Introduction
What is psychedelic therapy?
What is psilocybin?
The safety of psilocybin: evidence from trials
Psilocybin-assisted therapy for anxiety and depression associated with cancer
Psilocybin-assisted therapy for treatment-resistant depression
Psilocybin-assisted therapy for obsessive-compulsive disorder (OCD)
References
Further reading
Psilocybin-Assisted Therapy refers to the use of psilocybin, the active ingredient in psilocybin mushrooms, in the context of pharmacotherapy. It represents one of several forms of psychedelic therapy, and is currently not a standard medical practice – in many parts of the world, it is considered illegal.
There has been a renewed interest recently in psychedelic research as a result of contemporary studies demonstrating the safety and possible benefit of psychedelic drugs in psychiatric illnesses.
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Preliminary clinical results have so far demonstrated safety and efficacy, particularly among “treatment-resistant” conditions. As such, they have garnered increasing attention in the medical, psychiatric, and psychological fields.
Psilocybin is a classic hallucinogen with combined serotonergic and glutamatergic action. This makes psilocybin an attractive candidate for therapeutic approaches to neurological disorders. Preliminary evidence of the anti-depressive effects of psilocybin-assisted therapy, as documented among patients with life-threatening cancer or treatment-resistant depression, indicates psilocybin-assisted therapy is a novel form of antidepressant intervention.
Ketamine is also considered to be a novel form of therapy for neurological mood disorders; however, it is associated with long-term perceptual, neurological, and cognitive dysfunction, which makes psilocybin-assisted therapy the preferred option. This is particularly true as psilocybin has a lower liability for addiction and less toxic effects compared to ketamine.
What is psychedelic therapy?
Psychedelic therapy is an umbrella term that describes the professionally supervised use of psychedelic drugs such as ketamine, LSD, DMT, MDMA, psilocybin, and others in opposition to the use of conventional psychiatric medicine. In this form of therapy, patients remain in extended psychotherapy sessions during which the activity of the drug takes effect. Psychedelics are a class of hallucinogenic drugs that primarily stimulate non-ordinary states of consciousness.
What is psilocybin?
Psilocybin is known colloquially as magic mushrooms and is a tryptamine-related plant alkaloid that is found in many species of mushrooms that belong to the genus Psilocybe. Once ingested, it is dephosphorylated to produce psilocin, which is a mimetic of serotonin or hydroxytryptamine.
It exerts its effect via the antagonism of the 5-HT2A receptor. In humans, it results in a temporary state of altered consciousness. This state is characterized by perceptual alterations and disturbance of mood (‘affective’ effects). Psilocybin also results in a thought disorder that is traditionally associated with dreams and religious exaltation. Multiple recent studies conducted in healthy volunteers, as well as subpopulations of patients with psychiatric disorders, have demonstrated good tolerability and minimal adverse effects.
The safety of psilocybin: evidence from trials
According to an analysis of raw data obtained from 8 double-blind, placebo-controlled trials conducted between the years 1999 and 2008 in Switzerland, it was concluded that psilocybin is generally well-tolerated, both short and long term, by healthy volunteers. A total of 277 individual psilocybin sessions conducted on 110 subjects were evaluated to assess several physical and psychological symptoms.
The most common short-term adverse effects included lack of energy/ fatigue and headaches. These adverse effects, however, tended to be resolved in the first few weeks following drug administration. Moreover, no change in drug-seeking behavior, persisting perception disorder, long-term psychosis, or impaired function was observed in all subjects. Notably, only one subject required subsequent professional help for emotional instability, anxiety, and depression, which persisted for several weeks after the experiment. Following psychotherapy, this subject recovered and did not relapse.
The relationship between psilocybin and headaches was also verified in a separate study. As psilocybin is a serotonin receptor modulator, it shares similar structural characteristics with migraine medication – this presents the basis for the prevalence of headache as one of the most common adverse effects of psilocybin use. This group concluded that these headaches were not disabling or severe in the 18 healthy volunteers examined; moreover, no other significant adverse effects were reported.
Related: What is Psychedelic Microdosing?
Psilocybin-assisted therapy for anxiety and depression associated with cancer
There are few pharmacological treatments for patients suffering clinically significant and disabling depressive and anxiety disorders as a result of cancer. Conventional antidepressants show limited efficacy relative to placebo.
In 2010, a group from the Harbour-UCLA medical center investigated the safety and efficacy of psilocybin in treating 12 subjects with advanced-stage cancer. No statistically significant reduction in modal anxiety was observed; however, this study demonstrated that psilocybin could be administered safely with no reported clinically significant effects.
In 2016, two more studies compared psilocybin dose (very low versus very high) in 51 patients with advanced-stage cancer. The group found that 92% of participants showed clinical remission or a 50% reduction in the symptoms. Moreover, subjects continued to show reduced symptom severity or remission five weeks post-experiment and all adverse events were non-serious.
These studies, however, show selection bias and sub-optimal blinding - this is associated with the unique effect of psychedelic substances and is difficult to overcome even when using an active placebo, for example, niacin, which produces similar effects. Despite limitations, studies have demonstrated feasibility and safety - with the potential to alter the paradigm for treating psychiatric disorders in particular populations with unmet needs.
Psilocybin-assisted therapy for treatment-resistant depression
An open-label, non-controlled study of 12 patients which investigated the benefits of psilocybin in treatment-resistant depression demonstrated that 67% of patients received clinical remission, while 58 continued to meet the criteria for response three months following therapy. All patients had moderate to severe depression and had shown no prior improvement in their symptoms after two trials of antidepressants from different pharmacological classes.
In addition, no serious adverse events were observed; ‘mild’ adverse events included anxiety, mild thought disorder, mild nausea, headache, and transient confusion. This side effect profile compares positively to currently available treatment alternatives such as electroconvulsive therapy and vagal nerve stimulation. As such, psilocybin shows potential, particularly in the treatment of treatment-resistant depression.
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Psilocybin-assisted therapy for obsessive-compulsive disorder (OCD)
Approximately 40 to 60% of patients do not respond to SSRI medication for OCD. Even when patients switch to other forms of SSRIs and are complemented with cognitive behavior therapy, a significant proportion remain treatment refractory. At this point, alternative drug treatments such as electroconvulsive therapy, neurosurgery, or transcranial stimulation are considered. However, there is an inherent risk associated with these late-stage options, as they are invasive.
Psilocybin was studied in 9 subjects with OCD in a study conducted by the University of Arizona. All subjects had previous exposure to psychedelics and did not receive any antidepressant treatment for at least two weeks before psilocybin. When researchers aggregated results from four escalating doses of psilocybin administered in random order from very low to high, there was a 23 to 100% reduction in symptoms 24 hours following exposure. This preliminary study demonstrated a transient and acute benefit of psilocybin in patients with refractory OCD.
References
- Moreno FA, Wiegand CB, Taitano EK, Delgado PL. (2006) Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. doi: 10.4088/jcp.v67n1110. PMID: 17196053.
- Thomas K, Malcolm B, Lastra D. (2017) Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders. J Psychoactive Drugs. doi: 10.1080/02791072.2017.1320734.
- Davis AK, Barrett FS, May DG, et al. (2021) Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2020.3285.
- Griffiths RR, Johnson MW, Carducci MA, et al. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. doi:10.1177/0269881116675513.
Further Reading
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