Serious illness is a significant psychological burden
Feelings of hopelessness, loss of will to live, loss of meaning and dignity, feeling of being a burden to others. Sadness and fear. These are the symptoms of existential distress (Reiche et al 2018), which significantly reduces the quality of life of patients and their loved ones. Depression, anxiety or adjustment disorder occur in 29% of patients in palliative care and in 38% of patients in oncology and hematology care (Mitchell et al. 2011).
Current treatment options for existential distress are limited
A review and meta-analysis of the efficacy of standard antidepressant pharmacological therapy in early and advanced stage cancer patients (10 research studies, 885 patients) did not show any difference between the active substance (SSRIs and TCAs) and placebo (Ostuzzi et al. 2018).
Although the authors of an earlier meta-analysis (Rayner et al. 2011) focused on palliative care (25 studies, 1197 patients with different diagnoses) confirmed the difference in effect between antidepressants and placebo, they acknowledge that the result may be overestimated by selective publication.
Psychooncological interventions (psychotherapy, counselling, relaxation, etc.) have a small to medium effect in oncological patients (198 studies, 22238 patients) on alleviating mental suffering and improving quality of life (Faller et al. 2013), but are time consuming and not easily available.
Research into psychedelic-assisted psychotherapy is yielding promising results
Current research confirms the safety of psychedelics and suggests an unprecedented efficacy of psychedelic-assisted psychotherapy in alleviating anxiety and depression in patients with advanced stages of predominantly oncological diseases (Reiche et al 2018).
Three recently completed studies (double-blind, placebo-controlled) evaluated the effect of a single administration of psylocibyn at a dose of 0.2-0.3 mg/kg. The actual administration of the substance was always preceded by 4-6 hours of preparatory sessions and followed by 8-10 hours of integrative sessions.
The first study (n = 12) was conducted by a team led by Charles Grob at the University of California Los Angeles (Grob et al. 1999), the second study (n = 51) was led by Roland Griffiths at Johns Hopkins University, Maryland (Griffiths et al. 2016), the third study with 29 patients was consucted by Stephen Ross at New York University (Ross et al. 2016). These studies described a rapid, significant, and long-lasting effect accompanied by an improvement in quality of life in 60-80 % of participants even at 6 months after the therapy.
Sustained relief of anxiety and depression was seen in 60-80 % of surviving patients in the third study even after 4.5 years (n = 14). Most of them (71-100%) attributed positive changes in the quality of life to psilocibyn-assisted psychotherapy, ranking it among the most fundamental and meaningful life experiences (Agin-Liebes et al 2020).
The only modern study evaluating the effect of LSD-assisted psychotherapy on anxiety associated with a life-threatening illness was conducted by Peter Gasser in Switzerland. The study confirmed the safety of the method and the long-term reduction of anxiety in 12 participants/patients (Gasser et al 2014).
A pilot open-label study of psilocybin-assisted psychotherapy of 18 patients with AIDS confirmed feasibility, relative safety, and potential efficacy for demoralization symptoms. The team of Brian Anderson of UCSF introduced a new model of group preparation and integration (Anderson et al. 2020).
First double-blind placebo-controlled study of MDMA-assisted psychotherapy of 18 persons led by Philip Wolfson took place in California. The results suggest an effect on anxiety and other symptoms associated with life-threatening illness (Wolfson et al 2020).
Research on psychedelic-assisted psychotherapy in patients with advanced oncological diseases builds on the findings of studies from the 1950s-1970s, which do not meet the requirements of the current rigorous methodology. However, they include well-written case reports and valuable guidelines for therapeutic practice (Kast, 1966; Kast and Collins, 1964; Pahnke et al., 1969; Grof et al, 1973; Richards et al. 1980).
Agin-Liebes GI, Malone T, Yalch MM, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020;34(2):155-166.
Anderson BT, Danforth A, Daroff PR, Stauffer C, Ekman E, Agin-Liebes G, Trope A, Boden MT, Dilley PJ, Mitchell J, Woolley J. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine. 2020 Sep 24;27:100538.
Faller H, Schuler M, Richard M, Heckl U, Weis J, Küffner R. Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. J ClinOncol. 2013;31(6):782-793.
Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, Brenneisen R. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis. 2014 Jul;202(7):513-20.
Griffiths, R.R., Johnson, M.W., Carducci, M.A., Umbricht, A., Richards, W.A., Richards, B.D., Cosimano, M.P., Klinedinst, M.A., 2016. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol. 30, 1181-1197.
Grob, C.S., Danforth, A.L., Chopra, G.S., Hagerty, M., McKay, C.R., Halberstadt, A.L., Greer, G.R., 2011. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch. Gen. Psychiatry 68, 71-78.
Grof S, Goodman LE, Richards WA, Kurland AA. LSD-assisted psychotherapy in patients with terminal cancer. Int Pharmacopsychiatry. 1973;8(3):129-144.
Kast, E. (1966) LSD and the dying patient. The Chicago Medical School quarterly 26: 80-7.
Kast, E. C., Collins, V. J. (1964) Study of lysergic acid diethylamide as an analgesic agent. Anesthesia and analgesia 43: 285-91.
Mitchell, A.J., Chan, M., Bhatti, H., Halton, M., Grassi, L., Johansen, C., Meader, N., 2011. Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol. 12, 160-174.
Ostuzzi, G., Matcham, F, Dauchy, S., Barbui, C, Hotopf, M. Antidepressants for the treatment of depression in people with cancer. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD011006.
Pahnke, W.N., Kurland, A.A., Unger, S., Savage, C., Wolf, S., Goodman, L.E., 1970 Psychedelic therapy (utilizing LSD) with cancer patients. J. Psychedelic Drugs 3, 63-75.
Rayner L, Price A, Evans A, Valsraj K, Hotopf M, Higginson IJ. Antidepressants for the treatment of depression in palliative care: systematic review and meta-analysis. Palliative Medicine 2011; 25(1): 36-51.
Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majić T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:1-10.
Richards WA, Rhead JC, Grof S, Goodman LE, Di Leo F, Rush L. DPT as an Adjunct in Brief Psychotherapy with Cancer Patients. OMEGA - Journal of Death and Dying. 1980;10(1):9-26.
Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S.E., Belser, A., Kalliontzi, K., Babb, J., 2016. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 30, 1165-1180.
Wolfson PE, Andries J, Feduccia AA, Jerome L, Wang JB, Williams E, Carlin SC, Sola E, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep. 2020 Nov 24;10(1):20442.