Scientific Reports
October 9, 2017
Vanja Dakic, Juliana Minardi Nascimento, Rafaela Costa Sartore et al.
137 citations
5-MeO-DMT, a serotonin-like molecule found in traditional Amerindian medicine, alters the protein landscape of human cerebral organoids. Out of 6,728 identified proteins, 934 were differentially expressed after treatment. Computational analysis confirmed previously reported anti-inflammatory effects and revealed modulation of proteins involved in long-term potentiation, dendritic spine formation, cellular protrusion, microtubule dynamics, and cytoskeletal reorganization. These findings provide initial molecular insights into how this compound may affect human brain metabolism.
PeerJ
December 6, 2016
Vanja Dakic, Renata de Moraes Maciel, Hannah Drummond et al.
86 citations
Harmine, the main alkaloid in Ayahuasca, increased the pool of proliferating human neural progenitor cells by 71.5% after four days of treatment. Testing harmine analogs showed that a DYRK1A inhibitor (INDY) but not a monoamine oxidase inhibitor (pargyline) similarly boosted proliferation, suggesting harmine acts through DYRK1A inhibition. This mechanism may underlie both harmine's effects on neural cell growth and its reported antidepressant effects.
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 K. 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.
ACS Omega
August 27, 2024
Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento et al.
3 citations
Exposure to LSD alters the abundance of hundreds of proteins in lab-grown human brain tissue, affecting pathways related to protein quality control, energy metabolism, and the brain's ability to rewire itself. Mass spectrometry revealed changes in protein synthesis, folding, and degradation, as well as in glycolysis and oxidative phosphorylation. Follow-up experiments showed that LSD also promotes the growth of neuronal extensions, supporting its influence on neuroplasticity. These molecular changes may help explain how psychedelics could produce therapeutic effects in neuropsychiatric disorders.
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.
bioRxiv Preprint Server
January 30, 2024
Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento et al.
1 citation
preprint
Proteomic analysis of human cerebral organoids reveals that lysergic acid diethylamide (LSD) alters proteins involved in proteostasis, energy metabolism, and neuroplasticity-related pathways. LSD exposure changed protein synthesis, folding, autophagy, and proteasomal degradation, suggesting complex regulation of neural cell function. It also modulated glycolysis and oxidative phosphorylation, which are crucial for cellular energy management and synaptic function. Complementary experiments showed LSD enhanced neurite outgrowth in vitro, confirming its impact on neuroplasticity. These findings provide insight into molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.
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.
April 14, 2016
Vanja Dakic, Renata de Moraes Maciel, Hannah Drummond et al.
1 citation
Harmine, a β-carboline alkaloid found in the psychotropic plant decoction Ayahuasca, increased the pool of proliferating human neural progenitor cells (hNPCs) by 57% after 4 days of treatment. The effect appears to be mediated through inhibition of the DYRK1A enzyme, as an analog that inhibits DYRK1A (INDY) similarly induced proliferation, while an inhibitor of monoamine oxidase (pargyline) did not. Harmine also increased dendritic arborization, including total neurite length, number of segments, extremities, and nodes in MAP2-positive neurons. These findings suggest a biological activity that may 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.
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.
bioRxiv (Cold Spring Harbor Laboratory)
February 13, 2017
Vanja Dakic, Juliana Nascimento, Rafaela Sartore et al.
preprint
5-MeO-DMT, a hallucinogenic molecule found in traditional Amerindian medicine, alters the proteome of human cerebral organoids. Of 6,728 identified proteins, 934 were differentially expressed after treatment. Systems biology analyses indicate anti-inflammatory effects and modulation of proteins linked to long-term potentiation, dendritic spine formation, cellular protrusion, microtubule dynamics, and cytoskeletal reorganization. These findings provide mechanistic insights into the neuropsychological changes associated with dimethyltryptamine ingestion.