Psilocybin Proves as Effective as Antidepressants in Treating Depression

Medical researchers in London have conducted a double-blind, randomized, placebo-controlled study comparing the effectiveness of psilocybin and the antidepressant escitalopram in treating depression among 59 patients. Over the course of six weeks, both treatments showed positive results, with a slight advantage for psilocybin. The study was published in the New England Journal of Medicine.

What Is Psilocybin?

Psilocybin is the main active compound found in hallucinogenic mushrooms of the Psilocybe genus. Its effects are primarily due to stimulation of serotonin 5-HT2A receptors. Disruptions in serotonergic pathways are known to contribute to various mental disorders, with clinical depression being the most common.

The effectiveness of psilocybin in treating severe depression has been demonstrated in previous studies in 2016 and 2020. The U.S. Food and Drug Administration (FDA) has even granted psilocybin “breakthrough therapy” status for depression treatment, which is intended to accelerate its adoption in clinical practice. However, psilocybin and mushrooms containing it remain strictly regulated in most countries.

The Study: Psilocybin vs. Escitalopram

The new study compared psilocybin to escitalopram, a selective serotonin reuptake inhibitor (SSRI), in patients with moderate to severe, long-term depressive disorders. Led by Dr. Robin Carhart-Harris at Imperial College London, the trial included participants aged 18 to 80. This same research group had previously shown psilocybin’s effectiveness for severe depression.

Nearly 1,000 patients were screened by phone; 891 were excluded due to criteria such as comorbid psychiatric conditions, and 50 declined to participate. Ultimately, 59 patients were enrolled: 30 in the psilocybin group and 29 in the escitalopram group.

The study used a double-blind, randomized, placebo-controlled design. Participants were told they would receive psilocybin, but the dose was not disclosed. “Double-blind” means neither the participants nor the researchers knew which treatment was being administered, and “randomized” means group assignments were random. Placebos were used to ensure both groups had similar experiences and to rule out the placebo effect.

Treatment Protocols

• Psilocybin group: Received two doses of 25 mg psilocybin (a therapeutic dose) three weeks apart, plus daily placebo tablets (microcrystalline cellulose) for six weeks.
• Escitalopram group: Took 10 mg of escitalopram daily for three weeks, then increased to 20 mg daily for the remaining three weeks. They also received two doses of 1 mg psilocybin (a negligible dose) three weeks apart.

All participants received the same level of professional psychological support throughout the study.

Results and Outcomes

Depression severity was measured using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16), with scores ranging from 0 to 27 (higher scores indicate more severe depression). At the start, average scores were 14.5 in the psilocybin group and 16.4 in the escitalopram group. After six weeks, average scores dropped by -8.0 ± 1.0 in the psilocybin group and -6.0 ± 1.0 in the escitalopram group. The 2-point difference (95% CI: 5.0–0.9) indicated no significant difference between the groups.

• A 50% reduction in depression symptoms was observed in 70% of the psilocybin group and 48% of the escitalopram group.
• Remission (scores of 0–5) was achieved by 57% of the psilocybin group and 28% of the escitalopram group.

Side Effects and Additional Observations

Participants were also asked about side effects. Anxiety and dry mouth were more common in the escitalopram group, while headaches were more frequent in the psilocybin group. Those taking psilocybin reported increased crying, compassion, pleasure, and generally more intense emotions. Drowsiness was less pronounced in the psilocybin group compared to the escitalopram group. No participants experienced visual hallucinations, psychotic symptoms, or signs of dependence.

Some participants dropped out during the study: four from the escitalopram group stopped taking the antidepressant, and one reduced the dose due to side effects. No one in the psilocybin group requested to skip the second dose, but three missed the second session due to COVID-19.

Conclusions and Future Directions

The researchers emphasize the need for larger and longer-term studies to further compare psilocybin with standard depression treatments. Previous research has also explored psilocybin’s potential for treating migraines and its effects on the brain.