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.
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.
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.