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Orr Shahar

8 papers in the library · 171 citations · publishing 2022-2026

Papers

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Preclinical Comparison of DMT and 5-MeO-DMT Reveals Behavioral Dissociation, Distinct TrkB Activation and Differential Plasticity Profiles

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,...

MDMA-Enhanced Exposure Therapy Reverses PTSD-Like Features In a Learned Helplessness Mouse Model

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...

Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment

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...

Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.

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...

Effects of psilocybin, psychedelic mushroom extract and 5-hydroxytryptophan on brain immediate early gene expression: Interaction with serotonergic receptor modulators

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...

Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract

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...

Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder.

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...

Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications

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)...