Psilocybin for Chronic Pain and Depression

(TRANSCEND Trial)

Overseen By Muhammad Ishrat Husain, MBBS, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Methadone, Buprenorphine, Morphine

Disqualifiers: Pregnancy, Substance use disorder, Schizophrenia, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a component of magic mushrooms, can help individuals with chronic neuropathic pain and treatment-resistant depression. Researchers aim to assess participants' tolerance to psilocybin and its effectiveness in reducing symptoms. It suits adults who have experienced long-term nerve pain and have tried at least two antidepressants without success. As a Phase 2 trial, this research measures psilocybin's effectiveness in an initial, smaller group, offering a chance to potentially benefit from a novel treatment.

Will I have to stop taking my current medications?

Yes, you will need to taper off your current antidepressant and antipsychotic medications for at least 2 weeks before starting the trial and for the duration of the study, if your doctor confirms it's safe.

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

Research has shown that psilocybin, the main ingredient in "magic mushrooms," might be safe to use with therapy for depression that hasn't improved with other treatments. Studies have found that patients usually tolerate psilocybin well. In one study, patients took different doses, including 25 mg, and many experienced a significant reduction in depression symptoms. However, some people did experience mild to moderate side effects, such as headaches, nausea, or anxiety, which are common with many medications.

These results are encouraging, but it's important to note that this trial is still in phase 2. Researchers are still carefully studying the treatment's safety and effectiveness. Those considering joining a trial should consult a healthcare professional to understand the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for chronic pain and depression, which often include medications like antidepressants or opioids, psilocybin offers a novel approach. Psilocybin, the active ingredient derived from certain mushrooms, works on the brain's serotonin receptors, potentially leading to profound changes in mood and perception. Researchers are particularly excited because psilocybin has shown promise in providing relief after just one or two doses, unlike standard treatments that require daily use and may take weeks to become effective. This rapid and enduring effect could revolutionize how chronic pain and depression are managed.

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

Research has shown that psilocybin, a key component of magic mushrooms, can greatly reduce symptoms of depression. In one study, a single 25 mg dose of psilocybin led to significant improvements in depression scores over three weeks. Another study found that this dose maintained its antidepressant effects for up to a year. Psilocybin has shown particular promise for individuals with treatment-resistant depression, where other treatments have failed. While less information exists on psilocybin for chronic pain, its strong antidepressant effects suggest potential benefits, as pain and depression often require similar treatments. Participants in this trial will receive a 25 mg dose of psilocybin to evaluate its effects on chronic pain and depression. ^{1 3 5 6 7}

Who Is on the Research Team?

Muhammad Ishrat Husain, MBBS, MD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for adults with chronic nerve pain and depression that hasn't improved with standard treatments. Participants must be able to undergo psychotherapy sessions and take psilocybin safely.

Inclusion Criteria

I am willing to gradually stop taking my current antidepressant and antipsychotic medications under a doctor's care.

I have been diagnosed with major depression without psychosis.

Must be willing to comply with all study procedures

Exclusion Criteria

I have been diagnosed with a psychiatric disorder defined in the DSM-5.

I do not have any other serious health conditions that could affect the study or my safety.

I cannot take psilocybin due to health risks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 25 mg psilocybin orally with psychotherapy

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Long-term follow-up

Participants are monitored for adverse events and retention over 24 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study tests the effects of a single dose of Psilocybin (25 mg), combined with psychotherapy, on individuals suffering from long-term neuropathic pain and depression resistant to usual treatments.

How Is the Trial Designed?

Group I: Psilocybin (25 mg) Experimental Treatment 1 Intervention

One capsule of psilocybin 25 mg will be taken orally with a glass of water.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

Psychedelic compounds from mushrooms, such as LSD and psilocybin, show promise in treating mental health disorders like major depressive disorder and anxiety, with studies indicating rapid and long-lasting effects after micro-dosing or acute dosing.

These compounds not only have a good safety profile but also may modulate the immune system, suggesting potential applications in treating autoimmune diseases and chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain. Meade, E., Hehir, S., Rowan, N., et al.[2022]

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40047545/

Results From a Long-Term Observational Follow-Up Study ... Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

3. compasspathways.com compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England Journal ...

4. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression COMP360 showed a statistically significant reduction in TRD symptom severity compared to placebo, with a clinically meaningful MADRS score ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression For individuals undergoing psilocybin therapy for TRD, response outcomes at 3 and 12 weeks post-dosing could be predicted using the EBI measure or with NLP ...

6. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

News Details A single administration of COMP360 demonstrated a highly statistically significant and clinically meaningful reduction in symptom severity ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

Efficacy, Safety, and Tolerability of COMP360 in ... This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study.