Inclusion Criteria:
* Are between 19 and 65 years old.
* Have signed the informed consent form for the study
* Have moderate to severe amphetamine stimulant use disorder (ASUD) as determined by the Mini-International Neuropsychiatric Interview (MINI 7.0.1), and clinical review by the study physician. The focus will be on illicit methamphetamine use.
* Are treatment-seeking but not currently receiving other treatments for SUD.
* Have stable housing.
* Have a local support person (close friend or family member) that is available to accompany them home from the study drug session.
* Are of non-childbearing potential and/or using adequate contraception methods as defined by Health Canada.
* Non-childbearing potential is defined as (i) self-reported postmenopausal status (12 months of spontaneous amenorrhea and ≥ 45 years of age); or (ii) documented surgical sterilization
* Have a negative pregnancy test at screening and prior to the study drug session. Must agree to use adequate contraception through 10 days after the study drug session. Adequate contraception methods include intrauterine devices, oral hormones plus barrier contraception, abstinence, injectable or implanted hormonal methods, or vasectomized/non-sperm carrying sole partner. Barrier methods alone are not considered effective methods of contraception.
* Be willing to refrain from caffeine for ≥12 hours, cannabis and stimulants for ≥24 hours, and all other drugs for ≥5 days prior to PEX010 administration such that there are no clinical signs of intoxication or withdrawal.
* Able and willing to follow study procedure.
* Able to understand and communicate in English.
* Complete the Columbia Suicide Severity Rating Scale (CSSRS)
* Results from safety laboratory tests (CBC, AST and ALT, TSH, HbA1c) are within normal limits.
Exclusion Criteria:
* Are experiencing or at risk for significant withdrawal.
* Have any medical condition that would be contraindicated, including previously diagnosed conditions:
* seizure disorder or history of seizures;
* a history of significantly impaired hepatic function;
* a history of unstable or uncontrolled cardiovascular disease (coronary artery disease, heart failure, clinically significant ECG abnormality);
* uncontrolled hypertension, resting blood pressure \> 140/90 mmHg; baseline prolongation of QTc interval: \>450 ms in both males and females;
* a history of major central nervous system disease (history of cerebrovascular accident, masses, aneurysm);
* a history of uncontrolled obstructive airway disease or significant respiratory compromise;
* a history of uncontrolled thyroid disease;
* a history of uncontrolled insulin dependent diabetes that may preclude safe participation in the study;
* a history of narrow-angle glaucoma;
* gastrointestinal conditions which may affect psilocybin absorption (i.e. stenosing peptic ulcer, pyloroduodenal obstruction);
* a history of active obstructive urological conditions (i.e. symptomatic prostatic hypertrophy, bladder-neck obstruction) that may preclude safe participation in the study.
* Have a personality disorder deemed to be high risk (antisocial, borderline, narcissistic) assessed via the SCID-5-PD.
* Have a personal history or family history of either mania/hypomania or psychosis, including substance-induced psychosis.
* Have any history of Hallucinogen Perception Disorder
* Have a history of suicide attempt within the last 6 years or a suicidal ideation in the last year.
* Are currently taking medications with known interactions with psilocybin (e.g., antidepressants, antipsychotics)
* Are pregnant, breastfeeding, or not using adequate contraceptives if of childbearing potential.
* Any other finding(s) based on the screening process that the investigator determines makes the candidate unsuitable for the study
* Results from safety laboratory tests (CBC, AST and ALT, TSH, HbA1c) are not within normal limits
* Have baseline heart rate outside of normal limits (e.g., \>100 beats per minute).
* Subjects currently on medications with serotonergic activity, or taking inhibitors of UGT1A9, UGT1A10, MAO and aldehyde or alcohol dehydrogenase.
