Psilocybin rewires the brain for people with depression, study finds


Date:
April 11, 2022
Source:
University of California - San Francisco
Summary:
Psilocybin fosters greater connections between different regions
of the brain in depressed people, freeing them up from long-held
patterns of rumination and excessive self-focus, according to a
new study.



FULL STORY ========================================================================== Psilocybin fosters greater connections between different regions of
the brain in depressed people, freeing them up from long-held patterns
of rumination and excessive self-focus, according to a new study by
scientists at UC San Francisco and Imperial College London.


==========================================================================
The discovery points toward a general mechanism through which psychedelics
may be acting therapeutically on the brain to alleviate depression and
possibly other psychiatric conditions that are marked by fixed patterns
of thinking.

Scientists analyzed fMRI brain scans from nearly 60 people who
had participated in two psilocybin trials. In the first one, all
the participants had treatment- resistant depression and knew they
were being given psilocybin. In the second one, the participants were
depressed but not as severely, and they were not told whether they had
been given psilocybin or a placebo that turned out to be escitalopram,
an SSRI antidepressant. In addition to the drugs, all the participants
received the same type of psychotherapy.

The scans, which were done before and after treatment, showed the
psilocybin treatment reduced connections within brain areas that are
tightly connected in depression, including the default mode, salience,
and executive networks, and increased connections to other regions of
the brain that had not been well integrated.

Participants were also less emotionally avoidant and their cognitive functioning got better. The improvement in their depressive symptoms
correlated with changes to their brains, and these changes lasted until
the study ended three weeks after the second psilocybin dose. No such
changes were seen in the brains of those who received escitalopram,
suggesting that psilocybin acts differently on the brain than SSRIs.

Psilocybin and other serotonergic psychedelics like ayahuasca affect
5-HT2A receptors, which are plentiful in brain networks that become
overactive in depression. One hypothesis is that the drugs briefly
disrupt these connections, giving them a chance to reform in new ways
in the ensuing days and weeks.

"In previous studies we had seen a similar effect in the brain when
people were scanned whilst on a psychedelic, but here we're seeing it
weeks after treatment for depression, which suggests a carry-over of
the acute drug action," said Robin Carhart-Harris, PhD, who directs the Neuroscape Psychedelics Division at UCSF and is the senior author of
the study, which appears April 11, 2022, in Nature Medicine.

"We don't yet know how long the changes in brain activity seen with
psilocybin therapy last, and we need to do more research to understand
this," said Carhart-Harris, who is the Ralph Metzner Distinguished
Professor of Neurology, Psychiatry, and Behavioral Sciences and a member
of the UCSF Weill Institute for Neurosciences. "We do know that some
people relapse, and it may be that after a while their brains revert to
the rigid patterns of activity we see in depression." The authors caution
that while these findings are encouraging, patients with depression should
not attempt to self-medicate with psilocybin. The trials took place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support before, during,
and after dosing.

But the study points to a mechanism that, if it holds up, may explain
both how psilocybin helps to alleviate depression and potentially other debilitating psychiatric conditions.

"For the first time we find that psilocybin works differently from
conventional antidepressants -- making the brain more flexible and
fluid, and less entrenched in the negative thinking patterns associated
with depression," said David Nutt, DM, head of the Imperial Centre for Psychedelic Research. "This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments." Disclosures, as well as the full list of authors and funding are available
in the paper.


========================================================================== Story Source: Materials provided by
University_of_California_-_San_Francisco. Original written by Laura
Kurtzman. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D.

Sexton, Matthew B. Wall, David Erritzoe, Leor Roseman, David Nutt,
Robin Carhart-Harris. Increased global integration in the brain
after psilocybin therapy for depression. Nature Medicine, April 11,
2022; DOI: 10.1038/s41591-022-01744-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220411113727.htm

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