Early Trial Results Promising for Psilocybin as an Antidepressant

Robin Carhart-Harris, PhD (Imperial College London)

While there is hope psilocybin has antidepressant properties, there is a lack of data regarding how the psychedelic prodrug compound treatment compares to the current stable of depression medications.

A team, led by Robin Carhart-Harris, PhD, Imperial College London, compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor.

The Treatment

Psilocybin is a naturally occurring compound that can be often found in “magic mushrooms,” known to produce a number of mind-altering effects including visual and mental hallucinations, changes in perception, euphoria, a distorted sense of time, and spiritual experiences.

In the phase 2, double-blind, randomized, controlled trial, the researchers examined 59 patients with long-standing, moderate-to-severe major depressive disorder over a 6 week trial.

The patients were equally randomized to receive 2 separate doses of 25 mg psilocybin 3 weeks apart with 6 weeks of daily placebo (n = 30) or 2 separate doses of 1 mg psilocybin 2 weeks apart with 6 weeks of daily oral escitalopram (n = 29). The patients in each cohort also received psychological support.

Outcomes

The researchers sought primary outcomes of the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0-27, with higher scores indicating greater depression) at week 6.

The research team also sought 16 secondary outcomes, which included QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6.

Results

The overall mean scores on the QIDS-SR-16 at baseline was 14.5 in the psilocybin cohort and 16.4 in the escitalopram arm and the mean changes in scores from baseline to week 6 were −8.0±1.0 points in the psilocybin group and −6.0±1.0 in the escitalopram group (between-group difference, 2.0 points; 95% CI, -5.0 to 0.9; P = 0.17).

For about 70% of the target treatment group, there was a QIDS-SR-16 response, compared to just 48% in the escitalopram group (between-group difference, 22 percentage points; 95% CI, −3 to 48).

In addition, QIDS-SR-16 remission occurred in 57% and 28%, respectively (between-group difference, 28 percentage points; 95% CI, 2-54).

The investigators also found other secondary outcomes generally favored psilocybin, but the analyses were not corrected for multiple comparison.

The safety profile of psilocybin was also promising, with adverse event rates similar between the 2 trial groups.

The Future

With the promising results, the researchers are hoping longer and larger clinical trials will be developed in the future to further compare psilocybin with the more established antidepressants.

“On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients,” the authors wrote. “Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons.”

The study, “Trial of Psilocybin versus Escitalopram for Depression,” was published online in The New England Journal of Medicine.