Magic Mushroom Compound Investigated in Treatment-Resistant Depression

Results from a recent study published in The Lancet Psychiatry demonstrates preliminary support for the safety and efficacy of the hallucinogenic compound, psilocybin, for the management of treatment-resistant depression.

Results from a recent study published in The Lancet Psychiatry demonstrates preliminary support for the safety and efficacy of the hallucinogenic compound, psilocybin, for the management of treatment-resistant depression.

Psilocybin, a serotonin receptor agonist, is derived from certain mushroom species. Earlier studies have looked at the therapeutic potential of psilocybin for conditions such as end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence.

“This is the first time that psilocybin has been investigated as a potential treatment for major depression,” stated lead author Robin L Carhart-Harris, PhD, from the Imperial College London, London, UK. Dr. Carhart-Harris and coauthors investigated the efficacy and safety of psilocybin in patients with unipolar treatment-resistant depression. The open-label feasibility trial enrolled 6 men and 6 women with moderate-to-severe, unipolar, treatment-resistant major depression. They received oral doses of psilocybin 10mg (safety dose) and 25mg (treatment dose) one week apart; there was no control group.  Psychological support was given before, during, and after each session. 

The study’s primary measure for feasibility was patient-reported intensity of psilocybin’s effects. Symptoms of depression were evaluated with standard assessments from 1 week to 3 months post-treatment with the 16-item QIDS (Quick Inventory of Depressive Symptoms) utilized as the primary efficacy outcome. 

The acute psychedelic effects of psilocybin were detectable 30–60 minutes post-dose, peaked about 2–3 hours post-dose, and reduced to negligible levels at least 6 hours post-dose. Self-rated intensity on a scale of 0–1 was 0.51 (standard deviation [SD] 0.36) for the low-dose session and 0.75 (SD 0.27) for the high-dose session. 

Psilocybin was generally well tolerated with no serious or unexpected adverse events. All patients reported transient anxiety during drug onset, 9 patients reported transient confusion or thought disorder, and 4 patients reported mild and transient nausea and headache. 

Researchers saw a marked reduction in depressive symptoms 1 week (mean QIDS difference –11.8, 95% CI: –9.15 to –14.35; P=0.002) and 3 months (–9.2, 95% CI: –5.69 to –12.71;P=0.003) following high-dose treatment. Eight of the 12 patients (67%) achieved temporary remission and by 3 months, 7 patients (58%) continued to demonstrate symptom improvement with 5 still in remission. In addition, marked and lasting improvements in anxiety and anhedonia were also observed.

Study findings imply that psilocybin may hold value as a treatment option for treatment-resistant depression. Additional studies, “with more rigorous designs,” are needed to better evaluate the therapeutic potential of psilocybin, authors concluded.

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