How psychedelic-assisted therapies can be more effective

In just a few years, psychedelic-assisted therapy, which uses controlled substances like ketamine, MDMA, and psilocybin (the psychoactive compound found in magic mushrooms), has gone from relative obscurity to the furthest reaches of mainstream medical acceptance. Clinical studies have shown that its medical use can have positive effects for patients with depression and post-traumatic stress disorder. Sometimes these treatments prove effective where other, more widely prescribed medications fail. But new research suggests that close connections with a trained therapist are a key element that contributes to effective psychedelic treatment, especially psilocybin.

(Related: 4 Visionaries on the History and Future of Psychedelic Medicine )

An increase in interest in therapeutic uses of psychedelics has led to a growing industry of startups specializing in treatments. According to psychedelics industry tracker Psilocybin Alpha, more than 50 publicly traded companies currently offer psychedelic therapy (mainly ketamine) and psychedelic retreats. Still, 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 doctor, others rely on loose pandemic-era health orders to let patients take the medication at home, usually in the form of pills and lozenges. The latter method may entail risks. In some cases, the Federal Drug Administration, which has not yet approved psychedelic drugs for therapy, claims to have received reports of patients experiencing adverse health effects after taking medically prescribed ketamine at home without a doctor’s supervision. There are currently no legal at-home psilocybin treatments available, but individuals in Oregon were able to access 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 may play a crucial role in determining whether or not psychedelic-assisted therapy can be useful as a treatment for depression. The study, which analyzed a 2021 clinical trial involving 24 patients who used psilocybin-assisted therapy to treat major depression, found that participants with a stronger self-reported bond with their therapist were more likely to experience depression over the course of the time to report a decrease in depression.

In other words, the effectiveness of psilocybin treatment increases in the long term as a patient feels more connected to their doctor. The doctor spends hours preparing 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 broader clinical acceptance and adoption.

Patients with a stronger bond with their therapist reported better outcomes

Researchers at Ohio State University examined data from a 2021 clinical trial in which 24 adults seeking treatment for major depression received two doses of psilocybin, combined with 11 hours of psychotherapy. Patients completed survey questionnaires rating the strength of the relationship with their therapists, which the researchers call their “therapeutic alliance.” The patients also noted any mystical or insightful psychological experiences they had during treatment. Researchers say these experiences sometimes produce positive therapeutic outcomes, especially in the short and medium term. In this case, these experiences led to positive results approximately four weeks after introducing the psilocybin into the treatment.

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

“This concept is not new. What’s new is that very few people have explored this concept as part of psychedelic therapy,” said the paper’s senior author and Associate Professor Alan Davis of the Center for Psychedelic Drug Research and Education. “These data suggest that psychedelic therapy is highly dependent on the therapeutic alliance, just like any other treatment.”

The findings also reinforce the role that a patient’s environment and mindset, colloquially known as ‘set and setting’, can have in influencing positive experiences. In this case, hours of preparatory psychotherapy prior to psilocybin administration, along with “supportive, not direct” therapy during the actual psychedelic experience, were found to be significant variables contributing to the drug’s overall effectiveness. Patients who feel more comfortable with their doctor may be more receptive to therapy.

“That’s why I think this analysis has shown that the relationship is impactful – because the whole intervention is really about creating the trust and rapport necessary for someone to safely reach an alternative consciousness,” Davis added to.

The study’s findings come at a time that could be a turning point for psychedelic therapy research and treatment in the US. Despite still being labeled a Schedule 1 drug nationally, 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, to treat depression. Last year, the FDA published its first-ever draft guidance, outlining considerations for researchers looking to conduct clinical trials of psychedelic treatments. An MDMA therapy from the MAPS Public Benefit Corporation could reportedly win FDA approval by the end of the year.

Adam Levin, a resident of the Ohio State University College of Medicine and lead author of the paper, notes that his and his fellow researchers’ findings could highlight the importance of maintaining strong bonds between patients and doctors, especially as treatments will be applied on a larger scale in the coming years. Levin and others critical of efforts to accelerate access to psychedelic drugs without proper therapeutic support warn that such an approach could lead to unintended consequences and even hold back efforts to make psychedelic therapy more widely available .

“Our concern is that any attempt to minimize therapeutic support could lead to safety issues or side effects,” Levin said. “…What we have shown in this study is evidence of the importance of the alliance, not only in preventing these types of events, but also in optimizing therapeutic outcomes.”