A Phase 1, Open-label, Single-arm Basket Trial of the Intravenously Administered Psilocin (TRP-8803): Safety, Anxiety, and Quality of Life Across Health Conditions Characterised by Cognitive Inflexibility, Emotional Distress, and Persistent Bodily Symptom Burden
This Phase 1, open‑label, single‑arm basket trial (N=66) tests the safety and early clinical effects of intravenous psilocin (TRP‑8803) administered in two dosing sessions alongside psychotherapy over a 6‑week treatment period, with a 12‑week follow‑up. Conducted in Australia and sponsored by Tryp Therapeutics, the study enrols participants across ten diagnostic cohorts — anorexia nervosa, body dysmorphic disorder, chronic fatigue, fibromyalgia, generalised anxiety disorder, irritable bowel syndrome, long COVID, major depressive disorder, obsessive–compulsive disorder and post‑traumatic stress disorder — to evaluate tolerability and signals of benefit in anxiety and quality of life. As a Phase 1 trial the primary outcomes focus on safety and tolerability (adverse events, vital signs and treatment‑emergent effects), with secondary or exploratory outcomes assessing changes in anxiety symptoms and health‑related quality of life using standardised, validated instruments. The single‑arm, open‑label design means there is no placebo or active comparator, and efficacy assessments are intended to generate preliminary, hypothesis‑generating data to inform the design of subsequent controlled studies. The study began recruitment in November 2025.
Psychedelic medicine has emerged as a safe and promising therapeutic approach for a wide range of mental and physical health conditions. Psychedelics like psilocin facilitate profound psychological experiences that can interrupt rigid, maladaptive thought patterns commonly underlying chronic and treatment-resistant mental illnesses. This open-label study will evaluate the safety and preliminary effects of a novel intravenous (IV, i.e. into the vein) formulation of the psychedelic psilocin (TRP-8803) in 10 different mental and physical health conditions (Anorexia Nervosa, Body Dysmorphic Disorder, Chronic Fatigue, Fibromyalgia, Generalized Anxiety Disorder, Irritable Bowel Syndrome, Long COVID, Major Depressive Disorder, Obsessive Compulsive Disorder, Post Traumatic Stress Disorder). Eligible participants will complete two doses of TRP-8803, administered in conjunction with psychotherapy over a treatment period of 6 weeks, and followed up until 12 weeks post second dose.
Study Arms & Interventions
TRP-8803 (IV Psilocin)
experimental
Two doses of TRP-8803 (intravenous psilocin) administered in conjunction with psychotherapy over a 6-week treatment period, with 12-week follow-up.
Interventions
Psilocybin
via intravenous
TRP-8803 (novel IV psilocin formulation)
Participants
Inclusion Criteria
The following criteria must be met by all individuals considered for study participation:
Current diagnosis of one of the following conditions: Anorexia Nervosa, Body Dysmorphic Disorder, Chronic Fatigue, Fibromyalgia, Generalized Anxiety Disorder, Irritable Bowel Syndrome, Long COVID, Major Depressive Disorder, Obsessive Compulsive Disorder, Post Traumatic Stress Disorder
Aged 18 to 65 years (inclusive) at the time of completing Stage 1 online screening.
Voluntary consent to participate in the study (including follow-up visits) and to undergo all study procedures.
Ability to receive intravenous (IV) medication (i.e., adequate venous access) and willingness to adhere to the study regimen.
Medically stable, in the judgement of the Medical Officer and Lead Psychiatrist, as determined by medical history, physical examination, ECG, and routine laboratory assessments (including haematology, biochemistry, blood, and urinalysis).
Willing and able to follow dosing day instructions provided by the facilitating therapists, including:
o Consuming approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) as consumed on a usual morning. If not routinely consuming caffeine, participant must refrain from doing so on session days.
o Consuming no more than a light breakfast on the morning of dosing.
Agree to follow the directions of the Medical Officer regarding the consumption of non-prescription and prescription medications and supplements
Agree not to operate motor vehicles or heavy machinery for 24 hours following discharge after each dosing session.
Agree to arrange transport assistance by a support person following each dosing session.
Participants currently taking medications contraindicated with the study drug or its effects must undergo a supervised medication taper or cessation prior to baseline, as deemed appropriate and approved by the prescribing physician.
Able to provide contact details of their primary care physician or medical practice, and provide consent for trial staff to contact them if necessary.
Non-smokers
Agree not to use nicotine-containing products from 90 days prior to Stage 1 Screening through study termination.
No use of psychedelic drugs for at least 3 months prior to psilocin administration, and agree to refrain from psychedelic use (other than study drug) during the study. Psychedelics include, but are not limited to, psilocybin, lysergic acid diethylamide (LSD), methylenedioxymethamphetamine (MDMA), ibogaine, and ayahuasca. Any other suspected psychedelic use must be discussed with and approved by the Sponsor.
Women of childbearing potential (WOCBP) in sexual relationships with men must agree to use two acceptable forms of contraception from 30 days prior to screening until 30 days after the final dose of study drug.
Exclusion Criteria
Participant has a recent history of suicide attempt, defined as an active, interrupted, or aborted suicide attempt within the past 12 months, or presents with current suicidal ideation indicating elevated risk. Participants who report passive ideation only (e.g., wish to be dead, without plan or intent) may be considered to inclusion if deemed safe by the medical officer or lead psychiatrist.
Current or history of psychosis symptoms or related conditions, including bipolar disorder.
First-degree family history of bipolar disorder, or first- or second-degree family history of schizophrenia or schizoaffective disorder.
History of alcohol use disorder within 12 months prior to screening or regular abuse of alcohol within the past 12 months
History of substance use disorder (other than alcohol) within 12 months prior to screening or regular abuse of alcohol within the past 12 months.
Meets diagnostic criteria for borderline personality disorder.
Testing positive on urine drug screening for drugs of abuse.
History of adverse effects from psilocybin or other psychedelics (e.g., severe headache or severe hypertension requiring medical treatment), based on self-report.
History of Hallucinogen Persisting Perception Disorder (HPPD).
Presence of any serious medical condition that, in the judgement of the medical officer or lead psychiatrist, may interfere with safe participation in the trial (e.g., cardiovascular, metabolic, neurological, respiratory, oncological, haematological disorders, epilepsy, or seizures).
Currently under treatment for epilepsy.
Cardiovascular conditions including: uncontrolled hypertension, angina, clinically significant ECG abnormalities, transient ischaemic attack (TIA) within the past 6 months, stroke or cerebrovascular disease, peripheral or pulmonary vascular disease (if symptomatic or with active claudication). Exclusion also applies to abnormal ECG parameters identified at screening or from medical history, including QTc >450 ms for men and >470 ms for women, PR interval >220 ms, or QRS duration >120 ms.
Serious abnormal haematology, electrolyte, renal, or liver function test results at screening, including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal 2 x upper limit of normal (ULN), or total bilirubin greater than or equal to 1.5 x ULN. Individuals with certain abnormal values may participate if they received medical clearance from their medically qualified healthcare provider or the medical officer on a case-by-case basis.
WOCBP must agree to refrain from donating ova (eggs) for at least 30 days after the final dose of study drug.
Men must agree to avoid impregnating women and refrain from sperm donation during treatment and for 90 days after the final dose of study drug, using acceptable contraception methods.
Insulin-dependent diabetes mellitus. Participants with non-insulin-dependent diabetes treated with oral hypoglycaemic agents will be excluded if they have a history of hypoglycaemia.
Serious infection requiring hospitalisation within the past 28 days.
Women of childbearing potential who are pregnant, breastfeeding, or actively trying to conceive.
Participation in another clinical study involving investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to screening.
Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at screening.
Positive saliva test for illicit substances or drugs of abuse on the day of dosing, prior to session commencement.
Positive alcohol breathalyser reading on the day of dosing, prior to session commencement.
Donation of blood or blood products >500 mL within 30 days prior to screening.
Participants may be excluded at the discretion of the investigators if, in their judgment, participation poses a safety risk, would compromise data integrity, or would interfere with the safe and effective delivery of the intervention. This includes, but is not limited to, the presence of unmanaged psychiatric conditions (e.g., personality disorders, cPTSD), significant adverse childhood experiences (e.g., trauma), or current psychosocial instability (e.g., inadequate social support, unstable housing, or exposure to domestic violence) that would impair therapeutic rapport or the participant’s ability to safely undergo the intervention. This determination will be based on eligibility review and may include consultation with the participant’s healthcare team if appropriate.