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Psilocybin Treats Depression by Increasing the Number of Brain Connections, Study Finds

By Leo Bear-McGuinness

Published: Apr 11, 2022   
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The reasons behind psilocybin’s anti-depressive effects may have just become clearer.

The magic mushroom compound appears to stimulate certain neurons in the brain to interconnect, an effect not seen in the brains of people on more conventional anti-depressants.

The finding was observed in a new study published in Nature Medicine.

Feeling more connected

Psilocybin is the active psychedelic component of magic mushrooms and has shown promise when used in therapy settings for the treatment of depression.

But exactly how the compound treats depression isn’t fully clear. Previous research has suggested that the chemical acts on the body’s serotonin 2A receptors (5-HT2AR), which are widely found in the brain.

Now, the study from researchers at Imperial College London has found that the 5-HT2AR-rich networks in the brains of psilocybin users are indeed more interconnected and flexible than those found in the brains of people on more convention antidepressants.

To get their findings, the researchers recruited 43 people with major depressive disorder. Just over half of these participants (22) were initially given a 25 milligram (mg) dose of psilocybin; the others were given 1 mg (a dose considered negligible). After a therapy session, both groups then took unmarked pills over six weeks; the 25 mg psilocybin-patients received a placebo while the other group took the conventional antidepressant escitalopram.

By the end of the trial, the average depression scores of both groups had fallen by the same amount and the researchers concluded that the medications were just as effective as each other. These results were initially published in the New England Journal of Medicine last April.

The new Nature Medicine paper further reviewed the brain scans of the patients to assess the neural affects of psilocybin. And the researchers came across some interesting findings.

The scans of the psilocybin-patients showed more new brain connections and higher neural flexibility than the scans of the escitalopram-patients. Given that many of the neural connections in the brains of depressed people are often static, the researchers took this observed neural flexibility as a sign of psilocybin’s anti-depressive effects.

“The [neural] landscape in depression can be described as abnormally constricted, paralleling the narrow, internally focused, ruminative quality of mood and cognition in the disorder,” they wrote in their new study.

“In contrast, psilocybin seems to increase the brain’s ability to visit a broader state space, both acutely and after psilocybin therapy in patients who are depressed.”

Despite this beneficial effect, the paper’s authors have warned readers against replicating the study with illicitly sourced magic mushrooms.

“The authors caution that while these findings are encouraging, previous trials assessing psilocybin for depression took place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support before, during and after dosing, provided by mental health professionals,” the researchers said in a statement.

“Patients with depression should not attempt to self-medicate with psilocybin, as taking magic mushrooms or psilocybin in the absence of these careful safeguards may not have a positive outcome.”

Psilocybin and depression

Psilocybin may have been deemed an equally effective anti-depressant as escitalopram when the Imperial College’s research first came to light last April, but its benefits may even stretch beyond the borders of conventional depression medications.

One recent paper found that the magic mushroom chemical could reduce a person’s depression for at least a year after their initial psychotherapy sessions.

Published this February in the Journal of Psychopharmacology, the study followed 24 participants with a history of depression. All participants received two doses of psilocybin and supportive therapy sessions.

Almost all participants reported feeling significantly less depressed when they met up with the researchers a week after treatment, and most continued to report lower depression scores 3 months, 6 months, and 12 months after their second psilocybin trip.


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