Effects of Psilocybin in Post-Treatment Lyme Disease

NCT05305105 | Completed Phase 1 FDA Drug

• 2 other identifiers: IRB00281685132642
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effects of psilocybin on Lyme disease symptom burden and quality of life in people with Post-Treatment Lyme Disease (PTLD).

Conditions

Post-Treatment Lyme Disease; Chronic Lyme Disease; Lyme Disease, Chronic

Keywords

Psilocybin; Hallucinogen; Psychedelic

Outcome Measures

Primary Outcomes (2)

• Change in multi-system symptom burden as assessed by the General Symptom Questionnaire (GSQ-30) score

  The GSQ-30 is a validated and reliable instrument developed to assess multi-system symptom burden among patients with Lyme Disease. Total score ranges from 0 to 120, with higher scores indicating greater symptom burden.

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

• Change in functional health and well-being as assessed by the Short Health Form (SF-36) score

  The SF-36 (SF-36) is a multi-purpose, short form health survey that yields an 8-domain profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. The number of questions contributing to each domain varies from 2 to 10. Domain scores range from 0 (poorest health status) to 100 (best health status).

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

Secondary Outcomes (2)

• Change in fatigue as assessed by the Fatigue Severity Scale (FSS) score

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

• Change in pain as assessed by the Short-Form McGill Pain Questionnaire (SF-MPQ)

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

Other Outcomes (2)

• Change in depression as assessed by the Beck Depression Inventory-II (BDI-II)

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

• Change in sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI)

  Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose

Study Arms (1)

Psilocybin

EXPERIMENTAL

Participants will complete an 8-week course of study treatment including two doses of psilocybin with psychological support administered approximately 2 weeks apart.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Dosing at the first session will be 15mg. For the second session participants will either remain at the initial dose, or increase to 25mg.

Psilocybin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age.
• Capable of providing written informed consent for participation into the study.
• Willingness to allow the study team to review past medical records.
• At least one current PTLD-defining symptom (widespread pain, fatigue, or neurocognitive dysfunction) following completion of standard, recommended antibiotic therapy for treatment of Lyme disease, and that appeared in the first two years following first evidence of Lyme disease.
• Medical record documentation of meeting the Centers for Disease Control (CDC) case definition for clear diagnosis and treatment of early or late Lyme disease while living in a Lyme-endemic area. In other words, a history of physician-documented single or disseminated erythema migrans rash, late Lyme arthritis, or late Lyme neuropathy, OR Medical record documentation of meeting the CDC case definition for probable early or late Lyme disease. In other words, a history of abrupt onset of flu-like symptoms with or without a misdiagnosed rash, and concurrent positive serology while living in a Lyme-endemic area.
• Received treatment with a recommended course of antibiotics.
• Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests.
• Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be ≤300mg/day.

You may not qualify if:

• Meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for moderate or severe substance use disorder (excluding tobacco) within the past 5 years.
• Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be ≤300mg/day.
• Currently taking lithium or other primary centrally-acting serotonergic medications, whether over-the-counter or prescription (e.g., efavirenz, 5-hydroxytryptophan, St. John's wort).
• Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or corrected QT interval (QTc) \>450msec), transient ischaemic attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic \>139 or diastolic \>89, or heart rate \>90 bpm.
• Renal disease (creatinine clearance \< 40 ml/min using the Cockcroft-Gault equation).
• Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I or II Disorder.
• Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder.
• Past-year hallucinogen use
• Received the Lyme vaccine when it was available (1998-2002).
• Development of unexplained chronic pain, chronic fatigue syndrome, fibromyalgia, autoimmune disease, or unexplained neurologic symptoms before first evidence of Lyme disease.
• Cancer or malignancy in the past 2 years.
• Epilepsy with history of seizures.
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia.
• Current dementia or related disorders including but not limited to, Alzheimer's Disease, vascular dementia, Lewy body dementia, and frontotemporal disorders.
• Current or past major immunosuppressive illness or medications.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Steven & Alexandra Cohen Foundation: collaborator
• Usona Institute: collaborator

Study Sites (1)

Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (2)

• Fallon BA, Zubcevik N, Bennett C, Doshi S, Rebman AW, Kishon R, Moeller JR, Octavien NR, Aucott JN. The General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease. Front Med (Lausanne). 2019 Dec 6;6:283. doi: 10.3389/fmed.2019.00283. eCollection 2019.

  PMID: 31867334 BACKGROUND

• Rebman AW, Bechtold KT, Yang T, Mihm EA, Soloski MJ, Novak CB, Aucott JN. The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome. Front Med (Lausanne). 2017 Dec 14;4:224. doi: 10.3389/fmed.2017.00224. eCollection 2017.

  PMID: 29312942 BACKGROUND

Related Links

• Online Study Screener

MeSH Terms

Conditions

Post-Lyme Disease Syndrome

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Lyme Disease; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Albert Garcia-Romeu, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: March 31, 2022
• Study Start: July 1, 2022
• Primary Completion: October 26, 2024
• Study Completion: April 7, 2025
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)