The purpose of this study is to understand how kratom affects people. In this study, kratom will be compared with another substance and a placebo (an inactive substance). Researchers will also study how the substances move through and affect the body. This includes examining how the body absorbs, processes, and eliminates the drug (pharmacokinetics), as well as how the drug affects the body and how it may make you feel (pharmacodynamics). The information collected will help researchers better understand the effects and potential risks of kratom.

Inclusion Criteria:

1. English-speaking, 18- to 55-year-old males or females.

2. 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.

3. 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

4. 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.

5. No current or past diagnosis of severe mental illness, as determined by a clinical interview.

6. 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.

7. 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.

8. Able and willing to give signed informed consent, reliable, and willing to make themselves available for the study's duration and follow study procedures.

9. Agree not to consume any recreational drugs during the study (THC is excluded).

10. Able to perform study procedures as determined by clinical judgment.

11. Able to meet eligibility requirements of the Qualification Phase (i.e., drug discrimination) and Naloxone Challenges.

Exclusion Criteria:

1. Seeking treatment for a substance or alcohol use disorder as determined by self-report during the intake interview.
2. 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.
3. History of opioid overdose.
4. Using medication or supplements that might interact with kratom or oxycodone as determined by self-report during intake interview.
5. Treatment with any investigational drug during the last 30 days.
6. Participants on parole or probation.
7. 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.
8. Current or recent history of significant violent or suicidal behavior or suicidal/homicidal risk as determined by the C-SSRS.
9. Sensitivity, allergy, or contraindications/allergies to kratom, opioids, or similar compounds.
10. 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.
11. 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.
12. Positive alcohol breathalyzer test at each admission in the Qualification and Treatment Phase.
13. History of sensitivity to heparin or heparin-induced thrombocytopenia.
14. Has not donated blood or plasma within the last six weeks.
15. Has a history of increased intracranial pressure or brain tumors.
16. Has gastrointestinal obstruction, including paralytic ileus.
17. Has a history of seizure disorders.
18. Has a chronic obstructive pulmonary disease or cor pulmonale.
19. Has a history of anemia or any other significant hematologic disorder.
20. 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.
21. Has a major surgery planned within the next 6 months.