UK's First Publicly Funded Trial Shows Psilocybin Significantly Improves Treatment-Resistant Depression

The UK's first publicly funded randomized trial of psilocybin, the PsiDeR trial, has shown significant efficacy in treating treatment-resistant depression within an NHS setting. Led by King's College London, the study of 60 patients found that a single 25mg dose of psilocybin led to a 40% remission rate at three weeks, which was sustained at six weeks, compared to just 3% in the placebo group. The trial successfully demonstrated that psilocybin can be safely administered in community mental health settings rather than hospital wards.

PsiDeR trial methodology

• ▪The PsiDeR trial did not set an upper limit on the degree of treatment resistance, allowing participants with severe and chronic illness to enroll.
• ▪The PsiDeR trial evaluated a single 25 mg dose of psilocybin against a true placebo, with both groups receiving psychological support.
• ▪The Psilocybin in Depression Resistant to Standard Treatments (PsiDeR) trial was a randomized controlled trial in England that recruited 60 participants with treatment-resistant depression.
• ▪Blinding was not fully maintained in the PsiDeR trial, as 100% of the psilocybin group and 70% of the placebo group correctly guessed their treatment allocation.

Treatment-resistant depression prevalence

• ▪Treatment-resistant depression is commonly defined as a failure to respond to at least two antidepressants at therapeutic dose and duration.
• ▪Major depressive disorder affects approximately 300 million people worldwide, and treatment-resistant depression affects one-third of those individuals.

Psilocybin remission rates

• ▪The proportion of participants showing a treatment response rose to 56% in the psilocybin group at six weeks, compared to 3% in the placebo group.
• ▪In the PsiDeR trial, 40% of the psilocybin group met the threshold for depression remission at three weeks, compared with 3% of the placebo group.
• ▪At six weeks, the depression remission rate for the psilocybin group in the PsiDeR trial remained sustained at 40%, compared to 3% for the placebo group.

Psilocybin receptor mechanism

• ▪Psilocin, the active metabolite of psilocybin, acts as a partial agonist of the 5-HT2A serotonin receptor to produce its characteristic subjective effects.
• ▪The subjective effects of psilocin include heightened emotions, mystical experiences, altered perceptions, and ego dissolution, which may facilitate its therapeutic effects.

Patient emotional experiences

• ▪A participant in the PsiDeR trial stated that the psilocybin experience was very difficult and painful but helped them understand and feel their feelings.
• ▪One PsiDeR trial participant described experiencing an intense, emotional release during the psilocybin session, visualizing deceased family members.

NHS publicly funded research

• ▪The PsiDeR trial recruitment began at an NHS clinical research facility before moving to a community mental health research building.
• ▪The PsiDeR trial was the first publicly funded randomized controlled trial of psilocybin-assisted therapy delivered within an NHS setting in England.
• ▪Senior clinical trials manager Catherine Bird stated that moving the trial showed psilocybin can be administered safely outside of a hospital ward.