



“Expand your mind, man!” was a popular phrase that arose from the 1960’s counterculture movement. However, it was most likely not referring to the specific neurochemical pathways within the brain that are associated with clinical depression. Yet now, investigators from Imperial College London have just published evidence showing that patients taking psilocybin—the psychoactive compound that occurs naturally in magic mushrooms—to treat depression show reduced symptoms weeks after treatment following a “reset” of their brain activity. Findings from the study were published today in Scientific Reports, in an article entitled “Psilocybin for Treatment-Resistant Depression: fMRI-Measured Brain Mechanisms.”

In the new study, the researchers describe patient-reported benefits lasting up to five weeks after treatment in a small cohort of patients with depression in whom conventional treatment had failed. Moreover, the scientists believe the psychedelic compound may effectively reset the activity of key brain circuits known to play a role in depression.

Using fMRI, or functional magnetic resonance imaging, the investigators compared images of patients' brains before and one day after they received the drug treatment, revealing changes in brain activity that were associated with marked and lasting reductions in depressive symptoms.





“We have shown for the first-time clear changes in brain activity in depressed people treated with psilocybin after failing to respond to conventional treatments,” explained lead study investigator Robin Carhart-Harris, Ph.D., head of psychedelic research at Imperial College. “Several of our patients described feeling 'reset' after the treatment and often used computer analogies. For example, one said he felt like his brain had been 'defragged' like a computer hard drive, and another said he felt 'rebooted.' Psilocybin may be giving these individuals the temporary 'kick start' they need to break out of their depressive states, and these imaging results do tentatively support a 'reset' analogy. Similar brain effects to these have been seen with electroconvulsive therapy.”

Over the last decade or so, several clinical trials have been conducted to verify the safety and effectiveness of psychedelics in patients with conditions such as depression and addictions, yielding promising results. In this recent trial, the first with psilocybin in depression, 20 patients with a treatment-resistant form of the disorder were given two doses of psilocybin (10 mg and 25 mg), with the second dose a week after the first. Nineteen of these patients underwent initial brain imaging and then a second scan one day after the high-dose treatment. The research team used two main brain imaging methods to measure changes in blood flow and the crosstalk between brain regions, with patients reporting their depressive symptoms by completing clinical questionnaires.

Immediately following treatment with psilocybin, patients reported a decrease in depressive symptoms —corresponding with anecdotal reports of an “after-glow” effect characterized by improvements in mood and stress relief.

Imaging with fMRI revealed reduced blood flow in areas of the brain, including the amygdala, a small, almond-shaped region of the brain known to be involved in processing emotional responses, stress, and fear. They also found increased stability in another brain network, previously linked to psilocybin's immediate effects as well as to depression itself.

“Through collecting these imaging data, we have been able to provide a window into the aftereffects of psilocybin treatment in the brains of patients with chronic depression,” noted Dr. Carhart-Harris. “Based on what we know from various brain imaging studies with psychedelics, as well as taking heed of what people say about their experiences, it may be that psychedelics do indeed 'reset' the brain networks associated with depression, effectively enabling them to be lifted from the depressed state.”

These findings provide a new window into what happens in the brains of people after they have “come down” from a psychedelic drug dose, where an initial disintegration of brain networks during the drug “trip” is followed by a reintegration afterward.

While these new results are encouraging, the authors warned that the research is at an early stage and that patients with depression should not attempt to self-medicate. The team provided a special therapeutic context for the drug experience, and they noted that things may go awry if the extensive psychological component of the treatment is neglected. They add that future studies will include more robust designs and that they currently plan to test psilocybin against a leading antidepressant in a trial set to start early next year.

“Larger studies are needed to see if this positive effect can be reproduced in more patients,” concluded senior study investigator David Nutt, Ph.D., professor of neuropsychopharmacology and director of the neuropsychopharmacology unit in the division of brain sciences at Imperial College. “But these initial findings are exciting and provide another treatment avenue to explore.”























