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Leonard Lerer

Back of the Yards Algae Sciences - Parow Entheobiosciences, Chicago, IL, United States.

12 papers in the library · 123 citations · publishing 2022-2026

Papers

Psychedelic Mushrooms in the USA: Knowledge, Patterns of Use, and Association With Health Outcomes

Frontiers in Psychiatry January 3, 2022 Richard Matzopoulos, Robert Morlock, Amy Morlock et al. 43 citations

A national survey of American adults from November 2020 to March 2021 found that psychedelic mushroom use is common, with 63.6% of users citing general mental health and well-being as a reason. Users reported higher depression and anxiety scores on standard measures. Factors predicting use included being male and having a higher comorbidity burden, while having health insurance, older age, and living outside the western US reduced the likelihood. The findings indicate that many Americans are self-medicating with psychedelic mushrooms, and the link between use and poor mental health warrants further policy-relevant research.

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-containing mushroom extract (PME) may have stronger and longer-lasting effects on synaptic plasticity than chemically synthesized psilocybin (PSIL) alone. In male mice, both PME and PSIL increased synaptic proteins GAP43 and synaptophysin in brain regions linked to learning and memory, but PME increased more proteins across more brain areas after 11 days. Metabolomic analysis of the frontal cortex revealed a distinct metabolic profile for PME, with a progressive decline in purines associated with oxidative stress from vehicle to PSIL to PME. These findings suggest that other compounds in the mushroom extract contribute to enhanced neuroplasticity, though further research is needed to identify them.

Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming

Molecular Psychiatry October 11, 2024 Michal Brownstien, Michal Lazar, Alexander Botvinnik et al. 23 citations

In mice lacking the SAPAP3 gene, which display excessive self-grooming and anxiety similar to human obsessive-compulsive disorder, a single injection of psilocybin or psychedelic mushroom extract reduced self-grooming by about 15-19% over 21 days, while vehicle-treated mice showed a 119% increase. The effects lasted up to 7 weeks in responsive mice, and non-responsive mice later treated with psilocybin also improved. The mushroom extract was superior for reducing head-body twitches and anxiety. These results support clinical trials of psilocybin for OCD.

Incilius alvarius Cell-Based Synthesis of 5-Methoxy-N,N-Dimethyltryptamine.

Psychedelic medicine (New Rochelle, N.Y.) March 1, 2023 Leonard Lerer, Eric Reynolds, Jeet Varia et al. 6 citations

A cell line derived from the parotoid gland of the endangered Sonoran Desert toad (Incilius alvarius) can biosynthesize 5-MeO-DMT, a psychedelic compound with therapeutic potential for psychiatric disorders. The toad's secretions also contain other molecules such as bufotenine, bufagenins, bufotoxins, and indole alkylamines, which may have individual clinical utility or act as entourage molecules. The species faces ecological pressure from demand for natural 5-MeO-DMT and habitat loss. Cell-based biosynthesis offers a potentially cruelty-free and sustainable source of naturally derived 5-MeO-DMT for research and drug development.

Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming

bioRxiv (Cold Spring Harbor Laboratory) June 29, 2024 Michal Brownstien, Michal Lazar, Alexander Botvinnik et al. 5 citations preprint

In mice with a genetic deletion that causes excessive self-grooming and anxiety—behaviors resembling aspects of obsessive-compulsive disorder (OCD)—a single dose of psilocybin or psychedelic mushroom extract reduced self-grooming over 21 days, while vehicle-treated mice showed a 118.7% increase. Psilocybin and the extract both decreased self-grooming by about 15–19%, and improvements in secondary measures like twitches and anxiety were also significant. In responsive mice, benefits lasted up to 7 weeks. The extract was superior for alleviating head-body twitches and anxiety. These results support clinical trials of psilocybin for OCD.

Characteristics and mental health of psychedelic mushroom and multi-psychedelic users relative to non-psychedelic users in American adults, 2020-2021.

Frontiers in psychiatry January 1, 2025 Sofia Abramsky-Sze, Elliot Marseille, Richard Matzopoulos et al. 4 citations

A cross-sectional survey of 6,869 American adults found that those who used psychedelic mushrooms in the past year reported lower mental health scores and higher levels of anxiety and depression than non-users. The 256 psychedelic users (3.7% of the sample) included 122 who used only psilocybin mushrooms and 134 who used multiple psychedelics; the multi-psychedelic group had the poorest mental health. These differences persisted even after controlling for past-year anxiety and depression, suggesting that psychedelic use is associated with poorer mental health in some contexts. The authors call for more population-based research on exclusive psilocybin and combined psychedelic use.

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

Psilocybin-containing mushroom extract (PME) produces more potent and prolonged effects on synaptic plasticity in the mouse brain than chemically synthesized psilocybin alone. In male C57Bl/6j mice, both PME and psilocybin triggered similar head twitch responses, but PME increased four synaptic proteins (GAP43, PSD95, synaptophysin, SV2A) across all brain areas studied after 11 days, whereas psilocybin only increased two proteins in the hippocampus and amygdala. Metabolomic analysis of the prefrontal cortex showed a gradient of metabolic changes from vehicle to psilocybin to PME, with declines in purines linked to oxidative stress and energy production. The findings suggest that additional compounds in the mushroom extract may enhance psilocybin's effects on brain plasticity.

A long trip into the universe: Psychedelics and space travel

Frontiers in Space Technologies September 15, 2022 Leonard Lerer, Jeet Varia 2 citations

Psychedelics, particularly psychedelic mushrooms, could help astronauts cope with the physiological and psychological challenges of long-duration space travel. Current research shows psychedelics promote neuroplasticity, modulate the immune system, and reduce inflammation, in addition to their therapeutic potential in psychiatry. The authors suggest that psychedelics may be as transformative for 21st-century space travel as citrus fruits were for preventing scurvy during 18th-century sea voyages. They also argue that psychedelics could aid astronauts in processing and integrating the profound, spiritual experiences of deep space travel, ensuring their mental well-being on potentially perilous missions.

Psilocybin and human longevity

npj Aging April 3, 2026 Leonard Lerer

A small study compared mortality among prominent psychedelic personalities, researchers, and advocates who claimed psychedelic use (11 people) with cancer researchers (12 people) and aging researchers (5 people). All groups lived longer than the general population, which the authors attribute to socioeconomic advantage rather than psychedelic use. Psychedelic personalities did not outlive the other researcher groups. The findings underscore the need for rigorous mechanistic and epidemiological studies before inferring human anti-aging effects of psychedelics.

BEHAVIORAL PHENOTYPING AND METABOLOMIC COMPARISON OF CHEMICALLY SYNTHESIZED PSILOCYBIN AND PSYCHEDELIC MUSHROOM EXTRACT IN A ZEBRAFISH DEPRESSION MODEL

The International Journal of Neuropsychopharmacology February 1, 2025 Leonard Lerer, Kathleen Spear, Jeet Varia et al.

In a zebrafish model of depression, both synthetic psilocybin and an extract from psychedelic mushrooms reversed stress-induced behavioral changes, making the fish behave similarly to non-stressed controls. The mushroom extract produced more neurotransmitter precursors in the brain than synthetic psilocybin, though no significant behavioral differences between the two treatments were observed. Whole-brain metabolomics revealed increases in GABA, vitamin B6, glutamine, and NADH, along with a decrease in xanthosine, suggesting possible neuroplastic effects. This work demonstrates the potential of zebrafish models for studying psychedelic compounds.

Incilius alvarius cell-based synthesis of 5-MeO-DMT

bioRxiv (Cold Spring Harbor Laboratory) May 22, 2022 Leonard Lerer, Eric C. Reynolds, Jeet Varia et al. preprint

A sustainable source of 5-MeO-DMT, a promising compound for psychiatric treatment, has been developed using a cell line from the parotoid gland of the endangered Incilius alvarius toad. This innovative approach demonstrated successful biosynthesis of 5-MeO-DMT through chemical processes in vitro. Given that natural populations are under ecological threat due to habitat loss and demand, this method offers a cruelty-free alternative for producing 5-MeO-DMT, potentially supporting future psychedelics and drug studies while preserving biodiversity.