Mental health disorders such as depression and anxiety are major contributors to the overall global health burden. COVID-19 has further aggravated mental health disorders and also increased substance abuse due to lockdowns1. The Global Burden of Disease reported that the pandemic has led to a 27.6% increase in cases of major depressive disorder (MDD) and a 25.6% increase in cases of anxiety disorders2. An estimated 137.1 (95% UI: 92.5–190.6) additional disability-adjusted life years per 100 000 population for MDD and 116.1 per 100,000 population (95% UI: 79.3–163.80) for anxiety disorders have been incurred, as well, during this period3. Nearly 10%–30% of individuals with MDD have treatment-resistant depression, which has an inadequate response to at least 2 trials of antidepressants. These patients often have adverse behavioral outcomes such as suicide and self-injurious behavior4. With the dynamic nature of SARS-COV-2 that requires measures such as social distancing measures and lockdowns to be placed unexpectedly at different times of the year, interventions that are easily obtainable and can be applied independently by individuals can be immensely useful. Psilocybin, in recent studies, has shown promising results in the remission of depression and if its effectiveness is accurately gauged, could prove to be one such option, giving patients with mental health issues the ability for self-reliant care.
Psilocybin, informally known as the magic mushroom, has been employed in a variety of religious rites throughout history and is believed to possess therapeutic properties5. It is a serotonergic hallucinogen with promising benefits in the treatment of mental illness. It has been proven to decrease substance abuse such as smoking and drinking and reduce depression and anxiety in cancer patients while also improving their emotional well-being6–8. Psilocybin-assisted psychotherapy has proven to be more effective than psychotherapy and pharmacotherapy alone. Previous pharmacotherapies, such as ketamine, have demonstrated negative side effects and have low rates of depression remission9. A systematic review of 60 studies on the side effects of ketamine identified psychiatric, psychotomimetic, cardiovascular, and neurological side effects that were most frequently reported in acute dosing of ketamine10. Most commonly reported acute psychiatric side effects were reportedly anxiety, dissociation being the most psychotomimetic effect. Increased heart rate and raised blood pressure are the most frequent cardiovascular outcomes and headache and dizziness are some of the most common neurological side effects of ketamine. Kemp11 highlighted metabolic disorders such as weight gain and sedation and somnolence as one of the most common adverse effects of pharmacotherapy in treating bipolar depression. These side effects reduce adherence to treatment and reduce the clinical response of pharmacotherapies.
However, psilocybin has low toxicity and addictive potential5. Although the precise mechanism of action of psilocybin is unknown, a randomized clinical trial found that it had a persistent and fast antidepressant effect when compared with escitalopram, as well as improved global brain integration12.
The article by Davis et al6 entitled “Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial” has piqued the interest of the entire psychiatric community. The author highlights a novel finding of significant decreases in or remission of depression in people with MDD with Psilocybin-assisted therapy. A total of 27 participants were recruited, 11 of whom underwent immediate therapy while 13 underwent delayed therapy after 8 weeks. Psilocybin was administered in 2 sessions, with the first session being a moderate dose (20 mg/70 kg) and the second session containing a high dose (30 mg/70 kg). There was a significant decrease in depression in weeks 1 and 4 of follow-up in immediate treatment compared with weeks 5 and 8 of delayed treatment that had not started the therapy. Seventeen participants showed a >50% decrease in depression in weeks 1 and 4; 14 participants in week 1 and 13 participants in week 4 showed complete remission of depression. This study highlights potential breakthrough evidence that is beginning to emerge regarding psilocybin’s use. In January 2022, Rucker et al’s phase 1 trial results delineated that Psilocybin in doses of 10 or 25 mg, respectively, had no short-term or long-term detrimental effects on participants making the case for it being a plausibly relevant and safe alternative to other psychiatric treatments13.
However, for nearly 50 years, psychedelics had been prohibited for medical use owing to rigorous drug control policies and strongly held stigmatic beliefs labelling them as illicit recreational drugs only with no potential for medical benefit. Recent studies, on the other hand, have shown that psychedelics can alleviate depression and anxiety, but mental health professionals are still wary of using them for medicinal purposes14. This, in part, is because there was a lack of research regarding their efficacy, which when combined with the extreme scheduling of these drugs by law, has led to its widespread clinical use being, at best, delayed14. While most psychiatrists support its future use, many are concerned about its potential adverse effects. On the other hand, there appears to be a supportive attitude toward psychedelic use for medicinal purposes among the general populace. According to a survey, 63% of Psychedelic mushroom users reported using them for mental well-being but an alarming 19% also reported use after self-diagnosis of a mental disorder15. Nevertheless, there have been some notable shifts in perspective as legal frameworks regarding the use of psychedelics are being revised. Owing to efficacy data suggesting potential therapeutic benefits of these psychedelics, this “psychedelic renaissance” has brought about changes such as the statewide legalization of specific psychedelics, including psilocybin, in Oregon, USA16.
Although Davis et al’s6 findings do pave the way for furthering the discussion, especially as there were no adverse events reported with psilocybin use, results can be overstated due to the study’s small sample size. A survey on self-reported side effects of psilocybin showed that 11% of Psilocybin consumers put themselves or another person at harm, 2.6% behaved in a physically aggressive manner and 2.7% had to seek medical help17. These negative reactions have often been seen in trials where induced stressful situations have led to patients leaving the site18. There must be additional large-scale clinical trials undertaken across a spectrum of mental diseases before they can be definitively included in medical practice and guidelines for their use can be established. In addition, psychiatric comorbidities are a pressing concern that also needs to be addressed. To make results more generalizable, the risk of using psilocybin in this group needs to be explored19.
In a study evaluating the cost effectiveness of methylenedioxymethamphetamine (MDMA) associated psychotherapy in patients with posttraumatic stress disorder including 105 subjects of six double blinded phase 2 trials the MDMA saved 103.2 million dollars over a period of a 30 years and decreased 5553 quality adjusted life years compared with the standard practices20. According to a statement given by the author of this paper to multidisciplinary association for psychedelic studies MDMA has a potential to break even the cost of mental health in just over 3 years21. According to a study conducted by John Hopkins to assess the effect of psilocybin in personality changes, a single high dose of psilocybin was enough to bring about a measurable personality change such as increased openness in nearly 60% of the participants22. However researchers are still cautious of professing the cost effectiveness of psychedelic and require more data over a longer period of time to come to a conclusive finding.
The usage of psychedelics to alleviate anxiety and depression appears to be more pertinent now than ever. This, however, raises concerns about self-medication with psychedelics and their excessive usage. Ensuring psychedelics are obtained only through prescription and not as over-the-counter drugs can be an effective method to curb the self-medication of psychedelics. Campaigns that sensitize individuals regarding the health repercussions of resorting to self-medication should also be held at a large scale. Provision of health insurance has also shown to reduce the incidence of self-medication23 and encourages patients to seek guidance from health care professionals. In addition satisfaction with health care service and a good doctor patient relationship are important predictors of self-medication24,25. Workshops about the use of psychedelics in medicine and their possible risks and advantages should be conducted for psychologists and psychiatrists to assist in breaking down stigma and assisting them in making educated decisions for their patients.
Sources of funding
H.R.: conception of the study, drafting of the work, final approval and agreeing to the accuracy of the work. U.N.: conception of the study, drafting of the work, final approval and agreeing to the accuracy of the work. A.S.: conception of the study, drafting of the work, final approval and agreeing to the accuracy of the work. O.A.S.: conception of the study, drafting of the work, final approval and agreeing to the accuracy of the work.
Conflict of interest disclosures
The authors declare that they have no financial conflict of interest with regard to the content of this report.
Research registration unique identifying number
Hamna Raheel, Unaiza Naeem, Asim Shaikh, and Omer Ahmed Shaikh.
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