The hype has been deafening on psychedelics as a promising treatment for depression, sometimes justified, sometimes not. Seemingly everything, from DMT to magic mushrooms to (a personal favorite) the trip-inducing venom of the Colorado River toad, has seen its mettle tested in the lab in recent years.
But a sweeping new review scrutinizing the results of two dozen clinical trials has brought the volume down a little on that noise. A trio of psychiatric researchers from London, Philadelphia, and San Francisco have determined that, at least, some of the positive benefits attributed to psychedelics can be chalked up to the placebo effect.
Quite simply, you can’t not know when you’re taking psychedelics. No matter how hard clinical researchers try, their patient volunteers (trust me) are always well aware (vividly aware, third eye opened) of the fact that they’re tripping.
That reality has put traditional antidepressants at a disadvantage in clinical studies. In these studies, researchers are much more capable of neutralizing a subject’s awareness that they’re taking the actual drug versus an inert placebo via various “blinding” or treatment-anonymizing strategies. So, in order to level the playing field, the team restricted their new meta-analysis to only “open label” trials of traditional antidepressants—meaning studies that did not include “blinding”—for a fairer comparison against clinical studies that have examined psychedelics as antidepressants.
About the same, no better
Psychedelics and traditional antidepressants, the team found, performed more-or-less just as effectively as one another. In fact, traditional antidepressants appeared to just slightly outperform psychedelics by 0.3 units on a common depression-rating questionnaire for patients, the Hamilton Depression Rating Scale (HAM-D). The difference was not enough to prove either drug class as better in any statistically or clinically significant way, as they reported their results in the journal JAMA Psychiatry on Wednesday.
“Our results do not disprove the exciting results about psychedelic treatments,” study coauthor Balázs Szigeti, a clinical data scientist at the University of California, San Francisco (UCSF), emphasized to New Scientist. “We also show that psychedelics are effective at treating depression.”
“It is just that they are not more effective than open-label traditional antidepressants,” he explained, “which feels underwhelming given the attention.”
But psychedelics hit differently
Traditionally, whenever depression researchers have attempted to test psychedelics against a true inactive placebo, as a control, the mind-expanding drugs have dramatically outperformed.
Based on a 17-item version of the HAM-D, researchers found that psychedelics typically scored a mean of 7.3 HAM-D units better than a placebo. Conventional antidepressants, by contrast, only fared about 2.4 HAM-D units better than their placebos.
The researchers combed through the peer-reviewed journal literature, considering and discarding nearly 600 studies before landing on the 24 that helped them develop a more fair basis of comparison. They focused on 16 open-label trials of traditional antidepressants, with a total of 7,921 patients, in which the participants were expressly told whether they were taking the real drug or the placebo. They then compared these to eight studies of psychedelics, with a total of 249 patients, in which patients really couldn’t help but notice which kind of pill they had swallowed.
Despite all that effort, however, some researchers felt the team might have introduced errors by collating studies that could vary in terms of patient inclusion criteria, total sample size of the patient pool, and other factors.
Robin Carhart-Harris, a professor of neurology and psychiatry at UCSF who was unaffiliated with the work, described the results to New Scientist as inconclusive.
“It’s proposed as comparing apples with apples, when really it’s more like comparing apples with oranges,” said Carhart-Harris, whose own work has compared psychedelics to ordinary antidepressants head-on.
Clearly, a mind-expanding, higher consciousness will be needed to devise new testing methods that could finally remove these unintended biases from future psychedelics research. But for now, it’s not about the destination. It’s the trip.
