Quick Facts

• Single psilocybin dose combined with therapy gave smokers six times greater odds of quitting versus nicotine replacement
• 17 participants who took psilocybin stayed smoke-free at six months, compared to only 4 in the nicotine group
• First potential breakthrough smoking cessation medication in 20 years targets brain differently than existing treatments

A single dose of psilocybin helped smokers quit at dramatically higher rates than standard nicotine replacement therapy in a new Johns Hopkins study published Tuesday in JAMA Network Open.

The randomized trial of 82 current smokers found those who received psilocybin had more than six times greater odds of staying cigarette-free after six months. Seventeen participants in the psilocybin group remained abstinent at the half-year mark, while only four in the nicotine replacement group achieved this.

Novel Treatment Protocol

Participants received a relatively high dose of pure psilocybin in a controlled clinical setting. While under the drug’s influence, they lay in a room wearing eye shades and listening to soft music in what researchers called a “self-directed” experience with facilitator support.

All study participants also underwent 13 weeks of cognitive behavioral therapy for smoking cessation. The psilocybin session was designed to complement this therapeutic approach.

Brain-Based Breakthrough

“I was surprised by the sheer magnitude of the effect,” said Matthew Johnson, the study’s lead author and Johns Hopkins psychiatry professor.

Unlike current smoking cessation medications, psilocybin doesn’t target nicotine receptors. “It’s a very different treatment approach from just trying to replace or sort of mimic the drug that’s being misused,” said Dr. Brian Barnett, addiction psychiatrist at Cleveland Clinic who was not involved in the study.

Brain imaging results from the study, still being analyzed, may reveal why the treatment worked. Johnson noted that psilocybin causes the brain to “communicate with itself in very different ways.”

Filling Critical Treatment Gap

The results address a major public health need. Smoking remains the leading cause of preventable death in the United States, yet less than 1 in 10 adults who smoke succeed in quitting each year.

“It’s been 20 years since we’ve had a new medication to help people quit smoking,” said Megan Piper, who directs the UW Center for Tobacco and Research Intervention and was not involved in the research. “We need something novel, and this is definitely a novel approach.”

Currently, seven smoking cessation medications exist on the market. Most are nicotine replacement products like gums and patches. With optimal treatment combinations, success rates for quitting reach 25 to 35 percent at six months.

Next Steps

The National Institutes of Health has funded Johnson for a larger ongoing trial that includes a placebo arm. This addresses a key limitation of the current study – participants who received psilocybin knew they were getting the active drug.

The research builds on Johnson’s smaller trial from over 10 years ago and represents growing federal support for psychedelic research. Compass Pathways announced Tuesday it expects potential FDA approval for psilocybin depression treatment in late 2026 or early 2027.

“This is cutting-edge work,” Barnett said. “Smoking is still a massive public health problem.”

Read more: A dose of psilocybin helps smokers quit in new study