Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells.
Authors: Salerno JA, Dominguez ER, Karmirian K, Arrais BABMS, Alves J, Erjautz G, Kroening K, Souza LRQ, Ornelas I, Rehen S
Journal: ACS chemical neuroscience
mental health
psychology
open access
Abstract
-Dimethyltryptamine
(DMT) is a natural psychedelic
compound best known as the main psychoactive constituent of ayahuasca,
a traditional Amazonian decoction typically made from vines and leaves.
The β-carbolines in the vine act as
reversible monoamine oxidase A (MAO-A) inhibitors, enabling orally
ingested DMT from the leaves to reach
systemic circulation. In recent years,
clinical and preclinical studies indicate that DMT and related psychedelics
produce rapid and sustained antidepressant effects. A single dose
of ayahuasca or isolated DMT has been associated with clinical improvement
persisting for at least 1 week. The acute psychoactive effects of serotonergic
psychedelics arise
primarily from partial agonism at serotonin 5-HT2A receptors, but their therapeutic benefits for mood disorders are increasingly
attributed to rapid, activity-dependent plasticity in cortical neurons. and , DMT promotes fast
neurite outgrowth, spine formation and synaptogenesis at concentrations
consistent with central effects estimates in humans. Other cellular substrates, including neurogenesis and inflammation,
may contribute to DMT’s effects; however, it remains unclear
if such effects produce enduring benefits for the human brain. Neurogenesis is the multistage developmental process in which neural
precursors proliferate, survive, differentiate, migrate, and ultimately
integrate into pre-existing circuitry. Drug-induced adult neurogenesis
has been proposed to contribute to antidepressant-like effects in
rodents and nonhuman primates, but it often requires prolonged treatment,
which is challenging to reconcile with the rapid, single-dose antidepressant
effects reported for DMT in rodents and humans. Whereas chronic repeated DMT exposure was reported
to reduce the NSC population in rodents, other studies found pro-neurogenic
effects involving σ1R engagement, despite DMT’s relatively
low affinity for this target. Reflecting this unresolved
relationship, other serotonergic psychedelics have also produced mixed
drug-, dose-, and region-dependent effects on neurogenesis in rodent
models.
(DMT) is a natural psychedelic
compound best known as the main psychoactive constituent of ayahuasca,
a traditional Amazonian decoction typically made from vines and leaves.
The β-carbolines in the vine act as
reversible monoamine oxidase A (MAO-A) inhibitors, enabling orally
ingested DMT from the leaves to reach
systemic circulation. In recent years,
clinical and preclinical studies indicate that DMT and related psychedelics
produce rapid and sustained antidepressant effects. A single dose
of ayahuasca or isolated DMT has been associated with clinical improvement
persisting for at least 1 week. The acute psychoactive effects of serotonergic
psychedelics arise
primarily from partial agonism at serotonin 5-HT2A receptors, but their therapeutic benefits for mood disorders are increasingly
attributed to rapid, activity-dependent plasticity in cortical neurons. and , DMT promotes fast
neurite outgrowth, spine formation and synaptogenesis at concentrations
consistent with central effects estimates in humans. Other cellular substrates, including neurogenesis and inflammation,
may contribute to DMT’s effects; however, it remains unclear
if such effects produce enduring benefits for the human brain. Neurogenesis is the multistage developmental process in which neural
precursors proliferate, survive, differentiate, migrate, and ultimately
integrate into pre-existing circuitry. Drug-induced adult neurogenesis
has been proposed to contribute to antidepressant-like effects in
rodents and nonhuman primates, but it often requires prolonged treatment,
which is challenging to reconcile with the rapid, single-dose antidepressant
effects reported for DMT in rodents and humans. Whereas chronic repeated DMT exposure was reported
to reduce the NSC population in rodents, other studies found pro-neurogenic
effects involving σ1R engagement, despite DMT’s relatively
low affinity for this target. Reflecting this unresolved
relationship, other serotonergic psychedelics have also produced mixed
drug-, dose-, and region-dependent effects on neurogenesis in rodent
models.