Psychedelic Drug May Be As Effective as Your Antidepressants

Recent research is increasingly shining a light on the therapeutic effects of psilocybin—the compound in certain fungi that, when digested, produces hallucinogenic effects. And now, a new study finds that it may be just as effective as existing treatments for major depression.

Researchers at the Centre for Psychedelic Research at Imperial College London found that psilocybin may be at least as effective as antidepressants, including commonly-prescribed selective serotonin reuptake inhibitors (SSRIs), in treating moderate-to-severe depression. This marks the first published data from preliminary human trials examining the effect of psilocybin-assisted psychotherapy to treat major depressive disorder (MDD).

The current study also provides evidence that incorporating psilocybin into the clinical model may lead to more efficient therapies, Robin Carhart-Harris, PhD, study author and head of the research center, tells Verywell. "[Psilocybin therapy] improved depressive symptoms severity much more quickly than the SSRI," he says. This evidence for rapidity complements recent findings that the psychedelic produces longer-term effects—up to a month—after a single high dose. The study was published in the New England Journal of Medicine in mid-April.

Gabby Agin-Liebes, PhD, clinical psychologist and researcher at the University of California San Francisco, tells Verywell that the findings represent a milestone in her line of research. "This is the first study of its kind comparing two doses of psilocybin to the gold standard medication treatment (SSRI antidepressants) for depression in one of the top medical journals," she says.

While additional research in more diverse populations is needed, the results suggest that a revision of treatment options for disorders like depression is on the horizon. "If it turns out that psilocybin is as effective as SSRIs but can provide long-term relief after two doses and with fewer side effects, that's very impressive," Agin-Liebes adds.

And if evidence continues to support psilocybin as a treatment option, Carhart-Harris says, institutions will need to adapt to the science.

"It's going to take a brave society," Carhart-Harris says. "I think that's where we are right now. It requires some guts on the part of policymakers to try and work out how they can integrate this into social systems."

Psilocybin Versus Antidepressants

Researchers recruited 59 individuals with long-standing moderate-to-severe depression. They were randomized into two groups over a six-week period. To prevent participants from knowing which treatment they were getting, both groups were given one treatment and one placebo.

Psilocybin group: Thirty participants received two separate doses of 25 mg of psilocybin three weeks apart, plus six weeks of daily placebo pills.

Antidepressant group: Twenty-nine participants received two separate doses of 1 mg of psilocybin, doses so low that they were unlikely to have an effect, three weeks apart (placebo), plus six weeks of daily oral escitalopram, an SSRI commonly sold under the brand names Cipralex and Lexapro.

During the psilocybin sessions, researchers placed participants in a specialist clinical setting, in which they "listened to a curated music playlist and were guided through their experiences by a psychological support team, which included registered psychiatrists," the press release explained.

To evaluate changes in depression, participants rated the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) before and after the six weeks. On the QIDS-SR, scores range from zero to 27; the higher the score, the greater the depression. At baseline, the psilocybin group scored 14.5 whereas the escitalopram group scored 16.4.

Benefits Beyond Improving Depression

In general, participants from the psilocybin group showed a greater reduction in depression symptoms, although the difference between groups was not statistically significant. Still, Carhart-Harris says, psilocybin was more broadly effective, improving factors beyond just core depressive symptoms.

"For example, it made people feel better about themselves and about their life," he says. "They started enjoying and getting pleasure from stuff again, and they were more accepting of things. They were less anxious. They felt like they were flourishing more." Amidst all of these changes, he adds, they reported improvements in their work and social life.

More specifically, participants in the psilocybin group, when compared to the escitalopram group, saw:

• An average reduction in QIDS-SR score by eights points versus six points
• 70% experienced at least 50% reduction in symptoms, versus 48%
• 57% reported remission of symptoms, or a score of 0-5, versus 28%

While the data points to psilocybin as the more effective treatment, for now, researchers only claim it's at least as effective due to a lack of statistical significance.

At the same time, there are several limitations to this study. In addition to the small sample size and lack of a control group (that received both treatments as placebos), the majority of participants were white men from similar educational backgrounds. Because of this, the results can't be applied to society at large.

"We will need additional research with larger, more racially/ethnically diverse study samples and longer follow-up periods to fully address many questions," Agin-Liebes says. "Nevertheless, these findings are very encouraging."

How Psilocybin Works

The present study further supports a treatment that's already gaining traction across the U.S. In late 2020, Oregon became the first state to legalize the therapeutic use of psilocybin as scientists are learning more and more about its benefits.

When you ingest psilocybin, the body converts it to psilocin, which produces psychedelic experiences. In short, the drug is thought to "reset" the brain by quieting structures involved in the default-mode network (DMN), which is said to carry the ego or sense of self. The DMN is most active when ruminating on repeated thoughts, Agin-Liebes says. "Psilocybin seems to relax the activity in this network, which is hyperactive in individuals with major depression, and allows for helpful perspective shifts that may alleviate depressive thought patterns."

While the DMN is relaxed, brain regions that don't usually interact ramp up their connectivity, producing hallucinogenic effects such as seeing music or hearing colors.

Experiencing these effects after having ingested psilocybin, be it in the form of magic mushrooms or a pill, is known as "tripping." A trip usually lasts four to six hours, after which the brain is thought to integrate the new information, kind of like a computer turning on again after installing an update.

Past studies suggest that psilocybin-assisted therapy "helps individuals let go of rigid, negative thought patterns," Agin-Liebes says. "In other words, it gives them a break from the relentless barrage of self-criticism and judgment, and provides them increased access to their emotions." If these experiences go on to affect patients long-term, she adds, they can learn "to be present and break free of their habitual tendencies to become entangled with stressful patterns and negativity."

Agin-Liebes says other reported experiences include:

• Enhanced feelings of connectedness with the self, others, and the world
• Enhanced ability to confront, process, and accept difficult emotions that had been suppressed
• Catharsis and release, which can assist in coming to terms with long-term grief and other avoided emotions

To facilitate possible benefits, experts recommend taking the drug when prepped and in the presence of mental health professionals. "The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants," the survey authors write.

Agin-Liebes adds that psilocybin-assisted treatment could help people who haven't responded to, or who don't like the side effects of antidepressant drugs. "There is much we don't know about the long-term effects of daily SSRI use on brain health, and psilocybin-assisted therapy could be an attractive alternative treatment," she says.

The Future of Psychedelic Treatment

O. Pete Kelly, PhD, a clinical psychologist based in Ottawa, tells Verywell that psychedelic drugs like psilocybin could bring a sea of changes to therapeutic practice. "I can tell you as a psychotherapist—to move somebody's personality one standard deviation on a particular measure is unheard of," he says. "So these are clearly very powerful compounds that we're dealing with here."

At the same time, Kelly says he's not surprised by the findings. The evidence for psilocybin as a treatment for mood disorders, addiction, and even eating disorders has been mounting, and people share experiences that seem outside the realm of what traditional therapies can provide. "I've done a lot of therapy myself, and I wonder about the other dimensions out there," he says. "From a therapeutic perspective, I see the limitations of conventional psychotherapy and I wonder about how much more we could be unfolding this."

Carhart-Harris says he began studying psychedelics for the same reasons: to unfold untapped parts of the human psyche and bring them to the measurable, scientific realm. It all started a few decades ago when he became interested in psychoanalytic theories. "The idea that there is an unconscious mind, and then there's often conflict between the ego and the unconscious mind," he explains. "And then I thought, well, this is fascinating, but it doesn't look that scientific."

Now that his research is informing a movement in psychological treatment, the real challenge, he says, will be trying to adapt society to it. "It's more convenient if you just have to give a drug," he says, whereas psilocybin-assisted therapy isn't so simple. "We all want that human component, but it does bring in a cost factor, which is difficult when you have an industrialized healthcare system trying to treat the largest number of people possible."

But if science shows that psilocybin therapies work better than SSRIs, for example, and prevent relapse, then policymakers will have more reason to look long-term and see that incorporating these therapies can be economically viable.

"I don't think psychedelic psychotherapy is ever going to become the norm or displace normal everyday psychotherapy," Kelly says. Instead, psychedelics might be integrated into "stepped care," or programs designed to treat different levels of mental health problem severity. "Ultimately for many, but not all, psychedelic psychotherapy will reflect a higher intensity version of what we do day-to-day."