A paper published in Scientific Reports shows, for the first time, the brain changes potentially
underlying the post-acute phase of a psilocybin experience.
The study examined changes in the brain activity of patients with treatment-resistant depression.
And the overall goal of the research was to bridge the gap between observed psychological
changes and the physical activity of the brain.
Before getting into the study, let's review some background information.
There's a growing interest in using psychedelics, such as psilocybin and LSD, for the treatment
of psychiatric conditions.
Accumulating evidence suggests they could be useful for depression, addiction, anxiety,
and other conditions.
Efficacy may exist with and without cooccurring psychotherapy.
So a psychedelic even on its own, at least in a safe, supportive environment, can produce
beneficial effects for patients and perhaps for healthy people.
Findings in healthy volunteers and in patients have shown these drugs elicit powerful experiences
AND lasting psychological changes, such as an increase in openness and a general improvement
in one's quality of life.
There aren't many drug experiences known to facilitate lasting changes of this sort and
it's a pretty unique way of treating psychiatric conditions.
If you have a treatment that yields a lasting benefit, the need for ongoing medication or
psychotherapy is reduced.
This saves people time, money, and side effects.
The evidence doesn't indicate this will work for everyone, but there's been a fairly high
rate of response in the studies so far.
We already have some understanding of how brain activity changes under the influence
of psychedelics.
Research indicates they cause an increase in global connectivity around the brain.
While the integrity of core resting state networks, like the default mode network, declines.
This is a significant shift in how the brain functions.
It may be what allows introspective and sensory experiences to affect people in substantially
different ways when they're on psychedelics.
There's still a lot we need to learn and we know even less about how the brain changes
when a psychedelic wears off.
The goal of this study was to see how psilocybin, a prodrug for the 5-HT2A agonist psilocin,
could affect the brain after a treatment session.
fMRI was used to examine markers of activity prior to treatment and one day after treatment.
So although this doesn't tell use what's happening when someone experiences less depression 6
months later, it can give us insight into the immediate after effects.
A lot of people refer to the day-after effects as an "afterglow," and it's common for people
to feel different in this post-acute period before they return to "normal."
19 patients with treatment-resistant depression received 10 mg of psilocybin and then 25 mg
a week later.
Blood flow was measured using arterial spin labeling and the BOLD signal was used as a
proxy of brain activity.
BOLD allowed the researchers to examine resting state functional connectivity.
Meaning which localized brain regions are functioning together in a time-dependent manner
for a common purpose.
Only 16 ASL results and 15 BOLD results were ultimately available for analysis.
There was a significant decline in depression in connection with psilocybin treatment.
And those benefits were seen the day after treatment and 5 weeks later.
All 19 had at least some decline in symptoms after 1 week.
12 were considered "responders" at this point, meaning they had at least a 50% reduction
in depression.
By 5 weeks, 18 patients had some decrease and 47% were responders.
When looking at whole brain cerebral blood flow, only decreases were seen.
Those declines were significant in a number of areas, which you can see on the screen.
Reduced CBF could be indicative of reduced activity.
Because the amygdala was affected and increased activity in that region has been associated
with depressive symptoms, that data was analyzed further.
The initial post-acute depression reduction significantly correlated with reduced amygdala
CBF.
Though this day-after effect was not predictive of treatment response at 5 weeks.
Moving to the BOLD data, the researchers looked at four regions relevant to depression: the
subgenual anterior cingulate cortex, the ventromedial prefrontal cortex, the amygdala, and the parahippocampus.
RSFC with the amygdala wasn't altered, but there were changes with other regions.
An increase in connectivity between the sgACC and posterior cingulate cortex was observed,
but it didn't correlate with initial depression reduction or reduction at 5 weeks.
Another increase was seen between the vmPFC and inferior-lateral parietal cortex.
While this didn't correlate with reductions the day after, it did predict patient response
at 5 weeks, with responders showing significantly greater increases.
Lastly, there was a decline in connectivity between the PH and PFC.
This also didn't correlate with reductions the day after, yet it did predict response
at 5 weeks, with responders showing greater decreases.
One of the findings that's come up in psychedelic research is that the benefit could be tied
to mystical or peak experiences.
If you have those experiences, you might get more from the drug.
For this reason, the researchers looked to see if these experiences mediate differences
in parahippocampal RSFC.
Indeed, patients with the greatest peak scores had the greatest declines in PH RSFC with
limbic areas, like the amygdala, and with default mode network regions, like the posterior
cingulate cortex.
Based on these results, once you enter the post-acute period, there are changes in brain
activity, but they're substantially different from the acute period.
Acutely the changes are characterized by disintegration of resting state networks and global integration.
Yet post-acutely there seems to be a reintegration in those networks and relatively minimal effects
on global integration.
An example of this is the default mode network, which is best known for underlying the sense
of Self.
Psychedelics initially decrease DMN functional integrity, yet post-acutely, psilocybin seemed
to cause an increase in connectivity.
Post-treatment increases between certain DMN nodes even predicted response at 5 weeks.
Other studies have shown both increased and decreased DMN connectivity in depression,
so it's not clear how surprising this result is.
Regardless, the acute decline in RSFC followed by a seemingly beneficial increase, led the
researchers to suggest this could be considered a "reset" in the brain.
The DMN goes through a period of disintegration and then reintegrates to restore normal, non-problematic
functioning.
How a psychedelic like psilocybin causes this isn't known.
The researchers also focused on connectivity changes between the parahippocampus and prefrontal
cortex.
RSFC between these regions is typically elevated in depression, while psilocybin, at least
in the post-acute period, decreased connectivity.
And that decrease may be mediated by peak or mystical experiences.
In summary, this paper explored psilocybin's post-acute impact on blood flow and connectivity
for the first time.
Some functional connectivity within the default mode network seems to increase after treatment.
And specific increases between the vmPFC and iLPC nodes of the DMN were greatest in patients
with a response at 5 weeks.
It's important to remember that statistically significant correlations between brain activity
and psychological responses could be false positives.
Far more work is required before we'll know if these changes explain the post-acute effects,
not to mention treatment response weeks and months later.
The study was also limited by a small sample size and it didn't have a control condition.
So all of these things should be kept in mind when interpreting the results.
If you have any questions, feel free to put them in the comments.
You can also email me.
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