Psilocybin for Neuropathy

Overseen By Moran Amit, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

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

Disqualifiers: Bipolar, Psychosis, Uncontrolled diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if psilocybin, a compound in certain mushrooms, can reduce or prevent nerve damage from chemotherapy, known as chemotherapy-induced peripheral neuropathy (CIPN). It compares psilocybin treatment to standard supportive care and a placebo to assess effectiveness. The study seeks individuals diagnosed with breast, colorectal, or head and neck cancer who are about to begin specific chemotherapy types. Participants must travel to MD Anderson Cancer Center and adhere to specific guidelines during the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Do I need to stop my current medications for the trial?

Yes, you may need to stop certain medications. You must be off psychotropic medications (like antidepressants) for at least 2 weeks before the study, and some other medications must be stopped 5 half-lives before taking psilocybin. However, prescribed opiates and benzodiazepines can continue if you've been on a stable dose for a specified period.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, a compound in certain mushrooms, offers potential benefits. In studies on psilocybin therapy for chronic pain, 57% of participants reported a significant decrease in pain, suggesting its effectiveness in pain management. Additionally, psilocybin-assisted therapy has improved quality of life and pain control in patients with advanced cancer.

However, while psilocybin appears promising, information on its safety and tolerability remains limited. Most current evidence comes from animal studies or early human trials. In these studies, psilocybin was generally well-tolerated, but more detailed safety data, especially for conditions like nerve pain from chemotherapy, is still being gathered. Although the signs are encouraging, further research is necessary to fully understand psilocybin's safety for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuropathy?

Researchers are excited about using psilocybin for neuropathy because it offers a novel approach compared to traditional treatments like pain relievers and nerve-modulating drugs. Unlike standard options, psilocybin acts on serotonin receptors in the brain, potentially rewiring neural pathways to alleviate pain. One experimental approach involves giving two supervised oral doses before chemotherapy cycles, which might provide rapid relief and mood enhancement. Another approach uses subperceptual, or "microdosing," which could offer subtle symptom relief without significant psychedelic effects. These methods provide a fresh angle on managing neuropathy, sparking hope for more effective and faster-acting therapies.

What evidence suggests that psilocybin might be an effective treatment for chemotherapy-induced peripheral neuropathy?

Research has shown that psilocybin might help reduce pain linked to nerve damage. In studies with mice, psilocybin lowered pain behaviors and targeted brain areas to relieve pain. A single dose of psilocybin quickly and lastingly eased pain in situations similar to long-term nerve injury. A review of various studies found that 57% showed a significant drop in pain symptoms with psilocybin. While most findings come from animal studies, they suggest that psilocybin could potentially help manage pain in humans. This trial will explore different dosing strategies: Arm A involves two supervised oral doses one week apart before chemotherapy cycle 1, followed by two monthly supervised doses; Arm B involves subperceptual dosing every other day for two weeks during the pre-chemotherapy run-in; and Arm C follows standard care without the study drug. ^{1 2 3 6 7}

Who Is on the Research Team?

Moran Amit, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for English-speaking adults with breast, colorectal, or head and neck cancer scheduled for specific chemotherapy. They must be able to travel to MD Anderson Cancer Center, abstain from nicotine and certain drugs before psilocybin administration, have no major cognitive impairments or pre-existing neuropathy above Grade 1. Participants cannot have severe allergies, high suicide risk, unstable medical conditions, active substance use disorders, certain psychiatric conditions or family history of psychosis.

Inclusion Criteria

Fluent in English

Must demonstrate willingness to travel to MD Anderson Cancer center for all treatment and follow-up sessions, as well as consent to complete all evaluation instruments and assessments

My cancer (breast, colorectal, or head and neck) has been confirmed by lab tests.

Exclusion Criteria

Have an allergy or intolerance to any of the materials contained in either drug product

I am currently taking other medications.

Clinically significant suicidality or high risk of completed suicide

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Chemotherapy Dosing

Participants receive two supervised oral doses of psilocybin 1 week apart prior to chemotherapy cycle 1

2 weeks

2 visits (in-person)

Chemotherapy and Psilocybin Dosing

Participants receive two monthly supervised doses of psilocybin prior to chemotherapy cycles 2 and 3

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The NeuroGuard trial tests if psilocybin can prevent or lessen chemo-induced peripheral neuropathy compared to standard care and placebo in patients undergoing chemotherapy. It's a controlled study where participants are randomly assigned to receive either psilocybin or a non-active treatment while being monitored.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 1 Intervention

Standard of Care: Chemotherapy and supportive care per institutional guidelines; no study drug.

Group II: Arm B Experimental Treatment 1 Intervention

Subperceptual dosing every other day for 2 weeks during the pre-chemotherapy run-in (mailed 7×1 mg capsules in tamperevident packaging) prior to the first three cycles as above (21 total doses)

Group III: Arm A Experimental Treatment 1 Intervention

Two supervised oral doses 1 week apart prior to chemotherapy cycle 1 (Day 7 and Day 14), followed by two monthly supervised doses prior to chemotherapy cycles 2 and 3 (Day 42 and Day 70); total 4 doses.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12107474/

IUPHAR Article: Psilocybin induces long-lasting effects via 5 ... The present study suggests that classical psychedelics psilocybin and DOI are effective in reducing pain-like behaviors via 5-HT 2A R activation in two mouse ...

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

Single-dose psilocybin rapidly and sustainably relieves ... Psilocybin alleviates mood changes associated with chronic neuropathic and inflammatory pain-like states. We next assessed whether SNI- and CFA- ...

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

Psilocybin as a novel treatment for chronic pain - Askey We found that a single dose of psilocybin leads to a prolonged reduction in pain-like behaviours in a mouse model of neuropathy following ...

4. rapm.bmj.com rapm.bmj.com/content/50/11/845

Psilocybin and chronic neuropathic pain: a systematic review Psilocybin therapy demonstrated reductions in pain symptoms across various conditions listed, with 57% of the studies achieving statistically significant ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11271737/

Investigating the therapeutic efficacy of psilocybin in advanced ... Psilocybin-assisted therapy shows promising results in improving quality of life, pain control, and anxiety relief for patients with advanced cancer.

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

Preliminary safety and effectiveness of psilocybin-assisted ... However, clinical studies assessing the safety and tolerability of psilocybin and associated therapy in people with FM are limited.