Psychedelic prodrug in magic mushrooms may 'reset' the brain in treatment- resistant depression

Patients with treatment-resistant depression who were given psilocybin—the psychedelic prodrug found in “magic mushrooms”—reported a brain “reboot,” as well as rapid antidepressant effects that lasted up to 5 weeks, according to results of a study published in Scientific Reports.

“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,” said lead investigator Robin Carhart-Harris, PhD, Head of Psychedelic Research, Imperial College London’s Centre for Neuropsychopharmacology, London, UK.

“Psilocybin may be giving these individuals the temporary ‘kick start’ they need to break out of their depressive states,” Dr. Carhart-Harris noted.

Psilocybin is the prodrug of psilocin, a non-selective serotonin receptor agonist, which occurs naturally in the Psilocybe genus of mushrooms. Both psilocybin and psilocin are also structurally related to the neurotransmitter serotonin.

Previously, researchers had investigated the use of psilocybin for a range of psychiatric conditions, including end-of-life anxiety and depression, alcohol and tobacco addiction, and obsessive-compulsive disorder.

For this study, Dr. Carhart-Harris and colleagues evaluated symptoms of depression in 19 patients using the 16-item Quick Inventory of Depressive Symptoms (QIDS-SR16). They also used functional magnetic resonance imaging (fMRI) to compare cerebral blood flow in the brains of subjects before and after psilocybin injection.

The researchers found that depressive symptoms decreased in all 19 patients at 1 week post-treatment, and this effect persisted in approximately half of patients (47%) at 5 weeks. Post-treatment fMRI analyses showed decreases in cerebral blood flow in the temporal cortex, including the amygdala. Decreased cerebral blood flow in the amygdala correlated with reduced depressive symptoms, they found.

The fMRI scans also showed increased functional connectivity in the ventromedial prefrontal cortex and bilateral inferior lateral parietal cortex, which predicted treatment response at 5 weeks.

These brain effects are similar to the kind seen with electroconvulsive therapy, the researchers observed.

“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’,” Dr. Carhart-Harris said.

“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,” he explained.

“Larger studies are needed to see if this positive effect can be reproduced in more patients. But these initial findings are exciting and provide another treatment avenue to explore,” said the study’s senior author David Nutt, DM, FRCP, FRCPsych, Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences at Imperial College London.

The investigators are now planning a trial to begin early next year that will compare psilocybin against a leading antidepressant drug.