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Thinking Differently: The Potential of Psilocybin Therapy To Transform the Mental Healthcare Landscape

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The following article is an opinion piece written by Guy Goodwin. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.

It is estimated that 5% of adults currently suffer with depression globally, often in combination with anxiety. According to a UK publication, it is thought that as many as 10% of the population will experience depression within their lifetime.1

The consequences of mental disorders are far-reaching. Those suffering with conditions such as depression may perform poorly in lots of other areas of life. It is considered a leading cause of disability worldwide and in its most severe form is estimated to reduce life expectancy by 10-20 years compared to the general population.2

The prevalence of these disorders is increasing to crisis levels. There has been a 13% rise in mental health conditions in the last decade.3,4 COVID-19 has exacerbated this trend, particularly in young people. The effects of the pandemic have not yet been fully understood but the isolation produced by lockdown has been shown to have a negative effect on many people’s mental health. It has created new barriers for people already suffering with mental illness.

Depression promotes social withdrawal and a large proportion of people with mental disorders either receive no treatment at all or experience long delays. For those who do receive treatment, current methods are too often inadequate.5

There are two commonly used treatment pathways available to patients with depression. The first is psychological, where therapists guide patients through techniques such as cognitive behavioral therapy (CBT) to address their negative thought patterns. The second is medical, usually by prescribing selective serotonin reuptake inhibitors, or SSRIs. However, the effects of either approach are variable and only help around half of patients who receive treatment.

Where the effects of two or more trials of antidepressants are negligible, patients are said to have treatment-resistant depression. Very commonly, such patients remain in limbo between primary care, where the resources and options are limited, and secondary care, where patients are only admitted in extreme cases.

Despite the evident and growing need for effective mental health treatment there has been a critical lack of innovation in the field. New treatment options are needed to change the present impasse and tackle the growing mental health crisis. Important first steps towards this have been made, with the approval of esketamine as a therapy for treatment-resistant depression. The drug, a derivative of ketamine, is administered as a nasal spray in conjunction with oral antidepressants. More sophisticated brain stimulation therapies are also emerging that stimulate the brain by targeting specific areas with magnetic or electrical waves to help treat depression.   

Recent advances in psilocybin therapy have the potential to turn the page in the mental health crisis. Modern experimental techniques have revealed the mechanisms behind psychedelic compounds and the opportunity to harness that mechanism for medicinal use. Psilocybin, derived from magic mushrooms, was first isolated and identified in 1958 by Albert Hofmann. After a flurry of research in the following decade, medical supplies of the substance dropped as recreational use of the drug was banned. Following a hiatus of 50 years, scientific research has produced psilocybin in a pure and stable form as COMP360 and with a renewed therapy wrapper. We have now started to build evidence of its efficacy and effectiveness.

The process of psilocybin therapy, still under investigation, has three stages. First, patients get to know about the therapy and their therapist in a preparatory session so they can form an informed and trusting relationship. The patient receives their dose of psilocybin in the next session. They are placed in a supportive environment, listening to music and wearing an eye mask to help them focus internally. Two therapists are present throughout the session, which typically lasts 6-8 hours. In the final stage, patients are encouraged to discuss their experience with the therapist.

The promise of psilocybin therapy is unique. It is a hybrid strategy, combining the two treatment pathways currently available to those living with depression, incorporating psychological change and pharmaceutical intervention . Psilocybin is thought to stimulate neuroplasticity in the brain, encouraging new ways of thinking and shifting patient perspective. With the guidance of their therapists in the final session, it is thought that patients can use their experience to help them break fixed habits of unhelpful thinking and behavioral patterns.

Small-scale studies have given early indications of the potential effectiveness of psilocybin therapy but larger, multi-center trials are required to generate the evidence required for medical approval. The release of the COMPASS Pathways phase IIb trial results could mark a significant step on the road to providing safe access to these therapies.

The phase IIb trial is dose finding and investigates the effectiveness of the proprietary, synthesized formulation of psilocybin, COMP360, in patients with treatment-resistant depression. It involved 233 patients living with the disorder – the largest sample size for any trial investigating psilocybin or similar therapy. The study aims to provide the first instance of statistically powerful, scientifically rigorous evidence of psilocybin therapy’s effectiveness in treating a mental health condition.

COVID-19 has made the progression of studies like this one all the more important. It is a remarkable achievement that the study has progressed during and despite the pandemic and demonstrates the commitment of all staff and clinicians involved in the trial. Patients too have made sacrifices, disrupting their existing treatments to participate in the trial. The ease of patients withdrawing from the antidepressants they were previously on speaks to the acceptability of psilocybin therapy in the community and the sense of excitement at the idea of a potential new mental health care therapy.

The results will pave the way for larger phase III trials expected to begin in 2022. This is the next step on the journey in providing access to this therapy for those living with this debilitating condition. However, psilocybin therapy is not simply “antidepressant”. The treatment has more general effects that could, in time, be applied to other disorders. Any illness that involves repetitive, stuck thinking or behavior could benefit from psilocybin therapy; these will include eating disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The prospect of harnessing this powerful neurobiology has significant potential in treating many of the most serious mental disorders. If approved, psilocybin therapy may provide the tipping point to a new way of thinking about mental health care, stimulating innovation across conditions and benefitting a huge number of patients. This is only the beginning.

References

  1. Mental Health Foundation. Mental health statistics: the most common mental health problems (2021). Available at https://www.mentalhealth.org.uk/statistics/mental-health-statistics-most-common-mental-health-problems. Accessed October 2021.
  2. World Health Organization Europe. Fact sheets on sustainable development goals: health targets. Mental Health (2018). Available at https://www.euro.who.int/__data/assets/pdf_file/0017/348011/Fact-sheet-SDG-Mental-health-UPDATE-02-05-2018.pdf. Accessed October 2021.
  3. World Health Organization. Health topics, Mental health. Available at https://www.who.int/health-topics/mental-health#tab=tab_2. Accessed October 2021.
  4. McManus S, Meltzer H, Brugha T, Bebbington P, Jenkins R (eds), 2009. Adult Psychiatric Morbidity in England 2007: results of a household survey. NHS Information Centre for Health and Social Care. [online] Available at: https://digital.nhs.uk/data-and-information/publications/statistical/adult-psychiatric-morbidity-survey/adult-psychiatric-morbidity-in-england-2007-results-of-a-household-survey [Accessed 27 October 2021].
  5. Cuijpers P, Stringaris A, Wolpert M, 2020. Treatment outcomes for depression: challenges and opportunities. The Lancet Psychiatry. 7(11):925-927. doi: 10.1016/S2215-0366(20)30036-5.