Psilocybin + Psychotherapy for Irritable Bowel Syndrome

Overseen By Erin Mauney, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: TRYP Therapeutics

Must not be taking: Antidepressants, Opioids, Benzodiazepines, others

Disqualifiers: Hypertension, Heart disease, Diabetes, 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

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TRP-8802, which combines psilocybin (a compound found in certain mushrooms) with therapy to determine its effectiveness for irritable bowel syndrome (IBS). Researchers aim to discover if this treatment can quickly and lastingly reduce IBS symptoms, along with the anxiety and depression often associated with IBS. Participants will be divided into two groups: one will start treatment immediately, while the other will wait before beginning. Eligible participants must have IBS that has been difficult to treat with other methods and experience ongoing abdominal pain. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Yes, you may need to stop taking certain medications. Participants must refrain from using antidepressants, psychoactive prescription medications, and certain other drugs. There is a specific requirement to stop taking antidepressants at least 2 weeks (or 4 weeks for fluoxetine) before the screening visit. Additionally, participants must not take any medications with a primary centrally-acting serotonergic effect, and must refrain from using cannabis and other psychoactive drugs during the study. Please consult with the trial team for specific guidance on your medications.

Is there any evidence suggesting that TRP-8802 is likely to be safe for humans?

Research has shown that psilocybin, the active ingredient in TRP-8802, has been studied for its effects on various conditions beyond IBS. Although specific safety data for IBS patients is lacking, other studies provide some safety insights into psilocybin's use.

Studies have found that psilocybin is generally well-tolerated, with most participants experiencing mild to moderate side effects, such as temporary changes in mood, perception, or thought patterns, which are expected during treatment. Serious side effects are rare but can occur, so clinical trials include careful monitoring.

Psilocybin is also under investigation for treating depression and anxiety. In these studies, it has been safely administered under controlled conditions. The trial's phase 2 status indicates that earlier studies have already demonstrated some safety in humans. However, participants will be closely monitored to ensure safety throughout the trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for Irritable Bowel Syndrome, which often involve dietary changes, fiber supplements, and medications like antispasmodics or laxatives, TRP-8802 incorporates psilocybin, a psychedelic compound, along with psychotherapy. This combination is exciting because psilocybin is believed to target the brain-gut connection in a novel way, potentially altering how patients perceive and experience their symptoms. Researchers are intrigued by the possibility that this treatment could lead to more profound and lasting relief of IBS symptoms compared to conventional methods, which typically focus on managing rather than transforming the underlying experience of the condition.

What evidence suggests that TRP-8802 might be an effective treatment for IBS?

In this trial, participants will receive either an open-label oral psilocybin treatment or be placed on a waitlist control. Research has shown that psilocybin, like TRP-8802, may help treat irritable bowel syndrome (IBS) by affecting the connection between the gut and the brain. Early results suggest that psilocybin can ease IBS symptoms by changing serotonin levels, which influence mood and gut function. One study reported promising early results, showing improvements in IBS symptoms after using TRP-8802. These findings offer hope for psilocybin-assisted therapy in managing IBS symptoms. However, more research is needed to confirm these results and determine the best way to use this treatment. ^{1 3 6 7 8}

Who Is on the Research Team?

Franklin King, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 21-64 with IBS who've tried at least one diet change and one medication for over six weeks, and have had symptoms for more than a year. They must have a BMI of 18.5-29.9 and their condition can't be explained by another medical issue.

Inclusion Criteria

Your main stomach doctor has thoroughly checked your symptoms and believes that you have irritable bowel syndrome.

You have a body mass index (BMI) between 18.5 and 29.9.

My bowel habits have changed and it's not due to another known medical condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Baseline and Preparation

Participants undergo baseline assessments and preparation for treatment

3 weeks

Multiple visits for assessments and preparation

Treatment

Participants receive two doses of TRP-8802 with integration sessions

4 weeks

2 in-person visits for dosing, 4 integration sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• TRP-8802

Trial Overview The study tests TRP-8802 combined with psychotherapy on IBS patients. It compares immediate treatment to an 8-week delayed group using clinician/participant ratings of depression/anxiety, subjective drug effects, pain scores, stool frequency/consistency.

How Is the Trial Designed?

Group I: Waitlist Control Experimental Treatment 2 Interventions

Group II: Open Label Oral Psilocybin Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

TRYP Therapeutics

Lead Sponsor

Trials

4

Recruited

30+

Published Research Related to This Trial

Cognitive-behavioral therapy (CBT) has been shown to significantly reduce the severity of irritable bowel syndrome (IBS) symptoms and improve quality of life, based on multiple randomized controlled trials.

Despite its proven efficacy, access to CBT for IBS is limited due to a shortage of trained therapists, highlighting the need for increased training and the development of telemedicine platforms to make this treatment more widely available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights. Kinsinger, SW.[2022]

In a pilot study of irritable bowel syndrome (IBS) patients, distinct changes in endocannabinoid levels were observed: IBS-D patients had higher 2-AG and lower OEA and PEA levels, while IBS-C patients had higher OEA levels, indicating a potential link between these changes and IBS symptoms.

The study suggests that the endocannabinoid system (ECS) plays a role in IBS, as lower levels of PEA were associated with cramping abdominal pain, and reduced FAAH expression was noted in IBS-C patients, highlighting the ECS's involvement in the disorder's pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study. Fichna, J., Wood, JT., Papanastasiou, M., et al.[2022]

Irritable bowel syndrome (IBS) affects about 20% of the global population and is characterized by chronic abdominal pain and altered bowel habits, with its pathophysiology linked to dysregulation of the brain-gut axis.

Current treatments for IBS include traditional symptomatic therapies and novel approaches targeting neurotransmitter receptors, such as 5-HT3 antagonists for diarrhea and 5-HT4 agonists for constipation, highlighting the importance of understanding gut-brain communication in developing effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The brain-gut axis in irritable bowel syndrome--clinical aspects. Mach, T.[2022]

The IBS Outcome Study (IBSOS) is a multicenter trial involving 171 patients that aims to evaluate the efficacy of a self-administered version of cognitive behavior therapy (CBT) for treating irritable bowel syndrome (IBS), comparing it to standard CBT and an attention control.

This study seeks to determine not only the effectiveness of self-administered CBT in reducing IBS symptoms and improving quality of life but also to explore the durability of treatment effects over 12 months and identify patient characteristics that may influence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Irritable Bowel Syndrome Outcome Study (IBSOS): rationale and design of a randomized, placebo-controlled trial with 12 month follow up of self- versus clinician-administered CBT for moderate to severe irritable bowel syndrome. Lackner, JM., Keefer, L., Jaccard, J., et al.[2022]

Irritable bowel syndrome (IBS) is linked to altered brain-gut interactions, particularly involving serotonin (5-HT) and its receptors, which affect gastrointestinal function and symptom presentation.

The Rome criteria are the standard for diagnosing IBS, focusing on abdominal pain and altered bowel habits, while treatment strategies may include dietary changes, serotonin agonists, and psychological support to improve patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irritable bowel syndrome: update on pathogenesis and management. Alaradi, O., Barkin, JS.[2018]

Irritable bowel syndrome (IBS) affects 10-20% of the population, particularly women, and significantly impacts quality of life, necessitating a multifaceted treatment approach that includes dietary, lifestyle, behavioral, and pharmacologic therapies.

Calcium polycarbophil has been identified as a beneficial treatment for IBS patients experiencing constipation or alternating diarrhea and constipation, highlighting the importance of tailored therapies based on individual symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of irritable bowel syndrome. Torii, A., Toda, G.[2019]

In an 8-week study involving 850 patients with non-diarrhoea irritable bowel syndrome (non-D-IBS), tegaserod was found to be safe and well-tolerated, with 66% of patients reporting relief from symptoms after treatment.

While 38% of patients experienced adverse events, primarily mild to moderate diarrhea, these were mostly transient and resolved with continued treatment, indicating that tegaserod can be an effective option for managing non-D-IBS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tegaserod is safe, well tolerated and effective in the treatment of patients with non-diarrhoea irritable bowel syndrome. Fried, M., Beglinger, C., Bobalj, NG., et al.[2019]

Current therapies for Irritable Bowel Syndrome (IBS), including traditional treatments like antidepressants and fiber supplements, as well as alternative therapies like peppermint oil and herbal supplements, lack sufficient evidence to support their effectiveness.

The review highlights that no IBS treatments can be reliably recommended due to inadequate high-quality studies demonstrating their efficacy, emphasizing the need for better-designed clinical trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional therapies for irritable bowel syndrome: an evidence-based appraisal. Fennerty, MB.[2005]

Emerging pharmaceuticals for treating irritable bowel syndrome (IBS), particularly serotonin receptor modulators, aim to improve therapeutic management by addressing the complex interactions between the enteric and central nervous systems.

The FDA has approved two serotonin receptor modulators specifically for IBS, but the effectiveness of a single therapy remains uncertain due to the multifactorial nature of the disease, which includes biological, psychological, and social influences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update in the pharmaceutical therapy of the irritable bowel syndrome. Thielecke, F., Maxion-Bergemann, S., Abel, F., et al.[2019]

Irritable bowel syndrome (IBS) affects about 11% of the global population and is characterized by various symptoms due to complex interactions between the gut and brain, necessitating multi-targeted treatment approaches.

STW 5, a herbal preparation with nine extracts, has shown efficacy in addressing multiple IBS-related mechanisms, including gastrointestinal motility, inflammation, and gut microbiota, making it a promising multi-targeted treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-target Treatment for Irritable Bowel Syndrome with STW 5: Pharmacological Modes of Action. Allescher, HD., Burgell, R., Malfertheiner, P., et al.[2021]

Chinese herbal medicine (CHM) significantly improves global IBS symptoms compared to placebo, with a relative risk of 1.76 based on a meta-analysis of 10 trials involving 2,501 participants.

While CHM is effective for relieving IBS symptoms, it is associated with a higher rate of adverse events compared to placebo, indicating a need for careful consideration of its safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chinese Herbal Medicine for Irritable Bowel Syndrome: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials. Zheng, H., Jin, S., Shen, YL., et al.[2021]

In clinical trials for irritable bowel syndrome (IBS), a higher incidence of adverse events (AEs) in patients receiving active treatment is linked to better reported outcomes, suggesting that AEs may influence patient perceptions of treatment efficacy.

The study found a significant correlation between the attributable drug benefit and the average risk difference of AEs between treatment and placebo groups, indicating that AEs could lead to unblinding and affect the perceived effectiveness of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events appear to unblind clinical trials in irritable bowel syndrome. Shah, E., Triantafyllou, K., Hana, AA., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06206265

NCT06206265 | Assessment of Psilocybin (TRP-8802) in ... This study will involve a randomized waitlist control design to investigate the rapid and sustained effects of TRP-8802 following two experimental sessions.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06206265/assessment-of-psilocybin-trp-8802-in-concert-with-psychotherapy-in-patients-with-irritable-bowel-syndrome-ibs

Assessment of Psilocybin (TRP-8802) in Concert With ... This study will involve a randomized waitlist control design to investigate the rapid and sustained effects of TRP-8802 following two ...

3. listcorp.com listcorp.com/asx/typ/tryptamine-therapeutics-limited/news/positive-interim-results-in-phase-2a-trp-8802-ibs-trial-3132934.html

Positive interim results in Phase 2a TRP-8802 IBS trial ASX Release 18 December 2024 Positive interim results in Phase 2a TRP-8802 IBS trial conducted at the Massachusetts General Hospital ?

4. docwirenews.com docwirenews.com/post/psychedelics-show-promise-in-treating-ibs-and-gut-brain-disorders

Psychedelics Show Promise in Treating IBS and Gut-Brain ... Psilocybin-assisted therapy shows promise for IBS and gut-brain disorders, says Dr. Erin Mauney of Tufts Medicine.

5. withpower.com withpower.com/trial/phase-2-irritable-bowel-syndrome-1-2024-49f4f

Psilocybin + Psychotherapy for Irritable Bowel Syndrome The available research does not provide specific data on the effectiveness of Psilocybin + Psychotherapy for Irritable Bowel Syndrome. Instead, it discusses ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06760533

Psilocybin-Assisted Psychotherapy in Treating Irritable ... This study will serve as a pilot randomized controlled trial to assess the feasibility of Psilocybin-Assisted Psychotherapy (PAP) in Treating Irritable ...

7. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/psilocybinforibs

Psilocybin Assisted Psychotherapy Among Adult Patients with ... We want to know whether psilocybin-assisted talk therapy is safe and effective for patients with IBS. We are interested in if the therapy changes patients' ...

8. psychiatrictimes.com psychiatrictimes.com/view/the-gut-brain-connection-an-upcoming-study-on-psilocybin-assisted-psychotherapy-and-irritable-bowel-syndrome

An Upcoming Study on Psilocybin-Assisted Psychotherapy ... A phase 2A trial recently received confirmation to proceed in investigating psilocybin-assisted psychotherapy in the treatment of adult patients with IBS.