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Serotonin research published in 2025

151 studies whose primary subject is serotonin were published in 2025, up from 105 in 2024. Newest first. Back to the serotonin overview

Studies

Psilocybin as a Serotonergic Therapy in Epilepsy: Narrative Review of Therapeutic Potentials and Seizure Risks

December 29, 2025 Miguel Benjamín Cervera-Sánchez, Daniel San-Juan, Roberto Díaz-peregrino et al.

Background: Psilocybin has shown promise in neuropsychiatric disorders but presents a paradoxical relationship with seizures and epilepsy. Methods: A narrative review was conducted up to November 23, 2025. We conducted structured literature searches a

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 Martina Colognesi, Daniela Gabbia, Anna Signor et al. 3 citations

The therapeutic potential of low, non-psychedelic doses of psilocybin, a fungal tryptamine alkaloid, was investigated in metabolic disorders including obesity, type 2 diabetes mellitus (T2DM), and liver steatosis. Mice fed a high-fat/high-fructose diet received chronic treatment with psilocybin (0.05 mg/kg) for 12 weeks. Body weight, liver histology, insulin sensitivity, and skeletal muscle...

BPL-003

Archives of Psychiatry Research December 29, 2025 Darko Vlahović, D. Vlahovic

BPL-003 is a novel investigational psychedelic compound being developed for the treatment-resistant depression (TRD). Its active ingredient, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), is a serotonergic psychedelic with preferential agonism at 5-HT1A receptors and rapid pharmacokinetics, allowing for a brief, supervised in-clinic administration. Preclinical studies demonstrate that 5-MeO-DMT...

Deciphering Ibogaine’s Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses

Journal of the American Chemical Society December 26, 2025 Christopher Hwu, Václav Havel, Xavier Westergaard et al. 2 citations

) that has a unique therapeutic potential across multiple indications, including opioid dependence, substance use disorders, depression, anxiety, posttraumatic stress disorder (PTSD), and traumatic brain injury (TBI). We systematically examined the effects of ibogaine, its main metabolite noribogaine, and a series of iboga analogs at monoamine neurotransmitter transporters, some of which have...

DOI: 10.1021/jacs.5c06325 (opens in new tab) Serotonergic Monoamine neurotransmitter Serotonin transporter Vesicular monoamine transporter +9

Magic mushrooms and mood: exploring Psilocybin as a depression treatment

JPMA. The Journal of the Pakistan Medical Association December 20, 2025 Maria Rasool, Taha Hannan, Muhammad Imam

Dear Editor, In view of ongoing global research on mental health, especially Major Depressive Disorder, we would like to draw attention to a psychedelic substance, Psilocybin, which has been emerging as a viable treatment option for MDD. Psilocybin is a psychedelic compound derived from certain mushrooms that acts on Serotonergic receptors (primarily 5HT-2A). Psychedelic substances have...

Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats

Journal of Neuroscience December 19, 2025 Nicolas G. Glynos, Emma R. Huels, Trent Groenhout et al. 11 citations

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated for the treatment of psychiatric disorders. Although the neurophysiological effects of DMT in humans are well characterized, similar studies in animal models and data on the neurochemical effects of DMT are generally lacking, which are critical for a mechanistic understanding. Here, we combined behavioral...

Dual Modulation of 5-HT2A Receptors and SERT by α-Ethyltryptamine and Its Optical Isomers.

ACS Chemical Neuroscience December 17, 2025 Justin M Silverman, Michael Fiorillo, Jason Younkin et al. 1 citation

α-Ethyltryptamine (AET), a synthetic tryptamine formerly used as an antidepressant, has resurfaced as a compound of interest due to its structural and functional overlap with serotonergic psychedelics and entactogens. Here, we characterized the pharmacological properties of racemic AET and its optical isomers, R(-)-AET and S(+)-AET, focusing on their interactions with the serotonin (or...

DOI: 10.1021/acschemneuro.5c00468 (opens in new tab) Full text (opens in new tab) 5-ht2a receptor G protein-coupled receptor Head-twitch response Psychedelics +3

Transforming Amino Acids into Serotonin 5-HT 2A Receptor Ligands Using Photochemistry

Journal of the American Chemical Society December 16, 2025 J.O.S. Beckett, Ryan Buzdygon, Steven Nguyen et al. 1 citation

A light-induced cyclization via a radical spin-center shift process that results in the direct functionalization of the indole ring at the C4-position is developed into a practical method for the synthesis of medicinally active, ring-constrained tryptamine analogs. Amino acids were coupled to tryptamine and irradiated with UV light to produce a library of lactams bridging the C3- and...

Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain

Neuroscience & Biobehavioral Reviews December 16, 2025 Rivka Vollebregt, A. J. Storm, Paul J. Lucassen et al. 3 citations

Classical psychedelics, like lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and psilocybin, can alter perception, emotion, and cognition, and have shown promise as 're-purposed' treatments for some psychiatric disorders. Recent trials have, e.g., demonstrated rapid and sustained symptom relief in treatment-resistant depression. While promising as a treatment, the...

Psilocybin induces sex- and context-specific recruitment of the stress axis

Current Biology December 9, 2025 Sarah G. Cook, Stephanie J. Lee, Emma Ference et al. 3 citations

Following decades of prohibition, psychedelic drugs have reemerged as promising therapeutics for stress-related conditions, including depression and post-traumatic stress disorder. Still, their impact on stress-related brain regions and the hypothalamic-pituitary-adrenal (HPA) axis remains unclear. This work explores the acute effects of psilocybin on the primary regulators of the HPA axis:...

Unlocking the power of tryptamine alkaloids in Psilocybe fungi: chemistry, mental health potential and legal challenges

Mycological Progress December 8, 2025 Mohammad Reza Mirzadeh, Khalid Moinuddin, Vasso Apostolopoulos et al.

Psilocybin, psilocin and the associated tryptamines are psychoactive alkaloids which are naturally biosynthesised by Psilocybe (Fr.) P.Kumm. fungi, commonly referred to as magic mushrooms. These psychoactive fungi were used traditionally in healing rituals, and are now being studied in clinical studies to investigate their benefits as a treatment for a number of mental health disorders. Since...

Psychedelics as neuroplasticity enhancers: Mechanisms, therapeutic applications, and translational challenges

Advanced Neurology December 4, 2025 Taslim Uddin, Sharmin Akter, Kaustabh Ghosh

Psychedelics are gaining recognition for their effectiveness as modulators of neuroplasticity in the treatment of a range of neuropsychiatric disorders. Psilocybin, lysergic acid diethylamide, N,N-dimethyltryptamine, and ketamine are substances that mainly affect the serotonergic and glutamatergic systems. They induce rapid synaptogenesis, dendritic remodeling, and changes in functional...

Next-Generation MDMA Analogue SDMA: Pharmacological and Metabolic Insights

ACS Chemical Neuroscience December 2, 2025 Nina Kastner, Núria Nadal‐gratacós, Selina Hemmer et al.

3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, shows promise in treating depression and post-traumatic stress disorder (PTSD), resulting in breakthrough status. However, concerns regarding MDMA's abuse potential and cytotoxicity have sparked interest in developing safer analogues with similar therapeutic benefits. This study investigated the pharmacological properties of...

DOI: 10.1021/acschemneuro.5c00782 (opens in new tab) MDMA Norepinephrine transporter Monoamine neurotransmitter Dopamine transporter +8

Acute Blockade of the Serotonin Transporter With Low Doses of Escitalopram Does Not Alter the Behavioural Responses to Acute Psilocybin

European Journal of Neuroscience December 1, 2025 Nina Kleditzsch, James J Gattuso, Anthony J. Hannan et al.

ABSTRACT The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment‐resistant depression and has been reported to reduce symptoms of depression and anxiety. Psilocybin's active metabolite, psilocin, possesses a binding affinity for serotonin receptors as well as for the serotonin transporter (5‐HTT). We recently reported that in contrast to wild‐type mice,...

DOI: 10.1111/ejn.70351 (opens in new tab) Psilocybin Escitalopram Hallucinogen Serotonin transporter +7

A comparative assessment of the antidepressant efficacy of ketamine, psilocybin, and fluoxetine in a chronic stress model

Scientific Reports November 26, 2025 Małgorzata Domżalska, Joanna Kwiatkowska, Iwona Cichoń et al. 2 citations

Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and evaluating antidepressants...

Possible Involvement of Hallucinogenic Effects in the Aversive Effects Induced by Kappa‐Opioid and 5‐ HT 2A / 2C Receptor Agonists in Mice

Neuropsychopharmacology Reports November 23, 2025 Hideaki Kato, Yoshimi Ichimaru, Masaaki Kurihara et al. 1 citation

AIM: The regulation of new psychoactive and dangerous abused substances is very important for the prevention of drug abuse. A simple and effective evaluation method using laboratory animals is needed to regulate designated drugs with high accuracy and speed. METHODS: receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), which have a similar mechanism of action to...

DOI: 10.1002/npr2.70075 (opens in new tab) Serotonin Hallucinogen 5-HT Receptor Agonist +1

3,4-Methylenedioxymethamphetamine (MDMA) does not induce robust psychomotor activation and 50-kHz ultrasonic vocalisations in tryptophan hydroxylase 2 (Tph2)-deficient rats lacking serotonin in the central nervous system.

British Journal of Pharmacology November 23, 2025 Tianhua Wang, Rainer K.W. Schwarting, Markus Wöhr 1 citation

3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, is a psychostimulant with entactogenic properties and known to induce arousal and euphoria. As an amphetamine derivate, MDMA acts on the monoamine systems in the brain and stimulates release of dopamine (DA), noradrenaline (NA) and serotonin (5-HT), yet their individual contributions in driving arousal and euphoria remain...

DOI: 10.1111/bph.70226 (opens in new tab) Full text (opens in new tab) Locomotor activity Psychostimulant Tryptophan hydroxylase 2 Ecstasy effects: ecstasy +13

Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward.

Nature Communications November 20, 2025 Alaina M Jaster, Thomas M Hadlock, Belle Buzzi et al. 9 citations

Emerging evidence suggests that classical psychedelics may offer therapeutic potential for opioid use disorder (OUD) by alleviating key hallmarks such as altered reward processing and dependence. However, the mechanisms behind these effects remain unclear. Our data demonstrate that a single administration of the psychedelic psilocybin (PSI) reduces conditioned behavior and withdrawal induced by...

The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents

Molecular Psychiatry November 14, 2025 Núria Nadal‐gratacós, Pol Puigseslloses, Laura Hernández‐guzmán et al.

Psychedelics have garnered significant interest for their therapeutic potential in mental health conditions such as depression, anxiety, and post-traumatic stress disorder. While research has primarily focused on well-studied psychedelics, phenethylamine derivatives have also gathered interest for their potential therapeutic applications. Thus, this study aims to investigate the pharmacological...

DOI: 10.1038/s41380-025-03341-1 (opens in new tab) Full text (opens in new tab) Phenethylamine Antidepressant Dopamine Reboxetine +8

Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons

Biomedicine & Pharmacotherapy November 13, 2025 Abdeslam Chagraoui, Luis A Haro Santillan, Renata Bocian et al. 5 citations

This study evaluated the effects of ibogalogs on recognition and spatial memory in rodents, focusing on potential hippocampal mechanisms. The Barnes maze study demonstrated that ibogaminalog (DM506) and ibogainalog (IBG) improved short- (30 min) and long-term (24 and 72 h) spatial memory in mice, whereas tabernanthalog (TBG) showed less efficacy. The novel object recognition task (NORT) results...

DOI: 10.1016/j.biopha.2025.118742 (opens in new tab) Hippocampal formation Nmda receptor Hippocampus Glutamate receptor +9