Psilocybin for Chronic Pain

Overseen By Mehmet Sofuoglu, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, Anxiolytics

Disqualifiers: Diabetes, Epilepsy, Schizophrenia, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of psilocybin, a compound found in "magic mushrooms," to determine if it can manage chronic pain and boost motivation to quit smoking. Researchers aim to assess whether this psychedelic treatment is safe and well-tolerated for individuals dealing with ongoing pain who also smoke cigarettes. The trial seeks veterans who have smoked daily for at least a year, experience bothersome chronic pain, and are not currently seeking help to quit smoking. As an Early Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications, especially if you regularly use psychotropic medications like antidepressants or antipsychotics, as they can interact with psilocybin. It's best to discuss your specific medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that psilocybin therapy is likely to be safe for humans?

Earlier studies have found psilocybin safe when used in controlled environments, with some people experiencing only short-term side effects. Research shows that psilocybin may help with physical pain and mental health problems. Although not yet approved for medical use in the U.S., psilocybin has shown potential in treating conditions like chronic pain and depression. Safety data from studies indicate that while temporary side effects can occur, participants generally tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it offers a completely new approach to managing chronic pain by targeting the brain's serotonin receptors, which may alter perception and emotional response to pain. Unlike traditional pain medications that often rely on opioids or anti-inflammatory drugs, psilocybin's psychedelic properties could provide relief by rewiring pain pathways and reducing the emotional burden of chronic pain. Researchers are excited about this treatment because it has the potential to offer long-lasting relief with fewer doses and reduce the risk of addiction associated with conventional painkillers.

What evidence suggests that psilocybin might be an effective treatment for chronic pain?

Research has shown that psilocybin, the active ingredient in "magic mushrooms," may help treat chronic pain. Studies have found that psilocybin can reduce pain in conditions like nerve damage and inflammation. It affects brain areas related to pain, potentially offering long-lasting relief. Psilocybin also encourages neuroplasticity, helping the brain change and possibly improving pain symptoms over time. Although researchers are still studying its effects on chronic pain, early results suggest it might benefit people who smoke and have chronic pain. Participants in this trial will receive a 25mg dose of psilocybin to further investigate its potential benefits for chronic pain. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals who experience chronic pain following surgery and have chronic obstructive pulmonary disease (COPD). They must also be current smokers. The study aims to see if psilocybin, the active compound in 'magic mushrooms,' can help manage their pain and motivate them to quit smoking.

Inclusion Criteria

Not seeking treatment at the time of the study for tobacco use

In good health as verified by medical history, screening examination, and screening laboratory tests

For women, not pregnant as determined by pregnancy screening, nor breastfeeding, and using acceptable birth control methods (e.g., oral contraceptives)

Exclusion Criteria

Suicide attempt or ideation in the past year

A close family member has bipolar disorder or schizophrenia.

I am not on any antidepressants, antipsychotics, mood stabilizers, or anxiety medications that could react badly with psilocybin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Adaptation/Preparation

Participants undergo an adaptation/preparation session before treatment

1 week

1 visit (in-person)

Treatment

Participants receive a 25 mg oral dose of psilocybin under medical and psychiatric monitoring

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing the safety and effectiveness of psilocybin therapy on improving chronic pain and increasing motivation to stop smoking in patients with both conditions. Psilocybin's potential benefits for quitting smoking and certain types of chronic pain like migraines are being explored.

How Is the Trial Designed?

Group I: Psilocybin 25mg Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11811946/

Psychedelics and chronic pain: self-reported outcomes on ... Psilocybin was reported as the most effective psychedelic in treating both physical (29.4%; n = 137/466), and mental (48.9%; n = 133/270) health ...

2. pennmedicine.org pennmedicine.org/news/psilocybin-targets-brain-circuits-to-relieve-pain

Psilocybin targets brain circuits to relieve pain In studies using mice with chronic nerve injury and inflammatory pain, researchers found that a single dose of psilocybin reduced both pain and ...

3. nature.com nature.com/articles/s41593-025-02068-0

Single-dose psilocybin rapidly and sustainably relieves ... Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia ...

4. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.17420

Psilocybin as a novel treatment for chronic pain - Askey By promoting neuroplasticity, psilocybin could provide long-lasting improvements in pain-related affective and sensory dysfunction in ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05351541

Psilocybin Therapy for Chronic Low Back Pain This study evaluates whether psilocybin therapy helps patients cope with chronic low back pain more effectively.

6. sciencedirect.com sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ... The results of this study indicate that psilocybin appears to be safe in a controlled setting with transient adverse effects. The safety data can partially be ...

7. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1527783/full

Preliminary safety and effectiveness of psilocybin-assisted ... Survey studies have reported that a number of people using psilocybin and other psychedelics for a range of chronic pain conditions often report decreased pain ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06355414

Psilocybin in Chronic Low Back Pain and Depression This study seeks to provide insight on psilocybin's effects on mechanisms of chronic pain among patients with co-morbid chronic low back pain and depression ...