Wednesday, August 2, 2023

NIDA, NIMH Directors Describe Promise, Challenges Associated With Psychedelics Research

The research challenges associated with the use of psychedelics to safely treat mental illness and substance use disorders are enormous—but so too is the promise, wrote Nora Volkow, M.D., director of the National Institute on Drug Abuse (NIDA); Joshua Gordon, M.D., director of the National Institute on Mental Health (NIMH); and Eric Wargo, Ph.D., a science writer with NIDA, in a Viewpoint article in JAMA Psychiatry.

“Although existing pharmacologic treatments such as antidepressants and medications for opioid use disorder are valuable for many people with these conditions, a large proportion are not helped by those treatments. … [P]sychedelic drugs represent a promising psychotherapeutic frontier,” they wrote.

Yet so far, the therapeutic evidence for psychedelics is minimal, and “the hype has gotten ahead of science,” they continued. “Much remains unknown about how psychedelic compounds work, how to administer them most effectively and safely, and how to identify which patients are the best candidates and which are at risk of adverse outcomes.”

Volkow, Gordon, and Wargo outlined several challenges associated with the study of psychedelics:

  • Subjective experience: There is evidence to suggest that psilocybin’s therapeutic efficacy is tied to the mystical-type experiences commonly reported by people who take the drug. “This connection remains controversial, however, and researchers are exploring whether desired [effects on depression] can be decoupled from the cognitive and sensory distortions that raise questions about the safety of psychedelic drugs.”
  • Contextual factors: “The individual’s mindset going into the experience along with characteristics of the setting influence whether the individual has a positive or a negative experience,” they continued. The role of the therapist overseeing psychedelic therapy is believed to be crucial too. “Research must clarify wherein the therapeutic efficacy lies and establish what other contextual components are needed.”
  • Clinical trial design: Conducting clinical trials of psychedelics involves unique challenges—among them, study participants can usually tell if they have been given a psychedelic versus a placebo. Additionally, “greater standardization and harmonized protocols for clinical trials are needed so that results can be compared, along with longer follow-up studies to understand long-term outcomes.”
  • Past ethical lapses: “Current psychedelics research carries the baggage of past ethical transgressions, including egregious experimentation with LSD on unwitting study ‘participants’ including individuals with disabilities and those who were incarcerated in the 1950s. It places a unique burden on researchers to be transparent in their aims and methods and to establish a firm grounding of trust with study participants.”

Despite these challenges, Volkow, Gordon, and Wargo expressed optimism: “We know a great deal about what goes awry in the brains of people with mental illnesses including substance use disorders, but we know less about what goes right in the brains of people whose lives are full of meaning and connection and who may be more resilient to the development of psychiatric conditions. Better understanding of the mechanisms by which psychedelics may increase resilience could be highly valuable.”

For related information, see the Psychiatric News article “Experts Offer Tips on Talking With Patients About Psychedelics.”

(Image: iStock/Yarygin)

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