How psychedelic-assisted therapies can be more effective

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In just a few short years, psychedelic-assisted therapy involving controlled substances like ketamine, MDMA, and psilocybin (the psychoactive compound found in “magic mushrooms”) have evolved from relative obscurity to the far edges of mainstream medical acceptance. Clinical studies have shown that their medical use can have positive effects for patients living with depression and post-traumatic stress disorder. Sometimes, these treatments prove effective where other, more widely-prescribed medications fall short. But new research suggests close bonds with a trained therapist is a key element contributing to effective psychedelic-assisted treatment, specifically psilocybin.

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A surge in interest in therapeutic use of psychedelics has fostered a burgeoning industry of startups specializing in treatments. As of today, according to the psychedelics industry tracker Psilocybin Alpha, more than 50 publicly traded companies currently offer psychedelic therapy (mostly ketamine) and psychedelic retreats. Yet, the exact ways these companies administer psychedelics can vary widely. While some require patients to consume or inject the substance in the presence of a trained clinician, others lean on loose, pandemic-era health regulations to let patients take the medication at home, typically as pills and lozenges. The latter method can carry risks. In some cases, the Federal Drug Administration, which has yet to approve psychedelic drugs for therapy, claims it has received reports of patients experiencing adverse health effects after they’ve taken medically prescribed ketamine at home without a clinician’s supervision. There are currently no legal at-home psilocybin treatments available however individuals in Oregon were able to begin accessing the compound without a prescription last year. 

A new study published in the journal PLOS ONE this week suggests that strong relationships between patients and their therapists could play a crucial role determining whether or not psychedelic-assisted therapy can prove useful as treatments for depression. The study, which analyzed a 2021 clinical study involving 24 patients using psilocybin-assisted therapy to treat severe depression, found that participants with stronger self-reported connections with their therapist were more likely to report a decrease in depression over time.

In other words, the efficacy of psilocybin treatment increases over the long-term when a patient feels more connected to their clinician. The clinician provides hours or preparation and also guides the patient through the experience and dissects it days and weeks later. Findings like these could help influence treatment standards for psychedelic-assisted therapy treatments, especially as the practice gains more widespread clinical acceptance and adoption. 

Researchers from Ohio State University examined data from a 2021 clinical trial where 24 adults seeking treatment for severe depression received two doses of psilocybin paired with 11 hours of psychotherapy. Patients completed survey questionnaires where they assessed the strength of the relationship with their therapists, which the researchers refer to as their “therapeutic alliance.” The patients also noted down any mystical or insightful psychological experience they had during the treatment. Researchers say at times these experiences tend to yield positive therapeutic outcomes, particularly in the short and medium term. In this case, these experiences led to positive outcomes around four-weeks after introducing the psilocybin into treatment.

Higher alliance scores, or stronger relationships with therapists, correlated with longer-term psychological insights. One year after the treatments, patients who reported strong connections with their therapist also crucially provided lower self-reported depression scores one year following treatment than those who reported weaker relationships. The research builds off of past studies that show how a strong therapeutic alliance between a therapist and a patient often leads to a more effective outcome following therapy. This new study suggests those same basic findings similarly apply to psychedelic-assisted therapy. 

“This concept is not novel. What is novel is that very few people have explored this concept as part of psychedelic-assisted therapy,” paper senior author and Center for Psychedelic Drug Research and Education associate professor Alan Davis said in a statement. “This data suggests that psychedelic-assisted therapy relies heavily on the therapeutic alliance, just like any other treatment.”

The findings also reinforce the role a patient’s environment and mindset, known colloquially as “set and setting” can have on influencing positive experiences. In this case, hours of preparatory psychotherapy prior to administering psilocybin, along with “supportive, no direct” therapy during the actual psychedelic experience posed to be significant variables contributing to the drug’s overall effectiveness. Patients who were more comfortable with their clinician may be more receptive to the therapy.

“That’s why I think the relationship has been shown to be impactful in this analysis–because, really, the whole intervention is designed for us to establish the trust and rapport that’s needed for someone to go into an alternative consciousness safely,” Davis added.

The study’s findings come during what could be an inflection point for psychedelic-assisted therapy research and treatment in the US. Despite still being labeled a Schedule 1 drug on the national level, several cities including Denver, Oakland, and Washington have decriminalized psilocybin. On the medical front, the FDA in 2019 approved the use of a nasal spray called Spravato, which uses a derivative of ketamine, for treating depression. Just last year, the FDA released its first-ever draft guidance outlining considerations for researchers looking to conduct clinical trials for psychedelic treatments. An MDMA therapy from the MAPS Public Benefit Corporation could reportedly receive FDA approval by the end of the year. 

Ohio State University College of Medicine resident and paper lead author Adam Levin notes he and his fellow researchers’ findings could highlight the importance of maintaining strong connections between patients and physicians, especially with treatments posed to gain wider adoption in the coming years. Levin, and others critical of attempts to rush out access to psychedelic drugs without proper therapeutic support warn such an approach could lead to unintended consequences and even set back efforts to make psychedelic-assisted therapy more widely available. 

“Our concern is that any effort to minimize therapeutic support could lead to safety concerns or adverse events,” Levin said. “…What we showed in this study is evidence for the importance of the alliance in not just preventing those types of events, but also in optimizing therapeutic outcomes.”

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