Psychedelics and Depression Treatment: A Mixed Bag
There’s been a lot of chatter recently regarding psychedelics as potential treatments for depression. This buzz is sometimes warranted, but not always. From DMT to magic mushrooms, and even the venom of the Colorado River toad—quite an interesting option, I must say—many substances have been put through their paces in clinical environments lately.
However, a comprehensive review of around two dozen clinical trials has quieted some of that excitement. Researchers from London, Philadelphia, and San Francisco have concluded that at least some of the benefits often credited to psychedelics might actually stem from the placebo effect.
Let’s be real: when people are on psychedelics, they know it. No matter how much clinical teams try to create a blind study, participants are usually quite aware they’re experiencing something intense.
This awareness creates a challenge for traditional antidepressants in these studies. Researchers can more easily anonymous a subject’s experience of whether they’re taking the actual medication or a placebo through various blinding techniques. To make for a fairer comparison, the team focused on open-label trials of traditional antidepressants—meaning studies where participants are aware of what they are taking—against studies that have focused on psychedelics.
Comparative Results
In their analysis, the researchers found that psychedelics and traditional antidepressants performed similarly overall. In fact, traditional antidepressants had a slight edge, scoring 0.3 units better on the Hamilton Depression Rating Scale (HAM-D) compared to psychedelics. This difference, however, wasn’t substantial—statistically or clinically speaking—according to their findings published in JAMA Psychiatry.
“Our findings don’t negate the promising results around psychedelic treatments,” emphasized Balázs Szigeti, a clinical data scientist at UCSF. “We also demonstrate that psychedelics do help with depression,” he added, noting that they just don’t outperform traditional options in open-label scenarios, which feels a bit anticlimactic given the buzz.
Psychedelics vs. Placebo
It’s important to note that whenever studies have tested psychedelics against true inactive placebos, these drugs have often shone. Using a 17-item version of HAM-D, they found that psychedelics scored about 7.3 units better than a placebo, while conventional antidepressants scored around 2.4 units better than their placebos.
The researchers delved into a significant amount of peer-reviewed literature, considering nearly 600 studies before settling on 24 that provided a fair basis for comparison. They analyzed 16 open-label trials of traditional antidepressants involving 7,921 patients, alongside eight studies on psychedelics with just 249 patients, where participants were acutely aware of which treatment they received.
Despite all the thoroughness, some experts raised concerns about potential biases introduced by the differences in study design and patient criteria. Robin Carhart-Harris, a neurology and psychiatry professor at UCSF who wasn’t part of this particular research, described the outcomes as ambiguous. He stated, “It’s framed as comparing apples to apples, but it’s more like apples to oranges,” emphasizing the complexity of the comparisons.
Clearly, a fresh approach is needed to eliminate these unintended biases in future research on psychedelics. But for the time being, it’s not solely about the results; rather, it’s about the journey taken along the way.
