Comparison of psychedelic therapies versus placebo in the treatment of psychiatric illnesses: a systematic review of randomized trials including placebo controls

Abstract: Psychedelics have long been recognized for their powerful effects on the human psyche and psychedelic-assisted therapy is becoming increasingly acknowledged as an effective therapeutic intervention. Placebos are used in clinical research to validate the efficacy of a therapy or treatment. Researchers are interested in showing that a certain treatment is superior compared to the placebo. An evaluation of the methodological rigor in recent studies looking at the potential of psychedelics for the treatment of psychiatric illnesses is an important step forward to re-open a scientific study of these substances and their medical use for psychiatric patients. The aim of this systematic literature review was to investigate if psychedelic substances have an influence on symptom reduction for patients suffering from mental illness as compared to placebos and if placebo controls are valid in psychedelic trials, i.e., if the blinding is maintained. The review has presented that an overwhelming majority of the evaluated studies showed large and positive effects of psychedelics on participant’s symptom changes. Collectively the studies reviewed displayed a large degree of heterogeneity. In all nine studies the blinding was either insufficient or poor. In conclusion, reviewed studies show large and positive treatment outcomes for patients suffering from psychiatric illnesses such as alcohol use disorder, anxiety with or without a life-threatening disease, anxiety and depression during life-threatening cancer, treatment-resistant depression and major depressive disorder. The lack of successful blinding procedures indicates that the methodological shortcomings displayed in the psychedelic studies of the first wave of psychedelic research persist in these most recent studies on the subject.