MADRID—One of the natural components of ayahuasca tea is dimethyltryptamine (DMT), which promotes neurogenesis, according to research led by the Complutense University of Madrid (UCM). In addition to neurons, ayahuasca — which is typically used for shamanic purposes — also induces the formation of other neural cells, like astrocytes and oligodendrocytes.

“This capacity to modulate brain plasticity suggests that [ayahuasca] has great therapeutic potential for a wide range of psychiatric and neurological disorders, including neurodegenerative diseases,” said José Ángel Morales, a researcher in the UCM and the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Department of Cellular Biology.

The study, entitled “N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo,” was published in Translational Psychiatry, and reports the results of four years of in vitro and in vivo experimentation in mice.

“Our results in vitro and in vivo show that DMT is a key regulator in the activity of adult NSCs [neural stem cells], since this compound plays an important role in regulating the expansion and differentiation of the stem cell population located in the SGZ [subgranular zone], one of the main adult neurogenic niches,” the article states. “This is revealed in vitro by an increase in the number and size of primary neurospheres and an increased expression of ki67 and PCNA [proliferating cell nuclear antigen], which indicates a high rate of proliferation and loss of stemness after treatment with DMT. Increased proliferation does not indicate neuronal commitment⁶⁰; however, DMT also induced an increase in β-III-tubulin+ and MAP-2 + cells, suggesting promotion of differentiation toward a neuronal phenotype and increasing the total numbers of the neuron that reach neuronal maturity.”

“Interestingly, in contrast to that previously described on the action of carbolines in vitro, we have also found an increase in the number of other neural cells such as astrocytes and oligodendrocytes after DMT treatment. Similar results were observed in vivo, with an increased proliferation rate of the NSCs and a larger population of doublecortin expressing neuroblasts migrating to the hippocampal granular layer to generate new neurons,” continues the study. “Moreover, these have a functional impact since DMT treatment during 21 days clearly improved mouse performance in learning and memory tasks, in which the hippocampus is considered to play an essential role.” 

Ayahuasca is produced by mixing ayahuasca vine (Banisteriopsis caapi) and chacruna shrub (Psychotria viridis). The DMT in ayahuasca tea binds to a type-2A serotonergic brain receptor, which enhances its hallucinogenic effect.

But changing the receptor can eliminate the hallucinogenic effects. In this study, the receptor was changed to a sigma type receptor that doesn’t produce this effect. The researchers believe that the lack of these hallucinogenic effects will facilitate its use in a greater number of patients.

The article adds, “One of the main limitations that arise when designing a possible drug from the results obtained is to achieve the desired neurogenic effect without causing the patient hallucinogenic effects secondary to treatment with DMT, through the activation of 5-HT2A receptors. The results here obtained indicate that the observed effects of DMT are mediated by the activation of the S1R [sigma-1 receptor] … In humans, the use of S1R agonists, such as fluvoxamine, shows its involvement in neuroplasticity, suggesting an important role in improving learning mechanism.”

“In clinical studies, some S1R agonists, including fluvoxamine, donepezil, and neurosteroids, improve cognitive impairment. Adult hippocampal neurogenesis is widespread in mammals, including humans, and may act as a key regulator in cognition, memory, and emotion-related behavior. Deficits in adult neurogenesis are associated with the physiopathology of depression and modulation of neurogenesis is behind the action of several antidepressants,” explains the study.

The death of certain types of neurons causes the symptoms of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Although humans do have the capacity to generate new neuronal cells, this capacity depends on several factors and neurogenesis isn’t always possible.

“The challenge is to activate our dormant capacity to form neurons and thus replace the neurons that die as a result of the disease,” concluded Morales. “This study shows that DMT is capable of activating neural stem cells and forming new neurons.”