Post-Treatment Lyme DiseasePhase 1NCT05305105
Effects of Psilocybin in Post-Treatment Lyme Disease
A Phase 1 study testing Psilocybin in people with Post-Treatment Lyme Disease and Chronic Lyme Disease, run by Johns Hopkins University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-Treatment Lyme Disease, Chronic Lyme Disease, Lyme Disease, Chronic
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2022to 7 Apr 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- Currently pregnant or nursing.
- Currently of childbearing potential and not using effective methods of contraception.
- Not fluent in English.
- High risk for suicidal ideation or behavior (i.e., individuals who report suicidal ideation with intent or behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, or individuals with a suicide attempt within the past 3 years).
Trial locations and contacts
1 site in 1 country.
United States1 site
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
About this study
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).
Read the detailed description
This pilot study will evaluate the therapeutic potential of psilocybin in people with well-documented current Post-Treatment Lyme Disease (PTLD). Study measures will assess the impact of psilocybin-assisted treatment on overall symptom burden and quality of life in 20 people with PTLD. This is an open-label proof-of-concept trial in which participants will complete an 8-week course of study treatment including two psilocybin sessions (15mg in week 4 and 15 or 25mg in week 6) with psychological support, and follow-up assessments 1, 3, and 6 months after the final psilocybin session.
- Being tested
- Psilocybin
- Keywords
- Psilocybin, Hallucinogen, Psychedelic
- Medical subject headings
- Post-Lyme Disease Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Dosing at the first session will be 15mg. For the second session participants will either remain at the initial dose, or increase to 25mg.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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
The FSS was designed to detect and evaluate changes in fatigue over time in persons with chronic illness. Its research utility rests with its ability to measure fatigue severity and identify features that distinguish fatigue between other clinical features of chronic medical disorders, such as depression. Scores on the FSS range from a minimum of 9 to a maximum of 63, with higher scores indicating greater fatigue severity.
Measured: 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)
The Short-Form McGill Pain Questionnaire (SF-MPQ) was designed to provide a quantitative measure of pain that can be tested statistically and includes major classes of word descriptors used by patients to specify subjective pain experience. The SF-MPQ 15-item pain metric has summary scores ranging from 0 to 45 with a higher score indicating worse pain.
Measured: Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start1 Jul 2022
- Primary completion26 Oct 2024
- Study completion7 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Post-Treatment Lyme DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Steven & Alexandra Cohen Foundation, Usona Institute
- Responsible party
- Sponsor
- Investigators
- Albert Garcia-Romeu, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05305105
- Sponsor's protocol ID
- IRB00281685
- Other IDs
- 132642
- Status last verified
- Aug 2025
- First submitted
- 22 Mar 2022
- Last updated
- 20 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31867334Rebman 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.
PubMed 29312942Garcia-Romeu A, Naude GP, Rebman AW, So S, Yaffe A, Geithner I, Kozero EA, Yang T, Soloski MJ, Aucott JN. Pilot study of psilocybin in patients with post-treatment lyme disease. Sci Rep. 2026 Feb 25;16(1):7497. doi: 10.1038/s41598-026-38091-9.
PubMed 41741501
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Psilocybin in Post-Treatment Lyme Disease
- ClinicalTrials.gov ID
- NCT05305105
- Acronym / sponsor ID
- IRB00281685
- Keywords
- Psilocybin, Hallucinogen, Psychedelic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Steven & Alexandra Cohen Foundation, Usona Institute
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 26 Oct 2024 (actual)
- Study completion
- 7 Apr 2025 (actual)
- First posted
- 31 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This pilot study will evaluate the therapeutic potential of psilocybin in people with well-documented current Post-Treatment Lyme Disease (PTLD). Study measures will assess the impact of psilocybin-assisted treatment on overall symptom burden and quality of life in 20 people with PTLD. This is an open-label proof-of-concept trial in which participants will complete an 8-week course of study treatment including two psilocybin sessions (15mg in week 4 and 15 or 25mg in week 6) with psychological support, and follow-up assessments 1, 3, and 6 months after the final psilocybin session.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: PsilocybinParticipants will complete an 8-week course of study treatment including two doses of psilocybin with psychological support administered approximately 2 weeks apart. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ≥ 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.
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinDosing at the first session will be 15mg. For the second session participants will either remain at the initial dose, or increase to 25mg. | Drug | Psilocybin |
Primary outcome
Change in multi-system symptom burden as assessed by the General Symptom Questionnaire (GSQ-30) score
Time frame: Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose
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.
Change in functional health and well-being as assessed by the Short Health Form (SF-36) score
Time frame: Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose
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).
2 secondary outcomes
Change in fatigue as assessed by the Fatigue Severity Scale (FSS) score
Time frame: 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)
Time frame: Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Background: PubMed 31867334Fallon 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.
- Background: PubMed 29312942Rebman 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.
- Derived from this study: PubMed 41741501Garcia-Romeu A, Naude GP, Rebman AW, So S, Yaffe A, Geithner I, Kozero EA, Yang T, Soloski MJ, Aucott JN. Pilot study of psilocybin in patients with post-treatment lyme disease. Sci Rep. 2026 Feb 25;16(1):7497. doi: 10.1038/s41598-026-38091-9.
- Online Study ScreenerLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Garcia-Romeu, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Psilocybin in people with Post-Treatment Lyme Disease and Chronic Lyme Disease, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in multi-system symptom burden as assessed by the General Symptom Questionnaire (GSQ-30) score (time frame: Baseline, 2 weeks after final psilocybin dose, 1 month after final psilocybin dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05305105, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.