Psilocybin for Methamphetamine Addiction

Inclusion Criteria: * Age 25-65 at time of signing informed consent * Identification of methamphetamine as drug of choice * Score of at least 3 on the Severity of Dependence Scale * Have been at the designated local treatment facility for at least 7 days * Use of methamphetamine in the month preceding admission to the treatment center * Desire to cease methamphetamine use as indicated by a goal of complete methamphetamine abstinence on the Thoughts about Abstinence questionnaire * All English speakers, as all neuropsychological tasks will be given in English * No prior psychedelic use or it will have been at least 3 years since their last use of a psychedelic * Ability to attend two telehealth and one in person preparatory session appointments to establish comfort, trust and rapport between subjects and the research team and discuss the subjects' goals and aspirations with regard to the psilocybin administration. * Ability to attend two integration sessions via telehealth and 3 follow-up assessments in person and via telehealth. * Diagnosis of Stimulant Use Disorder - Amphetamine type on the MINI (Mini International Neuropsychiatric Interview), with no other substance dependence diagnoses other than nicotine or cannabis * In acute remission from methamphetamine for at least 7 days prior to experimental drug administration as assessed by self-report and confirmed by urine drug screen (UDS) as well as the lack of any acute signs of intoxication on psychoactive drugs other than nicotine Exclusion Criteria: * Meeting criteria for substance dependence diagnoses other than methamphetamine (except nicotine and cannabis) as assessed by the MINI * History of Hallucinogen Use Disorder or Hallucinogen Persisting Perceptive Disorder * Women who are pregnant, plan to become pregnant, or are breast feeding * Women who do not agree to engage in abstinence or are not using dual contraceptive methods at the time of enrollment and for the study duration * Current hypertension (exceeding 140 systolic and 90 diastolic at resting as described below) at screening or during vitals taken pre-dosing * Heart rate of less than 60 bpm and greater than 100 bpm at screening or during vitals taken pre-dosing * QTc of less than 350 msec or more than 460 msec * History of cardiovascular disease (other than controlled hypertension) or cerebral vascular disease * Unstable medical or psychiatric conditions or disorders as determined at the discretion of the attending psychiatrist * Clear diagnosis of schizophrenia or type 1 bipolar disorder (clear from confusion with drug-induced acute states) * Having current or recent (last 6 months) suicidal ideation, assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) * Subjects currently taking medications on the prohibited medications list or that are unwilling/unable to cease medication * History of significant brain injury or seizure disorder * Inability to understand the informed consent, study purpose and procedures, or other study materials involved in the research study * Those with moderate to severe hepatic impairment, as assessed by laboratory parameters. * Plans to move away from Shreveport-Bossier area in the next 6 months * Subjects whose laboratory blood tests demonstrate clinically significant abnormalities. Clinically acceptable ranges listed below: * Complete Blood Count (CBC) Red Blood Cell Count (RBC): 4.5 - 6.0 million cells/µL Hemoglobin (Hb or Hgb): * For men: 13.8 - 17.2 g/dL * For women: 12.1 - 15.1 g/dL Hematocrit (Hct): * For men: 38.3% - 48.6% * For women: 35.5% - 44.9% White Blood Cell Count (WBC): 4,500 - 11,000 cells/µL Platelet Count: 150,000 - 450,000 cells/µL * Blood Chemistry with Liver Function Tests Alanine Transaminase (ALT): 7 - 56 units/L Aspartate Transaminase (AST): 8 - 48 units/L Bilirubin (Total): 0.2 - 1.2 mg/dL * Renal Function Tests Blood Urea Nitrogen (BUN): 7 - 20 mg/dL Creatinine: 0.6 - 1.3 mg/dL * If there are abnormalities, or if the results are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to not be clinically significant, or indicative of an unstable medical condition. Prohibited Medications If subjects have a history of taking the following medications, they should be discontinued at least 5 half-lives prior to administering psilocybin. * Medications that antagonize the serotonin 2A receptor * Medications with serotonergic activity (e.g., SSRIs, SNRIs, efavirenz, lithium) * Medications that inhibit UGT1A9 or UGT1A10 enzymes * Monoamine Oxidase Inhibitors (MAOIs) * Medications that inhibit aldehyde or alcohol dehydrogenase