Brian Barnett, MD: Psychedelics Fitting into the SUDs Treatment Paradigm


In an interview with HCPLive, Barnett discussed the ethical concerns of using psychedelics for treating substance use disorders.

Psychedelics do not seem to be leaving the research space any time soon. Not only are psychedelics being assessed for anxiety and PTSD treatment but also for the treatment of substance use disorders (SUDs).1,2

Brian Barnett, MD, from the Center for Behavioral Health, Neurological Institute at Cleveland Clinic, presented the history and challenges surrounding using psychedelics in treating SUDS, along with how psychedelics could potentially fit into the existing SUDs treatment paradigm, at the annual American Psychiatric Association (APA) conference in New York.1

Back in the 1950s and 1960s, investigators did extensive research on psychedelics for the treatment of substance use disorders. Patients also had psychedelics in a clinical setting since at the time an FDA approval was not needed.

At the time, alcohol use disorder was a big problem, and investigators had an interest in using LSD to treat it. Many trials took place, but they resulted in mixed results. A study found participants who were more prepared and took the psychedelics in a soothing setting, rather than a hospital room or tied to a bed, had better outcomes.

Despite some studies suggesting psychedelics can improve SUDs, ethical concerns remain. In an interview with HCPLive, Barnett posed the question, “Can we give someone who already has a substance use disorder a psychoactive substance… that also has misuse potential?”

Barnett told HCPLive that out of all the classes of psychoactive drugs humans use, psychedelics have the “least addicting potential.”

He explained they are the least addictive for several reasons. The first one is that psychedelics are not enjoyable.

“Sometimes people associate psychedelics with euphoria, but for many people, that doesn’t happen,” he said. “They’re not euphoric; they actually find it to be quite a challenging experience.”

Another reason psychedelics are the least addictive is because they cannot be used for more than 3 days due to the property it has called Tachyphylaxis. If a psychedelic is used for 3 days, then it cannot be used for several days afterward.

“So that’s sort of a built-in protective feature,” Barnett said.

Additionally, research suggests psychedelics have serotonin 2c receptor agonists that activate serotonin receptors which ultimately reduces dopamine in the reward pathway. Since the dopamine in that area is what drives addiction, patients are less likely to get addicted to psychedelics.

Regardless, Barnett said clinicians should still warn their patients about the addiction risk. He also said clinicians should warn patients about the potential long-term personality or political changes, as well as other risks: suicidal ideation, psychosis, and for people with bipolar disorder, risk of mania.

“There are a lot of potential risks that we would have to talk about as we continue to gather more data to help us figure out who’s actually at risk for these things,” Barnett said. “We want to start out being as comprehensive as possible until we have more data to guide those discussions.”


  1. Barnett, B. Psychedelics in the Treatment of Substance Use Disorders. Session presented at: American Psychiatric Association (APA) 2024 Annual Meeting. New York, NY. May 7, 2024.
  2. Derman, C. Daniel Karlin, MD: FDA Grants Breakthrough Designation to MM120 for Anxiety. HCPLive. March 13, 2024. Accessed May 9, 2024.
  3. Derman, C. MDMA-Assisted Therapy for PTSD Awaits FDA Decision. HCPLive. December 21, 2023. Accessed May 9, 2024.
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