40 Participants Needed

Psilocybin for Depression

LC
AN
LT
Overseen ByLauren Turow
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of psilocybin, a compound found in certain mushrooms, on individuals with treatment-resistant major depressive disorder who experience anhedonia (a loss of interest or pleasure in daily activities). The trial includes two groups: one receives a 25mg dose of psilocybin, while the other receives a 1mg placebo dose, both with psychological support. Suitable candidates have major depressive disorder, have not responded well to at least two antidepressant treatments, and struggle to enjoy activities they once liked. As a Phase 2 trial, this research measures psilocybin's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but some medications are not allowed. You need to stop using drugs or supplements that interfere with the study, like certain antidepressants and serotonergic supplements, for 5 half-lives before the baseline visit. SSRIs and SNRIs may be allowed at the PI's discretion. Benzodiazepines and non-benzodiazepine sleeping meds can continue if stable for 6 weeks before screening. Psychostimulants must be stopped for 5 half-lives before the baseline visit.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but certain drugs like antipsychotics, trazodone, and others must be stopped for a period before the trial. Some medications, like SSRIs, may be allowed at the discretion of the investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, a substance found in certain mushrooms, has been studied for its safety in treating depression. In past studies, most participants tolerated psilocybin well. Some experienced mild side effects, such as nausea or headaches, but serious side effects were rare. It is important to remember that psilocybin is still under investigation, and its safety is not yet fully understood. However, its testing in a Phase 2 trial indicates that earlier studies found it safe enough to proceed. Always consult a healthcare provider before joining a trial.12345

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

Most treatments for depression, like SSRIs and SNRIs, work by altering serotonin levels over several weeks. But psilocybin, a psychedelic compound found in certain mushrooms, acts differently. It targets serotonin receptors in the brain more directly and can lead to rapid mood improvements. Researchers are excited because psilocybin has the potential to produce significant antidepressant effects in just a day or two, offering a faster-acting alternative to traditional medications.

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

Research has shown that psilocybin can help treat depression, even when other treatments have failed. In this trial, participants will receive either a 25 mg dose of psilocybin or a 1 mg active placebo. One study found that a single 25 mg dose of psilocybin reduced depression symptoms, while smaller doses did not. Another study showed that the positive effects of a 25 mg dose could last up to a year. Several studies consistently found that psilocybin reduces depression symptoms with few side effects. These findings suggest that psilocybin might help improve symptoms like losing interest or pleasure in activities for people with major depression.678910

Who Is on the Research Team?

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Andrew M Novick, MD PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for individuals who have major depressive disorder that hasn't improved with standard treatments. Participants should be experiencing anhedonia, which is the inability to feel pleasure.

Inclusion Criteria

Right-handed
I can avoid caffeine and nicotine for 2 hours before my MRI scan visits.
Currently under the care of a psychiatric practitioner who practices within the Department of Psychiatry at the University of Colorado Anschutz Medical Campus. Participants engaged in additional psychosocial treatments beyond seeing a psychiatric practitioner will be evaluated on a case-by-case basis
See 9 more

Exclusion Criteria

I don't have any physical or mental conditions that would make me unsuitable for the study, including claustrophobia, lack of internet access, weight over 300 pounds, unsafe metal in my body for MRI, or conditions making MRI unsafe. I am not allergic to clonidine, diazepam, or olanzapine and don't have myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, sleep apnea syndrome, acute narrow-angle glaucoma or a history of valvular heart disease.
I haven't taken certain psychiatric drugs or supplements recently and don't have allergies to the study drugs.
I have a significant brain condition or mental health issue confirmed by medical review.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Psilocybin 1mg or 25mg capsule orally, administered with psychological support, on dosing day

1 day
1 visit (in-person)

Follow-up

Participants are monitored for changes in depression and anhedonia scores post-dosing

8 weeks
Multiple assessments at 1, 4, and 8 weeks post-dosing

What Are the Treatments Tested in This Trial?

Interventions

  • Psilocybin
Trial Overview The study is testing the effects of psilocybin on depression symptoms. Two different doses of psilocybin (1mg and 25mg) are being compared to see how they affect anhedonia in participants.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: PsilocybinExperimental Treatment1 Intervention
Group II: Active PlaceboPlacebo Group1 Intervention

Psilocybin is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Psilocybin for:
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Approved in European Union as Psilocybin for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials
1,842
Recruited
3,028,000+

Published Research Related to This Trial

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.
In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.
Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice.Glatfelter, GC., Pottie, E., Partilla, JS., 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.
The pharmacology of psilocybin.Passie, T., Seifert, J., Schneider, U., et al.[2016]
Psilocybin, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.
The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.
A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder.Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40047545/
Results From a Long-Term Observational Follow-Up Study ...Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg.
Single-Dose Psilocybin for a Treatment-Resistant Episode ...In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced ...
Psilocybin, an Effective Treatment for Major Depressive ...It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects.
The role of the psychedelic experience in psilocybin ...Several exploratory trials have suggested that an exemplar, psilocybin, can reduce symptoms of major depressive disorder (MDD), including in ...
long-term-observational-follow-up-study-single-dose- ...Adverse events, including suicidal ideation and behavior, were reported in all dose groups. However, data on long-term efficacy and safety.
PsilocybinPsilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...
Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIHPsilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4.
PsilocinPsilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.
Psilocybine - the NIST WebBookPsilocybine. Formula: C12H17N2O4P ... 4-Phosphoryloxy-N,N-dimethyltryptamine; Psilocibin; Psilocin phosphate ester; Psilotsibin; Teonanacatl; Psylocybin ...
ZFIN ChEBI: psilocybinA tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...
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