Mushroom treatment offers hopeful results against depression

A research team at the University Center for Psychiatry of the UMCG participated in a large international study on the effect of a one-time psilocybin treatment in patients with intractable depression. The researchers found that psilocybin provided a positive effect on patients with depression. 

This study found that patients who received 25 mg of psilocybin had a greater positive effect on their depression than those who received the placebo treatment at 1 mg. The results of this study were published today in New England Journal of Medicine.

New treatment methods in depression necessary

Depression is associated with severe suffering for both the patient and his or her loved ones and negatively affects virtually all areas of life. Unfortunately, a significant proportion of patients with depressive disorder do not recover with regular antidepressants. Therefore, there is a need to find new treatment methods. Currently, the effects of several psychedelics are being investigated for application in intractable depression. 

Psilocybin as a treatment option 

One such substance is psilocybin, the active ingredient in mushrooms that has a hallucinogenic effect. Psilocybin, if the dosage is high enough, produces a psychedelic experience with a maximum duration of about seven hours. There is evidence that such a psilocybin session produces biological changes at the brain level that are beneficial for recovery from depression. Psychologically, it can bring about an inner mental journey that, although emotionally challenging, can actually be beneficial. For example, patients may gain new insights through the experience about their own situation and how to cope with it, and it may be helpful in processing previous negative life experiences.   

Study with patients in whom antidepressants do not work

For this international study, patients had to meet several criteria and have already tried at least two antidepressants without sufficient effect on depressive symptoms. In the weeks preceding psilocybin intake, their antidepressant medication was completely tapered off. A specially trained therapist also prepared the participants psychologically. It is the largest study of the effects of psilocybin in depression to date. 

Study design

The day of the psilocybin session, participants came to the clinic in the morning. They took 5 white tablets containing one of the three doses studied (25 mg, 10 mg or 1 mg). Neither the participant nor the study team members knew in advance which dose a person was receiving. The 1 mg dose served as a control or also known as a placebo, because the researchers did not expect an intense psychedelic experience from this dose of psilocybin. The participants spent the rest of the day in a homey room in the hospital, with two trained therapists by their side. Participants spent most of the time lying on a bed, listening to music. Upon request, they were given a soft eye mask. 

Hopeful results for proportion of patients

A total of 233 patients participated in this large international study; 24 patients were studied at UMCG. Three weeks after treatment, participants who received 25 mg had a greater positive effect on their depression than participants in the 10 mg and 1 mg groups; the latter two groups did not differ. In the 25 mg group, nearly 30% of participants were in remission after 3 weeks; this is a situation in which the patient is almost completely relieved of symptoms. However, this situation did not persist in each of them until 3 months after treatment. The most common immediate side effects were headache, nausea and dizziness. 

Professional counseling essential

Although the results are encouraging, some participants actually saw an increase in suicidal thoughts or self-harm behavior in the first 3 weeks after the psilocybin session (approximately in 9% of the 25 mg group, nearly 7% of the 10 mg and 1% of the 1 mg group). Suicidality is strongly associated with depression, and it represents yet another sign that proper counseling and professional monitoring are necessary even after such treatment.

This study was primarily aimed at determining the optimal dosage of psilocybin. The results give rise to another international, so-called phase III study, in which the UCP Groningen will also participate. In this study, the effectiveness and course over time in another large group of patients will be investigated. The expected start of this new study is June 2023. The study team can already be reached for questions at [email protected].

Psychedelics in psychiatry

Psychedelics are in high demand for application in various psychiatric disorders. Although promising, carefully designed studies with professional guidance are necessary before their introduction into current treatment guidelines can take place. This is underlined and propagated by a large group of Dutch psychiatrists and researchers in this field (link to manifesto)

The UMCG research group ‘Psychedelic Treatment and Mechanisms’ takes a transdiagnostic approach to studying novel substance-assisted treatments for patients with mental disorders using rigorous, interdisciplinary and complementary research methods (e.g. clinical trials, psychometrics, biomarkers, qualitative research methods). Our aim is to create and critically evaluate novel approaches, in order to develop safe, effective, and ethical treatments for patients with various severe, often treatment-resistant, disorders. Some of the questions we aim to answer include:

  • What works for whom; are specific compounds more or less effective for subgroups of patients, and how can they optimally be applied?
  • How can we predict who will respond (and who will not)?
  • What are the psychological and biological working mechanisms of psychedelic treatments?
  • How do contextual factors (e.g. in preparation, expectation, therapeutic model, physical setting, music) impact treatment experience and outcomes?
  • What models are best suited to provide high quality care on the long term?
  • What levels of professional training and regulation are needed to provide broader, safe and effective implementation?