Co-authors Jacob S. Aday, Alan K. Davis, Cayla M. Mitzkovitz, Emily K. Bloesch, and Christopher C. Davoli published their paper ‘Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects’ in the journal ACS Pharmacology & Translational Science. This review aims to identify which patients will likely have challenging experiences while under the influence of psychedelics and suggest areas of study for helping individuals have better outcomes in psychedelic-assisted therapy.
The authors decided on forty-two search terms to input in PubMed for mentions of individual reactions to the drugs psilocybin, LSD, and ayahuasca. They limited their search to studies from 1994 onwards because, as they explain, “Strassman et al. was the first study to administer classic psychedelic compounds to human participants in the US after several decades of prohibition.” Their search resulted in 1635 eligible articles, of which only ten met all the criteria for the review. An additional four studies were introduced by the authors of this review from outside sources. As well, they studied the anecdotal experiences reported on www.erowid.com to see if any correlations could be made.
The results of this review are anything but conclusive. All of the studies cited in this review either had small sample sizes of a few dozen people, were heavily skewed toward a white male demographic, or were retrospective studies and so could not control dosages. Part of the reason is that this is an emerging field of research, noticeably picking up in 2018. However, the authors stipulate, this is an important step in creating diagnostic tools to help patients using these novel treatments, as there are indications of where research can continue.
In terms of physiology, differences in the 5-HT2A Receptor – a kind of serotonin receptor implicated in psychedelic experiences – seem to indicate more intense experiences when using psilocybin. Still, sample sizes for these studies are small. More literature can be found on personality traits that seem to correlate with different experiences. The authors point to ‘absorption’ as the most important trait to having positive, spiritual experiences while under psychedelics. Conversely, anxiety and pessimism prime study participants to have challenging experiences, what may be colloquially known as a ‘bad trip’. Because micro-dosing psilocybin enhances absorption, the authors speculate that a micro-dosing phase of treatment before moving to full doses could help anxious patients get the most of their psychedelic therapy.
Another insight from the articles’ survey is that the ‘set’ is important to the therapy’s overall effectiveness. The set is where the psychedelic session takes place, but it’s also the conditions present at the time. For example, therapists may offer music or mood lighting to ease the patient into their altered state, much like recreational users are wont to do. But the review also includes mention of the religious practices among global cultures related to the use of psychoactive substances.
The review itself is lacking in detail, but only because researchers are only just now beginning to understand the set of conditions that lead to positive or negative experiences in this kind of therapy. The authors of the review hope that researchers will take their recommendations and incorporate them into future studies so that sufficient literature may be available in the future. Psychedelic therapy can provide more predictable results.