered intraperitoneally to...
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...