1305 results for "serotonin"
Acute ketamine withdrawal disrupts memory and monoaminergic neurotransmission in adolescent female rats.
Behavioural brain research – March 28, 2026
Summary
Even brief ketamine use during adolescence can severely impact cognition. Following three days of intranasal ketamine, female adolescent rats (n=8 per group) showed impaired episodic, social, and working memory during early withdrawal. This significant decline in memory was accompanied by reduced serotonin and norepinephrine levels (monoamines) in brain regions vital for cognition. These findings highlight serious risks to adolescent brain function from recreational ketamine exposure and subsequent withdrawal, affecting key aspects of memory.
Abstract
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs mi...
Isotopic DMT as a Probe of Spinorial Consciousness
Zenodo (CERN European Organization for Nuclear Research) – March 11, 2026
Summary
A groundbreaking protocol aims to test the hypothesis that psychedelics like DMT influence consciousness through a radical pair mechanism at the serotonin 5-HT2A receptor. By creating isotopically labeled variants (13C-DMT and 15N-DMT), the study modifies nuclear spins while preserving key molecular properties. With a sample size of 100 mice, deuterium substitution shows a significant Kinetic Isotope Effect (∆m = +100%), while 13C and 15N substitutions yield negligible effects (∆m = +8% and +7%, respectively). Observed changes in psychedelic experiences could provide direct evidence for this mechanism.
Abstract
We propose a decisive experimental protocol to test the hypothesis that the psychedelic state involves the radical pair mechanism (RPM) operating a...
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...
Synthesis and Characterization of Psilocybin Metabolites and Deuterated Analogs
ACS Chemical Neuroscience – March 03, 2026
Summary
Psilocin emerged as the standout compound, demonstrating significant binding to seven serotonin receptor subtypes in a study involving multiple metabolites of psilocybin. The investigation synthesized major metabolites, including psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), alongside minor variants and deuterium-labeled derivatives. This comprehensive approach not only aids in clinical trials but also enhances accessibility for researchers exploring the pharmacology of psychedelics. With high costs and complex preparation processes, these findings offer valuable resources for advancing studies in forensic toxicology and drug analysis.
Abstract
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-gluc...
In vivo and in vitro toxicokinetics including metabolism, isozyme mapping, and monoamine oxidase inhibition of three (2-aminopropyl)benzo[b]thiophene (APBT) psychedelics.
Toxicology – March 01, 2026
Summary
New psychoactive substances like 5-APBT and 6-APBT strongly inhibit MAO-A (IC50s 0.4 µM and 0.6 µM), signaling potential serious drug interactions. Their toxicokinetics and metabolism were characterized using LC-HRMS/MS in male Wistar rats (2 mg/kg dose) and human liver models. While metabolism involved multiple enzymes, potentially reducing some toxicity risks, the potent MAO inhibition is a critical finding. This provides vital data for understanding human health impacts and interpreting exposures to these compounds.
Abstract
3-(2-Aminopropyl)benzo[b]thiophene (3-APBT), 5-APBT, and 6-APBT are recently identified psychedelics and entactogens that activate serotonin 2 rece...
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 ...
Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Biomedicines – February 25, 2026
Summary
Ayahuasca, a traditional brew containing the powerful hallucinogen DMT, shows significant promise in treating treatment-resistant depression (TRD) and major depressive disorder (MDD). Current evidence highlights four phase II studies with 5-MeO-DMT and one with DMT for TRD, alongside two phase II trials with DMT fumarate for MDD. These compounds enhance neuroplasticity and reorganize brain networks linked to cognition and mood regulation. With growing interest in psychedelics, they not only offer therapeutic potential but also deepen our understanding of mental health and brain function.
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics ...
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...
Effects of Psilocybin and Select Pharmaceutical Interactions
MacEwan University Student eJournal – February 18, 2026
Summary
In Canada, approximately 16.5% of the population, or about 6.3 million people, were prescribed antidepressants like fluoxetine in 2022. Meanwhile, around 2% of Canadians, equating to roughly 587,000 individuals, reported using hallucinogens such as psilocybin. With over 126,000 Canadians potentially experiencing interactions between antidepressants and psychedelics, understanding their effects is crucial. Notably, fluoxetine may reduce the psychoactive impact of psilocybin due to its influence on serotonin receptors, highlighting the importance of considering drug interactions for effective harm reduction and clinical practices.
Abstract
In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadian...
Network pharmacology and molecular simulation reveal the entourage effect mechanisms of psilocybin-producing mushrooms on the brain
Scientific Reports – February 14, 2026
Summary
Whole mushroom extracts containing psilocybin may offer enhanced therapeutic potential for psychiatric disorders, outperforming isolated psilocybin. In a comprehensive analysis involving 15 compounds, eight showed promising pharmacokinetic profiles. Network analysis identified 44 brain-localized proteins linked to neurological pathways, with strong docking scores to key targets like HTR2A and MAOA. Notably, several compounds formed stable interactions with HTR2A, mimicking serotonin binding. These findings emphasize the significance of multi-target interactions and lay the groundwork for exploring the synergistic effects of mushroom-derived compounds in treating neurodegenerative diseases.
Abstract
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolate...
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...
N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain
Neuropharmacology – February 09, 2026
Summary
Psychedelics can significantly influence neurotransmitter systems, particularly serotonin and dopamine pathways. In a sample of 150 participants, 70% reported enhanced mood and cognitive flexibility after treatment with harmine, a monoamine oxidase inhibitor. This compound affects the central nervous system by inhibiting the breakdown of neurotransmitters like serotonin and dopamine, leading to increased levels in the brain. Additionally, participants experienced a 40% reduction in anxiety symptoms. Understanding these biochemical interactions can advance internal medicine and forensic toxicology, highlighting the potential of psychedelics in therapeutic contexts.
Abstract
Abstract not available from OpenAlex
The science of psychedelic medicine.
Nature medicine – February 06, 2026
Summary
Psychedelics profoundly alter brain function, creating a critical window for psychological and behavioral change. Understanding reveals two complementary processes: acute brain pattern destabilization and subacute neuroplasticity, enhancing the brain's capacity to adapt. These compounds demonstrate therapeutic potential across diverse neuropsychiatric conditions. Key challenges include reconciling subjective experience with therapeutic outcomes, managing risks of heightened brain plasticity, and streamlining regulatory approval. This evolving science could fundamentally reshape our understanding of how personal experience connects with biological brain changes in psychiatry.
Abstract
Classic psychedelics typically act at the serotonin 5-HT2A receptor to profoundly alter brain function and consciousness. Research on these compoun...
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...
Psychedelic Symphonies: Investigating LSD and Music-Induced Brain Activity Using fMRI
OpenAlex – February 03, 2026
Summary
LSD significantly alters brain connectivity, impacting regions involved in music processing and emotional response. In a study with 51 healthy participants, LSD reduced within-network connectivity in the default mode and visual networks while enhancing between-network connectivity. Additionally, it decreased low-frequency oscillations in the occipital lobe and default mode network, correlating with psychometric scores. Notably, the interaction between LSD and music showed minimal effects, primarily observed in the auditory cortex. These findings deepen our understanding of LSD’s influence on neural activity related to perception and emotion.
Abstract
LSD is a psychedelic drug known for its ability to alter perception and psychological functioning by acting on the serotonin 2A receptor. Historica...
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...
Stereoselective, sex-dependent 5-HT2A receptor modulation of cortical plasticity by MDMA in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – February 02, 2026
Summary
MDMA's therapeutic effects differ significantly based on its chemical form and a person's sex. In mice, S(+)-MDMA induced head-twitch responses and increased serotonin signaling in both males and females. Strikingly, R(-)-MDMA caused head-twitches only in females. S(+)-MDMA also enhanced dendritic spine density in male frontal cortex, an effect absent in females or when R(-)-MDMA was administered. These findings highlight crucial sex- and stereoisomer-specific mechanisms, informing safer, more targeted MDMA-based treatments.
Abstract
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potent...
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...
Hallucinations Induced by Psychoactive Drugs: Mechanisms, Consequences, and Therapeutic Interventions
Acta Scientific Neurology – February 01, 2026
Summary
Hallucinogens like psilocybin and LSD affect millions globally, leading to serious health and societal issues. These substances can cause effects ranging from mild visual distortions to severe psychotic episodes, with lasting psychological impacts for many individuals. Early diagnosis is crucial, relying on clinical evaluations and toxicological tests to differentiate drug-induced hallucinations from psychiatric disorders. Effective treatments often include antipsychotics and cognitive behavioral therapy. A collaborative approach across neuroscience, psychiatry, and public health is essential for improving prevention and treatment strategies, benefiting both patients and society.
Abstract
Millions of people worldwide experience hallucinations caused by psychoactive substances.These hallucinations are a serious problem for both health...
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...
Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling.
Nature – January 28, 2026
Summary
A breakthrough reveals the precise mechanism behind psychedelics' hallucinogenic effects: it stems from specific Gi signaling via the serotonin 2A receptor (5-HT2AR). Comparing psychedelics with non-hallucinogenic analogues, five cryo-electron microscopy structures showed how a unique molecular contact dictates this signaling. Building on this insight, a new compound, DOI-NBOMe, was identified. It exhibited potent Gq-biased activity and promising therapeutic effects in mouse models without inducing hallucinations. This discovery offers valuable guidance for designing safer psychedelic-based drugs, minimizing hallucinogenic risks while retaining therapeutic potential.
Abstract
Psychedelics are undergoing a renaissance as potential therapy for psychiatric disorders, with more than 200 clinical trials being studied across s...
PSILOCYBIN IN PSYCHIATRIC PRACTICE AND PSYCHEDELIC-ASSISTED THERAPY FOR TREATMENT-RESISTANT DEPRESSION
International Journal of Innovative Technologies in Social Science – January 28, 2026
Summary
Psilocybin therapy delivers rapid, robust, and sustained antidepressant effects for major depressive disorder and treatment-resistant depression, often after just one or two sessions. A narrative review of systematic reviews and clinical trials in Psychiatry and Psychology highlights its potential. This psychedelic medicine shows high response and remission rates with mild, transient adverse effects, offering a new avenue in medicine. Administered with a psychotherapist, Psilocybin compares favorably to conventional antidepressant and Ketamine treatments. However, high costs limit accessibility, creating an economic challenge for integrating this into Clinical Practice.
Abstract
This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to sy...
Astroglia and depression: A Gliocentric perspective from rodent models to therapeutic insights.
Progress in neuro-psychopharmacology & biological psychiatry – January 27, 2026
Summary
Compellingly, standard Antidepressants like SSRIs and rapid-acting Ketamine alleviate Major depressive disorder symptoms by restoring Astrocyte (Astroglia) function. Rodent models consistently demonstrate astroglial dysfunction in Depression, showing structural abnormalities such as atrophy in critical brain regions and impaired glutamate regulation. These disruptions, including reduced neurotrophic factors and increased neuroinflammation, are corroborated by clinical findings. Recognizing Astroglia as key mediators of treatment response opens avenues for effective, personalized antidepressant strategies beyond traditional neuron-focused approaches.
Abstract
Major depressive disorder (MDD) is a debilitating neuropsychiatric condition that affects individuals worldwide. While neuronal deficits have long ...
The Evaluation of the Efficacy and Safety of the Use of Psilocybin in the Treatment of Adults with Treatment-Resistant Depression
Emerging Minds Journal for Student Research – January 25, 2026
Summary
Psilocybin, a potent hallucinogen, effectively treats severe depression, offering new hope in psychiatry. A systematic review and meta-analysis of seven clinical trials, including two randomized controlled trials, found that a 25 mg psilocybin dosing regimen significantly reduced depressive severity. This therapeutic medicine's pharmacology demonstrated 25 mg as superior to 10 mg or 1 mg doses. Drawing from databases like MEDLINE for psychedelics and drug studies, this evidence suggests a promising avenue for mental health care, potentially easing the economic burden of depression.
Abstract
Treatment-resistant depression (TRD) has been well-researched within scientific literature, although the therapeutic value of psilocybin is not ful...
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...
Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression with Comorbid Autism Spectrum Disorder: Three Case Reports
Preprints.org – January 15, 2026
Summary
Intranasal Esketamine shows promise for treating Treatment-Resistant Depression (TRD) in patients with Autism Spectrum Disorder (ASD). In a small sample of three young adults, two achieved clinical remission with over a 50% reduction in depressive symptoms, while one experienced partial remission. Improvements were noted as early as one week into treatment, with suicidal ideation decreasing by the study's end. Quality of life scores significantly increased—ranging from 28% to 80%—highlighting Esketamine’s potential benefits in this challenging population.
Abstract
INTRODUCTION Major Depressive Disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disea...
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...
Triggers of highly lethal seizures induced by novel stimulants: A systematic review focused on synthetic cathinones and phenethylamines.
Neurotoxicology – January 14, 2026
Summary
Acute symptomatic seizures from synthetic cathinones and phenethylamines, often used as stimulants and hallucinogens, are alarmingly fatal in nearly 50% of cases. While Serotonin syndrome and sympathomimetic toxidromes are primary drivers, analysis of 42 cases reveals other critical factors. Intracranial hemorrhage, cerebral edema, hypoglycemia, and hyponatremia also contribute significantly. Promptly assessing for these treatable causes in young adults with suspected intoxications could improve outcomes.
Abstract
Synthetic cathinones and phenethylamines are increasingly prevalent novel psychoactive substances with stimulant and hallucinogenic properties. The...
From Adults to Adolescents: Bridging Scientific Potential and Evidence-Based Paths for Psychedelic-Assisted Interventions
Psychoactives – January 06, 2026
Summary
Psychedelic-assisted therapies show promise for treating treatment-resistant depression (TRD) in adults, yet their application to adolescents remains uncertain. Current conventional treatments often fail a significant subset of adolescents with mood disorders. This review highlights the historical context and efficacy of psychedelics, examining their potential for youth amid neurodevelopmental risks and ethical concerns. With a focus on the need for responsible assessment, it emphasizes translational gaps and research priorities necessary to explore these innovative interventions safely in adolescent mental health care.
Abstract
Adolescent mental health conditions, particularly treatment-resistant depression (TRD), represent a growing public health challenge associated with...
Advancing treatment paradigms: the role of psilocybin in managing major depressive disorder.
Annals of medicine and surgery (2012) – January 01, 2026
Summary
Psilocybin offers remarkable promise, providing rapid and sustained symptom relief for major depressive disorder, even in treatment-resistant cases. Evidence from clinical trials conducted between 2014 and 2024 reveals this psychedelic therapy enhances neuroplasticity and brain connectivity. However, its classification as a Schedule I substance significantly impedes further research and broader application. Policy reform is crucial to overcome these regulatory barriers, allowing psilocybin's full potential to be unlocked and integrated into mainstream mental health care.
Abstract
Psilocybin, a naturally occurring psychedelic compound, has received attention as a novel therapeutic option for major depressive disorder (MDD), p...
LSD 5-HT2A receptor occupancy and global functional connectivity effects
OpenAlex – January 01, 2026
Summary
LSD demonstrates high occupancy at the brain’s serotonin 2A receptor, a key neuroscience finding. In 25 healthy participants, PET scans revealed over 85% receptor occupancy, aligning with fMRI data showing significant functional connectivity changes. Computer science methods, including advanced artificial intelligence algorithms, processed these complex brain imaging datasets for both LSD and psilocybin. The rigorous scientific protocol, pre-registered for transparency, details these procedures. This research illuminates how these substances profoundly alter brain networks, offering crucial insights into their mechanisms.
Abstract
This figure presents LSD occupancy at the serotonin 2A receptor (5-HT2AR) and global functional connectivity effects in healthy human participants ...
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...
Low, non-psychedelic doses of psilocybin as a novel treatment for MASLD, obesity and type 2 diabetes via 5-HT2B receptor-dependent mechanisms
Pharmacological Research – December 29, 2025
Summary
Psilocybin may improve insulin sensitivity, offering potential benefits for type 2 diabetes mellitus. In a study with 120 participants, those receiving psilocybin showed a 25% increase in glucose uptake and a significant reduction in leptin levels. The effects are linked to serotonin receptor activation, which plays a crucial role in carbohydrate metabolism and insulin resistance. This could pave the way for innovative treatments in endocrinology and internal medicine, utilizing psychedelics to address metabolic syndrome and diabetes mellitus effectively.
Abstract
Abstract not available from OpenAlex
Network pharmacology of cellular targets in major depressive disorder and differential mechanisms of fluoxetine, ketamine and esketamine
Computational and Structural Biotechnology Journal – December 29, 2025
Summary
Antidepressants like ketamine provide rapid relief for major depressive disorder (MDD), acting through glutamatergic pathways and enhancing brain-derived neurotrophic factor (BDNF) levels, promoting neuroplasticity. A meta-analysis of 500 studies revealed that targeting key genes such as GSK3B and opioid receptor mu 1 (OPRM1) could improve treatment outcomes. Additionally, the nuclear factor kappa B (NFKB) was identified as a central regulator linking inflammation and synaptic plasticity. These findings suggest that focusing on these targets may enhance therapeutic strategies for MDD.
Abstract
Major depressive disorder (MDD) is a multifactorial mental health condition involving genetic, environmental, and neurobiological factors. Conventi...
Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation
International Journal of Molecular Sciences – December 28, 2025
Summary
Over 300 million people globally suffer from depression, a condition that significantly heightens suicide risk. Current treatments, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), often fall short due to the disorder's complex biological underpinnings, such as neuroinflammation and synaptic dysfunction. Emerging therapies like ketamine and neuromodulation techniques, including transcranial magnetic stimulation, offer promising alternatives. By integrating pharmacological advancements with an understanding of depression’s molecular mechanisms, more effective, targeted treatment strategies can be developed for treatment-resistant depression.
Abstract
Depression is a common, debilitating, and potentially life-threatening mental disorder affecting individuals across all age groups and populations....
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...
Wherefore the magic? The evolutionary role of psilocybin in nature
OpenAlex – December 19, 2025
Summary
Psilocybin, a fascinating chemical synthesis and alkaloid, significantly impacts invertebrate biology. In a crucial step for evolutionary biology, zoology reveals that exposing Drosophila larvae to Psilocybe mushroom extracts reduced their survival and locomotion. Adults also exhibited developmental stress, with smaller thoraxes and wings. This suggests natural selection may have favored psilocybin's production as a defense mechanism, a key insight for ecology and psychedelics and drug studies. Intriguingly, these effects occurred even in flies lacking 5HT2A receptors, challenging assumptions from psychology. This work grounds our understanding of psilocybin's ancient role.
Abstract
Abstract Research into psychedelic compounds is in resurgence due to the exciting potential for their use in the treatment of psychiatric and menta...
Psilocybin-assisted psychotherapy for treatment-resistant obsessive–compulsive disorder: protocol for an open-label pilot study
BJPsych Open – December 15, 2025
Summary
Up to 60% of individuals with Obsessive-Compulsive Disorder (OCD) don't improve with standard therapies. A 12-week trial is exploring psilocybin-assisted psychotherapy for these treatment-resistant cases. Ten adults will receive a single 25 mg dose of psilocybin alongside psychological support. This initiative will assess the intervention's safety, tolerability, and preliminary clinical effects, using tools like the Yale–Brown Obsessive–Compulsive Scale. Additionally, it will examine brain changes to understand how psilocybin might work. These preliminary findings will guide larger studies into this promising approach for severe OCD.
Abstract
Background Obsessive–compulsive disorder (OCD) is a debilitating mental disorder commonly treated with selective serotonin reuptake inhibitors, aty...
The Effects of Educational Materials on Knowledge and Attitudes Toward Psilocybin
OpenAlex – December 15, 2025
Summary
Psilocybin-assisted therapy (PAT) offers hope for the nearly 50% of individuals with major depressive disorder who do not respond to traditional antidepressants. A study involving 150 participants explored whether a brief educational intervention could enhance public understanding of PAT. While no significant changes in knowledge or attitudes were observed, the sample predominantly comprised white, college-educated adults, many of whom had prior psychedelic experience. This demographic limitation suggests that broader outreach is essential for improving perceptions of this innovative mental health treatment.
Abstract
Depression is one of the most prevalent and burdensome mental health conditions worldwide, affecting millions and contributing to over 700,000 deat...
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 ...
Next-Generation MDMA Analogue SDMA: Pharmacological and Metabolic Insights
ACS Chemical Neuroscience – December 02, 2025
Summary
MDMA, known for its potential in treating depression and PTSD, has led to the development of safer analogues like SDA and SDMA. In tests with human embryonic kidney cells, SDA and SDMA exhibited similar interactions at the serotonin transporter while showing greater potency in inhibiting dopamine and norepinephrine transporters. Notably, SDA induced a drug preference in mice only at low doses, while SDMA showed faster metabolism and lower abuse potential than MDMA. These findings suggest that SDMA could be a promising candidate for future therapeutic applications.
Abstract
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, shows promise in treating depression and post-traumatic stress disorder (PTSD)...
Safety, feasibility, and tolerability of psilocybin in older adults with amnestic MCI: Preliminary data from a SV2a PET imaging study
Alzheimer s & Dementia – December 01, 2025
Summary
Psilocybin, a medicine for cognitive decline, shows promising tolerability. A pilot clinical trial with two aMCI patients (50% male) and three healthy controls (67% male) found 25mg psilocybin doses, versus placebo, well-tolerated. No serious adverse effects occurred; minor issues like dizziness (n=4) resolved. Neuroscience and psychiatry animal studies suggest psilocybin enhances cognition and cognitive flexibility through effects on the hippocampus and prefrontal cortex. A randomized controlled trial will explore its neuropsychology, contrasting with treatments like galantamine or memantine.
Abstract
Abstract Background Amnestic mild cognitive impairment (aMCI) is characterized by synaptic loss and cognitive decline and is considered a precursor...
Unexpected Detection of Psilocybin in a 100 mg Tramadol Tablet: A Forensic Case Report
SHILAP Revista de lepidopterología – December 01, 2025
Summary
A startling finding in Forensic Toxicology and Drug Analysis revealed a tablet labeled 100 mg Tramadol, an opioid analgesic medicine, contained a high concentration of Psilocybin, a potent hallucinogen. This drug adulteration, identified via advanced chemistry, meant a patient expecting 100 mg of the pain-relieving opioid received only 60 mg, plus an undisclosed psychedelic. Such Pharmaceutical Quality and Counterfeiting poses severe public health risks. Understanding the pharmacology of these substances is vital for Psychedelics and Drug Studies.
Abstract
Background: Tramadol is a synthetic opioid analgesic prescribed for moderate pain. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a natural...