Psilocybin for Anorexia

(SPANYA Trial)

Overseen By Marissa Raymond-Flesch, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Marissa Raymond-Flesch, MD, MPH

Must not be taking: Amphetamines, Benzodiazepines, Cocaine, others

Disqualifiers: Pregnancy, Bipolar, Cardiovascular, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 10

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement for one week before each psilocybin session, unless approved by the research team. Prescription medications are not specifically mentioned, so it's best to discuss your current medications with the research team to see if any adjustments are needed.

What data supports the effectiveness of the drug psilocybin for treating anorexia?

Research shows that psilocybin, a compound found in certain mushrooms, has been effective in improving psychiatric distress and quality of life in patients with life-threatening cancer. It has also shown promise in treating various psychiatric disorders, suggesting potential benefits for conditions like anorexia, although more specific research is needed. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin is generally considered safe when used in controlled settings with screened and supported participants, though it can cause challenging psychological experiences and, in rare cases, enduring psychological distress. It is important to use it under medical supervision, especially for individuals with pre-existing health conditions. ^{2 6 7 8 9}

How is the drug psilocybin unique in treating anorexia?

Psilocybin is unique in treating anorexia because it is a psychedelic compound that works by affecting serotonin receptors in the brain, potentially altering perception and mood, which is different from traditional treatments that focus on nutritional rehabilitation and psychotherapy. This drug is being explored for its ability to enhance psychological therapy and improve motivation for recovery, offering a novel approach where few effective treatments currently exist. ^{2 6 10 11 12}

What is the purpose of this trial?

This is a single site trial of psilocybin therapy for the treatment of refractory Anorexia Nervosa in young adults. The psilocybin therapy will include three preparatory sessions, psilocybin dosing session one (20mg), two integration sessions, psilocybin dosing session two (30mg), and four final integration sessions. Eating disorder symptoms will be measured pre and post treatment. Two family members of each young adult participant will be enrolled in the study. One of which will be required to attend a portion of two preparatory sessions and a portion of two integration sessions and receive psychoeducation about supporting the young adult participant through preparation and integration for psilocybin therapy. Investigators hypothesize that psilocybin will increase cognitive flexibility and that this increase will predict long-term changes in cognitive rigidity, habitual eating, and exercise behaviors in patients with Anorexia Nervosa.

Research Team

Marissa Raymond-Flesch, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for young adults with severe Anorexia Nervosa who haven't improved with standard treatments. Participants must have two family members willing to be involved, one of whom will attend certain therapy sessions.

Inclusion Criteria

I have been diagnosed with Anorexia Nervosa.

I am currently experiencing symptoms of Anorexia Nervosa.

I understand the study and can give my consent.

Exclusion Criteria

I do not have any uncontrolled neurological conditions.

Simultaneous enrollment in another clinical trial

Significant and uncontrolled gastrointestinal illness at the discretion of the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Three preparatory sessions for psilocybin therapy, including psychoeducation for family members

3 weeks

3 visits (in-person)

Psilocybin Dosing and Integration

Psilocybin dosing session one (20mg), two integration sessions, psilocybin dosing session two (30mg), and four final integration sessions

4 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests psilocybin therapy's effect on Anorexia symptoms in young adults. It includes preparatory and integration sessions, two dosing sessions of psilocybin (20mg then 30mg), and measures changes in eating behaviors.

Participant Groups

Group I: Psilocybin Therapy Experimental Treatment 2 Interventions

The psilocybin therapy will include three preparatory sessions, psilocybin dosing session one (20mg), two integration sessions, psilocybin dosing session two (30mg), and four final integration sessions

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?

Marissa Raymond-Flesch, MD, MPH

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

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]

A long-term follow-up of 15 participants from a previous trial showed that psilocybin-assisted psychotherapy led to sustained reductions in anxiety, depression, and other distressing symptoms, with 60-80% of participants still experiencing significant improvements 3.2 to 4.5 years later.

Participants reported that the psilocybin therapy was among the most meaningful experiences of their lives, indicating its potential to enhance psychological and spiritual well-being in patients facing life-threatening cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Agin-Liebes, GI., Malone, T., Yalch, MM., et al.[2023]

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]

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]

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 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]

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-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]

A pilot study is currently underway at Imperial College London to explore the feasibility and potential efficacy of psilocybin-assisted therapy for anorexia nervosa, involving 20 female participants who will receive three doses of psilocybin over 6 weeks.

Public Patient Involvement (PPI) has played a crucial role in shaping the study by providing insights from individuals with lived experience of anorexia, helping to identify barriers and understand recovery, which may enhance participant engagement and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Protocol for "Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study". Spriggs, MJ., Douglass, HM., Park, RJ., et al.[2023]

In a feasibility study involving 10 adult females with anorexia nervosa, a single 25-mg dose of synthetic psilocybin was found to be safe and well-tolerated, with no significant adverse effects on vital signs or ECG.

Participants reported that the psilocybin treatment was generally acceptable, suggesting potential for further research into its efficacy as a novel treatment for anorexia nervosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. Peck, SK., Shao, S., Gruen, T., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

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

Psilocybin in Palliative Care: An Update. [2023]

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

The pharmacology of psilocybin. [2016]

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

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

6. 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]

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

Intravenous mushroom poisoning. [2019]

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. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Study Protocol for "Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study". [2023]

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

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. [2023]

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

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]