Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy

Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy for Individuals Living With Opioid Use Disorder: A Phase II, Placebo-controlled, Blinded, Pilot Study to Assess Safety and Feasibility (THC-MMT)

This pilot study will evaluate the feasibility and safety of using 1:1 tetrahydrocannabinol (THC):Cannabidiol (CBD) cannabis oil as an adjunct therapy to methadone-based Opioid Agonist Therapy (OAT) for individuals with opioid use disorder (OUD) in a community setting.

This is a single-site, two-phase pilot clinical trial evaluating the safety and feasibility of administering a balanced 1:1 ratio of THC:CBD cannabis oil alongside methadone-based opioid agonist therapy (OAT) in a community setting.

Phase 1 is a 12-week, double-blind, randomized controlled study involving 24 eligible participants with opioid use disorder (OUD) who recently initiated or re-initiated methadone-based OAT. Participants will be randomly assigned to receive either balanced THC:CBD cannabis oil or placebo oil. All participants will receive OUD clinical care, including OAT management, independent of research visits.

After the 12-week blinded treatment period (Phase 1), eligible participants will be invited to Phase 2, a 12-week open-label treatment extension study with all participants receiving balanced THC:CBD cannabis oil. Follow-up research visits will occur every two weeks from the start of open-label treatment.

Inclusion Criteria:

1. Individuals of at least 25 years of age or older;

2. Diagnosed with OUD as per DSM-5 criteria;

3. Initiated or re-initiated methadone-based OAT within the past 30 days prior to study entry;

4. Cannabis-use experienced, defined as having used any amount of cannabis in the six months prior to the screening visit;

5. Willing to only use study-provided cannabis as directed by study protocol, including abstention from non-study cannabis and cannabinoids;

6. Agree to keep all study medication stored in a secure location and not to share/distribute study medication to any other individual;

7. If assigned female sex at birth:

   1. Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and over 45 years of age); or (ii) documented surgical sterilization (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
   2. If of childbearing potential, be willing to use an acceptable method of contraception throughout the study and have a negative pregnancy test at screening;

8. Ability to understand and comply with study protocol procedures and to provide written informed consent.

Inclusion criteria for Phase 2

In addition to meeting all eligibility criteria outlined in Phase 1, participants will be eligible for Phase 2 provided they meet ALL the following criteria at Week 12:

1. Participants who have not experienced a study medication-related serious adverse event during Phase 1;
2. Participants who have not been lost to follow-up during Phase 1.

Exclusion Criteria:

1. Any disabling, severe, or unstable medical or psychiatric condition that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent, as assessed by medical and psychiatric history, physical examination, vital signs, and/or laboratory tests;
2. Any severe or unstable co-morbid substance use disorder (e.g., delirium tremens, acute alcohol intoxication) that, in the opinion of the study physician, precludes safe participation in the study;
3. Currently pregnant or breastfeeding, or planning to become pregnant;
4. Known or suspected allergy or hypersensitivity to cannabinoids;
5. History of respiratory disease, severe cardiovascular, cerebrovascular, renal or liver disease;
6. Current or historic cannabis use disorder;
7. Taking warfarin, clopidogrel, clobazam, theophylline, clozapine and olanzapine medications as they may interact with cannabinoids in a clinically significant manner if they cannot be switched to a different medication;
8. Any personal or family history (first degree relative) of primary psychotic disorders (i.e., schizophrenia, schizoaffective disorder) as per DSM-5 criteria;
9. Unable to abstain from driving any vehicle or operating machinery for at least 10 hours after taking the study medication. In cases where impairment persists beyond the initial 10-hour period, participants must continue to adhere to these restrictions until the impairment resolves;
10. Actively participating in other interventional clinical trial(s);
11. Incarcerated, pending legal action or other reasons that might prevent completion of the study.