Psilocybin for Depression

(LIGPATD Trial)

Overseen By Matthew R Hicks, ND, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Matthew Hicks

Must not be taking: Lithium

Disqualifiers: Schizophrenia, Psychosis, Mania, others

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

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of psilocybin (a compound found in certain mushrooms) as a group therapy treatment for individuals with major depression. The researchers aim to determine if this approach is safe and acceptable for low-income adults in Oregon. The study seeks to understand whether group sessions can provide a cost-effective way to deliver this therapy. It is recruiting Oregon residents with major depression who have stable housing and are already in therapy. Participants must be willing to attend all study sessions and have an income at or below 200% of the federal poverty level. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on innovative depression treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently prescribed lithium.

What prior data suggests that psilocybin is safe for treating depression?

Research has shown that psilocybin, the main ingredient in "magic mushrooms," is generally safe for people. In past studies, participants reported no serious harmful effects after taking psilocybin. Even a single dose proved safe, with no deaths linked to its use.

In psilocybin-assisted therapy, individuals often feel more relaxed or experience changes in perception and understanding. These effects are usually temporary and subside after the session. Long-term studies also found no serious side effects from psilocybin.

While researchers continue to study all the effects of psilocybin, current evidence suggests it is well-tolerated when used in a controlled setting, such as a clinical trial or therapy session. This makes it a promising option for treating depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Psilocybin is unique because it represents a completely different approach to treating depression compared to traditional methods like antidepressant medications and therapy. Unlike standard treatments that often require weeks to show effects, psilocybin has the potential to produce rapid improvements in mood and mental health after just one or two sessions. Researchers are excited about psilocybin because it works by affecting serotonin receptors in the brain in a novel way, which might lead to profound changes in perception and emotional processing. This new mechanism of action could offer hope for those who haven't found relief with existing treatments.

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

Research has shown that psilocybin can help with major depressive disorder (MDD). In many studies, more than half of the patients experienced improved symptoms of depression. A review of several studies found that psilocybin, especially at a 25 mg dose, had a strong and lasting effect. Patients reported feeling more empathetic, more accepting of themselves, and having better relationships. While some debate exists about its effectiveness for everyone, current evidence is promising for treating depression. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew R Hicks, ND, MS

Principal Investigator

National University of Natural Medicine

Are You a Good Fit for This Trial?

This trial is for adults in Oregon with incomes at or below 200% of the federal poverty level, diagnosed with major depression. Participants must be over 21, have stable housing for six months, attend all study events, and be engaged in ongoing psychotherapy. They cannot join if they don't meet these criteria.

Inclusion Criteria

I have been diagnosed with Major Depression Disorder.

Able to read and speak fluent English

Income 200% or below the Federal Poverty Line - this is the criteria for Oregon Medicaid (OHP)

Exclusion Criteria

Active suicidal ideations or history of suicide attempts. Passive ideation, such as 'I wouldn't mind if I never woke up again' is permissible

I am currently prescribed lithium.

Any form of personality disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo two group preparation sessions, two psilocybin sessions, and two group integration sessions

4 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collection at a follow-up visit

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial tests psilocybin-assisted group therapy's feasibility for treating depression among low-income individuals. It includes medical screening, questionnaires, two preparation sessions, two psilocybin sessions, two integration sessions and a follow-up after three months.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

This is an uncontrolled feasibility study with only one arm.

Who Is Running the Clinical Trial?

Matthew Hicks

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

In a feasibility trial involving 12 patients with treatment-resistant depression, psilocybin was found to be well tolerated, with no serious adverse events reported, although some patients experienced transient anxiety and confusion.

Patients showed significant reductions in depressive symptoms one week and three months after receiving high doses of psilocybin, indicating its potential efficacy as a treatment for unipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Carhart-Harris, RL., Bolstridge, M., Rucker, J., et al.[2022]

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 25 mg dose of psilocybin has shown short-term antidepressant effects in individuals with medication-resistant depression, suggesting it may be a promising treatment option.

Further research is needed to understand the relationship between psilocybin's psychedelic effects and its antidepressant benefits, as well as to assess potential risks, including suicide risk associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is psilocybin an effective antidepressant and what is its Mechanism of action? Mann, JJ.[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]

Psilocybin, a psychedelic drug, shows promising safety and efficacy in treating major depression and treatment-resistant depression (TRD), with initial phase 2 trials indicating positive outcomes when combined with psychological support.

The first international randomized controlled trial in 2022 found that a 25 mg dose of psilocybin was effective compared to an active placebo, and phase 3 trials are set to begin in 2023, suggesting a growing interest in psilocybin as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of psilocybin therapy for treatment-resistant depression: an update. Borissova, A., Rucker, JJ.[2023]

In a placebo-controlled study involving individuals with moderate to severe major depressive disorder, psilocybin (0.3 mg/kg) showed larger antidepressant effect sizes compared to placebo, with 66.7% of participants responding and 46.7% achieving remission after treatment.

The antidepressant effects of psilocybin persisted for an average of 2 months, indicating its potential as a long-lasting treatment option for depression, although the strength of the mystical experience during dosing did not correlate with these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. Sloshower, J., Skosnik, PD., Safi-Aghdam, H., et al.[2023]

In a phase II study involving 19 adults with treatment-resistant depression, a single 25 mg dose of synthetic psilocybin (COMP360) showed a significant reduction in depression scores, with a mean change of -14.9 on the MADRS scale after 3 weeks.

The treatment was generally safe, with 63.2% of participants experiencing mild treatment-emergent adverse events, but no serious adverse events or increased suicidal thoughts were reported, indicating a favorable safety profile for psilocybin in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Goodwin, GM., Croal, M., Feifel, D., et al.[2023]

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, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11456834/

Psilocybin for major depressive disorder: a systematic review ... Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836921

Control Group Outcomes in Trials of Psilocybin, SSRIs, or ... Meaning The poor control treatment outcomes in psilocybin trials suggest that it may not be as broadly effective for depression as estimated.

3. akjournals.com akjournals.com/view/journals/2054/aop/article-10.1556-2054.2025.00461/article-10.1556-2054.2025.00461.xml

Five-year outcomes of psilocybin-assisted therapy for ... Participants reported enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016517812400622X

Efficacy and safety of psilocybin in the treatment of Major ... This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect.

5. bmj.com bmj.com/content/385/bmj-2023-078084

Efficacy of psilocybin for treating symptoms of depression Conclusion Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ... No serious adverse reactions occurred. These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39670342/

The safety of psilocybin-assisted psychotherapy However, based on the available data, the safety of psilocybin-assisted psychotherapy is generally supported, and no deaths were attributed to psilocybin.

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2808950

Single-Dose Psilocybin Treatment for Major Depressive ... This randomized clinical trial examines the timing of onset of action, durability of benefit, and safety profile of single-dose psilocybin ...

9. hopkinsmedicine.org hopkinsmedicine.org/psychiatry/research/psychedelics-research

Psychedelics Research and Psilocybin Therapy 2022 Psilocybin Treatment for Major Depression May be Effective for Up to a Year. Previous studies by Johns Hopkins Medicine researchers showed that ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864328/

Efficacy and safety of psilocybin-assisted treatment for ... There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported ...