Psilocybin Effective for Treatment-Resistant Depression

Psychosis may be triggered by antibody reaction to brain protein
Psychosis may be triggered by antibody reaction to brain protein
This small-scale feasibility study did not include a control group.

Current therapeutic modalities targeting treatment-resistant depression are inadequate and clinical need is significant. Resistance to antidepressant drug treatment is observed in approximately 20% of patients with clinical depression and remains a great challenge. Progress is being made, however, with identification of alternative therapeutic candidates.1,2

Psilocin — the psychoactive metabolite of psilocybin, an ingredient of so-called “magic mushrooms”— significantly reduces depressive symptoms for up to 3 months after treatment in individuals diagnosed with treatment-resistant depression, according to a new study published in Lancet Psychiatry.1

Major depressive disorder (MDD) is a highly disabling condition that affects nearly 15 million American adults in a given year.3 It is characterized by significant comorbidity with illnesses including but not limited to diabetes, hypertension, cancer, stroke, heart attack, HIV, substance use, chronic pain, and other neuropsychiatric disorders such as anxiety, personality, and stress-related disorders.4,5

The present study, conducted by a group of investigators affiliated with the Imperial College London, University College London, and King’s College London, did not include a control group; however, the authors note in their publication that “Psilocybin has a novel pharmacological action in comparison with currently available treatments for depression (ie, 5-HT2A receptor agonism) and thus could constitute a useful addition to available therapies for the treatment of depression.”

The researchers assessed symptom severity of depression by using the Hamilton Rating Scale for Depression (HAM-D), Montgomery-Asberg Depression rating Scale (MADRS), Quick Inventory of Depressive Symptoms (QIDS), and Beck Depression Inventory (BDI). Only those individuals with moderate (n=3) to severe (n=9) depression at baseline as well as resistance to antidepressant drug treatment were included. None of the study participants had comorbid psychotic disorder, history of suicide attempts or mania, blood or needle phobia, or current drug or alcohol dependence. They were administered 2 oral doses of psilocybin, separated by 7 days: a low dose (10 mg) to establish safety and a subsequent higher treatment dose (25 mg).1

The findings indicate that depression scores in all participants were somewhat reduced from baseline even at 24 hours after treatment. Significantly reduced depression scores from baseline were observed in all patients at 1 week and were sustained until 3 months posttreatment. Complete remission was seen in 8 patients at 1 week after psilocybin administration, and 5 of these individuals met the same criteria after 90 days. A number of participants (n=7) met criteria for response (50% reduction in BDI score relative to baseline) at 3 months after psilocybin treatment. Both anxiety and anhedonia scores were also significantly reduced from baseline at 7 and 90 days posttreatment.1

“Because this was a small-scale feasibility study with an open-label design, strong inferences cannot be made about the treatment’s therapeutic efficacy. However, the data do suggest that further research is warranted,” the authors concluded.1

Aside from psilocybin, another alternative approach for treatment-resistant depression is ketamine, a glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist.2 Both of these highly promising therapeutic agents are receiving wide preclinical attention as potential treatment options in various clinical settings, including the area of treatment-resistant depression.

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1. Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016. doi: 10.1016/S2215-0366(16)30065-7. [Epub ahead of print]

2. DeWilde KE, Levitch CF, Murrough JW, et al. The promise of ketamine for treatment-resistant depression: current evidence and future directions. Ann N Y Acad Sci. 2015;1345:47-58.

3. Kessler RC, Chiu WT, Demier O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:617-627.

4. Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic disease, and decrements in health: results from the World Health Surveys. Lancet. 2007;370:851-858.

5. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105.