Psilocybin for hard-to-treat depression: Imperial College's first small study
The question
Some people with depression try medication after medication without real relief. Doctors call this treatment-resistant depression (depression that has not improved after at least two adequate courses of different antidepressants). Researchers at Imperial College London wanted to know something basic first: is it safe and practical to give psilocybin (the active compound in "magic mushrooms") with psychological support to people in this situation? And is there any sign it might help?
Who took part and what happened
This was an open-label feasibility study. "Open-label" means everyone knew they were getting psilocybin. "Feasibility" means the main aim was to see whether this kind of study can be done safely, not to prove it works. There was no control group.
- 12 adults (6 men, 6 women) with moderate to severe depression took part. Each had already tried at least two different antidepressants for at least 6 weeks each without success.
- People with a personal or close family history of psychosis, a past serious suicide attempt, or current drug or alcohol dependence were not included.
- Each person had two sessions, one week apart: first a lower "safety" dose of 10 mg, then a higher dose of 25 mg, taken by mouth as capsules.
- Sessions took place in a clinical research facility. Participants lay on a bed, listened to music, and had two psychiatrists with them throughout.
- Psychological support came before, during and after each session, including a preparation meeting of around four hours.
- Depression was tracked at 1, 2, 3 and 5 weeks, and at 3 months, after the higher dose.
What they found
- The sessions were well tolerated. There were no serious or unexpected side effects. Common short-lived effects were anxiety as the drug started working (in all 12, mostly mild), some confusion or muddled thinking (9 people), nausea (4) and headache (4). One person had brief paranoia. Effects wore off within about six hours.
- Depression scores dropped. On one standard self-rating scale, the average score fell from about 19 at the start to about 7 one week after the higher dose, and was about 10 at three months.
- One week after, 8 of the 12 participants (67%) scored in the range counted as remission (very low or no depression symptoms) on another common scale.
- At three months, 7 of 12 (58%) still showed at least a 50% reduction in symptoms, and 5 of 12 (42%) were still in remission.
- Anxiety and loss of pleasure in life (anhedonia) also improved.
- Not everyone kept the gains. Some participants saw symptoms return by three months.
What this study does not tell us
- No control group and no blinding. Everyone knew they got psilocybin, and there was no comparison group. Hope and expectations can strongly affect how people feel and report their mood.
- Very small. Twelve people is a starting point. Small early studies often show bigger effects than later, larger ones.
- Self-referred volunteers. Most participants sought out the study, which may mean they were especially hopeful about it.
- Drug and support came together. We can't tell how much of the change came from psilocybin and how much from the psychological support.
- Short follow-up. Three months says little about the longer term.
- Careful screening. People at higher risk were excluded, and sessions took place in a medical setting with trained staff. Results may not apply to other people or settings.
Why it matters
This was the first modern study of psilocybin for treatment-resistant depression. It showed that this kind of research could be done safely in a clinical setting, and it gave early signals that justified larger, controlled trials. The authors themselves describe the results as preliminary. It is a first step, and later research has been needed to test whether these early signals hold up.
This is a summary of published research for general information. It is not medical advice. The study took place in a clinical research setting with medical screening and professional support.
Source: Carhart-Harris RL, Bolstridge M, Rucker J, Day CMJ, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry, 3(7), 619–627. doi:10.1016/S2215-0366(16)30065-7 · PubMed
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