Psychedelics and Antidepressant Trials

The results of two studies using psilocybin, or psychedelics, to counteract the effects of depression were released this week and demonstrate how difficult these drugs are to study.

Psychadelic Studies

In one double-blind, German-based study, scientists gave 144 volunteers who had treatment-resistant depression a high or low dose of psilocybin or an “active” placebo, which has physical effects but is not hallucinatory, along with psychotherapy.

Volunteers who received the psilocybin showed some improvement and a larger reduction in symptoms six weeks later, authors of the study say, “the divergence between [the two results] renders the findings inconclusive.”

In another study, Balázs Szigeti at UCSF and his colleagues conducted an “open-label” study of psychedelics and traditional antidepressants. Volunteers for the study knew when they were receiving a psychedelic or antidepressant.

The research team assessed 24 trials to discover that psychedelics were not any more effective than traditional antidepressants.

Szigeti says, “When I set up the study, I wanted to be a really cool psychedelic scientist to show that even if you consider this blinding problem, psychedelics are so much better than traditional antidepressants, but unfortunately, the data came out the other way around.”

Study Highlights and Difficulties

In trials of traditional antidepressant drugs, the placebo effect is strong. Symptoms of depression are generally measured using a scale, and typically in trials, antidepressants lower symptoms by 10 points on that scale. Placebos can lower symptoms by eight points.

When psychedelics are used, there is a greater difference between the active drug and the placebo. David Owens, emeritus professor of clinical psychiatry at the University of Edinburgh, UK, says this is partly because volunteers who receive the hallucinogen know they are taking it and expect the drug to improve symptoms.

It is also partly because those who receive the placebo are also aware. Szigeti says the “nocebo” effect is placebo’s “evil twin — essentially, when you expect to feel worse, you will.”

Szigeti calls it the “knowcebo effect.” “It’s kind of like a negative psychedelic effect, because you have figured out that you’re taking the placebo.”

“While a placebo in a traditional antidepressant drug trial improves symptoms by eight points, placebos in psychedelic trials improve symptoms by a mere four points,” says Szigeti.

He adds, “If the active drug similarly improves symptoms by around 10 points, that makes it look as though the psychedelic is improving symptoms by around six points compared with a placebo. It gives the illusion of a huge effect.”

Owens believes those who work in the mental health field are desperate for new treatments, as there has been little innovation in 40 years, since the advent of selective serotonin reuptake inhibitors.

He says, “Psychiatry is hemmed in with old theories … and we don’t need another SSRI for depression.”

Szigeti says that psychedelics are inherently fascinating. “Culturally, they are exciting.”

He adds, “The placebo response is the expectation of a benefit. The better response patients are expecting, the better they’re going to get. Tempering the hype might end up making those drugs less effective.

“At the end of the day, the goal of medicine is to help patients. I think most [mental health] patients don’t care whether they feel better because of some expectancy and placebo effects or because of an active drug effect.”

Owens says, “These are potentially exciting times. But it’s really important we do this [research] well. And that means with eyes wide open.”

Sources:

New Scientist: Psychedelics may be no better than antidepressants for depression
Psychiatric Times: Dispelling Myths About Psychedelics: In Conversation With Guy Goodwin, MD
MIT Technology Review: Mind-altering substances are (still) falling short in clinical trials

Featured Image Courtesy of Leo Schleeo’s Flickr Page – Creative Commons License