Translational Psychiatry
September 1, 2026
Sandra M. Martin-Guerrero, Marco Taddei-Tardón, Jessica L. Maltman et al.
Abstract Psychedelic drugs can induce intense changes in perception and thought, and some also promote long-lasting adaptations in brain circuits that are being explored for treatment of mood and anxiety disorders. How these compounds differ at the level of intracellular signaling, and how hallucinogenic drugs diverge from related non-hallucinogenic forms, is poorly understood. A central...
Molecular Psychiatry
July 16, 2026
Marco Taddei-Tardón, Lidia Medina-Rodríguez, Jessica L Maltman et al.
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a neural stem cell-derived in vitro...
Elife
March 31, 2026
Jessica L Maltman, Javier González-Maeso
Human neurons derived from stem cells show increased structural complexity and stronger synaptic connections after exposure to psilocin, the active metabolite of the psychedelic psilocybin.
BMC Neuroscience
March 24, 2026
Michael Fiorillo, Javier González-Maeso
BACKGROUND: Neuroinflammation is a hallmark of numerous neuropsychiatric and neurodegenerative disorders. Psychedelics have garnered recent attention for their anti-inflammatory and neuroprotective effects. However, it remains unknown whether they can prophylactically prime immune pathways to prevent subsequent neuroinflammatory responses, and whether such effects depend on serotonin 5-HT2A...
bioRxiv (Cold Spring Harbor Laboratory)
March 23, 2026
Marco Taddei-Tardón, Lidia Medina-Rodríguez, Jessica L Maltman et al.
Abstract Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a neural stem cell-derived in...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 2, 2026
Maya C Gaines-Smith, Justin M Silverman, Michael Fiorillo et al.
3 citations
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potential psychotherapeutic adjunct for treatment-resistant psychiatric disorders, yet its neurobiological mechanisms - particularly those related to its stereoisomers and sex-specific effects - remain poorly understood. Here, we report stereoselective and...
ACS Chemical Neuroscience
January 2, 2026
Mario de la Fuente Revenga, Javier González-Maeso
1 citation
The distinct subjective effects that define psychedelics such as lysergic acid diethylamide (LSD), psilocybin, or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) as drug class are causally linked to the activation of the serotonin 2A receptor (5-HT 2A R). However, some aspects of 5-HT 2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from...
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...
bioRxiv : the preprint server for biology
November 26, 2025
Sandra M. Martin-Guerrero, Marco Taddei-Tardón, Jessica L Maltman et al.
preprint
Psychedelic drugs can induce intense changes in perception and thought, and some also promote long-lasting adaptations in brain circuits that are being explored for treatment of mood and anxiety disorders. How these compounds differ at the level of intracellular signalling, and how hallucinogenic drugs diverge from related non-hallucinogenic forms, is poorly understood. A central question is...
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...
Pharmacological Research
May 1, 2025
Eda Koseli, Belle Buzzi, Torin Honaker et al.
11 citations
Chronic pain is a debilitating disease with current treatments lacking efficacy and safety, therefore discovery of new treatments is crucial. Initial studies suggest that psychedelics may be feasible for targeting pain, however clinical and preclinical controlled studies are necessary to further investigate that possibility. In this study we assessed the effects of two classical psychedelics...
bioRxiv : the preprint server for biology
October 12, 2024
Mario de la Fuente Revenga, Javier González-Maeso
preprint
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT 2A R). However, some aspects of 5-HT 2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT 2A R agonists. We developed an ex vivo platform to obtain snapshots of...
Naunyn-Schmiedeberg's archives of pharmacology
May 1, 2024
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
31 citations
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the...
The Biochemist
January 19, 2024
Javier González-Maeso
Psychedelics, such as psilocybin, mescaline and lysergic acid diethylamide (LSD), are psychoactive substances that induce alterations in cognition, perception and sensory processing. Studies in rodent models and healthy human volunteers highlight the serotonin 5-HT2A receptor’s pivotal role in mediating hallucinogenic effects. More recent findings indicate that psychedelics induce lasting...
Molecular Psychiatry
September 1, 2023
Alaina M Jaster, Javier González-Maeso
50 citations
Psychedelics, also known as classical hallucinogens, have been investigated for decades due to their potential therapeutic effects in the treatment of neuropsychiatric and substance use disorders. The results from clinical trials have shown promise for the use of psychedelics to alleviate symptoms of depression and anxiety, as well as to promote substantial decreases in the use of nicotine and...
Research Square (Research Square)
July 7, 2023
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
4 citations
Abstract Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT 2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in...
Schizophrenia
2023
Alaina M Jaster, Javier González-Maeso
Head-twitch response (HTR) allows for the detection and classification of behavior associated with serotonin 2A receptor (5-HT_2AR) activation upon psychedelic administration in rodent models. This activation and functional output can be utilized to provide insights into molecular mechanisms associated with psychosis and to identify signaling processes related to existing and novel...
Neuroscience Letters
September 25, 2022
Alaina M Jaster, Jason Younkin, Travis Cuddy et al.
53 citations
Psychedelics, also known as classical hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin 5-HT2A receptor (5-HT2AR). This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed...
Psychopharmacology
June 1, 2022
Alaina M Jaster, Harrison Elder, Samuel A Marsh et al.
41 citations
Clinical studies suggest that psychedelics exert robust therapeutic benefits in a number of psychiatric conditions including substance use disorder. Preclinical studies focused on safety and efficacy of these compounds are necessary to determine the full range of psychedelics' effects. The present study explores the behavioral pharmacology of structurally distinct psychedelics in paradigms...
Journal of Neurochemistry
November 6, 2021
Alaina M Jaster, Mario de la Fuente Revenga, Javier González-Maeso
28 citations
Abstract Psychedelic research across different disciplines and biological levels is growing at a remarkably fast pace. In the prospect of a psychedelic drug becoming again an approved treatment, much of these efforts have been oriented toward exploring the relationship between the actual psychedelic effects and those manifestations of therapeutic interest. Considering the central role of the...
bioRxiv (Cold Spring Harbor Laboratory)
February 25, 2021
Mario de la Fuente Revenga, Bohan Zhu, Christopher A. Guevara et al.
11 citations
preprint
Clinical evidence suggests a potential therapeutic effect of classic psychedelics for the treatment of depression. The most outstanding and distinct characteristic is the rapid and sustained antidepressant action with one single exposure to the drug. However, the biological substrates and key mediators of psychedelics’ enduring action remain unknown. Here, we show that a single administration...
Scientific Reports
October 3, 2019
Mario de la Fuente Revenga, Jong M. Shin, Hiba Vohra et al.
57 citations
Abstract Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT 2A receptor (5-HT 2A R) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse’s head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of...
Current Topics in Behavioral Neurosciences
2017
Juan F López-Giménez, Javier González-Maeso
302 citations
The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic...
The International Journal of Neuropsychopharmacology
June 10, 2013
José L. Moreno, Javier González-Maeso
30 citations
Abstract One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed...
Journal of Neuroscience
January 16, 2013
Terrell Holloway, José L. Moreno, Adrienne Umali et al.
122 citations
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT 2A and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and...