Translational Psychiatry
October 6, 2025
Gavin P. Schmitz, Yi-Ting Chiu, Mia L. Foglesong et al.
13 citations
Psilocybin, and its active metabolite psilocin, have seen renewed interest due to studies suggesting potential therapeutic utility. 5-Hydroxytryptamine2A receptors (5-HT 2A Rs) are primary mediators of the psychoactive effects of psychedelics in animals and humans, but the underlying neurobiological mechanisms remain poorly understood. Functional magnetic resonance imaging identified...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 1, 2025
Marta L.c. Palhas, Rémi Corne, Raymond Mongeau
4 citations
After years of restrictions due to concerns about their potentially harmful effects, research on psychedelics has entered a new era. Increasing attention has been directed toward their immense therapeutic potential, particularly for psychiatric disorders. Pre-clinical and clinical studies have consistently demonstrated that psychedelic treatments produce therapeutic effects within hours of...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 1, 2025
Brandon Richardson, Antonio Inserra, Michael Pileggi et al.
2 citations
Psilocybin and lisuride are 5-HT2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects....
September 27, 2025
A. N. Fedorov
Major depression affects about 280 million people worldwide and costs around 326 billion dollars per year in the United States, though the standard medications take 2-3 months to take effect, so faster and longer-lasting treatments are needed.Serotonergic psychedelics such as psilocybin, DMT or ayahuasca, LSD, and mescaline can reduce depression and anxiety symptoms after only one or two doses,...
Journal of Medicinal Chemistry
September 25, 2025
Tyler G. Fenske, J. M. T. Mckee, Natalie G. Cavalco et al.
With a resurgence in interest in psychedelics as rapid-acting and durable neuroplastic therapies, there is a critical need to develop more selective 5-HT 2A agonists to investigate the basic neurobiological mechanisms of psychedelics. Here, we show that selectivity for 5-HT 2A over the closely related 5-HT 2C receptor can be leveraged using structure-based design to target residue L123 2.53 in...
European Journal of Pharmacology
September 15, 2025
Bin Li, Shanshan Jiang, Yi-shan Yao et al.
Psychedelics have demonstrated significant therapeutic potential in treating various psychiatric disorders; however, their effects on motor function remain poorly understood. This study investigated the impact of 2,5-dimethoxy-4-methylamphetamine (DOM), a classical phenethylamine psychedelic agent, on gait parameters in C57BL/6J mice using an active gait monitoring system. We found that 0.3-3...
ACS Chemical Neuroscience
September 13, 2025
Emma M. Bonniwell, Rana Alabdali, Joseph J. Hennessey et al.
3 citations
The serotonin 2C receptor (5-HT 2C ) is a G protein-coupled receptor implicated in multiple physiological and psychological processes and has been investigated as a therapeutic target for neuropsychiatric conditions such as obesity, drug abuse, and depression. With renewed interest in serotonergic psychedelics for treating depression, 5-HT 2C may contribute to psychedelic-induced therapeutic...
National Science Review
September 5, 2025
Huoqing Luo, Ming Chen, Yingjie Ning et al.
1 citation
-methyl-d-aspartate receptor (NMDAR) blockade is crucial for the rapid antidepressant effects of ketamine, the involvement of other mechanisms remains contentious, particularly regarding the role of serotonin, a key neurotransmitter in the target of traditional antidepressants. Here, we demonstrate that ketamine elevates serotonin levels by inhibiting the serotonin transporter (SERT). A...
ACS Chemical Neuroscience
September 3, 2025
Arabo A. Avanes, Hunter T Warren, Abinaya Senthil et al.
2 citations
Tropane alkaloids and their derivatives represent a diverse class of small molecules with a broad range of therapeutic applications. Many tropanes regulate synaptic levels of neuromodulators by interacting with monoamine transporters such as dopamine (DAT) and serotonin (SERT) transporters. While DAT inhibition plays an important role in the addictive potential of tropanes such as cocaine,...
Acta Neuropsychiatrica
September 3, 2025
Filipe Reis Teodoro Andrade, Tobias Buchborn, Gabriel Thalheimer et al.
3 citations
Abstract Background: Major depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-HT1A and 5-HT2C receptors....
Acta Pharmaceutica Sinica B
September 1, 2025
Michał K Jastrzębski, Piotr Wójcik, Angelika Grudzińska et al.
G protein-coupled receptors (GPCRs) represent key drug targets, with approximately 30%-40% of all medications acting on these receptors. Recent advancements have uncovered the complexity of GPCR signaling, including biased signaling, which allows selective activation of specific intracellular pathways-primarily mediated by G proteins and β-arrestins. Among aminergic GPCRs, the serotonin 5-HT2A...
PLoS Computational Biology
September 1, 2025
Jordy Peeters, Dimitri de Bundel, Kenno Vanommeslaeghe
The serotonin-2A receptor (5-HT2AR) is an interesting target for drug design in the context of antidepressants that might have a rapid onset of action and/or be effective in treatment-resistant cases. The main challenge, however, is that the activation of this receptor can provoke hallucinations. Recent studies have shown that activating the receptor with certain (partial) agonists could...
ACS Medicinal Chemistry Letters
August 25, 2025
Ram W. Sabnis
High Resolution Image Download MS PowerPoint Slide Provided herein are novel serotonergic psychedelic agents as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders, and processes for preparing such compounds.
Molecular Psychiatry
August 23, 2025
Adam J. Drewko, Ron L. P. Habets, Tibor M Brunt
4 citations
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In particular, the role of the serotonin...
Brain Sciences
August 21, 2025
Dean Bilenker, Nicole M. Avena
2 citations
Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics—particularly 5-HT2A receptor agonists such as psilocybin—in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN),...
Nature Communications
August 19, 2025
Maxwell B. Madden, Chloe Schaefgen, Binita Vedak et al.
4 citations
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilocybin, which is metabolized to the...
ACS Medicinal Chemistry Letters
August 15, 2025
Robert B. Kargbo
Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support phenalkylamines and psilocybin as...
European Journal of Pharmacology
August 15, 2025
Niharika Singh, Puja Panwar Hazari, Parul Mittal et al.
16 citations
Globally, depression affects millions of people of all ages, making it one of the significant contributors to deteriorating quality of life by causing neurological impairments that eventually weaken cognition, learning, and memory. According to the monoamine hypothesis, depression is associated with decreased serotonin, dopamine, and norepinephrine levels in the central nervous system. Drugs...
psychopraxis neuropraxis
August 11, 2025
Arif de Mendelssohn, Henriette Löffler-stastka
Zusammenfassung Serotonin (5-HT) ist ein fundamentaler Neuromodulator, dessen komplexe Rolle in der Psychiatrie oft auf vereinfachte Modelle wie die „Chemische-Dysbalance-Hypothese“ reduziert wurde. Ein zeitgemäßes Verständnis von höherem heuristischen Wert erfordert demgegenüber die Integration verschiedener wissenschaftlicher Ansätze. Dieser Artikel synthetisiert die Theorien von Mark Solms...
International Journal of Molecular Sciences
August 4, 2025
Masahide Arinaga, Jun Yamada, Shoichiro Maeda et al.
2 citations
Cancer-related cognitive impairment (CRCI)-encompassing anxiety, depression, and memory deficits-significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a...