Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease : A systematic review, Simon Reiche et al.,

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease : A systematic review

Simon Reiche, Leo Hermle, Stefan Gutwinskic Henrik Jungaberle, Peter Gasser, Tomislav Majić

Progress in Neuropsychopharmacology & Biological Psychiatry, 2018, 81, 1–10



Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with lifethreatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N =445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N =30). The 4 more recent randomized controlled trials (RCTs) (N =104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. 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. Some studies anecdotally reported improvements in patients ´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.

Keywords : Hallucinogen, LSD, Psilocybin, Anxiety, Life-threatening disease, Cancer


1. Introduction

Receiving a diagnosis of a life-threatening physical disease is usually a shocking event, associated with a significant degree of emotional suffering including fear, anger, despair, and social withdrawal. While some patients are capable of coping effectively with the challenges of their disease and the associated ‘existential distress’, others develop a broad range of psychological problems (Teunissen et al., 2007; Van Lancker et al., 2014), with a high prevalence of anxiety and depressive symptoms (Mitchell et al., 2011; Watts et al., 2015, 2014; Wilson et al., 2007). Existential distress includes core phenomena like feelings of hopelessness, a loss of will to live, a loss of meaning and sense of dignity, and a sense of being a burden to others and a desire for a hastened death (Boston et al., 2011; Boston and Mount, 2006; Chochinov et al., 2005a; Jaiswal et al., 2014; Kissane et al., 2001). These problems are often associated with poor treatment adherence (Arrieta et al., 2013) and higher mortality rates (Brown et al., 2003). In palliative care, there is a growing consensus that existential distress is a core determinant of poor well being and quality of life (QoL) in patients with a life-threatening disease, determining the effectiveness in coping with the challenges of the disease (Breitbart et al., 2005, 2000; Edwards et al., 2010; Jones et al., 2003; Kandasamy et al., 2011; McClain et al., 2003; Puchalski, 2012; Rodin et al., 2009). Thus, an increasing number of psychotherapeutic interventions are approaching existential distress by meaning enhancing interventions like the ‘Meaning-centered Group Psychotherapy’ (Breitbart et al., 2015, 2010), ‘Dignity Therapy’ (Chochinov et al., 2005b) or ‘Supportive-expressive Group Therapy’ (Reuter, 2010) (for a review see LeMay and Wilson, 2008). In contrast, there are currently no specific pharmacological treatment options regarding this particular type of distress (Breitbart et al., 2010). So far, treatment strategies mainly focus on reduction of symptoms like pain or sleep disturbances. Recently, the interest in the therapeutical potential of classic serotonergic hallucinogens (5-HT2A receptor agonists; ‘psychedelics’) has resumed, and there is some evidence for efficacy in certain indications (Majić et al., 2017). In the following we will give an overview over this group of substances and outline the history of using these substances in the treatment of anxiety and depression in patients suffering from life-threatening diseases.