Psilocybin, the active hallucinogen found in psychedelic mushrooms – also known as “magic mushrooms” – can effectively alleviate a severe bout of depression when administered in a single dose and combined with talk therapy, a new clinical study found.
Adults with depression who were administered a single 25-miligram dose of psilocybin were more likely to experience significant improvements in their mental health – both immediately and for up to three months – than others who were randomly assigned smaller doses of the same drug, said the peer-reviewed study, which was published Wednesday in the New England Journal of Medicine.
“There’s something about the psychedelic experience that leads to a rapid resolution of depression symptoms,” said James Rucker, a consultant psychiatrist at King’s College London who worked on the trial. “We don’t really know what that is at the moment, but it’s very different to standard antidepressants.”
The trial’s findings could be an encouraging sign for the 16 million Americans estimated each year by the Centers for Disease Control and Prevention to have depression, many of whom struggle to find treatments that work for them. Its authors hope the study – which was relatively small, with just 79 participants receiving the 25 mg dose – will pave the way for eventual regulatory approval of psilocybin by the Food and Drug Administration for use as a drug against depression.
The new study randomly assigned 233 adults with depression three doses of psilocybin – 25 mg, 10 mg and 1 mg – across 22 sites in 10 countries. The authors found that the group given the largest dose recorded the most significant improvements in their depression, both immediately and for several weeks after.
Two-thirds of the study’s adult participants who were given a 25 mg dose of the active hallucinogen recorded a significant improvement in their depression within as little as three weeks, the researchers found. Within the same period, nearly one-third of those who were given the largest dose found their symptoms had been alleviated to the extent that they no longer qualified for a clinical diagnosis of depression.
After taking a single psilocybin capsule, the study’s patients were supervised in an environment where they experienced the drug’s hallucinogenic effect while lying down, wearing an eye mask and listening to music. Then they discussed their six-to-eight-hour “trip” with a psychotherapist, who guided them through the insights offered by the experience.’
Notwithstanding the headaches, nausea and dizziness reported by many as adverse side effects, most of the adults enjoyed the experience.
“Patients describe it as like a waking dream,” Rucker said, where “the nature and breadth of experience is expanded.” But unlike in a dream, the patient is fully aware of what is happening to them and more likely to remember it as a result – a potential explanation for its alleviation of depression symptoms, Rucker said.
Another notable result of the study was the immediacy of the effect researchers identified psilocybin was having on patients – usually as soon as the next day. It stands them in contrast to conventional antidepressants, which have been known to initially exacerbate symptoms before only taking effect four to six weeks later, if at all, according to a 2012 review into existing research on therapy options for depression.
The precise mechanism by which psilocybin acts against depression is unclear, but it may be connected to the unique way the hallucinogen allows people to access and interrogate their own emotions, the study’s authors suggested.
“People often gain some clarity into the reasons they might be depressed. They might be grieving for someone, but they’re unable to get in touch with that grief – just as an example,” Rucker said. “With awareness comes a sort of clarity.”
The authors concluded that larger and longer-term clinical trials were necessary to effectively determine the medical efficacy and safety of psilocybin, but they were hopeful that the drug could eventually receive regulatory approval.
The trial is the latest in a number of clinical studies examining the potential of psychedelics for treating mental health disorders. Among the drugs attracting renewed interest is ketamine, an anesthetic often used recreationally by partygoers, but which a recent study also found significantly reduced symptoms of depression.
No long-term data is yet available on its effectiveness, but early small studies found that ketamine therapy significantly and rapidly reduced depression symptoms in about 50 to 70 percent of patients. The FDA has already approved esketamine, a nasal spray treatment for depression based on ketamine, to be taken alongside conventional oral medicines.
Barriers on conducting clinical research into certain restricted substances, including psilocybin, have also eased in recent years. In 2018, the Drug Enforcement Administration announced that it was streamlining its application process for researchers wishing to study Schedule I substances, defined in 1971 as having “no currently accepted medical use and a high potential for abuse,” and which includes psilocybin.
“What people forget about psychedelics is that they were being used as medicines prior to 1971 when they essentially got caught up in the drugs war,” Rucker said. “We’re just picking up the baton of history.”
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