Psilocybin as a treatment for major depression

Lead Research Organisation: Imperial College London


The aim of this project is to test the efficacy of psilocybin as a treatment for major depression. Psilocybin is a naturally occurring compound that is found in some species of mushroom. It is structurally similar to the brain neurotransmitter serotonin - which is implicated in mood (low brain serotonin levels are associated with low mood). Psilocybin has been used for centuries in spiritual healing contexts, and more recently in psychotherapy. Modern research has shown that single exposures to psilocybin can improve psychological well-being for over 1 year and decrease symptoms of depression for up to 6 months, without any adverse events. Using functional brain imaging (fMRI) and intravenous psilocybin, we recently found brain changes that can explain these positive mood effects of psilocybin. Here we propose a well powered, placebo-controlled design to study the efficacy of psilocybin as a treatment for major depression. We will recruit 44 patients with major depression that will be randomly allocated to either a placebo group or a psilocybin group. Neither the patients, nor the research staff will know which patients are in which group ('double-blind'). Psilocybin may be particularly beneficial for patients that struggle to adhere to chronic treatment schedules, as it is potentially effective after just one exposure. It may also be particularly beneficial for patients that hold rigidly pessimistic attitudes, since psychological and neurobiological data suggest that it targets brain mechanisms involved in habitual negative thinking.

Technical Summary

This will be a double-blind, randomised, placebo-controlled, between subjects study involving up to 44 patients (22 per group) with major depression of moderate to severe degree (scores of 14+ on the Hamilton Depression Rating scale). The main objective is to test the efficacy of psilocybin infusion as a treatment for major depression. All patients will be at least 21 years of age with decent physical health and at least one failed treatment with an antidepressant medication within the last 4 months. All patients will be medication free for at least 7 days prior to screening. Patients will be recruited via referrals and advertisement. The study will be adopted on to the Medical Health Research Network. Patients will be screened for suitability. Exclusion criteria will include: epilepsy, cardiovascular abnormalities, history of drug or alcohol dependence, history of psychosis, psychotic symptoms, bipolar disorder, or high schizotypy, and a history of suicide attempts or planning. The study duration from screening to the final formal follow-up will be 4 weeks. Upon enrolment, patients will be randomly allocated to 1 of 2 treatment groups: placebo (2 IV infusions of saline, 7 days apart) or psilocybin (2 IV infusions of psilocybin - a low dose (0.9mg) and then a high dose (1.8mg), 7 days apart). After screening, there will be a run in period of 7 days, followed by the first treatment session at day 7, a second treatment session at day 14 and a final follow-up at day 28 after which the study will end. The primary outcome will be change in BDI scores from baseline to week 4. We predict that patients in the psilocybin group will have significantly greater decreases in BDI scores than patients in the placebo group. Psilocybin will be given by IV infusion. Given IV, the acute subjective effects of psilocybin are short-lived and well-tolerated, lasting for approximately 40 minutes.

Planned Impact

Patients with depression will be the biggest beneficiaries of this research, both directly in those that are treated in the study, and later on in those that may receive the treatment if it is eventually licensed. Carers will also benefit, particularly if psilocybin is found to be effective after one or two exposures; a safe and effective single exposure therapy would have considerable value in terms of treatment efficiency and resources saved. Psilocybin may become seen as an attractive alternative to other single exposure therapies - such as electroconvulsive therapy, or perhaps, ketamine infusion. Longer-term, we might see psilocybin developed as an adjunct to cognitive behavioural therapy (CBT) and/or interpersonal psychotherapy.
In the commercial sector, if psilocybin is shown to be safer and more effective than competing treatments, pharmaceutical companies may become interested in its development. Consistent with the aims of the multidisciplinary association of psychedelic studies (MAPS) to develop MDMA (ecstasy) as a treatment for Post Traumatic Stress Disorder, an ultimate scenario for psilocybin as a treatment for depression may be that it is offered in specialised clinics - where an appropriately high level of care can be given to patients, e.g. with careful screening, preparation and aftercare.
In terms of lost productivity, the cost of depression for government and industry is presently immense and set to increase. Thus, if psilocybin is shown to be safe and effective in depression, increasing patients' optimism and well-being, then this would have broad positive consequences e.g. for economic performance. It is relevant to note here that certain luminaries in science and technology (e.g. Steve Jobs - Apple and Kary Mullis - PCR) have, in open press, attributed their achievements, in no small part, to insights gained on psychedelic drugs.
It may take 10 years to develop psilocybin as a licensed treatment for depression, but during this time, important knowledge will be acquired about how to maximise its potential.
We will be keen to disseminate our findings. David Nutt and Val Curran have excellent relations with media and are frequently invited to give radio and television interviews, public lectures and scientific presentations. Importantly, there is a natural public and scientific interest in this subject matter which will greatly assist the process of dissemination, and ultimately maximise impact.


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Carhart-Harris R (2014) Was it a vision or a waking dream? in Frontiers in Psychology

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Carhart-Harris RL (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. in Proceedings of the National Academy of Sciences of the United States of America

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Carhart-Harris RL (2013) Psychiatry's next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders. in Journal of psychopharmacology (Oxford, England)

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Carhart-Harris RL (2012) Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. in The British journal of psychiatry : the journal of mental science

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Carhart-Harris RL (2017) Serotonin and brain function: a tale of two receptors. in Journal of psychopharmacology (Oxford, England)

Description Mosley Foundation
Amount £600,000 (GBP)
Organisation Mosley Foundation 
Sector Private
Country United States
Start 01/2016 
End 01/2019
Title psilocybin as a drug treatment for depression 
Description innovative treatment for depression 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2020
Development Status Under active development/distribution
Clinical Trial? Yes
Impact a number of commercial pharmaceutical companies are now seeking to develop this new treatment