Johns Hopkins pilot study shows psilocybin may ease persistent Lyme disease symptoms

Lyme disease is the most common tick-borne illness in the United States, with nearly half a million people diagnosed each year. The infection responds well to antibiotics in many cases, but for a substantial portion of patients, the treatment marks only the beginning of their struggle. Months or years after the bacteria has been cleared, they remain trapped in cycles of exhaustion, cognitive fog, and persistent pain—symptoms that conventional medicine has largely failed to address.

This gap in treatment options has pushed some researchers and patients toward an unlikely candidate: psilocybin, the psychoactive compound found in certain mushrooms. A pilot study conducted at Johns Hopkins University and published in Scientific Reports offers preliminary evidence that the drug, administered under clinical supervision, may provide meaningful relief for people suffering from post-treatment Lyme disease.

The trial involved 20 participants who had documented histories of Lyme disease and were experiencing ongoing symptoms despite antibiotic treatment. Researchers, led by Albert Garcia-Romeu at the Johns Hopkins Center for Psychedelic and Consciousness Research, carefully selected participants using stringent criteria to rule out other conditions that mimic post-treatment Lyme disease symptoms. Over eight weeks, each volunteer received two doses of psilocybin—first 15 milligrams, then 25 milligrams two weeks later, with two participants remaining on the lower dose throughout. All sessions included close monitoring of vital signs and careful tracking of any adverse effects.

The results were striking. Two weeks after the final dose, participants reported a 52 percent reduction in overall symptom burden compared to their baseline. Six months later, that improvement held largely steady, with symptoms remaining 40 to 50 percent below where they started. Depression scores dropped 50 to 60 percent, sleep disturbance scores fell 40 to 50 percent, and fatigue severity decreased 25 to 30 percent. Pain scores declined roughly 40 to 50 percent across the trial. The researchers noted that these effect sizes were large and remained stable even when excluding statistical outliers. Side effects were mild and temporary—headaches, nausea, and elevated blood pressure occurred but resolved without serious incident.

Yet the researchers themselves are cautious about what these numbers actually mean. This was a small, uncontrolled trial with no placebo group, and participants knew they were receiving psilocybin. That knowledge alone can shape outcomes, particularly for subjective measures like fatigue and pain. Garcia-Romeu and his colleagues explicitly state that the results are preliminary and require rigorous, randomized, controlled, and blinded trials before any firm conclusions can be drawn about whether psilocybin actually caused the improvements or whether other factors were at play.

The interest in psilocybin for post-treatment Lyme disease sits within a broader exploration of psychedelics for chronic conditions that linger after infection. A 2025 pilot trial tested psilocybin-assisted therapy on five people with fibromyalgia and reported improvements in pain, mood, sleep, and overall functioning. A case study documented a woman whose long COVID symptoms allegedly improved after taking hallucinogens with a therapist, though details remain sparse. And in 2023, researchers published a case report of a 70-year-old man who had endured decades of Lyme disease and babesiosis, cycling through periods of remission and relapse, each lasting roughly two years. After three months of another relapse, he began microdosing psilocybin at 100 milligrams three times weekly, increasing to 125 milligrams after two weeks. Within two days his mood improved noticeably; within two weeks he reported feeling consistently well again and remained in remission while continuing the microdose regimen.

These scattered reports have drawn attention partly because conventional medicine offers so little for conditions like post-treatment Lyme disease, long COVID, and myalgic encephalomyelitis. No approved diagnostic test exists for post-treatment Lyme disease, and accepted treatments are largely absent. Patients and researchers are turning to hallucinogens out of necessity, not ideology. The Johns Hopkins team proposes that further investigation of psilocybin and other classic psychedelics should extend not only to post-treatment Lyme disease but also to long COVID, ME/CFS, and fibromyalgia—conditions that share similar patterns of lingering symptoms after infection or illness.

What comes next is the harder work: designing and executing the rigorous trials that can actually establish whether psilocybin causes these improvements or merely correlates with them. The researchers acknowledge that their current findings, while compelling, must be treated with caution. Biomarkers measured before and after treatment, along with detailed participant accounts, will be examined in future work. The study of hallucinogens for chronic pain, mental health, and inflammatory conditions is still in its infancy, and moving from preliminary pilot results to confirmed clinical efficacy will take years of careful research.