Psilocybin alcoholism trials highlight a problem for psychedelic science

A new study published in JAMA Psychiatry The first double-blind, placebo-controlled trial to treat alcohol use disorder has reported results from psilocybin-assisted psychotherapy. The headline results are promising, with nearly half of the psilocybin group found to have stopped drinking completely after treatment. However, with nearly every participant blinded and guessing as to whether they were given the active drug or a placebo, the study raises major questions about the veracity of these types of clinical trials for psychedelic drugs.

The new trial, led by a team at NYU Grossman School of Medicine, enrolled 93 subjects with clinically diagnosable alcohol use dependence. The cohort was equally randomized to either a psilocybin group or a placebo control.

All subjects, including those in the placebo group, underwent a psychotherapy protocol spanning several months: four sessions before starting any psychedelic treatment, four sessions between the first and second drug treatment, and four sessions at the end.

Those in the placebo group are called active placebos. In this case it was an anti-histamine called diphenhydramine, which can cause a flush or euphoria at high doses.

At an eight-month follow-up, the study found that 48% of the psilocybin group had completely stopped drinking compared to 24% of the placebo group. In terms of reduction in “heavy drinking” (defined as four to five more alcohol-drinking days), those in the psilocybin group saw their number of heavy-drinking days decrease by 83%, compared to a 51% decrease. placebo.

The results of the study are undoubtedly promising. The use of LSD to treat alcoholism was one of the first therapeutic targets discovered by researchers in the 1950s, and there is a relatively rich vein of older work exploring this modality. But these new findings highlight some important unresolved issues in the field of modern psychedelic clinical research.

A randomized, blinded, controlled trial is the gold standard of modern research. Taking two groups of people together to test an intervention, but blindly giving one group a placebo, is an important way scientists can gather empirical evidence about whether a novel treatment fundamentally works.

But in psychedelic science it can be impossible to give someone an inert placebo without them quickly realizing they haven’t been given a real drug. In the last few years this problem has been cited as potentially over-inflating effects in psychedelic clinical trials.

In this new study, NYU researchers had almost every subject correctly guess whether they were given psilocybin or a placebo. In the second drug session, about 95 percent of participants correctly guessed which group they were assigned to.

Not only did the study participants effectively “break the blind,” but the study physicians, who were also blinded, ultimately guessed the treatment groups. In the second drug session the therapists correctly guessed which patients were given placebo and which psilocybin with 97.4% accuracy.

So, considering that attempts to double-blind this study completely failed, it seems a bit disingenuous to even frame this study as blind. The fourth line of NYU Langone Health’s press release announcing the study clearly states, “Neither the researchers nor the study participants knew which drug they received.” A fact that may have been true at the beginning of the investigation but was definitely not true at the end.

Michael Bogenschutz, senior author of the new study, said using the antihistamine diphenhydramine as an active placebo was the team’s attempt to overcome this problem.

“In this case we were not very successful in retaining the blind,” admitted Bogenschutz. “Most people were able to guess which drug they got. A good placebo is not necessarily the case in our minds. So the drug you’re using has very active, clear psychoactive effects that can be easily distinguished.”

When announcing the results of the new study at a press conference, the researchers introduced two participants from the trial. Both men spoke enthusiastically about their positive experiences, each essentially giving up alcohol after the ordeal.

But at a strange moment late in the press conference it was revealed, through a reporter’s question, that one of the two participants belonged to the placebo group. Paul Mavis, who had previously described the treatment as “significant” and “game-changing” at a press conference, later emphasized the importance of psychotherapy in the positive experience from his trial.

Mavis also emphasized that she did not know that she had been given a placebo until literally a week ago, when she was approached to participate in this press conference, making her one of the very few participants in the trial who could not correctly guess their group. assignment. All test subjects were offered a third drug session with psilocybin, so those in the placebo group finally experienced the psychedelic session.

Mavis said that even after being given the actual dose of psilocybin, she didn’t expect her first two sessions to be the same as with the placebo. He explained the intense psychedelic experience he felt in that third session simply because of how open he had become to the drug after the previous two sessions. And Bogenschutz indicated that Mavis’ experience is a good example of how effective this common therapeutic protocol can be, even in the absence of psychedelic drugs.

However, it was not clear why subjects in the placebo group were presented in the media as trial success stories. Is this to suggest that the “psychedelic” in psychedelic-psychiatry is partly a placebo? Or is psychotherapy producing significant clinical benefits from this novel type of treatment, and why was there so little transparency in the details that this participant was really from the placebo group?

Patient biographies from seven participants in the trial were offered to the media and Mavis’ description does not indicate she was in the placebo group. Instead his biographical accounts reveal how meaningful the insights he gained during his sessions on testing were.

“During his first session in January 2019, he remembers having a conversation with himself about when and why he would drink again,” reads the NYU bio on Mavis. “This led to a sudden epiphany in which he realized that ‘drinking equals death. Boom. Like someone flipped a switch, I knew I’d given up drinks for good.’

The researchers have clarified that they have no direct financial stake in this particular work. Bogenschutz said the NYU Grossman School of Medicine has filed a provisional patent for the research, but stressed the reason behind it is that no commercial, for-profit organization can monopolize the treatment and make it financially accessible to many in the future.

All of this, however, suggests that there is a pre-existing belief that this type of psychedelic treatment works. Charles Marmer, chair of the department of psychiatry at NYU Langone, was open to expressing this belief at a recent press conference.

“We believe we will be successful in reaching FDA approval over time,” Marmer said. “We, at NYU School of Medicine, and in the field of psychedelic psychiatry in general, will achieve our milestones in the next five to 10 years in obtaining FDA approval for psilocybin and other drugs for addiction and mental illness.”

The new research findings are undeniably promising, indicating that psilocybin may be useful in the treatment of alcohol use disorder. But in presenting this new study, and downplaying the effect of the placebo problem, the researchers have somewhat exposed a bias relatively prevalent in the world of modern psychedelic science. The underlying belief that these drugs work will soon be approved, and the research currently being conducted is generated to serve and validate that pre-existing belief.

The new study was published in JAMA Psychiatry.

Source: NYU Langone Health

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