Would
you take a mushroom instead of your antidepressant?
Antidepressant
medication is ineffective in up to 30% of patients with depression. This could
be due to patient biological differences as well as the fact that medications
often take a long time to work, with some people quitting after a while. As a
result, there is a pressing need to broaden the pharmacological options
available to those suffering from depression.
Psychedelics,
such as psilocybin, the key ingredient in "magic mushrooms," have
received a lot of attention in recent years. Despite several clinical trials
demonstrating that psilocybin can effectively treat depression, including
cancer-related anxiety and despair, little is known about how psilocybin acts
in the brain to alleviate depression.
Two
new research published in The New England Journal of Medicine and Nature
Medicine has given some insight into this enigmatic process.
Psilocybin
is a hallucinogen that alters the response of the brain to the neurotransmitter
serotonin. It creates an altered state of consciousness and perception in users
when it is broken down by the liver (into "psilocin").
Psilocybin
appears to diminish activity in the medial prefrontal cortex, a part of the
brain that helps regulate a number of cognitive functions such as attention,
inhibitory control, habits, and memory, according to previous research
employing functional MRI (fMRI) brain scans. The chemical also reduces
connections between this area and the posterior cingulate cortex, which is
thought to be involved in memory and emotion regulation.
The
brain's "default mode network" usually includes an active connection
between these two locations. When we rest and focus inwards, whether
reminiscing about the past, visualising the future, or thinking about ourselves
or others, this network is active. Psilocybin may be loosening the restrictions
of the internal "self" by reducing network activity, with users
experiencing an "opened mind" and greater perception of the world
around them.
Rumination,
or being "stuck" in negative ideas, especially about oneself, is an
interesting feature of depression. We also know that patients with higher
levels of negative rumination had more activity in the default mode network
than in other networks at rest, making them less sensitive to their
surroundings. It's unclear if these changes in activity are caused by
depression symptoms or if those with a more active default mode network are
more likely to be depressed.
What
happened in a study that pitted mushrooms against medicine?
A
double-blind randomised controlled experiment (the gold standard of clinical
studies) compared a group of sad people taking psilocybin to a group of
depressed people using the existing antidepressant medicine escitalopram —
something that had never been done before. The trial's findings were compared
to those of another recent clinical trial employing fMRI brain images.
fMRI
measurements demonstrated an overall increase in connection across the brain's
various networks just one day after the initial dose of psilocybin, which is
generally lowered in patients with severe depression. The default mode network
was diminished at the same time that connectivity between it and other networks
was increased, corroborating prior, smaller research.
Some
persons had more connectedness as a result of the dose than others. The persons
who had the highest increase in network connectivity also had the greatest
improvement in their symptoms six months later, according to the study.
Six
weeks after starting treatment, the brains of persons taking escitalopram
exhibited no change in the connection between the default mode and other brain
networks. It's possible that escitalopram will cause modifications in the
future. However, because psilocybin's antidepressant effect takes action
quickly, it may be great for people who don't respond to other antidepressants.
The
researchers believe the impact is due to psilocybin's more concentrated
influence on brain receptors known as "serotonergic 5-HT2A receptors"
than escitalopram. Serotonin activates these receptors, which are found in all
network brain areas, including the default mode network. We already know that
psilocybin's amount of binding to these receptors causes psychedelic effects.
However, it is still unknown how their activation causes changes in network
connectivity.
Is
this the end of traditional antidepressants?
This
raises the question of whether changing brain network activity is required for
depression treatment. Many patients who take standard antidepressants claim
that their symptoms improve without them. In fact, the study found that both
groups reported improved symptoms six weeks after starting medication.
However,
psilocybin had the largest effect on total mental wellness, according to
several depression rating systems. In addition, patients treated with
psilocybin had a higher rate of clinical response than those treated with
escitalopram (70 per cent versus 48 per cent ). At six weeks, more patients in
the psilocybin group remained in remission (57 per cent versus 28 per cent). The
fact that some patients do not respond to psilocybin or relapse following
therapy demonstrates how tough depression treatment may be.
Furthermore,
both therapy groups received care from mental health specialists during and
after the trial. Psilocybin's success is highly reliant on the circumstances in
which it is consumed. This indicates that self-medicating with it is a poor
idea. Patients were also carefully chosen for psilocybin-assisted therapy based
on their medical history to avoid psychosis and other negative side effects.
Despite
the drawbacks, these trials are extremely promising and get us closer to
broadening the therapeutic options for depression patients. Internalized
negative thought processes are also not exclusive to depression. Other
diseases, like as addiction or anxiety, may benefit from psilocybin-assisted
therapy in the future.