Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress

This systematic review (2018) investigated studies that used psychedelics for the treatment of psychological distress related to cancer. It found 10 studies (n=445) that qualified of which four (n=104) were randomized controlled trials. Overall studies showed improvements in anxiety, depression, and fear of death.

Abstract

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960–2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.

Authors: Stephen Ross

Summary

Early-phase clinical research suggested that serotoninergic psychedelics (e.g. psilocybin, LSD) may be useful in treating cancer-related psychiatric distress. More recent research has demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.

Introduction

This article will systematically review the literature on the clinical use of serotoninergic psychedelics to treat cancer-related psychiatric distress. Although the use of psychedelics in cancer treatment is still in its incipiency, promising early-phase clinical research suggests promising results.

In the past decade, clinical trials have resumed using classic hallucinogens to treat various psychiatric illnesses and addictive disorders. The most studied indication is the use of psilocybin and LSD to treat cancer-related psychiatric disorders.

Search methodology

This review article uses a similar methodology as a recent systematic review of the use of serotoninergic psychedelics to treat depression and anxiety in patients with a life-threatening illness, but extends the search period until 1 February 2018 and focuses on the use of classical hallucinogens to treat patients with cancer diagnoses.

In a search of 10 clinical trials, we identified six open-label trials and four randomized controlled trials about the use of LSD, psilocybin, and DPT in patients with cancer-related psychiatric distress.

Prevalence and impact of psychiatric disorders (depression, anxiety, adjustment disorder) in cancer

The most common psychiatric disorders in cancer patients are depressive and anxiety spectrum disorders, as well as adjustment disorders. These disorders are associated with poor outcomes, including decreased quality-of-life, decreased social function, increased disability, medication non-adherence, increased emergency room visits and hospital stays, and suicide.

Impact of spiritual/existential distress in cancer patients, and existentially-based psychosocial treatment interventions

Dame Cicely Saunders and Victor Frankl emphasized the importance of existential and spiritual domains in individuals with terminal cancer diagnoses as symptoms of mental distress and treatment targets.

Patients with advanced or terminal cancer experience clinical symptoms of existential distress. These patients are at increased risk for adverse outcomes, including increased anxiety and depressive symptoms, increased desire for hastened death, increased suicidal ideation and behaviours, increased pain perception, increased healthcare visits, and decreased quality-of-life.

Mid 1950s to early 1960s

Valentina Wasson and Aldous Huxley were the first westerners to suggest the therapeutic effects of serotoninergic hallucinogens to alleviate emotional suffering associated with the dying process. The Wassons introduced psilocybin into western culture and medicine, and Huxley himself used LSD to ease his dying process.

1960s to early 1970s

Eric Kast MD, a psychiatrist and internist at the University of Chicago’s School of Medicine, conducted a comparative efficacy trial of LSD (100 mcg orally) compared to two oral opioids (Dilaudid 2 mg or Demerol 100 mg) in 50 severely medically ill patients. The LSD group had statistically significant reductions in pain.

Kast studied the anti-pain effects of LSD on 208 patients with terminal cancer and pain syndromes in an open-label design and found that patients reported decreased pain perception, decreased depressed mood, improved morale and outlook on life, decreased fear of cancer diagnoses and death, improved sleep, and reports of mystical-type experiences.

In the mid-1960s to mid-1970s, researchers at the Spring Grove State Hospital in Maryland began researching LSD-assisted psychotherapy to treat patients with alcoholism. After one of the nurses on the research team became ill with advanced breast cancer, the researchers decided to shift their focus towards LSD-assisted psychotherapy to help patients with terminal cancer-related psychological and existential distress. A total of 83 patients participated in open-label trials, of which 53 received high-dose oral LSD and 30 were administered intramuscular dipropyltryptamine. The trials demonstrated that 71% of participants were either dramatically improved or moderately improved.

Clinical research utilizing hallucinogens ceased in the early 1970s, but basic neuroscience research continued, and has contributed considerably to understanding basic mechanistic processes of the classic hallucinogens.

to treat cancer-related psychiatric illnesses (early 2000s–present)

Human research with the serotoninergic psychedelics resumed in the early 1990s, and a significant amount of data has been collected thus far on the use of psychedelics to treat cancer-related psychiatric illnesses.

Phase II trial: LSD-assisted psychotherapy for anxiety and depression associated with life-threatening disease

Clinical research utilizing LSD-assisted psychotherapy to treat psychological distress associated with life-threatening illnesses resumed in Switzerland with a small RCT. The experimental group had significant short-term reductions in anxiety, and no reported serious adverse medical or psychological outcomes related to LSD administration.

Phase II trials: psilocybin-assisted psychotherapy for cancer-related psychiatric disorders

RCTs utilizing psilocybin-assisted psychotherapy to treat psychological and existential distress associated with advanced or terminal cancer have resumed at three US academic medical centres.

Three RCTs were conducted to evaluate the effects of moderate-to-high-dose psilocybin on cancer-related anxiety and depression. These RCTs used double-blind design methodology, active placebo control, validated outcome measures, cross-over methodology, careful preparation of participants, and integration of the experience after the experimental sessions.

The three studies differed in the dose of psilocybin, the active control, the inclusion of non-terminally ill cancer patients, and the typology of cancer-related psychiatric distress.

In 2011, UCLA conducted a small cross-over trial to assess the efficacy of psilocybin-assisted psychotherapy in patients with cancer-related psychiatric distress. The trial demonstrated feasibility of recruitment and safety, with no psilocybin-related serious psychiatric or medical adverse events. The study failed to demonstrate significant between-group differences in terms of reduction of anxiety and depressive measures (prior to the cross-over at 2-weeks), but there were acute trends for reductions in anxiety and depression in the psilocybin-1st group over the niacin-1st group.

A cross-over trial was conducted at JHU and NYU Langone to compare a single high-dose of psilocybin to an active control for cancer-related depression and anxiety.

Psychiatric disorders were treated with psilocybin, including Major Depressive Disorder (MDD), Adjustment Disorder with Anxiety, Adjustment Disorder with Anxiety and Depression, Generalized Anxiety Disorder, and Dysthymic Disorder. High-dose psilocybin produced large and sustained improvements in depressive and anxiety symptoms associated with cancer, and improved quality-of-life, death acceptance, life meaning, and optimism. These effects were sustained at the final 6-month follow-up assessment. Psilocybin produced mystical-type experiences in both terminally ill cancer patients and normal volunteers, which correlated with and partially mediated the anxiolytic and anti-depressant effects of psilocybin.

The NYU Langone trial compared psilocybin to niacin in 29 individuals with life-threatening cancers. No SAEs were reported, and the most scientifically rigorous findings were that psilocybin was safe and effective for treating cancer-related anxiety and depression.

Psilocybin produced rapid, substantial, and sustained improvements in anxiety and depressive symptoms associated with cancer, compared to niacin, up to 7-weeks post single dosing. Psilocybin produced statistically significant improvements in quality-of-life, spiritual well-being, and existential distress at the final 6.5 month follow-up, in addition to an improvement in attitudes towards death and dying. In two RCTs, the psilocybin induced mystical experience was found to correlate with and partially mediate the anti-depressant and anxiolytic effects of psilocybin.

Historical early-phase research

This review identified 10 published clinical trials where serotoninergic psychedelics were studied in the treatment of cancer-related psychiatric illness. Six trials were published between 1964 and 1980 and predominantly studied LSD and reported improvements in cancer-related depression, anxiety, and fear of death.

Recent middle-phase RCT research

The promising findings from the early open-label trials using psilocybin to treat cancer-related psychiatric disorders set the stage for the next phase of research using psilocybin to treat cancer-related psychiatric disorders. The trials demonstrated correlation and partial mediation between the psilocybin occasioned mystical experience and therapeutic outcomes.

Advanced phase research (the future): phase III clinical trials, re-scheduling, and licensed psychedelic treatment clinics

The data from three trials has set the stage for proposed FDA phase III trials of psilocybin for MDD. These trials would focus on cancer patients with MDD and the general population. If the trials demonstrate a statistically and clinically meaningful therapeutic effect of psilocybin-assisted treatment (vs placebo) in patients with MDD, it could potentially lead to the re-scheduling of psilocybin out of the most restrictive category and into a category where it becomes available for therapeutic use in clinical populations. Psilocybin would likely be dispensed and administered in specially designated and certified psychedelic-assisted treatment clinics, with strict protocols to ensure drug accountability, patient safety, and treatment efficacy.

Psilocybin-assisted therapy could provide a novel and revolutionary treatment model for patients with cancer-related psychological and existential distress, including rapid onset of anxiolytic and anti-depressant action, sustained anxiolytic and anti-depressant effects from single dosing, and minimization of side-effects related to having to take an anti-depressant or anxiolytic chronically. Psilocybin can be used early in a cancer diagnosis to prevent progression of psychological symptoms, and may even protect against cancer disease progression.

Existential distress is under-recognized and undertreated in cancer patients. Psilocybin-assisted treatment could be a useful intervention for patients as they approach death, and could occasion a ‘good’ death process.