PSY-01: Evaluating how safe and effective different doses of PEX010 are when given as part of psilocybin-assisted psychotherapy for people struggling to adjust to the stressful event of their cancer diagnosis (adjustment disorder)A Phase 2b Double-blind, Randomized, Low-dose Comparator-controlled Clinical Trial to Assess the Efficacy and Safety of PEX010 in Psilocybin-assisted Psychotherapy for the Treatment of Adjustment Disorder Associated With Cancer.

Exclusion

Participants will be excluded from the study if one or more of the following criteria are applicable:

Psychiatric Exclusion Criteria:

1. Current Major Depressive Disorder MDD (or within 12 months of Screening) deemed independent from the cancer diagnosis, current or past diagnosis of schizophrenia, psychotic disorder, unless this was resulting from a medical condition (e.g. lupus or malaria etc.), bipolar disorder I and II, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, anti-social personality disorder or judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as determined using clinical judgement of past and present medical and psychiatric history by any specialist psychiatrist or registered medical professional under the authorized delegation of a specialist psychiatrist.
2. First-degree relative with a diagnosed psychotic disorder.
3. Scores from the screening psychiatrist (or registered medical professional under the authorized delegation of a specialist psychiatrist) and baseline (S-STS) that indicate that the participant is of clinically significant risk of suicide. A decision will be formed based on S-STS scores and used in combination with other clinically significant data at screening. Sites should refer to the medical monitor if required.
4. Has attempted suicide in the twelve months preceding the screening visit.
5. Current (< 1 year) alcohol or drug misuse as identified as moderate or severe during screening in accordance with Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, using the MINI 7.0.2, not able or willing to abstain from alcohol consumption in the period 12 hours prior to the dosing session.
6. Any other reason that might prevent a participant from engaging in therapeutic preparation and integration sessions.
7. Anyone who has taken a microdose of psilocybin within 5 days of baseline, taken a higher dose of psilocybin (e.g., dried mushrooms or capsules) within 30 days of baseline and experienced euphoria, hallucinations, or altered mental status, or used any classic psychedelics (LSD, ibogaine, ayahuasca, DMT, mescaline) within 3 months prior to baseline.

Medical Exclusion Criteria:

1. Diagnosed with brain metastases, glioblastoma, phaeochromocytoma, bowel obstruction or intestinal failure, active carcinoid syndrome, uncontrolled hypercalcaemia, or uncontrolled diabetes mellitus or insipidus.
2. Currently taking or planning to take any of the following: any typical or atypical antipsychotic and monoamine-oxidase inhibitors. Participants with prior use of these medications must be willing to discontinue their use for at least 2 weeks prior to the baseline visit and to Day 28.
3. Currently taking or planning to take any anticonvulsant or mood stabilizer, including carbamazepine, lithium, phenytoin, and valproate. Participants with prior use of these medications must be willing to discontinue their use for at least 1 week prior to the baseline visit and to Day 28.
4. Any form of fungal allergy.
5. Positive pregnancy test at screening, women who are breastfeeding or of childbearing potential who are unwilling or unable to use an effective form of contraception (or abstinence) for the study period and for 1 month post PEX010 dose will be excluded. Women will be required to conduct a serum pregnancy test at the in-person screening visit and urine test prior to dosing session. Male participants who do not agree to use contraception for the study period and for 90 days post PEX010 dose to mitigate the risk of pregnancy will also be excluded. Note: Refer to Section 4.3.2.1 for further details about contraception.
6. A diagnosis of epilepsy or at significant risk of seizures based on medical history.
7. Cardiovascular conditions including stroke and/or myocardial infarction (less than one year before providing informed consent), uncontrolled hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia at screening. Results are exempt if they are a direct result of the participant's cancer diagnosis and do not present a risk to administration of psilocybin, following discretion of the investigator.
8. Anyone who, at screening, has clinically significant findings on physical examination, including resting vital signs (HR below 40 or above 120 bpm, blood pressure below 90/60 or above 140/90), ECG (QTcF > 450 msec for males and >470 for females), and positive alcohol breath test. Note: Inclusion of individuals with any out-of-range values, including blood pressure, is at the discretion of the Investigator.
9. Liver dysfunction at screening as defined by AST and/or ALT > 1.5 times the upper level of normal or upper reference range. Results are exempt if they are a direct result of the participant's cancer diagnosis and do not present a risk to the administration of psilocybin, following discretion of the investigator.
10. Renal Function: estimated glomerular filtration rate <60 mL/min (calculated using Chronic Kidney Disease Epidemiology Collaboration) unless this is a direct result of the cancer diagnosis and does not present a risk to the administration of psilocybin, following the discretion of the investigator.
11. Any clinically significant laboratory abnormality(s) that in the opinion of the investigator would present a risk to the administration of psilocybin.
12. Any clinically significant renal, pulmonary, gastrointestinal, hepatic, or other illness that could affect the interpretation of results or be a potential health risk for the person if they were to be included in the study. Results are exempt if they are a direct result of the participant's cancer diagnosis and do not present a risk to administration of psilocybin, following discretion of the investigator.
13. Below 18 or above 32kg/m2 Body Mass Index (BMI) score at Screening.
14. Anyone with organic brain injury or diagnosed with any cognitive impairment.
15. Positive urine drug test for non-prescribed psychoactive substances at the dosing session visit. Positive urine drug test for psychoactive substances at the in-person screening should be referred to the medical monitor. Note: Testing may be repeated once at the discretion of the Investigator.
16. Anyone on a research study of an investigational drug or who has been on a clinical trial within 3 months of enrolment.