Psilocybin for Depression in Alzheimer's

Overseen by Albert Garcia-Romeu, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Johns Hopkins University

Must not be taking: Antipsychotics, MAO inhibitors, others

Disqualifiers: Age 86+, Cardiovascular conditions, Seizure, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if psilocybin, a substance from certain mushrooms, can safely improve depression and quality of life in people with early Alzheimer's or Mild Cognitive Impairment. It works by changing brain activity related to mood. Psilocybin has been studied for its potential to reduce depression and anxiety, particularly in patients with life-threatening conditions.

Will I have to stop taking my current medications?

You may need to stop certain medications. You can continue taking acetylcholinesterase inhibitors, SSRIs, SNRIs, and bupropion if they have been stable for a while. However, you cannot take antipsychotics, MAO inhibitors, or other antidepressants, and you must avoid certain medications like sildenafil within 72 hours of psilocybin administration.

What data supports the effectiveness of the drug psilocybin for depression in Alzheimer's patients?

Research shows that psilocybin has been effective in reducing symptoms of depression in various psychiatric disorders, including major depressive disorder, with patients experiencing significant improvements even after just a few sessions. While specific data for Alzheimer's patients is limited, these findings suggest potential benefits for depression in this group as well. ^{1 2 3 4 5}

Is psilocybin safe for use in humans?

Psilocybin has been studied in healthy adults with escalating doses, showing a safety profile that is generally well-tolerated. However, it can cause rapid effects on the central nervous system, such as hallucinations and physical symptoms like ataxia (loss of control of body movements). While some studies suggest it may be safe under controlled conditions, caution is advised, especially in people with heart conditions. ^{1 6 7 8 9}

How is the drug psilocybin unique in treating depression in Alzheimer's patients?

Psilocybin is unique because it acts quickly and can provide long-lasting relief from depression symptoms with just one or two doses, unlike traditional antidepressants that often require daily use. It works by activating serotonin receptors in the brain, which can lead to improved mood and well-being. ^{2 5 10 11 12}

Research Team

Albert Garcia-Romeu, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for people with mild cognitive impairment or early Alzheimer's who are currently depressed. Participants must be able to commit to several long treatment sessions in Baltimore, MD, and have a close friend or family member involved in the study. Exclusions include severe mental health conditions, certain cardiovascular issues, insulin-dependent diabetes, and those on specific medications.

Inclusion Criteria

I have been diagnosed with Alzheimer's or Mild Cognitive Impairment.

I can attend long treatment sessions in Baltimore and follow-up meetings.

I am currently experiencing a depressive episode.

Exclusion Criteria

You have been diagnosed with schizophrenia, a psychotic disorder (unless it was caused by drugs or a medical condition), or bipolar I disorder in the past or currently.

I have tried various treatments for my current depressive episode, including psychotherapy, medications, and possibly ECT.

I agree not to take medications like sildenafil within 72 hours before taking psilocybin.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an 8-week course of study treatment including weekly psychological support and two psilocybin sessions

8 weeks

Weekly visits for psychological support, 2 psilocybin sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Psilocybin (Hallucinogen)

Trial Overview The trial is testing psilocybin's safety and effectiveness for treating depression in individuals with mild cognitive impairment or early Alzheimer's Disease. It aims to see if it can also improve their quality of life.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

Council On Spiritual Practices

Collaborator

Trials

1

Recruited

20+

Heffter Research Institute

Collaborator

Trials

15

Recruited

520+

Findings from Research

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]

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]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., 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]

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

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]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

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]

A single, moderate dose of psilocybin significantly reduced depressive symptoms in 52 participants with major depressive disorder, showing a decrease of 13.0 points on the MADRS scale compared to baseline, which was significantly greater than the placebo group.

54% of participants in the psilocybin group met the criteria for remission of depression 14 days after treatment, and no serious adverse events were reported, indicating a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. von Rotz, R., Schindowski, EM., Jungwirth, J., et al.[2023]

A proof-of-concept randomized controlled trial is being conducted with 60 adults suffering from treatment-resistant depression (TRD) to assess the feasibility and safety of combining psilocybin with risperidone, which is expected to block the psychedelic effects of psilocybin.

The study aims to provide pilot data on the antidepressant effects of this combination compared to psilocybin alone, potentially allowing for psilocybin to be used as a treatment for TRD without the need for a psychedelic experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial. Husain, MI., Blumberger, DM., Castle, DJ., et al.[2023]

Psilocybin, a naturally occurring compound similar to LSD, has been found to not cause serious health issues or dependency, suggesting a favorable safety profile.

Recent studies indicate that psilocybin may enhance feelings of wellbeing and is being investigated for its potential therapeutic effects on mood and anxiety disorders due to its action on the 5-HT2A serotonin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of psilocybin in the treatment of depression. Mahapatra, A., Gupta, R.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

7. England 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. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Role of psilocybin in the treatment of depression. [2020]