bioRxiv (Cold Spring Harbor Laboratory)
December 6, 2019
Felipe Augusto Cini da Silva, Isis M. Ornelas, Encarni Marcos et al.
9 citations
preprint
A single dose of d-LSD, a potent serotonergic agonist, increased preference for novel objects in young and adult rats several days after treatment, but did not increase preference in old animals unless followed by a 6-day exposure to enriched environment, which rescued novelty preference to young levels. Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions with alterations of long-range synapses, and that better pattern separation within enriched environment explains its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.
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.
bioRxiv (Cold Spring Harbor Laboratory)
June 17, 2021
Karina Karmirian, Livia Goto‐silva, Juliana Nascimento et al.
1 citation
preprint
Harmine, a β-carboline found in the ayahuasca vine Banisteriopsis caapi, upregulates proteins in human brain organoids that are involved in synaptic vesicle cycling, cytoskeleton-dependent transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling. Treatment with harmine also increased levels of Akt and phosphorylated CREB after 24 hours. These findings point to cellular and molecular pathways that may explain harmine's potential neuroprotective effects, which have been suggested by previous animal studies to include anti-inflammatory and antioxidant activities. The work advances understanding of how harmine might contribute to the antidepressant effects observed with ayahuasca.
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.