Psilocybin for Depression in Autism

(PAT-DA Trial)

Overseen By Hsiang-Yuan Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Antidepressants, Antipsychotics, Ketamine, others

Disqualifiers: Pregnancy, Seizure disorder, Substance use, 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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

We propose a first-of-its-kind open-label clinical trial to investigate the feasibility, tolerability, and safety of administering psilocybin in autistic adults with treatment-resistant depression (TRD). In this study, 20 participants (intellectually able and fluent-speech adults) with autism and co-occurring TRD will receive around 20 hours of manualized psychotherapy that has previously been used with psilocybin (Agin-Liebes et al., 2020). They will also receive psilocybin at 2 different time points, firstly a safety dose of 10mg, followed by a treatment dose of 25mg. This study design is in accordance with previous studies investigating the use of psilocybin with psilocybin-assisted therapy (PAT) to treat TRD (Carhart-Harris et al., 2016, 2018)

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, as long as your doctor confirms it's safe for you to do so.

What data supports the effectiveness of the drug psilocybin for depression in autism?

Research shows that psilocybin has been studied for various psychiatric disorders, including depression, and has been well tolerated with some patients experiencing significant long-term improvements. Although more research is needed, these initial findings are promising for its potential use in treating depression. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin has been studied for its safety in humans, showing that while it can cause challenging experiences, the risk of long-term psychological distress or risky behavior is low when used in controlled settings with proper support. Some studies suggest it may be safe for use under medical supervision, but caution is advised, especially for those with heart conditions. ^{3 4 6 7 8}

How is the drug psilocybin unique in treating depression in autism?

Psilocybin is unique because it acts quickly and may provide long-lasting relief from depression symptoms after just one or a few doses, unlike traditional antidepressants that often require daily use. It works by activating serotonin receptors in the brain, which can lead to changes in mood and perception, and has shown promise in treating various psychiatric disorders with minimal side effects. ^{1 9 10 11 12}

Eligibility Criteria

This trial is for adults with autism who also have depression that hasn't improved with standard treatments. Participants should be able to communicate effectively and handle the demands of the study, which includes around 20 hours of specialized psychotherapy.

Inclusion Criteria

I am an adult between 18 and 65 years old with autism.

Must sign and date the informed consent form

Stated willingness to comply with all study procedures

Exclusion Criteria

Pregnant as assessed by a urine pregnancy test at Screening (V1) or individuals that intend to become pregnant during the study or are breastfeeding

Treatment with another investigational drug or other intervention within 30 days of Screening (V1)

Moderate or severe DSM-5 diagnosis of an alcohol or substance use disorder in the past 12 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Dosing Session

Participants receive a safety dose of 10mg psilocybin along with therapy and safety evaluations

1 week

1 visit (in-person)

Active Treatment Session

Participants receive a treatment dose of 25mg psilocybin along with therapy and safety evaluations

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial is testing psilocybin, a compound found in certain mushrooms, as a treatment for depression in autistic adults. It involves two doses: a smaller safety dose followed by a larger treatment dose, alongside psychotherapy designed to work with psilocybin.

Participant Groups

Group I: Open-label Experimental Treatment 1 Intervention

Safety Dosing Session (V3): 10mg of psilocybin + therapy + safety evaluations Active Treatment Session (V4): 25mg of psilocybin + therapy + safety evaluations

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+

Findings from Research

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 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, 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]

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]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[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]

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 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 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 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 single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

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. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Psilocybin in Palliative Care: An Update. [2023]

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

The pharmacology of psilocybin. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

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

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. [2022]

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

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