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      Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in end-stage cancer

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          Abstract

          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.

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          LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects.

          A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.
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            Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review.

            Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening 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.
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              A research study review of effectiveness of treatments for psychiatric conditions common to end-stage cancer patients: needs assessment for future research and an impassioned plea

              Background Rates of psychiatric conditions common to end-stage cancer patients (delirium, depression, anxiety disorders) remain unchanged. However, patient numbers have increased as the population has aged; indeed, cancer is a chief cause of mortality and morbidity in older populations. Effectiveness of psychiatric interventions and research to evaluate, inform, and improve interventions is critical to these patients’ care. This article’s intent is to report results from a recent review study on the effectiveness of interventions for psychiatric conditions common to end-stage cancer patients; the review study assessed the state of research regarding treatment effectiveness. Unlike previous review studies, this one included non-traditional/alternative therapies and spirituality interventions that have undergone scientific inquiry. Methods A five-phase systematic strategy and a theoretic grounded iterative methodology were used to identify studies for inclusion and to craft an integrated, synthesized, comprehensive, and reasonably current end-product. Results Psychiatric medication therapies undoubtedly are the most powerful treatments. Among them, the most effective (i.e., “best practices benchmarks”) are: (1) for delirium, typical antipsychotics—though there is no difference between typical vs. atypical and other antipsychotics, except for different side-effect profiles, (2) for depression, if patient life expectancy is ≥4–6 weeks, then a selective serotonin reuptake inhibitor (SSRI), and if < 3 weeks, then psychostimulants or ketamine, and these generally are useful anytime in the cancer disease course, and (3) for anxiety disorders, bio-diazepams (BDZs) are most used and most effective. A universal consensus suggests that psychosocial (i.e., talk) therapy and spirituality interventions fortify the therapeutic alliance and psychiatric medication protocols. However, trial studies have had mixed results regarding effectiveness in reducing psychiatric symptoms, even for touted psychotherapies. Conclusions This study’s findings prompted a testable linear conceptual model of co-factors and their importance for providing effective psychiatric care for end-stage cancer patients. The complicated and tricky part is negotiating patients’ diagnoses while articulating internal intricacies within and between each of the model’s co-factors. There is a relative absence of scientifically derived information and need for more large-scale, diverse scientific inquiry. Thus, this article is an impassioned plea for accelerated study and better care for end-stage cancer patients’ psychiatric conditions.
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                Author and article information

                Contributors
                + 55 16 3602 2703 , banisteria@gmail.com
                jcbouso@iceers.org
                jechallak@gmail.com
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                28 October 2019
                28 October 2019
                2019
                : 19
                : 321
                Affiliations
                [1 ]ISNI 0000 0004 1937 0722, GRID grid.11899.38, Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, , Universidade de São Paulo (USP), Hospital das Clínicas, ; Terceiro Andar, Av. Bandeirantes, Ribeirão Preto, São Paulo, 3900 Brazil
                [2 ]Instituto Nacional de Ciência e Tecnologia – Medicina Translacional, Ribeirão Preto, Brazil
                [3 ]ICEERS Foundation (International Center for Ethnobotanical Education, Research and Services), Barcelona, Spain
                Author information
                http://orcid.org/0000-0003-2388-4745
                Article
                2288
                10.1186/s12888-019-2288-z
                6816167
                31660905
                99bbd10d-d4c5-4598-a966-e9919016e2bc
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 October 2018
                : 12 September 2019
                Categories
                Commentary
                Custom metadata
                © The Author(s) 2019

                Clinical Psychology & Psychiatry
                psychiatry,psycho-oncology,end-stage cancer care,depression,anxiety,hallucinogens,psychedelics,lysergic acid diethylamide,psilocybin

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