bioRxiv (Cold Spring Harbor Laboratory)
August 12, 2026
Orr Shahar, Perettz Golding, Masha Chaykin et al.
preprint
Abstract Post-traumatic stress disorder (PTSD) is a highly prevalent, debilitating psychiatric condition. Existing treatments are ineffective for many patients. 3,4- methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has demonstrated substantial clinical efficacy but relies on prolonged, resource-intensive therapeutic protocols that limit scalability and accessibility. Here, we...
bioRxiv (Cold Spring Harbor Laboratory)
August 12, 2026
Orr Shahar, Alexander Botvinnik, Masha Chaykin et al.
preprint
Abstract N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) are structurally related tryptamine psychedelics with emerging therapeutic potential, yet their comparative acute pharmacology and longer-term neuroplastic effects remain incompletely defined. Here we show that DMT produces a bell-shaped dose–response curve in the mouse head-twitch response (HTR) assay,...
Acta Neuropsychiatrica
February 13, 2026
Tanya Calvey, Demi Govender, Gavin Owen et al.
Ibogaine is a psychedelic alkaloid without an approved indication. Observational clinical research shows linkages between single administration of ibogaine and relief of symptoms of neuropsychiatric conditions including substance use disorder, multiple sclerosis, and traumatic brain injury. Ibogaine has multi-receptor actions, but the neurobiological mechanisms underlying such putative effects...
Zenodo (CERN European Organization for Nuclear Research)
November 4, 2025
Uri Bertocchi, Amit Schwartz, Gali Umschweif et al.
Background: Psilocybin, a serotonergic psychedelic compound, has demonstrated long-term antidepressant effects, yet its underlying mechanisms remain unclear. Emerging evidence suggests that epigenetic modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), may play a role in its therapeutic action. Unlike passive demethylation, which requires cell division and...
The International Journal of Neuropsychopharmacology
August 1, 2025
Bernard Lerer, T. Tal, Ilana Pogodin et al.
Abstract Background The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the potential synergistic benefits of combining...
The International Journal of Neuropsychopharmacology
August 1, 2025
Bernard Lerer, Michal Brownstien, Mitchell A. Lazar et al.
Abstract Background Obsessive-compulsive disorder (OCD) is associated with significant personal suffering and functional impairment. At least a third of OCD patients do not respond to conventional treatments. There is a substantial anecdotal literature suggesting that psychedelic agents, specifically psilocybin and psilocybin-containing psychedelic mushroom extract (PME), may be therapeutic in...
International Journal of Neuropsychopharmacology
August 1, 2025
Bernard Lerer, Peretz Golding, Michal Brownstien et al.
Abstract Background We have designed a novel psychedelic-derived compound (HBL20017) characterized by high functional efficacy at 5-HT2A, 5-HT1A, and 5-HT2C receptors. We assessed its hallucinogenic properties and its potential for OCD treatment on the marble burying test (MBT) and in mice homozygous for deletion of the Synapse Associated Protein 3 (SAPAP3) gene. These mice manifest severe,...
Translational Psychiatry
June 13, 2025
Tom Ben-Tal, Ilana Pogodin, Alexander Botvinnik et al.
2 citations
The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the synergistic benefits of combining psilocybin (PSIL) with...
The International Journal of Neuropsychopharmacology
March 29, 2025
Michal Lazar, Michal Brownstien, Alexander Botvinnik et al.
3 citations
Abstract Background SAPAP3-knockout (SAPAP3-KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors...
The International Journal of Neuropsychopharmacology
February 1, 2025
Leonard Lerer, Kathleen Spear, Jeet Varia et al.
Abstract Background Psilocybin research in depression has been generated using chemically synthesized psilocybin (PSI). Psychedelic mushrooms produce additional tryptamines that may enhance the neuroplastic effect of psilocybin. In a rodent depression model, an extract of a psychedelic mushroom (PME) had a stronger and more prolonged effect than PSI on behavior[1]. Aims and Objectives To...
Molecular Psychiatry
October 11, 2024
Michal Brownstien, Michal Lazar, Alexander Botvinnik et al.
23 citations
Abstract Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches...
Molecular Psychiatry
July 1, 2024
Orr Shahar, Alexander Botvinnik, Amit Shwartz et al.
37 citations
Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects...
Frontiers in Pharmacology
April 18, 2024
Elad Lerer, Alexander Botvinnik, Orr Shahar et al.
14 citations
Background: Immediate early genes (IEGs) are rapidly activated and initiate diverse cellular processes including neuroplasticity. We report the effect of psilocybin (PSIL), PSIL-containing psychedelic mushroom extract (PME) and 5-hydroxytryptophan (5-HTP) on expression of the IEGs, cfos, egr1 , and egr2 in mouse somatosensory cortex (SSC). Methods: In our initial experiment, male C57Bl/6j mice...
Psychedelics
January 25, 2024
Bernard Lerer
Professor Bernard Lerer is in the Faculty of Medicine, Hebrew University, Jerusalem, Israel, where he is Director the Center for Psychedelic Research (https://cfpr.brainlabs.org.il/) at Hadassah Medical Center, in Jerusalem. The Center has a growing staff that includes senior scientists, post-docs, Ph.D. and graduate students, technicians, and psychiatrists undergoing research training. Their...
Molecular Psychiatry
2024
Uriel Heresco-Levy, Bernard Lerer
17 citations
Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involving the ionotropic glutamate...
Research Square
July 20, 2023
Orr Shahar, Alexander Botvinnik, Amit Shwartz et al.
3 citations
Abstract Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or “full spectrum” (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the...
Translational Psychiatry
May 10, 2023
Sandeep Singh, Alexander Botvinnik, Orr Shahar et al.
54 citations
Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. However, the receptor mechanisms implicated in the putative anti-obsessional effect are not clear. On this background, we set out to explore (1) the role of serotonin 2A (5-HT2A) and serotonin...
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2023
Leonard Lerer, Eric Reynolds, Jeet Varia et al.
6 citations
There is growing interest in the therapeutic potential of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) for psychiatric disorders. Although 5-MeO-DMT can be chemically synthesized, the parotoid gland secretions of Incilius alvarius (also known as the Colorado River or Sonoran Desert toad) contain 5-MeO-DMT and other molecules including bufotenine, bufagenins, bufotoxins, and indole alkylamines...
Molecular Psychiatry
2023
Gilly Wolf, Sandeep Singh, Karin Blakolmer et al.
Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported....
International Journal of Molecular Sciences
November 16, 2022
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz et al.
60 citations
There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1)...
bioRxiv (Cold Spring Harbor Laboratory)
May 22, 2022
Leonard Lerer, Eric Reynolds, Jeet Varia et al.
preprint
Abstract There is growing interest in the therapeutic potential of 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) for psychiatric disorders. While 5-MeO-DMT can be chemically synthesized, the parotoid gland secretions of Incilius alvarius (also known as the Colorado River or Sonoran Desert toad) contain 5-MeO-DMT and other molecules including bufotenine, bufagenins, bufotoxins, and indole...
Frontiers in Psychiatry
January 3, 2022
Richard Matzopoulos, Robert Morlock, Amy Morlock et al.
43 citations
Introduction: Popular media coverage of psychedelics use, growing research into this class of compounds for psychiatry and decriminalization initiatives, are transforming the public perception of psychedelics. However, little is known about levels of knowledge and psychedelic mushroom (PM) use among American adults. Methods: We examined PM use and various measures of health status, quality of...