A new study published in JAMA Psychiatry reported results from the first double-blind, placebo-controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder. The main results are promising, finding that nearly half of the psilocybin group stopped drinking altogether after treatment. However, with almost every participant being blinded and guessing whether they were given an active drug or a placebo, the study raises big questions about the validity of these types of clinical trials for psychedelic drugs.

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

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

Those in the placebo group were given what is known as an active placebo. In this case it was an antihistamine called diphenhydramine, which in high doses can generate feelings of flushing or even euphoria.

At the eight-month follow-up, the study found that 48% of those in the psilocybin group had stopped drinking completely, compared to 24% in the placebo group. In terms of reductions in “heavy drinking” (defined as days where more than four to five alcoholic drinks were consumed), those in the psilocybin group had reduced the number of heavy drinking days by 83%, compared to a 51% decrease in placebo.

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

A randomized, blinded control trial is the gold standard of modern research. Bringing two groups of people together to test an intervention, but blindly giving one group a placebo, is an essential way for scientists to gather empirical evidence about whether a new treatment actually works.

But in psychedelic science it can be virtually impossible to give someone an inactive placebo without realizing very quickly that they haven’t been given the real drug. In recent years this problem has been cited as potentially leading to excessive effects in psychedelic clinical trials.

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

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

So, given that the attempt to replicate this study failed completely, it seems a bit disingenuous to even call the study blind. The fourth line of a press release from NYU Langone Health announcing the study explicitly states, “Neither the researchers nor the study participants knew what medication they received.” A fact that may have been true at the beginning of the research, but certainly wasn’t true by the end.

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

“In this case we weren’t terribly successful in holding the blind,” Bogenschutz admitted. “Most people were able to guess what medication they received. We don’t necessarily have a better placebo condition in mind. So it comes with the territory when the drug you’re using has very active and visible psychological effects that are easily discernible.”

In 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 quitting drinking after the ordeal.

But in a strange moment at the end of the press conference it was revealed, through a reporter’s question, that one of the two participants was actually from the placebo group. Paul Mavis, who had glowingly described the treatment earlier in the press conference as “important” and a “game changer”, then highlighted the importance of psychotherapy in his positive experience from the trial.

Mavis also stated 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 few participants in the trial who did not correctly guessed their group. task. All test subjects were offered a third session of the psilocybin drug, so those in the placebo group finally experienced a psychedelic session.

Mavis said that even after being given a real dose of psilocybin, he still didn’t think his first two sessions had been with a placebo. He simply interpreted the acute psychedelic experience he felt in that third session as being due to how receptive 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 general therapeutic protocol can be even in the absence of psychedelic drugs.

However, it was unclear why a subject from the placebo group was presented in the media as a success story from the trial. Is this to suggest that the “psychedelic” in psychedelic psychotherapy is partly placebo? Or is psychotherapy generating significant clinical benefits from this new type of treatment, and why was there little transparency on the details that this participant was really from the placebo group?

Patient biographies from seven trial participants were released to the media, and Mavis’s details did not indicate he was in the placebo group. Instead, his biographical details showed how meaningful the knowledge he gained during his trial sessions was.

“During his first session in January 2019, he recalls negotiating with himself when he would drink again and why,” the NYU biography on Mavis read. ‚ÄúThis led to a sudden epiphany in which he realized that ‘drinking equals death. Boom. If someone turned the key, I knew I was done drinking for good.’

The researchers are clear to clarify that they have no direct financial interest in this particular work. Bogenschutz said the NYU Grossman School of Medicine has filed a provisional patent for the research, but stressed that the reason behind this is to ensure that no for-profit commercial entity can monopolize the treatment and make it financially out of reach for many people in the future.

All of this, however, suggests that there is a pre-existing belief that this type of psychedelic treatment works. Charles Marmar, chairman of the department of psychiatry at NYU Langone, was candid in expressing this belief during a recent press conference.

“We believe we will be successful over time in achieving FDA approval,” Marmar 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 psychiatric illness. “

The findings in the new research are certainly promising, showing that psilocybin may be useful in the treatment of alcohol use disorder. But in presenting this new study and underestimating the impact of the placebo problem, the researchers have somewhat uncovered a bias that is relatively widespread in the world of modern psychedelic science. A fundamental belief that these drugs work will soon be adopted, and the research currently being conducted is designed to serve and validate that preexisting belief.

The new study was published in JAMA Psychiatry.

Source: NYU Langone Health

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