This post was made by Floris Wolswijk in cooperation, and co-published↗, with the MIND Foundation

The positive effects of serotonergic hallucinogens have long been recognized by recreational users, however, the history of academic research on the therapeutic potential of psychedelics has been turbulent, to say the least.

For more than a decade we have been observing a Psychedelic Renaissance – a growing interest in the exploration of the potential of psychedelics in the treatment of mental health disorders. Substances such as psilocybin, LSD, DMT, and ayahuasca are being investigated the world over. From university research groups to forward-looking therapists’ offices. All with the hope of establishing effective methods of improving global mental health. 

In this top 10, we will introduce the history and current state of the research on psychedelic-assisted therapy, as well as its challenges and future perspectives.

Top 10 Psychedelic-Assisted Therapy Papers Walkthrough

1. Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry

A very straightforward and down-to-earth briefing of the problems involved in psychedelic research has been published by Ben Sessa in 2014. In ‘Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry’ the UK-based psychotherapist argues that we have to reject the enthusiastic, yet naïve notion of creating a utopian society thanks to the use of psychedelics. Instead, researchers and healthcare professionals should focus on realistic and non-biased views of psychedelics as novel players in the pharmaceutical market. 

2. Psychedelics: Where we are now, why we got here, what we must do

The historical context of research on psychedelics is extensively discussed in ‘Psychedelics: Where we are now, why we got here, what we must do’. In their 2018 commentary, Belouina and Henningfield travel through the rise, the fall, and the current renaissance of psychedelics as medical agents. Drawing conclusions from the historical context and paying close attention to health policymakers and their influence on science, the authors set a trajectory for the immediate future of clinical advances in the field of psychedelic research.

3. Psychedelics as Medicines: An emerging new paradigm

A strictly medical perspective is offered by David E. Nichols, Matthew Johnson, and Charles D. Nichols in their state-of-the-art review from 2016. ‘Psychedelics as Medicines: An emerging new paradigm’ compares various clinical trials with patients suffering from several psychiatric disorders and presents the psychedelic mechanisms of action on a cellular level.

4. Therapeutic use of serotoninergic hallucinogens

Four years later, two pioneers of psychedelic research in Brazil teamed up and published a detailed review of the therapeutic potential of LSD, psilocybin, and ayahuasca. ‘Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms‘ by Guimarães & Hallak (2020) scrutinizes the effects of psychedelics in substance use disorders, as well as in anxiety and depression related to cancer and other life-threatening diseases. 

5. Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

Living with a life-threatening disease can lead to many mental health problems. General anxiety, loneliness, the anguish about unresolved personal relationships, and managing pain are but a few of these problems. In 2014 a joint effort of researchers from Switzerland and the US has led to a detailed investigation of the ‘Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases’. The study, partially funded by MAPS, resulted in a positive trend in the reduction of anxiety after only two LSD-assisted therapy sessions. In a follow-up study, they found that the effects persisted 12 months later.

6. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer

Parallel to LSD, psilocybin has also been investigated in order to establish its potential in reducing depression and anxiety in patients suffering from life-threatening cancer. Scientists from Johns Hopkins University School of Medicine established, that ‘Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial’ (2016) whilst producing no adverse effects. The reported improvements in quality of life, life meaning, death acceptance, and optimism persisted for at least six months after psilocybin administration.

7. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease

Studying the effects of psychedelics in patients in terminal life stages is, however, extremely challenging, not only because of the delicate nature of the subject, but also because of the study design and sample size. ‘Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review’ (2018) written by Simon Reiche and colleagues analyzed over 50 years of clinical trials and discussed their significance, safety, and limitations, although making the reader aware that there are still many questions to be answered. 

8. Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users

Psychedelic therapy can involve the use of not only LSD or psilocybin, but often also of ayahuasca. Although originally only found in the Amazon jungle, the plant-based brew has been consumed by users worldwide. In 2017 recent ayahuasca users (527 participants) filled out a survey prepared by an international team of researchers. ‘Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey’ shone a light on self-rated contentment, drinking habits, and trip-related experience of those who drank ayahuasca in the recent past.

9. Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Drawing from the REBUS model proposed by Robin Carhart-Harris, Max Wolff and colleagues (2020) constructed a cognitive-behavioral model to explain the mechanisms of beneficial effects in psychedelic interventions. ‘Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance’ proposes that the relaxation of avoidance-related beliefs can be achieved during a psychedelic-assisted therapy session. It allows the patient to reach an emotional breakthrough, which is an insightful and rewarding experience able to re-wire the previous avoidance patterns. The relaxed-belief state can potentially induce ego-dissolution, leading to long-term improvements in overcoming anxiety-provoking situations through revision and reinterpretation of pathological belief systems.

10. The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD

A very pragmatic analysis has been presented by Marseille and colleagues in ‘The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD’ (2020). The article focuses on the costs of medical care required for patients suffering from PTSD. The developed model of medical care cost suggests that MDMA-assisted psychotherapy is highly cost-effective and therefore beneficial not only to the patients but also to the society and healthcare providers.