Psilocybin for Depression in Alzheimer's

Overseen By Hillary Jackson

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Antipsychotics, MAO inhibitors, others

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

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

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a hallucinogenic drug, can safely and effectively reduce depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). Researchers will assess if it can also enhance the quality of life for these individuals. Participants will receive psychological support and two doses of psilocybin during the study. The trial seeks individuals diagnosed with MCI or mild Alzheimer's who are experiencing depression. As an Early Phase 1 trial, this research aims to understand how psilocybin works in people, offering participants the opportunity to be among the first to explore its potential benefits.

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.

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

Research has shown that psilocybin is generally well-tolerated. For example, one study found that a 25 mg dose of psilocybin caused no serious side effects. This suggests that psilocybin might be safe for humans, especially in a controlled setting. However, psilocybin can cause temporary feelings of anxiety or confusion, common with hallucinogenic drugs. Overall, existing studies offer some reassurance about its safety, but close monitoring of participants during treatment remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it offers a new approach to treating depression in Alzheimer's patients. Unlike traditional antidepressants that often alter chemical levels like serotonin over extended periods, psilocybin works by inducing a profound, albeit temporary, shift in consciousness which can lead to new perspectives and psychological insights. Researchers are excited because psilocybin's mechanism may provide rapid antidepressant effects, potentially offering relief in just a few sessions. This is particularly promising for patients with Alzheimer's, where cognitive decline can make prolonged treatments challenging.

What evidence suggests that psilocybin might be an effective treatment for depression in Alzheimer's?

Research suggests that psilocybin, a compound in certain mushrooms, may help treat depression, especially in major depressive disorder and treatment-resistant depression. Studies have found that psilocybin can reduce depression with effects lasting up to a year after a single dose. It may also lessen anxiety, which could benefit people with Alzheimer's disease. Although specific data on Alzheimer's is limited, easing depression and anxiety could improve the quality of life for those with the disease. This trial will investigate psilocybin's potential to treat depression in Alzheimer's patients, offering hope for better mental health outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Albert Garcia-Romeu, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

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.

How Is the Trial Designed?

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.

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Council On Spiritual Practices

Collaborator

Trials

1

Recruited

20+

Heffter Research Institute

Collaborator

Trials

15

Recruited

520+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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 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]

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]

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]

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