The Aztecs and Timothy Leary touted the psychological benefits of mind-altering psychedelic drugs. Now, science is finding out they may have been right.

Researchers are investigating the use of the mind-altering drugs psilocybin, for depression associated with advanced cancer, and MDMA, for post-traumatic stress disorder (PTSD). These drugs may also prove to be useful for other treatment-resistant psychiatric conditions. In fact, the entire December 2016 issue of the Journal of Psychopharmacology was devoted to the clinical utility of psychedelic drugs.

Psilocybin for cancer-related depression

Two small studies in this special issue of the Journal of Psychopharmacology looked at the effects of psilocybin, the active compound in what are commonly called magic mushrooms, on patients with advanced cancer who were experiencing depression and anxiety. The studies, from New York University (29 patients) and Johns Hopkins University (51 patients), found that treatment with a single dose of psilocybin, in combination with psychotherapy, led to an substantial reduction in depression and anxiety symptoms compared to a placebo (a very low dose of psilocybin. The benefit lasted up to eight months, with no serious side effects. These two studies were the most rigorous controlled trials of psychedelics in 50 years, according to the accompanying editorial.

Psilocybin was also shown to be safe and effective for treatment-resistant depression in a previous trial, published in The Lancet in 2015. But it included only 12 subjects.

Researchers are still not sure how psilocybin works. They speculate that a sub-type receptor for serotonin—the same neurotransmitter that many antidepressant drugs work on—is activated by the drug. But what would cause psilocybin to have the unusually long-lasting effect observed in the studies remains unclear.

MDMA for post-traumatic stress

The euphoric party drug 3,4-methylenedioxy-methamphetamine (MDMA), also known as Ecstasy or Molly, could be on its way to FDA approval for the treatment of PTSD. The FDA recently agreed to the start of a phase III clinical trial—the final step on a drug’s path to approval—for at least 230 patients. Researchers are so confident in the drug’s efficacy, they applied for “breakthrough therapy” status with the FDA, which could fast track its approval and availability to as early as 2021.

Eight million adults have PTSD in a given year, and 7 to 8 percent of people are likely to experience it sometime in their life, according to the Department of Veteran Affairs. In an unpublished study of MDMA-assisted psychotherapy, subjects diagnosed with PTSD were given either MDMA or a placebo during two eight-hour sessions, spaced drug three to five weeks apart. They continued with weekly psychotherapy in between. At a two-month follow-up, 83 percent of patients in the MDMA group no longer qualified as having PTSD, versus less than one-quarter of patients in the placebo (psychotherapy only) group. The benefits were maintained on average at a follow-up 4 years later, according to the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which funded the research.

Sexual assault victims, combat veterans, and police and firefighters were among the PTSD patients treated in two of six qualifying studies for the phase III trial. They had suffered from their PTSD symptoms for an average for 17 years, and none had responded to traditional prescription drugs or psychotherapy.