Just 1 dose of LSD could relieve anxiety for months, trial finds

A single dose of the psychedelic drug LSD may ease generalized anxiety disorder for months, a clinical trial has found.

The trial results, published Thursday (Sept. 4) in JAMA, include data from 194 people with moderate to severe anxiety across the U.S. The study compared these participants' responses to different doses of LSD against a placebo treatment. It found that the drug alleviated symptoms in many patients for at least three months after just one exposure.

That said, participants who were given low doses of LSD — either 25 or 50 micrograms — did not see a significant change in their symptoms. The effect kicked in only at higher doses — either 100 or 200 micrograms — and those given 100-microgram doses had the best results.

In fact, 12 weeks out from treatment, about 47% of the people who were given 100 micrograms were in remission, based on a standardized anxiety rating scale. And about 65% of the people in that group saw their scores on the scale fall by at least half. By comparison, only about 20% of the placebo group was in remission at the 12-week mark and about 30% saw their scores halved.

"This work has the potential to make significant contributions to the emerging field of psychedelic drug research," Dr. Claudio Soares, a professor of psychiatry at the Queen's University School of Medicine in Ontario, wrote in a commentary about the trial. It's the first study to examine how different doses of LSD compare with a placebo for relieving anxiety. In addition, the trial didn't explicitly incorporate psychotherapy into the treatment, meaning it could help pin down whether LSD in and of itself has an anti-anxiety effect, he added.

"Furthermore, the study highlighted an early response to treatment and positive effects on comorbid depressive symptoms, both of which are promising findings that should guide future trials," Soares said.

Related: 1 psychedelic psilocybin dose eases depression for years, study reveals

While there are approved anti-anxiety drugs, not all patients respond to them, the trial runners noted in their report. Estimates suggest about 50% of patients do not have an adequate response to first-line anxiety treatments, such as benzodiazepines or serotonin selective reuptake inhibitors (SSRIs, which are also used for depression).

As such, there's still a need for more effective, well-tolerated anti-anxiety medicines, the trial runners argue.

Enter LSD. The psychedelic is thought to trigger its mind-altering effects — such as visual hallucinations and a feeling of being high — in part by enabling communication between brain cells that don't normally interact. It's thought that this action might trigger a period of enhanced plasticity in the brain, during which a person with anxiety could break out of the harmful thought patterns that characterize the condition. But this mechanism is not fully understood and is still being studied.

Trials that have combined LSD with psychotherapy hinted that the drug can have a positive and sustained effect in treating anxiety. But because these trials were testing two interventions — LSD plus therapy — it's hard to know what LSD was contributing on its own.

The new trial aimed to investigate that question by including people who were not undergoing psychotherapy. In all, 18% of the participants were receiving external psychotherapy when they entered the study and continued receiving therapy during the study, the report noted.

At baseline, the 194 participants scored an average of 30 on an anxiety scale from 0 to 56, where the threshold for "severe" anxiety is 24. A score of 7 or less indicates remission. Patients given the 100-microgram dose saw, on average, a 21-point drop in their scores.

"A treatment effect emerged 1 day after the dosing day and persisted through week 12," the report authors noted.

The vast majority of side effects tied to the treatment were expected and resolved once the dosing of the drug concluded. These effects included visual perception changes, nausea, headache and euphoric mood. Notably, side effects were reported across all the study groups, including the placebo group, but occurred at the highest rates in the high-dose groups. For instance, more than 90% of the 100-microgram group reported hallucinations, as did 100% of the 200-microgram group.

Two people reported "feeling intoxicated" in the 50- and 100-microgram groups, respectively, but felt normal by the end of the dosing session.

Although the side effects were generally mild to moderate in severity, they did prompt a handful of people to drop out of the trial, so the LSD treatment may not be tolerable to all patients.

The trial does have some limitations, including the short follow-up time of only three months and the inclusion of some patients who still underwent therapy during the trial, Soares said. But in all, the trial provides crucial data that could help "further inform regulatory pathways for the use of psychedelic drugs as stand-alone treatments," he said.

Future research will be needed to evaluate how well the effects of the drug last over longer time frames, particularly after a single dose, he concluded.