Psilocybin, the hallucinogen behind the trippy effects of "magic mushrooms," may help people with alcohol use disorder cut down on or stop drinking when they take the drug in conjunction with talk therapy.
In a recent clinical trial, the results of which were published Wednesday (Aug. 24) in the journal JAMA Psychiatry, people with alcohol dependence received two doses of either psilocybin or a placebo medication – specifically, diphenhydramine (Benadryl), which would not be expected to affect the participants' symptoms.
Once considered a distinct condition, alcohol dependence now falls under the broader classification of alcohol use disorder, a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences.
In addition to medication, all participants were offered psychotherapy sessions during the trial: four sessions prior to their first medication dose; four between the first and second doses; and four during the month after treatment.
Both treatment groups reduced their drinking during the 32-week trial, but the group given psilocybin improved more dramatically.
The rate of heavy drinking in the psilocybin group dropped by about 83 percent compared with pretreatment levels, compared with a drop of about 51 percent in the placebo group.
Eight months after receiving their first dose, 48 percent of the psilocybin group had stopped drinking altogether, compared with 24 percent of the placebo group.
"I stopped drinking right after my first psilocybin session. It worked that quickly for me," Jon Kostas, a trial participant in the psilocybin group, told reporters at a news conference Aug. 24. "This eliminated all my cravings."
The therapeutic effects of psilocybin and therapy were "considerably larger" than those reported for existing drugs used to treat alcohol use disorder, and it's "remarkable" that the effects persisted for months after treatment, Dr. Michael Bogenschutz, lead study author and the director of the NYU Langone Center for Psychedelic Medicine, said at the news conference.
"If these effects hold up in future trials, psilocybin could be a breakthrough in the treatment of alcohol use disorder," he said.
The idea of using psychedelics to treat alcohol use disorder (AUD) dates to the 1960s and 1970s, when scientists began testing LSD ( lysergic acid diethylamide) for this purpose, Dr. Henry Kranzler, director of the Center for Studies of Addiction at the University of Pennsylvania (UPenn) Perelman School of Medicine, and Emily Hartwell, a clinical psychologist at UPenn, who were not involved in the trial, wrote in a commentary also published in JAMA Psychiatry.
Although relatively small, those early LSD trials hinted that the trip-inducing drug could help patients reduce their alcohol consumption and avoid the negative consequences of alcohol use more effectively than placebo pills or stimulants, such as ephedrine or amphetamine, could. However, political pressures soon brought such psychedelic research to a grinding halt, Nature News reported.
"The article by Bogenschutz et al. in this issue of JAMA Psychiatry reflects a rekindling of interest in the use of hallucinogens to treat AUD, an approach that, despite its early promise, has been quiescent for half a century," Kranzler and Hartwell wrote.
The new trial included 93 participants, ages 25 to 65, who had been diagnosed with alcohol dependence based on criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4); in the newer DSM-5, the condition would be classified as alcohol use disorder.
In the 12 weeks prior to screening, the participants drank alcohol on three-quarters of the days included in that time frame, and they drank heavily on more than half of the days. (Heavy drinking is defined as five or more drinks in a day for men and four or more drinks in a day for women.)
Once recruited, the participants were randomly sorted into two treatment groups – psilocybin or placebo – and in an attempt to reduce bias, both the participants and the trial organizers were unaware of these assignments.
However, more than 90 percent of the participants and supervising therapists correctly guessed which medication had been administered, likely due to the drugs' dissimilar effects. This somewhat limits the study's results because the trial was not truly double-blinded, as intended.
Diphenhydramine can be mildly psychoactive at the doses used in the trial, but the placebo still didn't come close to mimicking the mind-altering effects of psilocybin, Bogenschutz said. This lack of appropriate placebos is an inherent challenge of conducting psychedelic research, he added.
The treatment sessions took place four weeks apart and were supervised by a team of therapists and medical staff. Participants received a slightly higher drug dose during their second session, provided they agreed to the increase.
At the first session, people in the psilocybin group received 25 milligrams per 154 pounds (70 kilograms) of body weight, and during the second, the dose was either 30 mg or 40 mg for the same amount of weight, depending on how intense each participant's first trip had been.
Several mild, short-lived side effects – including headache, nausea, and anxiousness – were more common in the psilocybin group than in the placebo group.
That said, several serious adverse events took place outside the clinic during the trial and all of these occurred in the placebo group. These included severe vomiting and psychiatric admissions due to suicidal ideation that happened during binge drinking episodes.
"We did not detect any significant safety issues related to psilocybin," Bogenschutz said. However, because the drug raises blood pressure and heart rate and can sometimes cause incapacitating psychological effects, it's critical that patients take the drug only under careful supervision, he noted.
Trial participants experienced a range of emotions and perceptual experiences while on psilocybin – some pleasant, some painful.
However, following the acute experience of their trip, many patients in the placebo group reaped significant benefits from taking the drug, in combination with undergoing therapy.
"It definitely impacted my life, and I'd say it saved my life," Kostas said.
But how, exactly, does the treatment work? "The truth is, we don't know," but researchers have proposed some possible explanations, Bogenschutz said.
Like LSD, psilocybin plugs into structures in the brain called serotonin 2A receptors, which appear in high quantities in regions of the wrinkled cerebral cortex involved in high-level cognitive functions, such as introspection and executive function, Live Science previously reported.
It's thought that, by activating these receptors, psychedelics can boost connectivity between brain networks, allowing signals to zip between different brain areas with greater ease than usual.
In the context of depression, it's thought that this psychedelic-driven mechanism may help people break out of rigid, negative patterns of thinking.
More broadly, psilocybin may "reset" brain circuits in such a way that "new learning is possible in a way it wasn't before," Dr. Charles Marmar, chair of the Department of Psychiatry at NYU Langone Health, said at the news conference.
This, in turn, may accelerate the learning process facilitated by talk therapy, he said.
"We can hypothesize that there's this enhanced potential for change, and in the context of therapy … the psilocybin may enhance the ability of people to make those changes," Bogenschutz said.
But again, more research is needed to fully understand the mechanism by which psilocybin treats alcohol addiction.
Next year, Bogenschutz and his colleagues will launch a larger trial that will take place at 15 sites and likely take two to three years to complete.
At that point, the US Food and Drug Administration will dictate if and when the treatment can be approved for widespread use.
Although the timeline for when that may happen is uncertain, Marmar said the NYU team anticipates the approval will eventually come.
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