Psychedelic science in post-COVID-19 psychiatry

This commentary (2020) examines how the COVID-19 pandemic has affected the trajectory of clinical trials investigating psilocybin treatment for a wide range of conditions, some of which are likely to become even more prevalent in post-COVID-19 clinical psychiatry. Although many of these clinical trials have been temporarily stagnant due to safety measures, ongoing efforts from large scale clinical studies of psilocybin will provide valuable information on its safety, dose optimization, and its efficacy compared to a conventional selective serotonin reuptake inhibitor (SSRI) and additional studies will elucidate whether it is safe to combine them with psilocybin therapy.

Abstract

“Introduction: The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.”

Authors: J. R. Kelly, M. T. Crockett, L. Alexander, M. Haran, A. Baker, L. Burke, C. Brennan and V. O’ Keane

Summary

Crises induce a wide range of psychological reactions, with varying degrees of adaptability. The COVID-19 pandemic may cause increased psychological and psychiatric problems, with an excess burden on vulnerable groups.

Psilocybin therapy may be effective in the treatment of depression, obsessive compulsive disorder and addiction disorders, and there may be a role for psilocybin therapy in the treatment of anxiety disorders.

Recent advances in psychedelic science are gradually unravelling the multimodal mechanisms underlying the therapeutic effect of psilocybin therapy. Psilocybin alters an individual’s state of consciousness, probably through agonist mechanisms at the 5-HT2A receptor, especially in the deep pyramidal cells in the cortex.

Psilocybin therapy provides a translatable, transdiagnostic treatment strategy that can be further refined by a precise-personalised approach. Moreover, a dimensional framework that aligns with bio-psycho signatures may also be leveraged to enhance the targeted application of psilocybin therapy.

Despite limitations, preclinical data suggest that serotonergic psychedelics, including psilocybin, can induce hippocampal neurogenesis, promote dendritic spine growth and stimulate synapse formation in the prefrontal cortex.

Researchers from Johns Hopkins University studied the claustrum, a thin sheet of grey matter embedded in the white matter of the cerebral hemispheres, and found that psilocybin altered activity and connectivity in this region.

In an open-label pilot study, 12 healthy volunteers showed reduced negative affect and amygdala responses to emotional stimuli, whereas in a larger study, 19 subjects with treatment-resistant depression showed increased amygdala responses and decreased functional connectivity.

In the midst of the ‘Psychedelic Revolution in Psychiatry’ and potential increasing recreational psychedelic use, the Royal Australian and New Zealand College of Psychiatrists published a clinical memorandum on the therapeutic use of psychedelic substances.

Results from the Global Drug Survey (2019) showed that only 18% of people who have never used psychedelics would accept psilocybin therapy for depression or PTSD, and that 59% of people who had previously tried psychedelics would accept it. However, high-quality clinical data is lacking.

HPPD may be caused by arousal-altering drugs, including non-hallucinogenic substances. However, regular psychedelic use may have a limited impact on the brain.

Dublin is one of the clinical trial centres participating in a double-blind randomised controlled phase 2b COMPASS trial of psilocybin therapy in treatment-resistant depression. The trial will address concerns regarding psilocybin safety, efficacy and dose optimisation, and will also examine the effects of psilocybin therapy in conjunction with SSRIs.

A new study will be launched in Dublin and San Diego to determine the antidepressant effect of psilocybin therapy in people with TRD who continue SSRI medication. The results of this study may have important practical implications for the future of psilocybin therapy.

Clinical and research psychiatry have been transformed by COVID-19, and additional strategies are needed to overcome the considerable challenges. These include respiratory symptom checklists, regular temperature checks, access to COVID-19 testing, and meticulous attention to extra hygiene measures.