Psilocybin for ALS

Overseen By Betsy Mosmiller

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Atypical antidepressants, Tricyclics, MAOIs, others

Disqualifiers: Severe speech impairments, Cardiovascular conditions, Epilepsy, Renal disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a psychedelic compound, can improve mood and quality of life for people with Amyotrophic Lateral Sclerosis (ALS) who also experience depression. Researchers aim to determine if this treatment can ease depression, enhance overall well-being, and improve daily functioning. The trial includes an open-label group where all participants receive psilocybin. Suitable candidates are those with ALS who can swallow tablets and have noticeable depressive symptoms. As an Early Phase 1 trial, this research focuses on understanding how psilocybin works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

If you are currently taking certain antidepressants, MAOIs, or other specified medications, you will need to stop them to participate in the trial. The protocol lists specific medications that cannot be taken regularly with psilocybin.

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

Research has shown that psilocybin can cause psychological side effects, such as hallucinations, and potential physical harm, depending on the dosage. Not everyone may tolerate psilocybin well. Current trials are in the early stages, so limited information exists on its safety for people with ALS. However, studies have explored psilocybin's effects on depression and distress, indicating some possible benefits. As this is an early trial, researchers continue to learn about its safety and proceed with caution. ^{1 2 3 4 5}

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

Unlike the standard treatments for ALS, which often include medications like Riluzole and Edaravone that aim to slow disease progression, psilocybin offers a novel approach by targeting the brain's neural circuits. Researchers are excited about psilocybin because it is derived from psychedelic compounds found in certain mushrooms, which may promote neuroplasticity—essentially helping the brain to reorganize and form new connections. This unique mechanism could potentially improve symptoms related to mood, cognition, and quality of life in ALS patients, areas where current treatments have limited impact.

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

Studies have shown that psilocybin might help slow the progression of ALS by entering the brain, influencing the growth of new brain cells, and reducing inflammation. Research suggests that psilocybin could also improve mood by affecting serotonin, a brain chemical that influences mood. This is important for ALS patients, who often experience depression. Early signs from animal studies suggest possible benefits, but studies in humans remain limited. More research is needed to confirm these effects in people with ALS. In this trial, all participants will receive psilocybin in an open-label arm to further investigate these potential benefits. ^{1 2 3 5 6}

Who Is on the Research Team?

Ambereen K Mehta, MD, MPH, FAAHPM

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ALS who meet specific diagnostic criteria, have a lung function measure (FVC) above 50%, can swallow tablets, and show significant depressive symptoms. It's not suitable for those who cannot take psilocybin orally or have conditions that exclude them from the study.

Inclusion Criteria

My condition meets the criteria for a diagnosis of ALS.

My lung function is more than half of what is considered normal.

I can swallow tablets by mouth, even if I have a feeding tube.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive psilocybin therapy over an 8-week course, including two psilocybin sessions at weeks 4 and 6

8 weeks

2 psilocybin sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 1 week, 1 month, 3 months, and 6 months post-treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing the safety and effects of psilocybin therapy on mood in ALS patients. It aims to see if this treatment can improve depression, quality of life, hopelessness, and functional status over six months.

How Is the Trial Designed?

Group I: Psilocybin Experimental Treatment 1 Intervention

All subjects will be in the same, open label arm

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a one-year double-blind trial involving 22 patients with amyotrophic lateral sclerosis (ALS), those treated with branched-chain amino acids (12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine) maintained muscle strength and walking ability, unlike the placebo group which experienced a decline.

The results suggest that branched-chain amino acids may provide a therapeutic benefit in preserving muscle function in ALS patients, highlighting their potential role in managing this progressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. Plaitakis, A., Smith, J., Mandeli, J., et al.[2019]

In a study of 153 ALS patients, riluzole was found to have an acceptable safety profile, with 50.3% experiencing adverse effects, primarily gastrointestinal issues, hepatotoxicity, and fatigue.

Riluzole's mechanism of action suggests it may also be beneficial for other neurodegenerative diseases related to glutamate excitotoxicity, warranting further investigation and monitoring for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis]. Roch-Torreilles, I., Camu, W., Hillaire-Buys, D.[2013]

A signal was detected indicating a potential link between statin use and amyotrophic lateral sclerosis (ALS) based on reports in the FDA's adverse event reporting system, with 91 cases identified.

However, a comprehensive analysis of 41 long-term clinical trials involving around 200,000 patient-years of exposure showed no increased incidence of ALS in patients treated with statins compared to those on placebo, suggesting that the initial signal may not indicate a true causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA's spontaneous adverse event reporting system. Colman, E., Szarfman, A., Wyeth, J., et al.[2019]

A new self-reported ALS disability scale called the Rasch-Built Overall ALS Disability Scale (ROADS) was developed, consisting of 28 questions that showed improved item targeting and high test-retest reliability (0.97) compared to the existing ALS Functional Rating Scale (ALSFRS-R).

The ROADS scale demonstrated better psychometric properties and responsiveness, making it a potentially valuable tool for assessing disability in ALS patients during clinical trials and in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS). Fournier, CN., Bedlack, R., Quinn, C., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06656702?term=psilocybin&aggFilters=status:rec%20act&viewType=Table&rank=8

Effects of Psilocybin in Patients With Amyotrophic Lateral ... This study aims to study the feasibility of psilocybin therapy for patients with Amyotropic Lateral Sclerosis (ALS) with depressed mood.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37167080/

Exploring the Potential Utility of Psychedelic Therapy for ... Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/21678421.2024.2441274

Full article: ALSUntangled #77: Psilocybin Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation ...

4. liebertpub.com liebertpub.com/doi/10.1089/jpm.2022.0604?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Exploring the Potential Utility of Psychedelic Therapy for ... If serotonergic psychedelics demonstrate efficacy in ALS rodent models, a head-to-head efficacy study would assist in identifying the most promising candidate ...

5. withpower.com withpower.com/trial/early-phase-1-sclerosis-10-2024-4d5c2

Psilocybin for ALS · Recruiting Participants for Phase ... This study aims to study the feasibility of psilocybin therapy for patients with Amyotropic Lateral Sclerosis (ALS) with depressed mood.

6. neals.org neals.org/people-living-with-als/educational-webinars/examining-psilocybin-for-existential-distress-in-patients-with-als

Examining Psilocybin for Existential Distress in People with ... This webinar will review current clinical data on psilocybin for depression and existential distress, discuss its potential therapeutic benefits/risks in ...