Human minibrains reveal effects of psychedelic substance

A Brazilian study, published in
Scientific Reports on October 09, 2017, has identified changes in signaling
pathways associated with neural plasticity, inflammation and neurodegeneration triggered
by a compound from the family of dimethyltryptamine known as 5-MeO-DMT.

“For the first time we could
describe psychedelic related changes in the molecular functioning of human
neural tissue”, states Stevens Rehen, study leader, Professor of Federal
University of Rio de Janeiro (UFRJ) and Head of Research at D’Or Institute for
Research and Education (IDOR).

Though
recent studies have demonstrated that psychedelic substances, such as LSD
(Lysergic acid diethylamide), MDMA (Methylenedioxymethamphetamine) and
ayahuasca brew which contains DMT, hold therapeutic potential with possible anti-inflammatory
and antidepressant effects, the lack of appropriate biological tools has been
shown as a critical limitation for the identification of molecular pathways
targeted by psychedelics in the brain.

In order to unveil the effects
of 5-MeO-DMT, Vanja Daki? (IDOR) and Juliana Minardi Nascimento (IDOR and University of Campinas) have
exposed cerebral organoids, which are 3D cultures of neural cells that mimic a
developing human brain, to a single dose of the psychedelic.

By employing mass
spectrometry-based proteomics to analyze cerebral organoids, they identified
that 5-MeO-DMT altered the expression of nearly thousand proteins. Then, they
mapped which proteins were impacted by the psychedelic substance and their role
in the human brain.

Researchers found that
proteins important for synaptic formation and maintenance were upregulated. Among
them, proteins related to cellular mechanisms of learning and memory, key
components of brain functioning.

On the other hand, proteins
involved in inflammation, degeneration and brain lesion were downregulated,
suggesting a potential neuroprotective role for the psychedelic substance.

“Results suggest that classic psychedelics
are powerful inducers of neuroplasticity, a tool of psychobiological
transformation that we know very little about”, states Sidarta Ribeiro, Director
of the Brain Institute of Federal University of Rio Grande do Norte (UFRN) and
coauthor of the study.

“Our study reinforces the
hidden clinical potential of substances that are under legal restrictions, but which
deserve attention of medical and scientific communities”, Dr. Rehen said.

This study is a result of a
collaboration between IDOR, UFRJ, UFRN and UNICAMP, and was funded by the
following Brazilian funding agencies: National Council for Scientific and
Technological Development (CNPq), Research Support Foundation of the State of
Rio de Janeiro (FAPERJ), Coordination for the Improvement of Higher Education
Personnel (CAPES), Funding Authority for Studies and Projects (FINEP),
Brazilian Development Bank (BNDES) and São Paulo Research Foundation (FAPESP).

Short term changes in the
proteome of human cerebral organoids induced by 5-MeO-DMT. Freely available
online at www.nature.com/articles/s41598-017-12779-5