Evaluation of the Safety and Effects of Psychoactive Substances in People With Past Opioid Use

Inclusion criteria

• English-speaking, 18- to 55-year-old males or females.
• Female subjects must have a negative serum pregnancy test at time of screening and negative urine pregnancy test upon admission. In addition, female subjects must meet one of the following conditions:

• Is a woman of non-childbearing potential defined as no menses for at least 12 months with status confirmed by FSH and estradiol levels at screening or surgically sterile at screening visit OR
• Is a woman of childbearing potential and using a contraceptive method that is highly effective, with a failure rate of <1%, from Screening until 9 months after receiving the study medication. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the dose of study intervention.
• Male subjects must agree to the following from Day 1 until 9 months after receiving the study medication:

• Not donate fresh unwashed semen

Plus, either:

• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
• Use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
• Use a male condom when engaging in any activity that allows for passage of ejaculate to another person
• Physically healthy, as determined by a clinical interview with a physician, laboratory tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, and self-reported medical history.
• No current or past diagnosis of severe mental illness, as determined by a clinical interview.
• Clinical laboratory test results (CMP, CBC, etc.) must be within the normal reference range or with acceptable deviations that are judged to be not clinically significant by a study physician.
• Have a history of self-reported recreational opioid use as defined by at least 10 times in the past year and at least once in the 12 weeks before screening.
• Able and willing to give signed informed consent, reliable, and willing to make themselves available for the study's duration and follow study procedures.
• Agree not to consume any recreational drugs during the study (THC is excluded).
• Able to perform study procedures as determined by clinical judgment.
• Able to meet eligibility requirements of the Qualification Phase (i.e., drug discrimination) and Naloxone Challenges.

Exclusion criteria

• Seeking treatment for a substance or alcohol use disorder as determined by self-report during the intake interview.
• Current or past diagnosis of opioid use disorder or other substance use disorder (SUD) within the past year, excluding THC and nicotine-containing products. With regard to marijuana/THC, an individual must be able to tolerate 48 hours of abstinence from marijuana/THC products.
• History of opioid overdose.
• Using medication or supplements that might interact with kratom or oxycodone as determined by self-report during intake interview.
• Treatment with any investigational drug during the last 30 days.
• Participants on parole or probation.
• Currently pregnant or trying to conceive or currently lactating as determined by blood pregnancy testing at screening, urine pregnancy testing at admission, and self-reporting during interview and study visits.
• Current or recent history of significant violent or suicidal behavior or suicidal/homicidal risk as determined by the C-SSRS.
• Sensitivity, allergy, or contraindications/allergies to kratom, opioids, or similar compounds.
• Use prescription or nonprescription drugs and dietary supplements within seven days or five half-lives (whichever is longer) that, in the opinion of the study clinician may interfere with the investigational product.
• Positive urine drug screen (UDS) for substances of abuse at each admission in the Qualification and Treatment phases, excluding tetrahydrocannabinol (THC). If a participant presents with a positive UDS excluding THC at any admission or any visit, the investigator, at their discretion, may reschedule a repeat of UDS until the UDS is negative, excluding THC, before the participant is permitted to participate in any phase of the study.
• Positive alcohol breathalyzer test at each admission in the Qualification and Treatment Phase.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Has not donated blood or plasma within the last six weeks.
• Has a history of increased intracranial pressure or brain tumors.
• Has gastrointestinal obstruction, including paralytic ileus.
• Has a history of seizure disorders.
• Has a chronic obstructive pulmonary disease or cor pulmonale.
• Has a history of anemia or any other significant hematologic disorder.
• Has a condition or abnormality that, in the opinion of the PI or Study Physician, would compromise the safety of the patient or the quality of the data.
• Has a major surgery planned within the next 6 months.