# Pilot study of psilocybin in patients with post-treatment lyme disease

## TL;DR

A pilot study found that psilocybin treatment significantly improved symptoms and quality of life in patients with post-treatment Lyme disease, with effects lasting up to six months.

## Contribution

This is the first pilot study to investigate psilocybin as a potential treatment for post-treatment Lyme disease symptoms.

## Key findings

- Participants showed significant improvements in PTLD symptom burden and quality of life after psilocybin treatment.
- Improvements in mental and physical health scores were sustained for six months following treatment.
- Psilocybin was well-tolerated with no serious adverse events reported.

## Abstract

Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. Although antibiotics effectively treat most cases, an estimated 10–20% of patients develop post-treatment Lyme disease (PTLD), a chronic syndrome marked by fatigue, pain, cognitive difficulties, mood disturbance, and reduced quality of life. There are no established treatments for PTLD. The serotonin 2A receptor agonist psychedelic psilocybin has recently shown potential antidepressant and anxiolytic effects in clinical trials as well as preliminary evidence for anti-inflammatory effects in animals. This open-label, single-arm pilot study evaluated the effects of psilocybin in 20 participants with well-characterized PTLD. The 8-week intervention included two psilocybin sessions (15 mg in week 4; 15 or 25 mg in week 6) with psychological support. Participants (11 women, 9 men, mean age 44, median illness duration 5.7 years) showed significant improvements in PTLD symptom burden and quality of life from study enrollment through 1-month following the second dose of psilocybin (primary endpoint), with significant benefits sustained through 6 months. At the 6-month follow-up, general PTLD symptom burden (GSQ-30) was decreased 40% from baseline (p < .001; Cohen’s dz = − 1.22, 95% CI [− 2.12, − 0.78]), and health-related quality of life improved across both SF-36 domains, with Mental (MCS) and Physical (PCS) component scores increasing 13% (p ≤ .013; Cohen’s dz = 0.46–0.59). Secondary outcomes assessing mood, fatigue, sleep quality, and pain also showed significant and sustained improvement through 6 months (all p ≤ .003; Cohen’s dz = 0.56–1.25). No serious adverse events (AEs) related to the study intervention occurred. The most common AEs attributed to psilocybin were transient hypertension (90%), headache (65%), tachycardia (35%), pain (20%), and fatigue (15%). Preliminary findings support that psilocybin-assisted treatment was feasible and well-tolerated among the sample. Clinical outcomes indicated potentially long-lasting benefits of psilocybin-assisted treatment, warranting further investigation for PTLD.

Trial registration: ClinicalTrials.gov Identifier NCT05305105, registered 22/03/2022.

The online version contains supplementary material available at 10.1038/s41598-026-38091-9.