810 results for "serotonergic"
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats
Psychopharmacology – March 04, 2026
Summary
MDMA-assisted psychotherapy shows promise for treating post-traumatic stress disorder (PTSD) with low doses potentially being well-tolerated. In a study involving male and female Sprague Dawley rats, administering 2.5 mg/kg MDMA resulted in mild anxiety-like behavior one day post-treatment, but this was not observed 15 days later. Additionally, serotonin levels significantly decreased in the nucleus accumbens after MDMA exposure. Importantly, anhedonia-related behavior remained unaffected, suggesting that low-dose MDMA may have transient effects without hindering its therapeutic potential.
Abstract
MDMA (3–4 methylenedioxymethamphetamine) assisted psychotherapy has gained considerable attention as a potential adjuvant therapy for post-traumati...
Inhibition of cortico-amygdala projections underlies affective bias modification by psilocybin
OpenAlex – March 04, 2026
Summary
Psilocybin, a serotonergic psychedelic, demonstrates rapid and lasting antidepressant effects in patients with major depressive disorder. In a rodent model, psilocin, its active metabolite, was found to significantly modulate negative affective biases by selectively suppressing excitatory inputs to cortico-amygdala projection neurons while enhancing inputs to cortico-cortical targets. Notably, these changes persisted for 24 hours post-infusion. Chemogenetic inhibition of specific neuron types mirrored psilocybin's effects, highlighting the prelimbic cortex's role in altering synaptic transmission and potentially explaining psilocybin's sustained therapeutic benefits.
Abstract
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (...
Psychedelic Therapy: A Primer for Primary Care Clinicians—Mescaline
OpenAlex – February 28, 2026
Summary
Mescaline, a classic psychedelic, shows promise in psychiatric therapy, with observational data indicating a favorable safety profile. In randomized, placebo-controlled trials involving healthy participants, mescaline produced moderate effects without serious complications, suggesting it is generally well-tolerated. Adverse reactions were mostly self-limited, with studies reporting a 70% satisfaction rate among users. However, concerns remain regarding its effects on individuals with cardiovascular or psychiatric conditions, highlighting the need for further clinical trials to fully understand its therapeutic potential and long-term safety.
Abstract
Background: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is ...
SSRIs, Psilocybin, MDMA, and Disease Modeling: Strategies to Advance PTSD Treatment
OpenAlex – February 24, 2026
Summary
Psilocybin and MDMA, alongside traditional SSRIs, show promise as effective treatments for Post-Traumatic Stress Disorder (PTSD) by modulating serotonin-related neural circuits. With a focus on their biological mechanisms, this position paper emphasizes the need for a deeper understanding of these substances at molecular and neural levels. The exploration of their therapeutic potential could lead to innovative treatment modalities for the 7-8% of the population affected by PTSD. A multidisciplinary approach is essential for developing effective therapies that address complex PTSD symptoms.
Abstract
S elective S erotonin R euptake I nhibitors (SSRIs) and two psychedelics, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and MDMA (3,4-Methyl...
Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A
Biomedicines – February 21, 2026
Summary
Salvinorin A, a potent compound from *Salvia divinorum*, uniquely activates the kappa opioid receptor (KOR), diverging from traditional serotonergic models. In studies involving over 100 human neuroimaging trials and various animal models, KOR activation was linked to significant alterations in consciousness and brain network fragmentation. Unlike classical psychedelics, salvinorin A's effects include rapid receptor desensitization and low abuse potential due to aversive experiences. This insight into the endogenous opioid system opens new avenues for treating conditions like addiction and chronic pain, highlighting diverse neurochemical pathways in psychedelics.
Abstract
The neuropharmacology of psychedelics has traditionally focused on serotonergic mechanisms, particularly 5-HT2A receptor activation. However, this ...
Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling
Frontiers in Molecular Biosciences – February 18, 2026
Summary
Ayahuasca may significantly amplify the effects of SSRIs, such as paroxetine and fluoxetine, even with modest increases in DMT exposure. This interaction raises concerns for individuals on antidepressant therapy, highlighting a need for caution. With a focus on pharmacodynamics and drug interactions, the findings offer a quantitative framework that aids clinical decision-making and harm reduction, particularly when controlled studies are impractical. Understanding these risks is crucial for safe integration of psychedelics like ayahuasca into treatment regimens involving serotonin reuptake inhibitors.
Abstract
The findings suggest a clinically relevant interaction between ayahuasca and SSRIs, as even modest increases in DMT exposure may intensify serotone...
MDMA-Assisted Therapy for PTSD: Neuroplastic Change or Psychotherapeutic Catalyst?
Translation The University of Toledo Journal of Medical Sciences – February 17, 2026
Summary
MDMA-assisted psychotherapy shows significant promise for treating PTSD, especially in patients resistant to traditional therapies. Clinical trials indicate up to 67% of participants experience lasting symptom relief. The treatment appears to reduce amygdala activity and enhance hippocampal connectivity, promoting neuroplasticity. Additionally, MDMA's prosocial effects improve therapeutic relationships, crucial for effective outcomes. This dual-action model suggests that MDMA not only aids cognitive processing but also fosters emotional safety, enhancing interpersonal communication during therapy. Such insights could refine protocols and therapist training in psychedelic-assisted approaches.
Abstract
MDMA-assisted psychotherapy has emerged as a promising treatment for post-traumatic stress disorder (PTSD), particularly in individuals unresponsiv...
Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway
Neuropsychopharmacology – February 13, 2026
Summary
Psilocybin microdosing significantly improved object recognition memory in a rat model of Fragile X Syndrome (FXS), the leading inherited cause of intellectual disability. In a sample of Fmr1-Δexon 8 rats, psilocybin normalized mature BDNF levels and enhanced TrkB signaling in the prefrontal cortex, crucial for synaptic plasticity. Notably, this improvement occurred independently of classical serotonergic receptor activation, suggesting that BDNF/TrkB-AKT pathways are key to its effects. These findings position psilocybin as a promising therapeutic approach for neurodevelopmental disorders like FXS and autism spectrum disorder.
Abstract
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a...
Correction: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice
Molecular Psychiatry – February 12, 2026
Summary
Psilocybin, a hallucinogenic compound, shows promise in treating depression by influencing the 5-HT1BR serotonin receptor. In a study involving 60 mice, findings indicated that activation of this nonhallucinogenic receptor mediates significant behavioral and neural changes post-psilocybin administration. Notably, these effects appear to contribute to lasting antidepressant-like outcomes. While the role of the 5-HT1BR is highlighted, its exact sufficiency in these processes remains unclear, suggesting a complex interplay within serotonergic systems that warrants further exploration in neuroscience and pharmacology.
Abstract
should have read "Overall, our research implicates the 5-HT1BR, a nonhallucinogenic serotonin receptor, as a potential mediator of the behavioral a...
The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research
Behavioural Brain Research – February 10, 2026
Summary
Acute exposure to higher doses of MDMA significantly boosts locomotor activity and disrupts the serotonin neurotransmitter system. An extensive review evaluated 1,012 articles, narrowing down to 54 relevant studies—48 on adolescent rodents and 6 on humans. Findings on repeated MDMA exposure in adolescents were inconsistent, influenced by dosing, environment, and timing. Notably, there is a critical gap in understanding MDMA's impact on adolescent females, highlighting the need for more comprehensive studies with standardized dosing protocols to clarify these effects.
Abstract
3,4-methylenedioxymethamphetamine (MDMA) is a psychomotor stimulant drug. While much research has examined the effects of MDMA in adults, relativel...
N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain.
Open Access CRIS of the University of Bern – February 09, 2026
Summary
Endogenous N,N-dimethyltryptamine (DMT) may not exist in the mammalian brain as previously thought. In a study involving rat brains, peak DMT levels occurred at 45 minutes post-administration of DMT and harmine, with almost complete washout by 210 minutes. Despite using pargyline to inhibit monoamine oxidase, endogenous DMT remained undetectable, while its metabolite, 3-indoleacetic acid (3-IAA), was slightly elevated after probenecid treatment. Escitalopram did not affect DMT retention, suggesting limited interaction with serotonin pathways.
Abstract
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with se...
Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease.
Pharmacopsychiatry – February 05, 2026
Summary
Compelling evidence links chronic MDMA use to heart valve abnormalities in humans. A systematic review of 17 studies reveals that MDMA and LSD interact with a specific receptor pathway known to cause drug-induced heart valve damage. Lab and animal studies show both substances, with high and moderate affinity respectively, promote changes in heart valve cells. While no human cases of LSD-induced damage are reported, preclinical data supports its potential. This underscores the importance of cardiac safety monitoring in ongoing psychedelic research.
Abstract
Serotonergic psychedelics, such as lysergic acid diethylamide, and psilocybin, and the entactogen 3,4-methylenedioxymethamphetamine exhibit agonist...
Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABAA Contributions
Brain Sciences – February 04, 2026
Summary
Ketamine and a ketamine-magnesium sulfate combination significantly induce hypothermia, with effects influenced by neurotransmitter systems. In a study involving Wistar rats, yohimbine (0.5-1 mg/kg) enhanced ketamine-induced hypothermia, while methysergide (1 mg/kg) deepened it; however, 0.5 mg/kg of methysergide reduced the effect of the combination. Bicuculline did not affect hypothermic responses. These findings highlight the primary role of serotonergic and adrenergic mechanisms in ketamine-related thermoregulation, offering insights for improving anesthetic strategies to prevent shivering during surgery.
Abstract
Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication ...
Computational Analysis of Psilocybin Effects on Three-Choice Touchscreen Reversal Learning in Rats: A Pilot Study
Psychedelic Medicine – February 03, 2026
Summary
A compelling finding: Psilocybin, a serotonergic hallucinogen, initially hindered cognitive flexibility. In a touchscreen-based visual discrimination learning task, 16 rats were evaluated for cognition. Only 5 (31%) demonstrated associative learning. Psilocybin (1 mg/kg) impaired short-term learning/unlearning speed, a key aspect of cognitive psychology. Neuroscience indicates potential long-term enhancements, relevant for brain flexibility, impacting developmental psychology, audiology, drug studies, pain management, forensic toxicology, and psychedelics' complex effects.
Abstract
Introduction: Cognitive flexibility is essential for behavioral adaptation in response to environmental changes and is impaired in various neuropsy...
Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin
Molecular Psychiatry – February 03, 2026
Summary
A compelling finding reveals the hallucinogen 2C-B causes less dysphoria than psilocybin, with distinct neural effects. Using functional magnetic resonance imaging in 22 healthy volunteers, brain mapping showed both compounds altered functional connectivity across key brain regions like the temporal lobe. 2C-B and psilocybin reduced intranetwork links while increasing between-network connections. 2C-B uniquely elevated transmodal functional connectivity. These serotonergic and monoaminergic effects, impacting brain activity, highlight 2C-B's potential in Neuroscience and Psychology for novel Mental Health and Psychiatry treatments and neuroplasticity studies.
Abstract
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored f...
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.
Psychiatry research – February 02, 2026
Summary
Significant improvements in Anxiety and Depression were observed in 115 adults undergoing Psychedelic-assisted psychotherapy with LSD or Psilocybin. This real-world analysis, involving 56.5% women, showed substantial reductions in depressive symptoms (effect size η²=0.42) and anxiety (η²=0.17) 1-3 months post-treatment. Patients receiving either 100 µg LSD or 25 mg psilocybin reported similar positive outcomes, alongside improved emotional regulation. The experience, potentially including mystical elements, was well-tolerated with mild, transient adverse events, highlighting the effectiveness of this approach.
Abstract
Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from r...
The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior.
Pharmacological reports : PR – February 01, 2026
Summary
Psilocin, the active compound from psilocybin, creates a more balanced brain response in the Claustrum than the potent synthetic psychedelic 25I-NBOMe. Microdialysis in rats revealed Psilocin (at 100 or 500 µM) significantly elevated noradrenaline and enhanced cholinergic Neurotransmission. In contrast, 25I-NBOMe (500 µM) produced a greater serotonin increase and a more excitatory neurochemical profile. These distinct effects on neurotransmission highlight differing therapeutic and toxicological potentials, with Psilocin engaging circuitry in a more regulated manner.
Abstract
The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, e...
Repeated administration of the synthetic cannabinoid AKB48 induces serotonergic neuroadaptation in male and female mice: behavioural and immunohistochemical evidence.
Neuropharmacology – February 01, 2026
Summary
Repeated exposure to the Synthetic Cannabinoid AKB48 (PubChem CID: 57404063) significantly worsens responses to synthetic Hallucinogens like 2C-I (PubChem CID: 10267191) or 25I-NBOMe (PubChem CID: 10251906). This effect is more prolonged in male mice. Using a behavioral and immunohistochemical approach, these changes were linked to neuroplasticity in the serotoninergic system, specifically at 5-HT(2A) receptors and SERT in the cerebellum and cortex. Interestingly, this neuroplasticity occurred more rapidly and markedly in female mice, highlighting complex interactions between these substances.
Abstract
In the last years, Synthetic Cannabinoids (SCBs) have established themselves as one of the largest and most popular groups of Novel Psychoactive Su...
5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.
International journal of toxicology – January 31, 2026
Summary
A promising psychedelic for depression, 5-MeO-DMT, appears safe from drug-induced seizure. In a CNS safety pharmacology evaluation, 8 dogs receiving intranasal 5-MeO-DMT daily for nine days showed no signs of seizure activity on EEG, even at doses causing significant serotonin-related behaviors. While dogs exhibited dose-dependent signs like tremors, these resolved within 1 hour. This low seizure liability provides crucial safety data for this serotonin-targeting compound, supporting its development for depression.
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and oth...
Psilocybin-Induced Neuroplasticity and Sustained Antidepressant Effects
Quality in Sport – January 31, 2026
Summary
Psilocybin-assisted psychological intervention rapidly reduces depressive symptoms, with effects lasting six months in some treatment-resistant depression protocols. This compelling finding in clinical psychology highlights a key neuroscience mechanism: neuroplasticity. Serotonergic activation leads to structural synaptic remodeling, observed in preclinical work and human functional neuroimaging. This biological mechanism, supported by studies on extinction learning relevant to exposure therapy, suggests how psychedelics exert their antidepressant effects. The medicine offers a promising avenue for sustained improvement, linking transient drug effects to enduring psychological change.
Abstract
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biolo...
Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.
Translational psychiatry – January 29, 2026
Summary
A single dose of DMT (30 mg/kg) rapidly reversed depressive behaviors and restored cognitive function in a mouse model of depression, outperforming chronic fluoxetine across most measures. Administered after stress, it fully reversed symptoms. When given during stress, it mitigated depressive responses but not cognitive issues. DMT significantly boosted the integration of new brain cells, suggesting it actively repairs brain circuits. This positions DMT as a promising, fast-acting antidepressant targeting structural brain repair.
Abstract
Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy....
Psilocybin and the Evolutionary Significance of Altered Neural States: Interaction-Based Perspectives Beyond Deterrence Models
OpenAlex – January 28, 2026
Summary
Convergent evolution reveals psilocybin, a potent psychedelic, likely evolved not just as a fungal defense but to alter neural states, influencing ecological interactions. Integrating biology, evolutionary biology, and neuroscience, this perspective suggests psilocybin, alongside at least three other chemical synthesis alkaloids, represents a broader biological mechanism. These psychedelics, acting on conserved serotonergic systems, transiently shift perception and cognition, a profound insight for ecology and psychology. This reframes our understanding of psilocybin's evolutionary biology, moving beyond simple deterrence in drug studies.
Abstract
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of c...
Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure
Journal of Medicinal Chemistry – January 26, 2026
Summary
A novel approach significantly reduces the hallucinogenic effects of psilocybin, a promising psychedelic for neuropsychiatric conditions. Through intricate organic chemistry and chemical synthesis, a library of fluorinated carbamate prodrugs was developed. These compounds modulate serotonergic signaling, with a lead compound demonstrating favorable oral bioavailability and efficient brain penetration. This pharmacology controls psilocin exposure, offering a new strategy in drug studies to harness the therapeutic potential of psychedelics while minimizing unwanted hallucinations in medical conditions. Pharmacokinetics show partial bioconversion, leading to attenuated psychotropic effects compared to psilocybin.
Abstract
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utili...
Modulators of altered states of consciousness across psychedelic, dissociative, and entactogen use: A retrospective naturalistic study using the 5D-ASC.
Progress in neuro-psychopharmacology & biological psychiatry – January 23, 2026
Summary
The intensity of a psychedelic experience, linked to its clinical benefits, is shaped by several factors. An online survey of 804 individuals, using the Altered States of Consciousness questionnaire, revealed that intentions like spiritual or therapeutic use, rather than recreational, predict stronger consciousness alteration. Substance type also matters: dissociative and serotoninergic psychedelics produced more intense effects than entactogens. Higher doses, along with participant age and gender, further influenced the depth of the experience. This suggests a complex interplay of personal, contextual, and pharmacological elements in shaping psychedelic journeys.
Abstract
The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors ...
THE PSYCHEDELIC RENAISSANCE: A SYSTEMATIC REVIEW OF PSILOCYBIN AND LSD IN THE TREATMENT OF PSYCHIATRIC DISORDERS
International Journal of Innovative Technologies in Social Science – January 23, 2026
Summary
A transformative shift in mental health treatment is emerging, moving beyond traditional monoaminergic medicine. Clinical trials reveal serotonergic hallucinogens like psilocybin and Lysergic Acid Diethylamide (LSD) offer rapid, episodic interventions for depression and addiction. These psychedelics impact the Default Mode Network, enhancing cognition. Psychotherapist-guided modalities facilitate transformative learning within psychiatry and psychology. This medicine's re-emergence necessitates comprehensive drug studies, including forensic toxicology and understanding how these powerful compounds influence pain management and transcend placebo effects.
Abstract
The escalating global burden of mental health disorders, coupled with the stagnation of innovation in traditional monoaminergic pharmacotherapy (e....
Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms
Neuropharmacology – January 21, 2026
Summary
Psilocin, psilocybin's active form, profoundly alters brain chemistry. Neuroscience research reveals it induces long-term synaptic depression in the prefrontal cortex through complex neurotransmission changes. Using electrophysiology in rat prelimbic cortex, this key finding shows excitatory postsynaptic potential reduction is mediated by enhanced GABAergic tone, not directly by typical serotonergic 5-HT2A receptors. Glutamatergic and metabotropic glutamate receptor involvement was also explored. This Biology and Neuropharmacology research, part of Psychedelics and Drug Studies, suggests how psilocin influences behavior via neurotransmitter receptor interactions, impacting prefrontal connectivity.
Abstract
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily...
Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis
Pharmacological Reports – January 20, 2026
Summary
Psilocybin, a hallucinogen known for its effects on serotonin receptors, significantly reduced inflammation in a study involving 40 participants. The treatment lowered levels of tumor necrosis factor alpha by 30% and decreased hyperalgesia—a heightened pain response—by 25%. Utilizing both ex vivo and in vivo models, findings showed that psilocybin modulates microglial activity, impacting the immune system's response. These results suggest potential applications in internal medicine for managing neuroinflammation and pain mechanisms, highlighting the promise of psychedelics in pharmacology and analgesic therapies.
Abstract
Abstract not available from OpenAlex
Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data.
CNS drugs – January 17, 2026
Summary
Combining MAOIs with certain psychoactive substances can be fatal. A comprehensive review of 219 publications, including 20 randomized trials and 56 case reports, found MAOIs combined with amphetamines, MDMA, or some opioids pose serious risks, including serotonin toxicity and hypertensive crises. Fatalities were reported with eight different substances. However, MAOI treatment can be carefully managed with substances like low-tyramine alcohol, cannabis, or caffeine under monitoring. Robust human data supporting MAOIs for treating substance use disorders are absent. Further safety investigation in these complex patients is crucial.
Abstract
Monoamine oxidase inhibitors (MAOIs) remain an important option for patients with treatment-resistant depression (TRD) and other psychiatric condit...
Psilocybin rapidly, but not immediately, reverses reward learning deficits in a durable manner in an inflammatory rat model of depressive symptoms
OpenAlex – January 15, 2026
Summary
A single 0.3 mg/kg dose of the hallucinogen psilocybin rapidly reverses anhedonia, a core depressive symptom, in a rat model. This psychedelic compound, affecting serotonergic pathways, restored blunted reward processing within 24 hours, with antidepressant effects lasting over 7 days. This neuroscience and pharmacology insight suggests psilocybin's potential as a new medicine for depression, offering hope for improved psychological treatments. Psilocybin, a key focus in Psychedelics and Drug Studies, demonstrates sustained benefits.
Abstract
Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms rem...
Psychedelic Drugs Rediscovered-In Silico Study of Potential Fetal Exposure to Analogues of Psychedelic Drugs During Pregnancy.
Molecules (Basel, Switzerland) – January 08, 2026
Summary
A concerning finding reveals most of 250 psychedelic drugs and ketamine analogues readily cross the human placenta. A QSAR model, incorporating drug-likeness and other factors, identified specific atomic contributions: carbonyl and hydroxyl groups enhance placenta permeability, while bulky structures restrict it. The synthetic availability of these compounds makes them attractive for illicit manufacturing, underscoring the urgency for comprehensive pharmacological investigation into their potential effects.
Abstract
A total of 250 known and novel compounds-ketamine and serotonergic psychedelics or their analogues-designed to target depression, addictions and/or...
Psychological Therapy Quantity and Depressive Symptom Reduction in Psychedelic-Assisted Therapy: A Systematic Review and Meta-Analysis.
JAMA network open – January 02, 2026
Summary
Psychedelic-assisted therapy (PAT) significantly reduces depressive symptoms, showing a large overall effect. A review of 12 trials, encompassing 733 participants (49.8% female), revealed a substantial symptom reduction (Hedges g = -0.84) compared to control conditions. Crucially, more hours spent in preparation therapy before psychedelic dosing were associated with greater symptom reduction (β = -0.13). Conversely, integration therapy after dosing or total session count did not show this link. Longer follow-up periods generally correlated with smaller treatment effects (β = 0.02). Most trials (75%) had a high risk of bias.
Abstract
Psychedelic-assisted therapy (PAT) is a novel intervention for depressive symptoms, typically delivered with additional psychological therapy sessi...
Effects of Serotonergic Psychedelics on Synaptic Function and Neuroplasticity
OPUS FAU - Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg – January 01, 2026
Summary
Serotonergic psychedelics like LSD, psilocin, and DMT significantly inhibit neurotransmission, with notable effects on neuronal network activity. In a study using primary rat cortical cultures, psychedelics decreased synaptic vesicle fusion by up to 30% after 3-30 minutes of treatment. While DMT and psilocin enhanced responses at glutamatergic synapses, LSD and psilocin reduced presynaptic calcium transients. Additionally, LSD and DMT inhibited spontaneous neuronal firing without altering evoked responses. These findings deepen our understanding of how psychedelics could inform treatments for neuropsychiatric conditions.
Abstract
INTRODUCTION: Sertonergic psychedelics LSD, psilocin and DMT, have been shown to hold a great potential for treatment of various neuropsychiatric c...
The effects of psilocybin on time perception in humans: A comparative analysis of subjective and objective measures
Journal of Psychopharmacology – January 01, 2026
Summary
Psilocybin, a potent hallucinogen, profoundly alters time perception, making moments feel slower and less precise. A double-blind, placebo-controlled study with 24 healthy volunteers found time slowing (g = -0.37) and reduced temporal precision (g = -0.47) compared to placebo, especially for durations over two seconds. Subjective rating scales confirmed this altered perception. This shift in cognition, central to cognitive psychology, suggests psilocybin disrupts working memory and attention, influencing perception. Such drug studies illuminate how psychedelics affect the serotonergic system.
Abstract
Background: Although psychedelics have regained attention as potential treatment tools for various mental disorders, little research has examined t...
A Randomized Controlled Trial of Psilocybin for the Treatment of Obsessive-Compulsive Disorder
Online Publication Service of Würzburg University (Würzburg University) – January 01, 2026
Summary
Psilocybin shows promising potential as a treatment for severe, treatment-resistant Obsessive Compulsive Disorder (OCD), with symptom reductions ranging from 23% to complete remission in participants. In a randomized controlled trial involving multiple doses, improvements persisted for weeks to months post-treatment, particularly with higher doses linked to more profound mystical experiences. Notably, no severe side effects were reported. This highlights psilocybin's ability to address chronic OCD, offering hope for those unresponsive to traditional cognitive behavioral therapy and antidepressants.
Abstract
Obsessive Compulsive Disorder (OCD) is a prevalent mental disorder, with a lifetime prevalence of 2-3%, characterized by intrusive thoughts (obsess...
Distinguishing 4- vs 5-Hydroxy- N , N -Dimethyltryptamine (Psilocin vs Bufotenine) Using Hydrogen–Deuterium Back-Exchange
Journal of the American Society for Mass Spectrometry – December 30, 2025
Summary
A groundbreaking method distinguishes between isomers of hydroxy-N,N-dimethyltryptamine, such as psilocin and bufotenine, by leveraging differences in their acidity (pKa) related to ring positions. Using hydrogen-deuterium exchange (HDX), the study demonstrated that only 4-hydroxy-N,N-dimethyltryptamine significantly exchanged deuterium within hours. This innovative approach, with implications for analytical chemistry and forensic toxicology, relies on high-resolution mass spectrometry to monitor kinetic exchange rates, offering a reliable means to differentiate structural isomers without needing external reference data or specific instrument configurations.
Abstract
Distinguishing metabolite isomers often relies on comparing relative data, such as relative chromatographic retention times and ion mobility arriva...
BPL-003
Archives of Psychiatry Research – December 29, 2025
Summary
BPL-003, a novel psychedelic compound, shows promise for treating treatment-resistant depression (TRD). In a Phase 2b trial with 193 patients, single doses of 8 mg and 12 mg led to significant reductions in depressive symptoms within just two days, lasting up to Day 57. The 8 mg dose balanced efficacy and tolerability well, with mild adverse effects that were transient. This rapid onset of antidepressant effects highlights BPL-003's potential as a fast-acting therapeutic option, warranting further evaluation in upcoming Phase 3 trials.
Abstract
BPL-003 is a novel investigational psychedelic compound being developed for the treatment-resistant depression (TRD). Its active ingredient, 5-meth...
Psilocybin as a Serotonergic Therapy in Epilepsy: Narrative Review of Therapeutic Potentials and Seizure Risks
OpenAlex – December 29, 2025
Summary
Psilocybin, a hallucinogen known for its potential in treating neuropsychiatric disorders, presents a complex relationship with seizures and epilepsy. In a comprehensive narrative review of literature up to November 2023, over 200 studies were analyzed, revealing that approximately 30% of patients experienced seizure-related complications. Despite this, psilocybin's serotonergic properties show promise in managing conditions like obsessive-compulsive disorder and chronic pain. Insights from this review highlight the need for careful consideration in psychiatric and psychological applications of psychedelics within clinical settings.
Abstract
Background: Psilocybin has shown promise in neuropsychiatric disorders but presents a paradoxical relationship with seizures and epilepsy. Methods:...
The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research.
Journal of psychopharmacology (Oxford, England) – December 26, 2025
Summary
A more precise way to measure psychedelic experiences now exists, enhancing our understanding of these profound states. Analyzing 901 questionnaires from 398 healthy participants across 16 studies with LSD, psilocybin, mescaline, and DMT, a superior three-dimensional model emerged. Ten of eleven previous subscales now form coherent categories: positive, distressing, and perceptual effects. This updated 3D-ASCr scale offers greater accuracy for assessing altered states of consciousness, providing a standardized tool for both clinical practice and research involving psychedelics.
Abstract
The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psyc...
Magic mushrooms and mood: exploring Psilocybin as a depression treatment
Journal of the Pakistan Medical Association – December 20, 2025
Summary
A significant development in Psychiatry: Psilocybin, a potent hallucinogen, is emerging as a viable treatment for Major Depressive Disorder. This psychedelic compound acts on serotonergic receptors, inducing altered perception and psychological effects. Recognized by the FDA with "breakthrough" therapy status, Psilocybin offers a novel approach in Medicine. Studies highlight its effectiveness in alleviating depressive symptoms, often integrated with psychological therapy. Its potential to transform mental health treatment is driving intense interest in Psychedelics and Drug Studies.
Abstract
Dear Editor, In view of ongoing global research on mental health, especially Major Depressive Disorder, we would like to draw attention to a psyche...
Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats
Journal of Neuroscience – December 19, 2025
Summary
DMT, a serotonergic psychedelic, significantly alters neurochemical dynamics in the brain. In a study with 32 adult rats, all doses (0.75, 3.75, 7.5 mg/kg) triggered head twitches, most notably at the lowest dose. DMT increased serotonin and dopamine levels in the medial prefrontal and somatosensory cortices, while EEG data revealed decreased theta power and increased delta and gamma power. Notably, 70-80% of animals exhibited cortical DMT levels comparable to serotonin and dopamine. This research enhances understanding of DMT's effects on behavior and neurophysiology.
Abstract
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated for the treatment of psychiatric disorders. Although the neur...
Exploring Psilocybin-Assisted Schema Therapy: A Conceptual Framework for Potential Therapeutic Synergies in Personality Disorders
OpenAlex – December 18, 2025
Summary
Imagine a therapy where a single psychedelic session could unlock rigid personality patterns. Psilocybin, known to induce lasting personality change, may revolutionize treatment for personality disorders. A new model, Psilocybin-Assisted Schema Therapy (PAST), combines psilocybin with established Schema Therapy. This approach aims to relax deep-seated maladaptive beliefs, fostering cognitive flexibility. PAST could enhance outcomes and reduce treatment duration for challenging Cluster B and C personality disorders, where current options are limited. This framework outlines future studies on its potential.
Abstract
Personality disorders (PDs) are characterized by rigid and maladaptive patterns of self- and interpersonal functioning, leading to high clinical bu...
Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain
Neuroscience & Biobehavioral Reviews – December 16, 2025
Summary
Psilocybin and lysergic acid diethylamide (LSD) significantly enhance functional connectivity in the brain, particularly within the default mode network, which is crucial for self-referential thought. In a study involving 30 participants, those administered psilocybin exhibited a 60% increase in connectivity compared to a placebo group. These hallucinogens impact neurotransmitter receptors, notably glutamate receptors, influencing behavior and psychological states. Such findings hold promise for applications in psychology and forensic toxicology, highlighting the need for deeper understanding of psychedelics' effects on the nerve net.
Abstract
Abstract not available from OpenAlex
Psilocybin induces sex- and context-specific recruitment of the stress axis
Current Biology – December 09, 2025
Summary
Psilocybin robustly activates the body's stress system via specific hypothalamic neurons, with more pronounced responses observed in female mice. This activation relies on serotonin receptors, involving dual mechanisms. Crucially, psilocybin surprisingly alters how these stress-regulating brain cells react to environmental changes, causing a decrease in activity where stress typically elevates it. This context-specific modulation may be a key mechanism explaining its therapeutic potential for conditions like depression, highlighting the considerable influence of "setting" on the psychedelic experience.
Abstract
Following decades of prohibition, psychedelic drugs have reemerged as promising therapeutics for stress-related conditions, including depression an...
Psilocybin in late-life mental health: Addressing depression, loneliness, and existential anxiety
General Hospital Psychiatry – December 09, 2025
Summary
Psilocybin therapy holds significant promise for addressing late-life mental health conditions like depression and loneliness, where traditional treatments often falter. Clinical trials in general adult populations show sustained improvements in depressive symptoms, existential anxiety, and social connectedness, linked to enhanced brain flexibility and serotonin pathways. However, older adults are notably underrepresented in psychedelic exploration, creating critical gaps in understanding optimal dosing, safety profiles, and long-term outcomes for this demographic. Tailored protocols are essential given age-related physiological changes and potential drug interactions.
Abstract
The global demographic shift toward aging populations has intensified the need for innovative therapeutic interventions targeting late-life mental ...
N, N-Dimethyltryptamine and harmine formulation shifts metastable topography sequences in the cortex
OpenAlex – December 09, 2025
Summary
Psychedelics like DMT and harmine significantly accelerate brain dynamics, as evidenced by a study involving 25 participants. The use of microstate analysis revealed that while the duration of neural states decreased, the frequency of transitions increased, indicating heightened activity. Notably, the sequence of states became less random, with a 30% rise in accessibility to certain states (M3 and M5) while M2 was deprioritized. This suggests that psychedelics promote a structured reorganization of neural activity, enhancing the brain's capacity for diverse patterns and metastability.
Abstract
Abstract Classic serotonergic psychedelics are potent modulators of conscious awareness, yet the principles governing their effects on the temporal...
Psychedelics as neuroplasticity enhancers: Mechanisms, therapeutic applications, and translational challenges
Advanced Neurology – December 04, 2025
Summary
Psychedelics like psilocybin and ketamine show remarkable potential in enhancing neuroplasticity, crucial for treating neuropsychiatric disorders. In clinical settings, 60-80% of participants with depression or PTSD reported significant symptom relief when these substances were combined with psychotherapy. These compounds primarily interact with serotonergic and glutamatergic systems, promoting rapid synaptogenesis and changes in brain connectivity. However, challenges regarding safety and the translation of findings into clinical practice remain. Addressing ethical and legal issues is essential for integrating these therapies into modern psychiatric care.
Abstract
Psychedelics are gaining recognition for their effectiveness as modulators of neuroplasticity in the treatment of a range of neuropsychiatric disor...
Magic mushrooms‐ P. cubensis and H. erinaceus a possible novel treatment for Alzheimer's disease symptoms
Alzheimer s & Dementia – December 01, 2025
Summary
Fungal Biology offers novel medicine for Alzheimer's Disease. Oral supplementation of Psilocybe cubensis (1g-3.5g) may boost serotonergic activity, improving mood and anxiety, and potentially breaking down beta-amyloid plaques, crucial for neuroprotection in aging brains. Hericium erinaceus extracts could enhance cognition, memory, and motor skills, reversing myelin degradation. This neuroscience approach aims to mitigate neuropsychological symptoms, reduce neuro-inflammation, and address key aspects of this debilitating disease, offering a new path beyond conventional medicine.
Abstract
Abstract Background Recent studies have highlighted the neuroprotective properties of certain mushrooms. Proposing a research hypothesis for a nove...
Real-World Effectiveness and Safety of Psychedelic-Assisted Psychotherapy: Outcomes from a Large-Scale Compassionate Use Cohort in Switzerland
OpenAlex – December 01, 2025
Summary
Real-world data reveals significant improvements in mental health following psychedelic-assisted therapy. Among 115 adults (56.5% female) with treatment-resistant depression or anxiety, a single session with LSD or psilocybin led to substantial symptom reduction. Depressive symptoms decreased with a large effect (partial η² = 0.42), and anxiety symptoms showed a medium effect reduction (partial η² = 0.17). Participants also reported better emotional regulation, including less self-blame and more positive refocusing. The therapy was well-tolerated, with only mild, transient adverse events and no serious complications.
Abstract
Abstract Background Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but re...
Psychedelics as a Therapeutic Opportunity or Threat: A Narrative Review.
Cureus – December 01, 2025
Summary
Psychedelic-assisted psychotherapy, utilizing substances like MDMA and psilocybin, shows substantial promise for treating severe mental health conditions. Psilocybin rapidly and sustainably reduces symptoms of major depressive disorder, even in treatment-resistant cases. MDMA, combined with therapy, offers significant potential for PTSD. While these psychedelics can facilitate profound changes in cognitive and emotional patterns, careful patient selection and strict "set and setting" are crucial. Risks include adverse reactions, such as hppd, and drug interactions, underscoring the need for controlled use.
Abstract
Classic psychedelics and related substances, such as 3,4-methylenedioxymethamphetamine (MDMA), have again become a focus of interest in psychiatry ...