The Australian Therapeutic Goods Administration (TGA) has, from July 1 2023 approved prescription of psilocybin for treatment resistant depression and MDMA for post-traumatic stress disorder. There are limited conditions under which these drugs can be used.
Dr Steve Kisely (1) and others have raised many questions about this decision. They include: accessibility, cost (15 to 35 thousand dollars), strength of evidence for and against, and “dangers of psychological harm if these agents are given to unsuitable patients, or by psychiatrists without the necessary training”.
However, I want to concentrate here on trying to understand one aspect of how these treatments may work. My source is a ‘Viewpoint’ article in JAMA (2). The authors Colloca, Nikayin and Sanacora emphasise the significance of Sets, Settings and Expectations for the therapeutic use of these drugs.
‘Sets’ refers to the patient’s mindset, taking in both their expectations before the therapy and their mindset that may develop during the therapy process. The therapy involves extensive preparation – up to eight hours with therapists. Then the drug sessions (lasting many hours) usually include the close attention by two therapists. The drugs themselves appear to promote a loosening and change in mindset associated, probably, with an effect on brain plasticity. Heightened suggestibility was noted by Leary and others (3) way back in the sixties. This is thought to be a component of the patient’s opening up to the positive effects of psychotherapy. But of course, there can be negative effects of psychotherapy.
‘Setting’ refers to the physical and social environment. It has been observed since psilocybin and LSD were first widely used that the setting in which they were taken often influences whether the person has a good or bad ‘trip’. The intensively supportive regime required for this therapy reduces the risk of adverse experiences such as panic or psychosis. The same supportive regime provides the ‘psychotherapy’, central to the therapeutic aspect of the experience. Whether the drugs by themselves can be therapeutic is more controversial.
‘Outcome Expectations’. These form part of the person’s mindset approaching psychedelic therapy. They can be reinforced or modified by the intensive process of the therapy and by the direct action of the drug in making the brain more malleable, more receptive to the talking therapy. For example the JAMA article describes how ‘these treatments may modify existing beliefs and expectations of future events’, including moving from a pessimism bias (e.g. Eeyore in Winnie the Pooh) to an optimism bias.
1. Kisely S. The down-scheduling of MDMA and psilocybin(e): Too fast and too soon ANZJP 2023. Vol. 57(7) 933-934 DOI: 10.1177/00048674231174171
2. Colloca L, Nikayin S, Sanacora G. The Intricate Interaction Between Expectations and Therapeutic Outcomes of Psychedelic Agents. JAMA Psychiatry Published online July 5, 2023 https://pubmed.ncbi.nim.nih.gov/37405764/