Progress in neuro-psychopharmacology & biological psychiatry
June 7, 2025
Damian Swieczkowski, Aleksander Kwaśny, Wiesław Jerzy Cubała
5 citations
Treatment-resistant depression (TRD) is difficult to treat because many patients do not respond to standard antidepressants. NN-dimethyltryptamine (DMT), a fast-acting psychedelic, may offer benefits due to its rapid onset and short duration. This systematic review of five clinical trials found that DMT was generally well-tolerated, with no serious adverse events. Intravenous DMT caused temporary increases in systolic blood pressure (up to 25.7%) and heart rate at higher doses. Inhalation led to mild throat discomfort, and oral or intranasal use caused mild nausea and dizziness, all short-lived. Psychotomimetic effects like ego dissolution were dose-dependent but manageable. Larger, well-controlled studies are needed to confirm safety and efficacy in TRD patients.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Simon Reiche, Tim Hirschfeld, Anna Lena Gröticke et al.
5 citations
People who have used psychedelics such as psilocybin, LSD, or ayahuasca a mild to moderate number of times over their lives show broadly equivalent neuropsychological performance to non-users, but with a modest advantage in executive functions, particularly cognitive flexibility as measured by the Wisconsin Card Sorting Test (WCST). In matched-pair analyses, users performed better on the WCST, and dose-response analyses within the user group found that greater lifetime use was positively associated with fewer total errors, perseverative responses, perseverative errors, non-perseverative errors, and more conceptual level responses. The study did not find any negative associations between sporadic psychedelic use and cognition.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
B Romeo, E Kervadec, B Fauvel et al.
5 citations
The intensity of mystical experiences during naturalistic psychedelic use is associated with several factors, including the type of substance, dosage, and the user's intentions. Analyzing data from 1657 participants across four retrospective surveys, higher mystical experience questionnaire scores were linked to spiritual, therapeutic, or self-exploration motives (versus recreational), use of ayahuasca or LSD (versus psilocybin), higher subjective doses, more sessions, longer time since the experience, and no concurrent alcohol use. Concomitant alcohol use was associated with less intense experiences, highlighting the need to screen for substance use in research.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Ting-Ting Zhu, Ming-Ming Zhao, Dan Xu et al.
5 citations
Postoperative cognitive dysfunction (POCD) involves declines in memory, attention, and executive abilities after surgery, with no effective drugs available. In a mouse model of POCD, a single injection of arketamine (10 mg/kg) improved cognitive function and reduced demyelination in the corpus callosum. Blocking TGF-β receptor 1 with RepSox (10 mg/kg) prevented these benefits, while intranasal TGF-β1 (3.0 μg/kg) alone alleviated cognitive impairments and demyelination. The findings indicate arketamine acts through a TGF-β1-dependent mechanism, suggesting it as a potential treatment for POCD.
Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2024
Kaylene K A Scheil, Carla L Sánchez-Lafuente, Brady S Reive et al.
5 citations
Chronic stress reduces reelin, a brain protein, in the hippocampus and causes depression-like behavior. A single dose of reelin or ketamine each reversed these behavioral and molecular effects within one hour, and the benefit lasted at least one week. When given together, reelin and ketamine showed additive effects after one week. The findings suggest that reelin-based treatments could become a new class of rapid-acting antidepressants.
Progress in neuro-psychopharmacology & biological psychiatry
July 14, 2025
Zoe Plummer, Josh Allen, Justin Brand et al.
4 citations
Traumatic brain injury (TBI) causes neuroinflammation, oxidative stress, impaired neuroplasticity, neurotransmitter imbalances, and cell death, leading to neurological and psychiatric disorders. The serotonergic psychedelics psilocybin and 5-MeO-DMT may help treat TBI by promoting neuroplasticity, reducing inflammation, and protecting neurons. Psilocybin acts through 5-HT1A, 5-HT2A, and neurotrophic TrkB receptors, while 5-MeO-DMT targets sigma-1 receptors with neuroprotective properties. Preclinical and clinical research suggests these compounds can alleviate cognitive and affective dysfunction and neuroinflammation after TBI. The review critically examines safety, dosing, and clinical challenges, highlighting the potential of these psychedelics as adjunctive treatments in neurorehabilitation.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
Yong Yue, Xiayun Wan, Guilin Liu et al.
4 citations
The gut-brain axis, specifically the subdiaphragmatic vagus nerve, is critical for MDMA's effects on the oxytocin system in rats. Cutting this nerve (subdiaphragmatic vagotomy) lowered baseline oxytocin levels in the blood and reduced oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus. It also dampened MDMA-induced increases in blood oxytocin and the expression of oxytocin and c-Fos in those brain regions. The findings suggest the vagus nerve mediates brain-body communication that underlies MDMA's pharmacological actions on oxytocin.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Dan Xu, Akifumi Eguchi, Rumi Murayama et al.
4 citations
Repeated oral administration of MDMA (10 mg/kg/day for 14 days) to male rats significantly altered gut microbiota composition in the small intestine, cecum, and colon, with distinct effects in each region. Analysis of microbial functional capabilities indicated shifts in several metabolic pathways. Untargeted metabolomics showed that MDMA changed levels of two metabolites in the colon—ferulic acid and methylmalonic acid—without affecting levels in blood, small intestine, or cecum. Methylmalonic acid levels in the colon positively correlated with the bacteria Lawsonibacter and Oscillibacter. These results suggest that repeated MDMA treatment can modify gut microbiota across intestinal regions, which may contribute to its pharmacological effects.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Lenka Seillier, Barbora Čechová, Alexandre Seillier et al.
3 citations
A single dose of psilocybin at 0.32 mg/kg, but not lower or higher doses, produced short- and long-term antidepressant-like effects in Wistar rats, as measured by the forced swim test, and also increased social interaction and sucrose preference. Higher doses of 1.0 and 3.2 mg/kg lacked antidepressant-like activity and instead reduced body temperature, locomotor activity, and weight gain. Brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex increased linearly with dose, dissociating from the inverted-U-shaped behavioral effects. The findings suggest a narrow therapeutic window for psilocybin, with the intermediate dose providing benefits without adverse effects seen at higher doses.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
Kristýna Štefková-mazochová, Hynek Danda, Vladimír Mazoch et al.
3 citations
Methoxphenidine (MXP), a new psychoactive substance, rapidly crosses the blood-brain barrier in Wistar rats, reaching peak concentrations in serum and brain 30 minutes after injection, with a half-life of 2.15 hours. Low to moderate doses (10-20 mg/kg) increase locomotor activity in an open field test, while a higher dose (40 mg/kg) decreases it. All doses disrupt sensorimotor gating (prepulse inhibition), an effect linked to psychosis. MXP shows moderate acute toxicity with an estimated LD50 of 500 mg/kg subcutaneously. The drug exhibits a profile similar to dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses and sedative effects at higher doses, indicating risks of serious adverse health outcomes from recreational use.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
Steven A. Barker
3 citations
Renewed interest in psychedelic drugs highlights DMT's therapeutic effectiveness and its role as a neuroplastogen. DMT binds to intracellular sigma-1 and 5-HT2a receptors, with the latter located on the Golgi apparatus in cortical neurons, and fails to occupy cell surface 5-HT2a receptors. DMT is proposed as the endogenous ligand for intracellular 5-HT2a receptors, which serotonin cannot access. Brain levels of DMT are elevated by stress in rats and appear under inducible, adaptive physiological regulation. These findings suggest DMT may be involved in brain development and explain subjective effects of psychedelics.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Peipei Wang, Junmei Hu, Congliang Chen et al.
2 citations
Ketamine, a psychoactive substance strictly regulated by international drug conventions, is classified as a new type drug due to its excitatory, hallucinogenic, or inhibitory effects. The immune regulatory mechanism is the most prominent among several theories explaining ketamine-induced psychiatric symptoms. Recent research highlights the interaction between the immune system and nervous system in neuropsychiatric disorders, with peripheral lymphocyte infiltration into the central nervous system as an early hallmark. This article provides a comprehensive overview of pathophysiological processes in psychiatric disorders, including those from ketamine, covering nerve damage, central immune alterations, and peripheral immune regulation. It emphasizes the crosstalk between peripheral and central immune systems in the onset and progression of psychiatric diseases, offering fresh perspectives on mechanisms, diagnosis, and therapeutic strategies for drug abuse-related mental disorders.
Progress in neuro-psychopharmacology & biological psychiatry
January 23, 2026
B Romeo, E Kervadec, B Fauvel et al.
1 citation
The intensity of a psychedelic experience, which is linked to clinical benefits, depends on multiple factors. In an online survey of 804 people, stronger altered states of consciousness were reported when the experience was intended for spiritual, therapeutic, or self-exploratory purposes rather than recreation; when dissociative or serotonergic psychedelics were used instead of entactogens; and with moderate to very high doses compared to very low doses. Age and gender also played a role. The findings suggest that experiential intensity arises from a combination of pharmacological, personal, and contextual elements, and that similarities with mystical experiences may point to a shared neurobiological sensitivity rather than a unique category of experience.
Progress in neuro-psychopharmacology & biological psychiatry
July 5, 2025
Hynek Danda, Kristýna Mazochová, Klára Šíchová et al.
1 citation
Baeocystin, a compound found in psychoactive mushrooms, has minimal to no behavioral effects in rats, likely because it poorly crosses the blood-brain barrier. After subcutaneous doses of 1.25 or 5 mg/kg, baeocystin and its metabolite norpsilocin showed very limited brain penetration. Consistent with this, the compound had no significant effects on locomotor activity, exploratory behavior, anxiety-like responses, or sensorimotor gating in Wistar rats. The findings suggest baeocystin's negligible neurobiological and psychedelic activity is due to its poor permeability across the blood-brain barrier.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Anastasia Ruban, Mikołaj Magnuski, Justyna Hobot et al.
1 citation
People who use psychedelics in natural settings show weaker increases in alpha and beta brainwave power when thinking about themselves, compared to non-users, especially in regions like the posterior cingulate cortex that handle self-related information and memory. However, these differences were not replicated in a second, smaller dataset, limiting confidence in the finding. The results contribute to ongoing debate about how long psychedelic effects last in brain circuits linked to self-processing and question the specific role of default-mode network hubs in such changes.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Xin Ding, Kenji Hashimoto, Jian-Jun Yang
Xanomeline and ketamine, two mechanistically distinct antidepressants, partially converge on common molecular pathways despite acting through different upstream receptors. Network pharmacology and molecular docking identified 368 overlapping targets for xanomeline with major depressive disorder and 714 for ketamine. Three shared signaling pathways emerged: EGFR tyrosine kinase inhibitor resistance, Ras signaling, and Rap1 signaling. Three core proteins—EGFR, IGF1R, and SRC—were common to both drugs. Xanomeline associated more strongly with receptor tyrosine kinase and PI3K/AKT signaling, while ketamine linked more to synaptic transmission, NMDA receptors, and glutamatergic signaling. These hypothesis-generating findings suggest partial convergence on downstream plasticity-related signaling nodes.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Ewen Kervadec, Pauline Mathieu, Baptiste Fauvel et al.
A French translation of the Altered States of Consciousness (5D-ASC) questionnaire was psychometrically validated using data from 777 participants who recalled a past naturalistic psychedelic experience. The 11-subscale structure showed better fit than higher-order models, though fit indices fell slightly below conventional thresholds. Internal consistency was excellent for global scores (α = 0.95) and satisfactory across subscales (α = 0.63–0.84). Measurement invariance across substance categories was confirmed, with latent factor differences aligning with known pharmacological profiles. The findings provide preliminary evidence supporting the French 5D-ASC's validity, enabling francophone research linking subjective experience to therapeutic outcomes.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Aline Freyssin, Reina Benabou, Hanna Zoe Müller et al.
A novel compound, RST-01, a fluoroalkyl derivative of amantadine, shows promise as a treatment for early PTSD in preclinical rat models, producing efficacy without the dissociative side effects or neurotoxic Olney's lesions associated with R,S-ketamine and memantine. In vitro electrophysiological assays measuring IC₅₀ values for human GluN1/GluN2A-D receptors revealed that RST-01 has a more differentiated selectivity profile across the four GluN2 subunits compared to ketamine or memantine. This distinct subunit-specific pharmacological signature offers a mechanistic explanation for the improved safety margins observed, supporting development of safer NMDAR-targeting therapies.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Jen-Ping Chen, Chih-Wei Hsu, Yi-Ya Fang et al.
Esketamine initiation, compared with oral antidepressant monotherapy, was associated with a 26% lower risk of all-cause mortality over two years among adults aged 18–74 with cancer-related depression, according to a target trial emulation using electronic health records. After propensity score matching of 1,751 patients per group, esketamine also corresponded to lower risks of emergency room visits, intensive care unit visits, ischemic stroke, and psychotherapy utilization. Safety outcomes were generally comparable between groups. The associations were more pronounced in older patients. These real-world findings support esketamine as a potential therapeutic option for managing cancer-related depression.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Zhen Xuen Brandon Low
Autism Spectrum Disorder involves social-communication deficits, cognitive rigidity, and atypical sensory processing, with current drugs providing only limited relief. Dysregulated serotonin signaling, impaired neuroplasticity, and chronic neuroimmune activation are central features. Serotonergic psychedelics like psilocybin and LSD, which act as 5-HT2A receptor agonists, may relax overly rigid cortical priors, reopen critical periods for social learning, and recalibrate neural circuits. They enhance synaptic plasticity via BDNF and mTOR signaling, modulate cortical oscillations, and suppress neuroinflammation. Systems-level frameworks suggest these compounds induce less constrained brain states that counteract hyper-segregated connectivity in ASD. Preclinical and early human studies report improvements in sociability, sensory responsiveness, and behavioral flexibility, but rigorous clinical trials are needed to establish safety and efficacy.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas et al.
Two doses of psilocybin (0.6 mg/kg, given subcutaneously seven days apart) reversed anhedonia, produced antidepressant-like effects in the forced swim test, and reduced anxiety in the light/dark box, elevated plus maze, and open field tests in rats exposed to chronic unpredictable mild stress. Psilocybin also increased hippocampal neurogenesis, shown by higher numbers of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed animals. Stress-induced reductions in brain-derived neurotrophic factor (BDNF) expression appeared linked to normalization of hypothalamic-pituitary-adrenal (HPA) axis activity. The findings highlight psilocybin-induced neuroplasticity as a key mechanism for its antidepressant and anxiolytic effects.
Progress in neuro-psychopharmacology & biological psychiatry
January 27, 2026
Rhea Subba, Surendar Ellappan, Sugato Banerjee et al.
Astroglial dysfunction is a fundamental component of the pathophysiology of major depressive disorder. Rodent models of depression consistently show structural astroglial abnormalities, including atrophy in the prefrontal cortex and hippocampus, reduced glial fibrillary acidic protein expression, impaired glutamate homeostasis, decreased neurotrophic factor production, disrupted gap junction communication, diminished lactate release, increased neuroinflammation, and synaptic deficits. Clinical postmortem and serum biomarker studies corroborate astroglial dysfunction in cortical regions of patients with MDD. Standard antidepressants (SSRIs, SNRIs, tricyclics, serotonin modulators) and rapid-acting ones like ketamine and esketamine exert therapeutic effects at least partially by restoring astroglial homeostasis, positioning astroglia as critical mediators of treatment response and a promising target for personalized antidepressant strategies.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2025
Joana Mielko, Julia Pakulska, Amelia Oszczyk et al.
Drug repurposing—finding new uses for existing medications—offers a faster, cheaper alternative to traditional drug development, especially for neurological and psychiatric disorders. This narrative review examines preclinical and clinical studies on anesthetics including ketamine, nitrous oxide, isoflurane, sevoflurane, propofol, dexmedetomidine, and sodium oxybate for treating central nervous system disorders. Anesthetics show potential for rapid antidepressant effects, enhanced learning and memory, improved synaptic plasticity, and neuroprotection, suggesting promise for depression, post-traumatic stress disorder, cognitive decline, traumatic brain injury, and neurodegenerative disorders. These effects likely involve modulation of GABAergic and glutamatergic pathways. Challenges include dose-dependent neurotoxicity, variability in outcomes, and environmental concerns. Further research is needed to optimize dosing, ensure long-term safety, and clarify mechanisms.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Viktoriia Kurkova, Olga Winkler, Andrew Greenshaw et al.
A scoping review of 10 studies out of 11,734 publications examined whether psychedelic-assisted psychotherapy (PAP) can help people recover from moral injury—deep distress from morally challenging experiences. None of the studies focused specifically on moral injury; they involved psilocybin, MDMA, or LSD for conditions such as PTSD, alcohol use disorder, depression, and anxiety. Across these studies, PAP was associated with rapid, sustained increases in self-compassion, self-forgiveness, and self-acceptance, along with reduced demoralization and lower drinking scores. The authors suggest PAP holds promise for treating moral injury, especially when it co-occurs with PTSD, but conclude that direct research is needed.