Psilocybin pilot study in post-treatment Lyme disease: symptoms down 40% at six months, but no control group

A small study from Johns Hopkins University School of Medicine, published in Scientific Reports and covered by PsyPost on 3 October 2026, tested psilocybin — the psychoactive compound in “magic mushrooms” — in people with post-treatment Lyme disease (PTLD).

The condition

Lyme disease is a tick-borne bacterial infection that usually responds to antibiotics, but an estimated 10–20% of patients keep having fatigue, pain, sleep problems or trouble concentrating after treatment. There is currently no established treatment for PTLD, and persistent symptoms do not necessarily mean the infection is still active.

What the researchers did

• Design: open-label pilot study, no control group; everyone knew they were receiving psilocybin.
• Participants: 20 adults with documented, treated Lyme disease and persistent symptoms (486 people were pre-screened). Average age 44, 11 women, 90% white, median illness duration 5.7 years.
• Treatment: an 8-week programme with preparatory and follow-up sessions with facilitators and two supervised psilocybin doses — 15 mg in week 4 and, in week 6, 25 mg for 18 participants (two stayed at 15 mg after strong reactions).

Results

• At the main endpoint, one month after the second dose, general symptom burden was 42% lower than at baseline (52% lower at two weeks).
• At six months it remained 40% lower; mental and physical quality-of-life scores were each about 13% higher.
• Depressive symptoms, sleep problems, fatigue and pain also improved across follow-ups.
• No serious adverse events were judged related to psilocybin. Common side effects were temporary rises in blood pressure (90%), headache (65%) and rapid heart rate (35%). Two serious events — passive suicidal thoughts after starting a new antidepressant, and a rectal-cancer diagnosis — were judged unrelated.

Limitations

Without a control group it is impossible to tell whether the changes came from psilocybin, the psychological support, participants’ expectations, the natural course of the illness or regression to the mean. The sample was small, mostly white and highly educated, and cognitive problems — a core PTLD complaint — were not measured. The authors call the findings preliminary and say randomised controlled trials are warranted. Psilocybin is illegal or tightly controlled in many countries; this is research, not a treatment recommendation — talk to your doctor about persistent symptoms.