Psilocybin Decreases Depressive Symptoms in Treatment-Resistant Patients


The naturally occurring psychoactive ingredient decreased mean depressive scores by 8.1 QIDS-SR-16 points.

Dr Robin Carhart-Harris

Dr. Robin Carhart-Harris

Robin Carhart-Harris, PhD

Psilocybin, a naturally occurring psychoactive ingredient found in more than 200 species of mushrooms, has been shown to decrease depressive symptoms in patients experiencing treatment-resistant major depression.

A study led by Robin Carhart-Harris, PhD, the head of the Psychedelic Research, Centre for Neuropsychopharmacology at the Imperial College London, explored the use of psilocybin 25 mg to treat major depressive disorder in 19 patients. They completed pre- and post-treatment magnetic resonance imaging (MRI) scans and the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) to assess depression scores.

The mean depression score prior to treatment was 16.9 ± 5.1, but it decreased to 8.8 ± 6.2 post-treatment (change = -8.1 ± 6, t = -5.2, P <.001). This was after a brief increase at baseline, as the mean was 18.9 ± 3 at baseline.

Researchers measured cerebral blood flow (CBF) and functional connectivity via arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) resting state 1-day post-treatment, as “it has been suggested that the days subsequent to a psychedelic experience constitute a distinct phase… that is characterized by mood improvements and stress relief,” according to the authors. They rationalized the measurements to record brain changes that could correlate with mood improvement and longer-term prognoses.

The BOLD analyses showed a mean QIDS-SR-16 change of -7.3 ± 5.3 from scan 1 to scan 2, and -8.2 ± 5.2 from baseline to 5-weeks post-treatment (t = -5.2, -6.2; P <.001), both considered statistically significant. Of the 15 patients included in the BOLD analyses and the 16 in ASL, 6 achieved response criteria (≤50% QIDS-SR-16 score reduction) at the 5-week mark.

“Of the full 19 patients, all showed some decrease in depressive symptoms at 1 week, with 12 meeting criteria for response,” Carhart-Harris wrote. “ All but 1 patient showed some decrease in QIDS-SR-16 score at week 5 (with one showing no change) and 47% met criteria for response.”

Decreases in CBF in the amygdala - which increase when depression is present - were only observed post-treatment, and were compared with the reductions in depressive symptoms from scan 1 to scan 2, found to be statistically significant (r = 0.59; P = 0.01). However, no significant difference was found 5 weeks post-treatment (t = 0.11; P = 0.46).

“The present study goes some way to addressing an important knowledge gap concerning the post-acute brain effects of serotonergic psychedelics,” Carhart-Harris and colleague wrote. “Its findings suggest that changes in brain activity observed just one-day after a high dose psychedelic experience are very different to those found during the acute psychedelic state. Specifically, whereas the acute psychedelic state in healthy volunteers is characterized by modular disintegration and global integration there are trends towards modular (re)integration and minimal effects on global integration/segregation post psilocybin for depression.”

The study was concluded by pointing out the correlation between reductions in depressive moods and the decreased blood flow in the amygdala.

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