iScience
March 28, 2024
José Alexandre Salerno, Stevens Rehen
4 citations
Psychedelics are re-emerging as fast-acting treatments for mood and substance use disorders, but their cellular and molecular mechanisms remain unclear. Current research using murine neurons and immortalized cell lines has identified the serotonin 2A receptor as the primary driver of neuroplastic changes, yet these models fail to capture human- and disease-specific features. Incorporating human pluripotent stem cells (PSCs) can address this gap by differentiating into diverse brain cell types that mirror natural gene expression and disease phenotypes. Brain organoids derived from PSCs replicate cell diversity and regional patterning, enabling study of circuit-level changes. PSC-based models offer a promising approach to uncover the cellular and molecular basis of psychedelic-induced recovery in neuropsychiatric conditions.
Neuroscience letters
August 10, 2024
Isis M Ornelas, Beatriz de S Carrilho, Matheus Antonio V de C Ventura et al.
3 citations
Lysergic acid diethylamide (LSD), a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders, is absorbed by the nematode Caenorhabditis elegans and acutely reduces its speed, an effect similar to that of endogenous serotonin. This response is partially mediated by the serotonergic receptors SER-1 and SER-4. The findings highlight the potential of C. elegans as a new experimental model for psychedelic research.
Figshare
July 10, 2026
José Alexandre Salerno, Elizabeth R. Dominguez, Karina Karmirian et al.
A brief 24-hour exposure to the serotonergic psychedelic DMT increases proliferation of human neural stem cells derived from induced pluripotent stem cells. The effect was concentration-dependent, with half-maximal effect at 59.7 nM. DMT treatment also altered trophic gene expression, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, the primed stem cells formed larger neurospheres, with progenitor and early neuronal marker composition matching controls by day 10. These findings demonstrate that brief DMT exposure engages proliferative and neurotrophin-associated responses in human neural stem cells at concentrations consistent with those reported for DMT-induced plasticity in other systems.
ACS chemical neuroscience
July 9, 2026
José Alexandre Salerno, Elizabeth R Dominguez, Karina Karmirian et al.
Brief exposure to the psychedelic N,N-dimethyltryptamine (DMT) increases proliferation of human neural stem cells derived from induced pluripotent stem cells. A 24-hour DMT treatment boosted cell division in a concentration-dependent way, with half-maximal effect at 59.7 nM, and raised levels of G1 cell-cycle regulators. DMT also altered expression of trophic genes, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, treated stem cells formed larger neurospheres, with progenitor and early neuron markers matching controls by day 10. The findings indicate DMT can engage proliferative and neurotrophin-related responses in human neural stem cells at concentrations linked to plasticity in other systems.
bioRxiv Preprint Server
June 16, 2025
Beatriz de S. Carrilho, Aline Duarte, Isabelle Martins et al.
preprint
Lysergic acid diethylamide (LSD) extends lifespan and reduces age-related lipofuscin accumulation in the roundworm Caenorhabditis elegans, suggesting delayed aging. LSD produces effects similar to caloric restriction, such as reduced reproduction and smaller body size, without decreasing food intake. LSD also alters lipid stores and other cellular markers linked to nutrient-sensing pathways. These findings indicate that LSD engages evolutionarily conserved longevity pathways and may serve as a tool for studying serotonergic regulation of aging.