Clinical trial NCT05985850: Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder
Methadone
Cannabis
Fentanyl
Keywords: addiction
Opioid Use Disorder
Cannabis
Harm Reduction
Opioid
Pain
Quality of Life
Cannabidiol
Lead sponsor: BC Centre on Substance Use
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2023-08-14
Enrollment: 24
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1: 1:1 randomization Phase 2: Open-label
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 28 weeks
measure: Risk of Treatment Contamination
timeFrame: 24 weeks
measure: Participants' adherence to treatment
timeFrame: 24 weeks
measure: Acceptability
timeFrame: 24 weeks
measure: Blinding effectiveness
timeFrame: 24 weeks
measure: Adequacy of Dose
timeFrame: 24 weeks
Secondary outcomes:
measure: The number of potential participants referred to the study
timeFrame: 24 weeks
measure: The screening failure rates
timeFrame: 24 weeks
measure: The monthly enrolment rates
timeFrame: 24 weeks
measure: The proportion of eligible participants who are willing to be randomized, willing to initiate the intervention and willing to complete 12-week assessments by study arm
timeFrame: 24 weeks
measure: The proportion of scheduled study visits completed by study arm
timeFrame: 24 weeks
Other outcomes:
measure: Retention in OAT
timeFrame: 24 weeks
measure: Illicit opioid use
timeFrame: 24 weeks
measure: Pain Intensity
timeFrame: 24 weeks
measure: Pain Interference
timeFrame: 24 weeks
measure: Anxiety
timeFrame: 24 weeks
measure: Depression
timeFrame: 24 weeks
measure: Changes in health-related quality of life
timeFrame: 24 weeks
measure: Changes in substance-use related problems
timeFrame: 24 weeks
measure: Opioid Craving
timeFrame: 24 weeks
Locations:
city: Vancouver
country: Canada
facility: Rapid Access Addiction Clinic (RAAC), St. Paul's Hospital
state: British Columbia
Study officials:
affiliation: Assistant Professor, Department of Medicine, University of British Columbia
name: M Eugenia Socias, MD, MSc.
role: PRINCIPAL_INVESTIGATOR
References: