Just one dose of psilocybin relieves OCD symptoms for months

A single dose of psilocybin—the active ingredient in magic mushrooms—rapidly alleviates symptoms of obsessive-compulsive disorder (OCD), according to the first placebo-controlled study to test the psychedelic for a mental health condition. The effects also appear to persist for at least 12 weeks, suggesting that psilocybin could provide lasting relief.

“If we give you a trip, we think we can break the cycles of obsessive thinking and behavior,” he says David Nutt at Imperial College London, who was not involved in the research. “The whole point of OCD therapy is to teach people to behave differently. So instead of checking the lights 15 times, you check them twice.”

O 1 to 3 percent of people have OCDa condition characterized by obsessive thoughts and compulsive habits that can be overwhelming. Treatment usually includes talking therapy and antidepressants, but between 40 and 60 percent of people with OCD don’t respond to them.

Psilocybin—and other psychedelics like ketamine—have shown promise for mental health conditions. To get a more detailed idea of ​​its potential, Christopher Pittenger at the Yale School of Medicine and his colleagues decided to test psilocybin for OCD in the first randomized, placebo-controlled trial.

The team recruited 28 adults who had lived with OCD for an average of two decades and had tried at least two different treatments without success. All were rated for the severity of their symptoms using a standard scale that gives a score between 0 and 40. They were then randomly assigned to either receive a single oral dose of psilocybin (0.25 milligrams per kilogram of body weight) or niacin (250 milligrams), also known as vitamin B3, which acted as a placebo.

The dose of psilocybin was sufficient to give participants a psychedelic trip, which tends to involve major changes in perception, thinking and emotion. “It’s pretty intense, although it varies from person to person,” says Pittenger.

After 48 hours, the symptom scores of the 14 people who received psilocybin decreased by an average of 9.76 points, while those who took niacin remained about the same. “The speed and durability of the improvement seen after a single dose of psilocybin is remarkable,” he says Alex Kwan at Cornell University in Ithaca, New York.

A week later, about 70 percent of those taking psilocybin still had about a 35 percent reduction in symptom scores, and the benefits persisted at a 12-week follow-up. “It’s definitely better and faster than other OCD medications,” says Nutt, who participated in a recent non-placebo-group study that similarly found a small dose of psilocybin reduced OCD symptoms.

Kwan says that seeing such improvement in people who have already tried several standard treatments suggests that psilocybin is wiring the brain in a fundamentally different way, but its exact mechanism for helping with OCD is unclear. “If we can uncover this biology, it could change the way we think about treating many psychiatric disorders, not just OCD,” he says.

One idea is that psilocybin increases the plasticity of the brain, so that thoughts that seemed rigid and dominant can become less powerful. This is profound in all psychedelics, says Nutt, who recently showed that a single dose of the psychedelic DMT reduced symptoms of depression. “Before, their thinking was dominated by depressive thoughts, but after psychedelics, their brains are more flexible and they push them aside instead of agreeing with them,” he says.

Another idea is that psilocybin recalibrates the relationship between the brain’s default mode network, which is involved in rumination and self-perception, and other areas of it, Pittenger says. We also know that a single dose of psilocybin can rewire the brain and can also boost mental health by reducing inflammation.

However, the drug could have safety concerns. While studying at Yale, one person who already had persistent suicidal thoughts began actively planning it. The danger subsided after standard monitoring, but Pittenger says it underscores the need for clinical safeguards when administering psilocybin medically. Larger studies also need to confirm the drug’s effectiveness and safety, the best dose and who is most likely to benefit or be at risk, he says.

Another recurring problem with psychedelic research is that the effects of these drugs mean that study participants can often judge whether they received them or a placebo. The team tried to mitigate this by using a dose of niacin, which can cause psychedelic events such as flushing and increased heart rate. However, Pittenger says most participants still had a clear idea of ​​what they were getting. “That’s a weakness of the study, as it is with most fieldwork like this,” he says.

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