Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in endstage cancer, Rafael Guimarães dos Santos et al., 2019

Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in endstage cancer

Rafael Guimarães dos Santos, José Carlos Bouso and Jaime E. C. Hallak

BMC Psychiatry, 2019, 19, 321



In a recent issue of the BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was reviewed (Johnson, 2018). The review was comprehensive, and included traditional and non-traditional/alternative treatments, including herbal medicines and spirituality. However, evidence showing that classic or serotonergic hallucinogens/psychedelics such as psilocybin and lysergic acid diethylamide (LSD) could be effective treatments for depressive and anxiety disorders in end-stage cancer was not included. In this commentary, we expand the information available on the original article by briefly reviewing data from recent placebo-controlled, double-blind, cross-over clinical trials showing evidence that administration of single (or few) doses of LSD and psilocybin was associated with rapid and sustained reductions in depressive and anxiety symptoms in patients with end-stage cancer and other life-threatening diseases (e.g., Bechterew’s disease, Parkinson’s disease, Celiac disease). Since these substances seem to produce rapid and sustained therapeutic effects with single (or few) doses and well tolerated, large-scale, prospective, multi-site studies of end-stage cancer and classical/serotonergic hallucinogens/psychedelics should be performed to improve our understanding of the therapeutic potentials of these drugs and their use on clinical practice.

Keywords : Psychiatry, Psycho-oncology, End-stage cancer care, Depression, Anxiety, Hallucinogens, Psychedelics, Lysergic acid diethylamide, Psilocybin


In a recent review article published on BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was critically and rigorously assessed [1]. The review is a comprehensive evaluation of the state of research in this area, regarding specifically the treatment for delirium, depression and anxiety. The author performed a complex, five-phase systematic strategy to find citations using four databases (PubMed, Medscape, Cochranes, and Oxford), and included “abstracts, reviews, raw reports, observational studies, and (random) controlled clinical trials found relevant”. Importantly, the review included not only conventional pharmacological treatments, but also non-traditional/alternative therapies and spirituality intervention, unlike previous reviews. Therefore, it is a timely and welcome review on an important topic.

However, we observed that the review did not include studies on classical or serotonergic hallucinogens /psychedelics such as lysergic acid diethylamide (LSD) and psilocybin in end-stage cancer. This is somewhat surprising, since these compounds were investigated for treating symptoms of depression and anxiety in patients suffering life-threatening diseases since the early 1960’s [2]. A recent systematic review showed that 11 clinical trials, involving a total of 445 participants, were performed between 1964 and 2016 assessing the effects of serotonergic hallucinogens/psychedelics in this clinical population [2]. Five open-label studies, using LSD or dipropyltryptamine (DPT) (another serotonergic hallucinogen/ psychedelic), were published between 1960 and 2000. Four randomized, double-blind, placebo controlled, cross-over studies, using LSD or psilocybin, were published between 2000 and 2017. The review concluded that “Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens” [2]. Moreover, some studies reported improved quality of life and reduced fear of death in patients, and treatments were well tolerated and associated with low rates of adverse effects.

Since the four more recent trials reviewed in the above-mentioned systematic review (2011–2016) are all randomized, double-blind, placebo-controlled, cross-over clinical trials, only their data will be briefly discussed further [3–7]. In the first of these cross-over trials, performed in the United States, a single dose of psilocybin (0.2mg/ kg) or an active placebo (niacin, 250 mg), associated with psychological support, were administered for 12 patients with anxiety and depressive disorders associated with advanced-staged cancer [3]. Compared to niacin, psilocybin administration was associated with significant reductions in anxiety symptoms (State- Trait Anxiety Inventory, trait anxiety) one and 3 months after treatment, and in depressive symptoms (Beck Depression Inventory) 6 months after treatment. Psilocybin was well tolerated, inducing only mild and transitory statistically significant elevations of heartrate and blood pressure when compared with niacinplacebo.