Can the psychoactive substance found in “magic mushrooms” be used to treat depression?
Psilocybin is a hallucinogenic drug present in some species of mushrooms. This compound was utilized in the 1960’s for various psychiatric conditions before being classified as a schedule I substance by the FDA in 1970.
Schedule I substances have no current acceptable medical use and have a high potential for abuse.
Some examples of Schedule I substances are heroin, LSD, and PCP.
Recently, some cities have decriminalized psilocybin. The first to do so was Denver, Colorado, in May of 2019.
The first state to legalize psilocybin is Oregon, where I live. Measure 109 passed in November of 2020. This measure allows the Oregon Health Authority (OHA) to develop a program to enable licensed providers to administer mushrooms and fungi containing psilocybin to individuals over 21.
This measure opens the door for psilocybin to be used for psychiatric conditions where traditional treatment has failed.
What is Psilocybin?
Psilocybin is a psychedelic substance that alters consciousness through interaction with serotonin (5HT2A) receptors.
The question is whether this substance has any benefit for these conditions. To answer this question, I looked at the available studies.
Psilocybin Treatment for Anxiety and Depression in Cancer Patients
Cancer patients commonly suffer from significant anxiety and depression. It is estimated that 30-40% of these patients are affected by these disorders when hospitalized.
Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies.1
Anxiety and depression are associated with a variety of symptoms that lead to poor outcomes. Some of these include:
- Increased suicide rates.
- Increased disability
- Poor medication compliance.
- Increased health care utilization.
- Decreased quality of life.
- Increased pain.
- Decreased social functioning.
- Decreased survival rates.
Although this is a significant problem, no FDA-approved pharmacotherapies are approved for psychological distress related to cancer. Antidepressant agents take time to take effect, side effects compromise treatment adherence, many treatments are ineffective, and relapse rates are significant.5
A double-blind, placebo-controlled, crossover trial involving 29 patients with cancer-related anxiety and depression was published in the Journal of Psychopharmacology in December of 2016.7
This study was designed to determine the efficacy of a single psilocybin dosing session compared to an active control (niacin 250mg) in treating cancer patients with anxiety and depression.
The investigators concluded that moderate-dose psilocybin (along with psychotherapy) produced rapid and sustained anxiolytic and anti-depressant effects. These effects lasted anywhere from 7 weeks to 8 months. These patients exhibited decreased cancer-related existential distress, increased spiritual well-being, quality of life, and improved attitudes towards death.
There were no serious adverse effects reported during this study in either group.
Psilocybin in Unipolar Depression
An open-label study of 12 patients with moderate-to-severe, unipolar depression was published in Lancer Psychiatry in July of 2016. This was a feasibility trial involving six men and six women.8
These patients received two oral doses of psilocybin (10mg and 25mg) seven days apart. The figure below represents the Schedule of study interventions for this trial.
This study’s main objective was to create an optimized protocol for psilocybin administration and gain information about its efficacy in treating unipolar depression.
No severe adverse effects occurred during this study, and the psilocybin was well-tolerated. The side effects that did appear were:
- Anxiety (mostly mild)
- Confusion or thought disorder
No prolonged psychosis was observed in any of the subjects.
Depression severity was measured using the Quick Inventory of Depressive Symptomatology (QIDS) score. Scoring is as follows:
>21 – Very severe depression
16-20 – Severe depression
11-15 – Moderate depression
6-10 – mild depression
5 or below – No depression
<=9 – Indicates remission of depression
All scoring was completed at the intervals shown on the graph below. The time period reflects time passed after the high-dose session. The figure below shows the results over time. These results were also confirmed using the Beck’s Depression Inventory Scale.
Every patient had a reduction in depression severity one week after the high-dose session. Week 2 showed the most significant results. Eight of the twelve patients (67%) achieved complete remission at week one, and five of these (42%) were still in remission at three months.
Although this was a study with a small sample size and no control group, it is promising that many of these treatment-resistant patients achieved remission of their depression. More studies are needed to confirm what was gleaned from this study, but it appears that psilocybin can be safely administered to patients who are appropriately screened and receive adequate support.
Anxiety and depression are prevalent in today’s society. Many of our traditional antidepressant medications take weeks to work and are often ineffective. Psilocybin shows promise in the management of those with treatment-resistant anxiety and depression.
Psilocybin is also associated with only minor side effects. It does not typically cause compulsive drug-seeking behaviors and is relatively non-toxic.
In addition to the studies mentioned above, psilocybin has also had positive effects on smoking cessation.9
It has also been shown to significantly decrease alcohol consumption in alcoholic patients.10
More studies need to be conducted to determine the optimal dose and frequency of psilocybin administration in treating psychiatric disorders. One thing is certain; we desperately need more treatments for anxiety and depression.
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As always, have a happy week and stay safe!
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- Mitchell AJ, Chan M, Bhatti H, Halton M, Grassi L, Johansen C, Meader N. Lancet Oncol. 2011 Feb; 12(2):160-74.
- Arrieta O, Angulo LP, Núñez-Valencia C, Dorantes-Gallareta Y, Macedo EO, Martínez-López D, Alvarado S, Corona-Cruz JF, Oñate-Ocaña LF. Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol. 2013 Jun; 20(6):1941-8.
- Psychological distress and cancer survival: a follow-up 10 years after diagnosis. Brown KW, Levy AR, Rosberger Z, Edgar L. Psychosom Med. 2003 Jul-Aug; 65(4):636-43.
- Review A comprehensive review of palliative care in patients with cancer. Jaiswal R, Alici Y, Breitbart W. Int Rev Psychiatry. 2014 Feb; 26(1):87-101.
- Freedman R. Abrupt withdrawal of antidepressant treatment. Am J Psychiatry. 2010 Aug; 167(8):886-8.
- Review of pharmacological treatment in mood disorders and future directions for drug development. Li X, Frye MA, Shelton RC. Neuropsychopharmacology. 2012 Jan; 37(1):77-101.
- Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165-1180.
- Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17. PMID: 27210031.
- Johnson MW, Garcia-Romeu A, Cosimano MP,Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.J Psychopharmacol. 2014; 28: 983-992.
- Bogenschutz MP, et al. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.J Psychopharmacol. 2015; 29: 289-299.