Executive summary #

Anxiety is prevalent in cancer patients and survivors, and is associated with poorer outcomes. There is no specific guidance for the treatment of cancer-related anxiety. For generalised anxiety disorder, NICE recommends the selective serotonin reuptake inhibitor (SSRI) sertraline, however meta-analyses of antidepressants have failed to demonstrate a treatment effect over placebo in cancer patients. Few novel pharmacological interventions are being investigated in this area.

Psilocybin is a naturally-occurring, serotonergic psychedelic compound produced by fungi whose scientific and clinical research has been growing significantly in the last ten years. Because of psilocybin’s mood enhancing effect, one of the therapeutic areas of interest is in the modulation of anxiety and depression, particularly in cancer patients and those with life-threatening illnesses.

A review of the clinical evidence base identified three independent phase 2 randomised controlled trials (RCTs) in a total of 92 patients (mostly female and Caucasian, mean age ~55 years) with advanced cancer and anxiety. In these patients, an acute dose of psilocybin (0.2-0.4mg/kg, oral, capsule, administered in a supervised 6 hour session) caused significant and long-lasting improvements in various measures of anxiety and depression. Preclinical data suggests this is primarily driven by 5-HT2A receptors. Long-term (uncontrolled) follow up data suggests that the positive effects of psilocybin are sustained for up to 4 years. Multiple physical and psychological adverse effects were observed with psilocybin administration, but none were serious, requiring pharmacological intervention, or with long-lasting effects. This evidence warrants further dose-ranging research in larger patient numbers in a parallel arm, controlled design.

Microdosing is a relatively new phenomenon where individuals ingest smaller quantities of psychedelics (between 5-10% of a recreational dose) for therapeutic or wellbeing purposes. An online questionnaire of 887 microdosers found that individuals perceive microdosing to be more effective for the amelioration of mental health symptoms than current medications (Hutten et al., 2019). A very limited amount of preclinical data supports this observation. This suggests lower frequent dosing of psilocybin may be effective at reducing cancer-related anxiety, although this remains to be tested through controlled clinical research.

Based on the analysis of the current literature on the anxiolytic effects of psilocybin, future research should be conducted in otherwise medically healthy cancer patients with an anxiety disorder via the Diagnostic and Statistical Manual of Mental Disorders (DSMIV- TR; American Psychiatric Association, 2000) criteria. Possible cohorts could be those at end of life in a palliative care setting, patients with advanced cancer with a prognosis <1-2 years, or cancer survivors living with anxiety. Although these is no current evidence to stratify which patients for whom psilocybin might be most effective, consider female cancers where anxiety prevalence is high. Suitable endpoints include State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale and Beck Depression Inventory-II.

The gaps in the current evidence base that could be answered by future research include whether pure psilocybin or a standardised extract is superior, what the therapeutic window is for acute dosing, how long the effects of a single dose of psilocybin last, whether an acute dose of psilocybin could help treat end of life mental distress and whether repeated microdosing induces an anxiolytic effect. Further details on these recommendations are outlined in the report.

There are 27 active registered clinical trials (all phase 1-2) on clinicaltrials.gov investigating the therapeutic potential of psilocybin, but only one of these is in a cancer setting. All are using a single dose of a fixed quantity of psilocybin and none of the registered studies are investigating microdosing. Only one company (COMPASS Pathways) has active clinical research ongoing.

Several notable studies have been outlined in the PDF below.