In a post on Nora’s Blog, the director of the National Institute on Drug Abuse (NIDA), Dr. Nora Volkow, wrote that psychedelic compounds “represent a potential paradigm shift in the way we address substance use disorders.”

Dr. Volkow points to the fact that two psychedelic drugs have been labeled “breakthrough therapies” by the Food and Drug Administration (FDA), allowing for “expedited development and review.” Those psychedelic drugs are:

• psilocybin, the active ingredient in “magic mushrooms”
• MDMA, a “club drug” also known as Molly and Ecstasy

Psilocybin has been approved for the treatment of depression, and MDMA has been approved for the treatment of PTSD, according to the blog post. Esketamine, a variant of the psychedelic drug ketamine, has also been approved for treating depression.

The efficacy of psychedelic drugs in the treatment of substance use disorders is believed to be a result of their impact on neuroplasticity. Specifically, it is proven that substance use disorders corrupt the brain’s reward system. Psychedelic drugs have been shown to energize reward networks in novel ways that can give addicts a reprieve and a tool to use in recovery.

Dr. Volkow cites research showing these psychedelic drugs can have “relatively long-lasting effects, even with just one or a few administrations.” Surprisingly, Dr. Volkow then throws shade on the research with this unsourced line:

Whether a patient has a positive or negative experience depends to a significant extent upon their mindset going into the experience and whether the setting is one in which they feel secure.

How is a medical professional supposed to prescribe a drug whose efficacy depends upon the mindset of the patient at the time of use? Dr. Volkow suggests more studies are needed to separate the impact of the drug from the setting.

Dr. Volkow points out that psilocybin and its variants “do not interact with the receptors for addictive substances (e.g., opioid receptors, cannabinoid receptors, nicotinic receptors).” Therefore, it is suggested that psilocybin is less likely to be dependency-forming. Ketamine and MDMA, however, increase dopamine in the brain’s reward centers and have an “addiction liability.”

Dr. Volkow then further clouds the water by suggesting that the efficacy of psychedelic drugs may be due, in part, to a “spiritual experience” on the part of the user, such as “the acknowledgment of a higher power.” Where, exactly, is the science to support that? Have other approved medicines been tested to determine what percentage of their efficacy, if any, is attributable to a “spiritual experience”?

A search of Google Scholar for studies on how setting impacts drug effectiveness turns up almost nothing written in this century. This belief that setting determines the efficacy of psychedelic drugs leads Dr. Volkow to prescribe that “protocols to train clinicians will be needed for these therapies to enter mainstream psychiatric treatment.”

In other words, you can’t just buy the drug; you must buy the setting with it, and that setting must include a trained clinician. That is certainly going to limit the ability to use psychedelic drugs to treat substance use disorders. Dr. Volkow acknowledges that “with adjunctive psychotherapy these treatments will be expensive.”

Dr. Volkow points out that NIDA is currently funding clinical trials of psychedelic drugs, including psilocybin for smoking cessation, ketamine for stimulant use disorder, and both psilocybin and ketamine as ingredients in medications for opioid use disorder. I seriously hope they will not include data on the “spiritual experience” of users.

Written by Steve O’Keefe. First published January 26, 2026.

Sources:

“Could psychedelics harness neuroplasticity to treat addiction and other mental illness?,” Nora’s Blog, National Institute on Drug Abuse, January 13, 2026.

Image Copyright: teeradej.