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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of psilocybin, a compound in certain mushrooms, for treating depression in adults with autism who haven't improved with other treatments. Participants will receive psilocybin in two different doses, along with therapy sessions, to determine its impact on persistent depression. The trial seeks autistic adults who have experienced depression unresponsive to standard treatments and are comfortable speaking and reading English. As a Phase 1 trial, this research focuses on understanding how the treatment 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?

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.

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

Research has shown that psilocybin has been studied for its safety in treating treatment-resistant depression (TRD). A study published in the New England Journal of Medicine administered psilocybin in doses of 1mg, 10mg, and 25mg to participants. The results indicated that psilocybin was generally safe, with the 25mg dose being the most effective in reducing depression symptoms. Some participants experienced mild side effects, such as headaches and nausea.

Another study on psilocybin treatment also found that the 25mg dose significantly reduced depression symptoms. This study reported mild and temporary side effects, such as dizziness or tiredness.

Overall, these findings suggest that psilocybin can be safe for humans at the doses tested in the current trial. However, potential participants should be aware of possible mild side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression in autism?

Unlike the standard treatments for depression in autism, which typically involve antidepressants or therapy, psilocybin stands out due to its unique mechanism of action. Psilocybin is a psychedelic compound that primarily works by affecting serotonin receptors in the brain, potentially leading to more rapid and profound changes in mood and perception. Researchers are excited about psilocybin because it may offer quicker relief and a different therapeutic pathway compared to traditional antidepressants, which often take weeks to have an effect. Additionally, psilocybin's use in conjunction with therapy could enhance its effectiveness, offering a novel approach to managing depression in individuals with autism.

What evidence suggests that psilocybin might be an effective treatment for depression in autism?

Research shows that psilocybin, which participants in this trial will receive, has promising results in treating depression, especially for those who haven't improved with other treatments. Several studies have demonstrated significant and lasting symptom improvements in people with treatment-resistant depression (TRD) after taking psilocybin. These studies highlight its potential as a strong antidepressant. Additionally, evidence suggests that psilocybin may help with some behavioral challenges in autism. Although this study focuses on individuals with both autism and TRD, existing research on psilocybin's effects on depression remains encouraging. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11044362/

The 'PSILAUT' protocol: an experimental medicine study of ... This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain.

2. sciencedirect.com sciencedirect.com/science/article/pii/S027858462500003X

Clinical and preclinical evidence of psilocybin as ... Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06731621

Psilocybin for Treatment-Resistant Depression in Autism ... PAT has shown impressive antidepressant effects in people with TRD or severe MDD in at least six modern-era clinical trials (Andersen et al., 2021). Other Names ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8846292/

Evaluating the Potential Use of Serotonergic Psychedelics ... In this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of ASD.

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1429373/full

A narrative exploration of psilocybin's potential in mental ... This review aims to deepen our understanding of the clinical impact of psilocybin, elucidate its therapeutic value, and propose directions for future research.

6. 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05651126

Psilocybin in Adults With and Without Autism Spectrum ... Case-control comparison of EEG Event Related Potentials in response to auditory tones during placebo and when serotonin system is activated with psilocybin.

8. 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 ...

9. 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 ...