Psilocybin for depression

This open-label trial (n=12), also known as PSILODEP-PILOT is the first to test psilocybin in patients in the UK. The study found psilocybin (10-25mg, x2) to be well-tolerated.

Status Completed
Results Published Yes
Start date 01 April 2015
End date 01 December 2015
Chance of happening 100%
Phase Phase II
Design Open
Type Interventional
Generation First
Participants 12
Sex All
Age 18- 99
Therapy No

Trial Details

Depression affects people in different ways and can cause a wide variety of symptoms. They range from lasting feelings of sadness and hopelessness (low mood), to feeling very tearful at unexpected moments (emotional lability). Many people with depression also have symptoms of anxiety. Treatment for depression involves either medication or talking treatments, but these do not work for everybody because some people have depression that is treatment-resistant. Psilocybin is a hallucinogenic drug that comes from what is often called ‘magic mushrooms’. The drug can put some people in a euphoric mood for a number of hours and reduce anxiety. Psilocybin has been given to healthy volunteers and to patients suffering from Obsessive Compulsive Disorder (OCD) and anxiety before with positive results, but it has not been tested in depression. The aim of this initial study is to investigate how this drug works on patients with treatment-resistant depression. We also want to find out which dose gives predictable results in improving peoples’ mood.

NCT Number

Sponsors & Collaborators

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Papers

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Psychedelics work differently than SSRIs and are hypothesized to treat the underlying disconnect with emotions, getting someone in touch with them again. This analysis of an open-label study (n=20) supports this argument with fMRI studies that showed increased amygdala responses to emotional stimuli.

Brain dynamics predictive of response to psilocybin for treatment-resistant depression
This fMRI study (n=15) reanalysed data from a previous open-label study in which psilocybin (10-25mg) was used in the treatment of depression (TRD). After using whole-brain models to fit the spatiotemporal brain dynamics, dynamic sensitivity analysis identified brain regions in transition from a depressive brain state to a healthy one. The identified regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, providing further evidence for the role of serotonergic signalling in the recovery of depression via psilocybin.

Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity
This machine learning study (n=16) examines baseline resting-state functional connectivity (FC) measured with fMRI as a predictor of symptom severity in psilocybin-assisted therapy for treatment-resistant depression (TRD). Results show that FC of visual, default mode, and executive networks predicted early symptom improvement, with the salience network predicting responders up to 24 weeks after treatment.

Body mass index (BMI) does not predict responses to psilocybin
This pooled analysis (n=77) of body mass index (BMI) data from three psilocybin (25mg) trials finds that BMI doesn't predict the intensity of the response to psilocybin. A fixed-dosing schedule (instead of dosage based on weight which is common for MDMA and ketamine) is probably best going forward in psilocybin-assisted trials.

The hidden therapist: evidence for a central role of music in psychedelic therapy
This open-label qualitative interview study (n=19) assessed the role of music during psychedelic therapy with psilocybin (25mg) for treatment-resistant depression (TRD). It identified several ways in which music influenced their experience, most frequently related to the intensification of emotions and mental imagery, and the music appeared to be a significant source of guidance, creating a sense of grounding, as well as a sense of carrying the listener into different psychological places.

Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression
This re-analysis (n=15) of a trial with psilocybin (25mg) for depression (TRD) finds that music-evoked emotions are increased after treatment. The finding correlates with decreased anhedonia (inability to feel pleasure). fMRI measures also show a decrease in connectivity (FC) between the nucleus accumbens (NAc, music-related area) and the default mode network (DMN).

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
This is the first modern study (n=12) on psilocybin and its effects on treatment-resistant depression (TRD). It shows that two sessions with psilocybin (10mg and 25mg) in combination with psychological support can reduce depressive symptoms over periods of one week to three months after treatment. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred.

Data attribution

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