The long-running campaign against smoking could find reinforcements from the new wave of research into psychedelics.
Though much of the attention around psychedelics has focused on depression and other mental health conditions, researchers believe these substances also hold the potential to transform addiction treatment.
A new study makes the strongest case yet for a psychedelic drug's impact on smoking, which remains the leading cause of preventable death in the U.S.
The trial, conducted by a team at Johns Hopkins University, compared nicotine patches to the active ingredient in magic mushrooms, known as psilocybin.
At the end of six months, those who had taken just one dose of psilocybin had more than six times greater odds of being abstinent from cigarettes than their counterparts who relied on the nicotine substitute.
Everyone in the study also underwent cognitive behavioral therapy for smoking cessation over the course of 13 weeks.
"I was surprised by the sheer magnitude of the effect," says Matthew Johnson, the study's author and a professor of psychiatry at Johns Hopkins.
The findings, published in the medical journal JAMA Network Open on Tuesday, came from a sample of 82 current smokers, who were randomly separated into two groups.
Similar to other psychedelic trials, the participants had support from facilitators to make sure they were comfortable and prepared for their trip. They ingested a relatively high dose of pure psilocybin.
While under the influence, they lay in a room wearing eye shades and listening to soft music, but their overall experience was "self-directed," says Johnson.
Because there was no placebo, everyone who took psilocybin knew they were getting the drug.
While this can skew the results, Johnson says ensuring that participants are properly blinded has been an ongoing challenge in the study of psychedelics, given the mind-altering effects, which is why they opted for a different study design.
In total, 17 participants who took psilocybin had stayed off cigarettes at the half-year mark; only four in the nicotine group had achieved that.
The findings will need to be replicated in a larger study — and ideally in a more diverse population — but they raise an "exciting" prospect, says Megan Piper, who directs the UW Center for Tobacco and Research Intervention and was not involved in the current research.
"It's been 20 years since we've had a new medication to help people quit smoking," she says. "We need something novel, and this is definitely a novel approach."
Currently, there are seven medications on the market for smoking cessation. Most of them are nicotine replacement products, such as gums, lozenges and patches. There are also two medications, varenicline and bupropion.
A third could receive drug approval later this year.
The chance of successfully quitting cigarettes without any support is dismal. If you take medication and have counseling, Piper says the long-term success rate hovers between 20% to 30% per attempt.
"That still means 70% of people are returning to smoking. So how do we help those folks?" she says.
There are relatively few well-controlled studies on psychedelics and addiction. Psilocybin for alcohol dependence has shown promise, and trials are ongoing. Interest in ibogaine, particularly for opioid use disorder, has gained traction in recent years.
However, investment in psychedelic research has largely centered on proving its effectiveness for mental health conditions such as depression, anxiety and post-traumatic stress disorder, says addiction psychiatrist Dr. Brian Barnett, who's at the Cleveland Clinic Lerner College of Medicine and wasn't part of the study.
"This is cutting-edge work," he says. "Smoking is still a massive public health problem."
And unlike the current mainstays of smoking cessation, psilocybin doesn't target nicotine receptors, meaning "it's a very different treatment approach from just trying to replace or sort of mimic the drug that's being misused," says Barnett.
He suspects the intensive therapeutic support was also crucial to the trial's success.
"It's not the drug by itself here," he says. "It's really harnessing the neuroplastic and learning effects that happen after the [drug] exposure."
This new study builds on promising data from a smaller trial, also done by Johnson, more than 10 years ago. Those earlier findings, paired with these more recent results, led the National Institutes of Health to award him funding for a larger, ongoing trial that includes a placebo arm.
Brain imaging results from this latest study, which are still being analyzed, may offer further clues as to why the treatment worked. "We already know that when people are on a compound like psilocybin, the brain is communicating with itself in very different ways," he says.
What's evident from conversations with past study participants is that psilocybin can occasion a shift in perspective — and a new sense of agency.
"Rather than falling into the same stories, these same patterns, it seems that things are shaken up and they can step outside of that and try something different," he says.
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