Ca psilocybin, the active ingredient in psychedelic mushrooms, corresponds to the antidepressant ability of a commonly prescribed antidepressant?
The first comparison, conducted by scientists from the Center for Psychedelic Research at Imperial College London and published in the New England Journal of Medicine on Wednesday, indicated that the psychedelic had at least the symptoms of the condition as well as escitalopram, an antidepressant better known under the brand name Lexapro. However, outside experts said the study is designed to make it impossible to know whether psychedelic mushrooms are actually more effective than escitalopram in other measures of well-being, a limitation they describe as ‘unfortunate’.
These researchers praised the authors of the study for paving new ground with more careful research on psilocybin – a significant achievement for a stigmatized and in many places illegal drug. But they also criticized the decision to make a single, basic depression questionnaire for the primary outcome of the study, as the researchers also did a number of other wellness assessments that could give psilocybine a head start.
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‘What is important about this is that the first randomized study with an appropriate [drug] comparison group to see how effective psilocybine can be, ”said Boris Heifets, a neuroscience researcher at Stanford who studied psychedelics and was not part of the new study.
But although there were ‘very strong positive signals that psilocybine actually performed better than the antidepressant, the study was designed to prevent any conclusions from being drawn about the results’, Heifets added.
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As for the signals, ‘it’s a wash,’ he said.
Robin Carhart-Harris, lead author of the journal and head of the Imperial Center for Psychedelic Research, said he regretted the decision to cite the depression measure as the primary outcome of the study, but noted that the criterion is regulated internationally. the past.
“In retrospect, I want us to make these other measures of well-being the primary measure,” he said. “However, the world – the Food and Drug Administration, the European Medicines Agency – does not recognize the measures as valid.”
Carhart-Harris and his co-authors included the other measures in the supplementary material of the study, although it could not be used to draw clinical conclusions in the paper.
The research, a randomized controlled trial that took place over the course of six weeks, involved treating participants with medication and intensive psychotherapy, including a mix of personal and telephone-based sessions during which participants were invited to discuss their illness and any problems. discuss the study. There were also two long sessions with psilocybin therapy, where participants were linked to two mental health professionals, including a psychologist or psychiatrist who supervised their psychedelic experience.
The 59 participants in the study, aged 18 to 80 years, of whom 66% were male and 88% white, were divided into two treatment groups. One received daily antidepressants and two very small doses of psilocybin during the sessions; the other one received daily placebo pills in place of the antidepressants and two heavy doses of psilocybin during the sessions.
All participants met the clinical definition of major depressive disorder and were told to stop taking the current medication before starting the study. The researchers or participants were not told what treatment they would receive. To meet expectations in general, both groups were told they would receive psilocybin, but the dose amounts were not disclosed.
Psilocybin is known to produce powerful, vivid hallucinations and colorful visualizations, which is why the researchers worked during the sessions to create a kind of safe haven for participants. It took place in an Imperial College research facility on two days with a distance of three weeks.
“It’s often a very intense emotional, roller coaster ride for people,” said Rosalind Watts, clinical director of the Imperial Center for Psychedelic Research and co-author of the article.
Under the care of two mental health professionals, including one to two psychiatrists or psychologists, participants were invited to lie down, cover their eyes, play on a playlist of soft forest breezes, chirping birds, soft guitar and low chanting, and even holding hands. with one of the professionals.
While members of the psychedelic cohort received 25 milligrams of psilocybin during the sessions, which are considered a medium to heavy dose of the drug, those in the antidepressant group received 1 milligram. Such a low dose is usually offered in psychedelic studies instead of a placebo to control the impact of disappointment on the results. Without it, ‘you might see the so-called nocebo effect where people know they are in the placebo arm and it actively aggravates their psychiatric condition,’ Heifets said.
At the beginning and end of the six-week study, participants completed the primary depression questionnaire, a 16-item self-study designed to determine the severity of depression, called the QIDS-SR-16. They also conducted ten other wellness tests, including one designed to evaluate their sense of connection with nature and other people, one to measure anxiety levels and another to evaluate functionality at work and in social environments. No serious adverse events were reported in the study, and the rates of such incidents were similar between the two groups.
The depression scores showed no statistically significant difference in improvement outcomes between the two groups; on average, depression scores dropped – meaning it improved – by eight points in the psychedelic group and six points in the antidepressant group. Almost all of the other ten tests showed more benefits for psilocybin than escitalopram.
Of the nearly a dozen clinical scales they used to measure depressive symptoms, they somehow chose the one scale that showed no difference between the two treatments as their most important. [primary] outcome measure, ”Heifets said.
And as secondary measures, the other ten scales lack the detailed statistical analysis required of primary measures, so no definitive clinical conclusions can be drawn about them or included in the study results.
What could cause the differences between the two drugs in the secondary outcomes have Carhart-Harris, Heifets and Watts theories.
Psychedelics are believed to produce their antidepressant effects by interfering with negative and isolating thought patterns, but rather encouraging greater and more widespread feelings of connection with other people, nature or both.
Previous studies have suggested that it helps to explain in part why drugs seem to act as enhancers of psychotherapy: it encourages openness to intense emotions and seems to enable fresh perspectives on past and present behaviors. Watts and Heifets said they believe they see the effects through the lines of the supplementary material of the study, where psilocybin participants saw higher improvements in social and work functionality and reported more emotional breakthroughs.
“The mechanism of the change almost seems to be that the people in the psilocibin group are really thriving and showing a whole bunch of things that are really related to this kind of connection,” Watts said.
Heifets agreed. “It does show that psychedelics catalyzes a process of human engagement,” he said. ‘This is what’s so remarkable here. This is assisted psychotherapy. ”
Olivia Goldhill reported.