Cannabis Oil Adjunct for Opioid Use Disorder

(THC-MMT Trial)

Overseen By Sukhpreet Klaire, MD CCFP (AM)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BC Centre on Substance Use

Must be taking: Methadone

Must not be taking: Warfarin, Clopidogrel, Clobazam, others

Disqualifiers: Pregnancy, Respiratory disease, Psychotic disorders, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether cannabis oil can safely and effectively support individuals currently using methadone therapy for opioid use disorder (OUD). Participants will receive either a cannabis oil with equal parts THC (Tetrahydrocannabinol) and CBD or a placebo to assess its impact on their treatment. The study seeks individuals diagnosed with OUD who began methadone therapy within the past month and have used cannabis in the last six months. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like warfarin, clopidogrel, clobazam, theophylline, clozapine, and olanzapine, as they may interact with the study medication. If you are on these, you may need to switch to a different medication.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabis oil with equal parts THC and CBD might aid individuals with opioid use disorder. Other studies have found that similar THC and CBD combinations can reduce symptoms such as cravings and anxiety.

Regarding safety, medicines derived from cannabis have generally been well-tolerated by patients. For instance, a study on a similar product called Sativex, which also contains a 1:1 ratio of THC and CBD, found that 71% of patients experienced relief from nausea and vomiting. However, like any treatment, there can be risks and side effects.

Although this trial remains in its early stages, the safe use of similar treatments in other studies is encouraging. It is important to consult a healthcare provider for the best advice on joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Unlike the standard treatments for opioid use disorder, which often rely on medications like methadone or buprenorphine, the investigational treatment uses a balanced 1:1 ratio of THC and CBD. This unique approach taps into the potential benefits of cannabinoids, aiming to reduce opioid cravings and withdrawal symptoms in a novel way. Researchers are excited because THC and CBD may offer a new mechanism of action by interacting with the body's endocannabinoid system, potentially providing relief with fewer side effects than traditional options. Additionally, the sublingual self-administration method could make it easier for patients to adjust their dosing and manage their treatment comfortably.

What evidence suggests that this treatment might be an effective treatment for opioid use disorder?

Research has shown that THC can reduce pain, while CBD might lessen cravings for opioids. Some studies suggest that CBD can mitigate the unwanted effects of THC, making the combination more manageable. In this trial, participants will receive either Aurora 1:1 Drops, containing a balanced 1:1 ratio of THC and CBD, or a placebo. Early findings indicate that using both THC and CBD together could help people with opioid use disorder by reducing cravings and possibly preventing relapses. Although the data is still developing, this combination has shown promise in addressing symptoms related to opioid use disorder. Overall, these cannabis compounds could offer a new way to support recovery. ^{1 6 7 8 9}

Who Is on the Research Team?

M Eugenia Socias, MD, MSc.

Principal Investigator

Assistant Professor, Department of Medicine, University of British Columbia

Are You a Good Fit for This Trial?

This trial is for adults over 25 with opioid use disorder who recently started methadone treatment. Participants must agree to only use the study's cannabis oil, secure it properly, and not share it. Women of childbearing age must use contraception and have a negative pregnancy test.

Inclusion Criteria

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

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

I didn't have serious side effects from the study drug and wasn't lost to follow-up in Phase 1.

Exclusion Criteria

Currently pregnant or breastfeeding, or planning to become pregnant

Current or historic cannabis use disorder

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

12-week double-blind, randomized controlled study with THC:CBD or placebo

12 weeks

Regular visits for monitoring and assessment

Open-label Extension (Phase 2)

12-week open-label treatment with THC:CBD cannabis oil

12 weeks

Follow-up research visits every two weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tetrahydrocannabinol (THC)

Trial Overview The study tests if THC:CBD cannabis oil can help alongside methadone therapy for opioid addiction in a community setting. It compares the effects of this cannabis oil against a placebo in people already using methadone.

How Is the Trial Designed?

Group I: Aurora 1:1 Drops (Indica) Experimental Treatment 1 Intervention

Aurora 1:1 Drops (Indica) Balanced 1:1 ratio of THC and CBD packaged in a 30 mL bottle: THC: 16.8 mg/g (+/- 15%) CBD: 16.8 mg/g (+/- 15%) Induction and dosing will be ad libitum and sublingually self-administered. Initial dose will be 5 mg (equivalent to 0.25 mL)/day and participants will be able to titrate in increments of 2.5mg (0.125 mL)/day up to a maximum of 40 mg (2 mL)/day, in consultation with a study physician.

Group II: Placebo Placebo Group 1 Intervention

Formulated using the same medium chain triglyceride (MCT) oil as Aurora 1:1 Drops (Indica) Induction and dosing will be ad libitum and sublingually self-administered. Initial dose will be 5 mg (equivalent to 0.25 mL)/day and participants will be able to titrate in increments of 2.5mg (0.125 mL)/day up to a maximum of 40 mg (2 mL)/day, in consultation with a study physician.

Who Is Running the Clinical Trial?

BC Centre on Substance Use

Lead Sponsor

Trials

4

Recruited

10,300+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

In a study of 63 opioid-dependent patients undergoing naltrexone treatment, those with intermittent cannabis use showed significantly better retention in treatment compared to those who were abstinent or had consistent cannabis use, suggesting a potential benefit of moderate cannabis use.

The findings indicate that intermittent cannabis use is linked to better adherence to naltrexone medication, and intensive behavioral therapy may help mitigate negative effects in patients with consistent cannabis use, highlighting the need for further research into the mechanisms behind these associations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence. Raby, WN., Carpenter, KM., Rothenberg, J., et al.[2021]

In a study involving mice dependent on morphine, delta9-THC significantly reduced withdrawal symptoms, including jumping, defecation, and rearing behavior, when administered before naloxone.

These results suggest that delta9-THC or its derivatives could be beneficial in helping with narcotic detoxification, indicating a potential therapeutic use in managing opioid withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of naloxone-induced withdrawal in morphine dependent mice by 1-trans-delta9-tetrahydrocannabinol. Bhargava, HN.[2019]

This study provides the first plasma pharmacokinetic data on free THC concentrations after repeated high-dose oral administration, showing that THC levels remained above 1 microgram/L for at least 24 hours after dosing.

The research indicates that while free THC levels did not increase during oral dosing, metabolites like 11-OH-THC and THCCOOH steadily rose, suggesting that the body processes THC differently over time, which is important for understanding its effects and duration in the system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Schwilke, EW., Schwope, DM., Karschner, EL., et al.[2021]

This study will evaluate the effectiveness of cannabis in reducing opioid use and managing chronic non-cancer pain in 250 adults currently taking prescription opioids, as part of a comprehensive behavioral pain management program.

Participants will be randomly assigned to either use cannabis or abstain for 6 months, with primary outcomes focusing on changes in opioid dosage and pain interference, while also monitoring for any adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol. Jashinski, J., Grossman, E., Quaye, A., et al.[2023]

In a study involving 25 individuals on methadone therapy for opioid use disorder, a 10 mg dose of THC was found to provide greater self-reported pain relief compared to a 20 mg dose, suggesting that lower doses may be more effective for pain management.

The study indicated no significant abuse potential or harmful cognitive effects from THC, and there was no interaction between THC and methadone doses, highlighting the potential safety of using cannabinoids in conjunction with opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study. De Aquino, JP., Meyerovich, J., Xie, CZ., et al.[2023]

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has well-documented therapeutic benefits, including reducing nausea from chemotherapy, increasing appetite, alleviating pain, and relieving symptoms of multiple sclerosis, supported by extensive research over the past 30 years.

While Delta(9)-THC can impair cognitive functions such as memory and perception, and may induce negative psychological effects like panic and hallucinations, the long-term impacts are still unknown, leading to a proposal by WHO to reschedule it as a low-risk substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The good and the bad effects of (-) trans-delta-9-tetrahydrocannabinol (Delta 9-THC) on humans. Carlini, EA.[2013]

Adding medical cannabis to prescription opioids for chronic pain patients showed very low certainty evidence of reducing opioid use, with no significant impact on pain relief or sleep disturbance based on five randomized trials and twelve observational studies.

However, the addition of cannabis was associated with an increased risk of nausea and vomiting, indicating potential adverse effects that need to be considered when evaluating its use in chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies. Noori, A., Miroshnychenko, A., Shergill, Y., et al.[2022]

In a study involving six volunteers, both liquid and capsule forms of THC-containing hemp oils produced plasma THC levels comparable to synthetic THC (dronabinol) used for appetite stimulation, indicating their potential efficacy as dietary supplements.

The study found that THC and its metabolites were detectable in plasma for varying durations, with THCCOOH persisting for up to 39.5 hours after dosing, suggesting a prolonged effect of THC from hemp oils compared to synthetic forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids. Goodwin, RS., Gustafson, RA., Barnes, A., et al.[2022]

In a study involving 11 cannabis smokers over 51 days, oral THC dosing significantly influenced the levels of THCCOOH in oral fluid, indicating its potential for monitoring cannabis use during treatment.

However, oral THC had minimal impact on THC concentrations in oral fluid, suggesting that previous cannabis smoking was the main source of cannabinoids detected, highlighting the complexity of cannabinoid metabolism and tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral fluid cannabinoids in chronic cannabis smokers during oral δ9-tetrahydrocannabinol therapy and smoked cannabis challenge. Lee, D., Vandrey, R., Mendu, DR., et al.[2021]

A survey of delta-8-THC consumers revealed that over half (51%) use it to treat various health conditions, with anxiety and stress being the most common, suggesting potential therapeutic benefits.

Participants reported favorably comparing delta-8-THC to delta-9-THC and pharmaceutical drugs, indicating it may have similar efficacy with potentially fewer adverse effects, although knowledge about safe dosages and medical integration remains low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumer Experiences with Delta-8-THC: Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC. Kruger, DJ., Kruger, JS.[2023]

A review of 41 studies on cannabis use during medication-based treatment for opioid use disorder (MOUD) found that most studies showed no significant impact of cannabis on treatment outcomes like opioid use, adherence, or retention.

While some studies suggested potential benefits or harms of cannabis use, particularly in relation to cravings and withdrawal, overall, cannabis use does not appear to independently threaten the effectiveness of MOUD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review. Lake, S., St Pierre, M.[2021]

Citations

1. reporter.nih.gov reporter.nih.gov/search/N57exlUatUONBdJjml6TjA/project-details/11036387

Combination of THC and CBD as a Novel Treatment for Co ... THC has been shown to mitigate pain, while CBD reduces cue-induced opioid craving. Some evidence also suggests that CBD may counterbalance THC's undesired ...

2. cannabisevidence.org cannabisevidence.org/registered-ongoing-studies/

Registered Ongoing Studies This research aims to determine the effects and safety of cannabidiol (CBD) (ATL5 softgel capsules) as an adjunctive therapy for patients who have Opioid Use ...

3. withpower.com withpower.com/trial/phase-2-opioid-related-disorders-8-2023-21718

Cannabis Oil Adjunct for Opioid Use Disorder (THC-MMT Trial) This pilot study will evaluate the feasibility and safety of using 1:1 tetrahydrocannabinol (THC):Cannabidiol (CBD) cannabis oil as an adjunct therapy to ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06940674

Adjunctive Cannabidiol for Recovery From Opioid Study The long-term goal of the project is to determine whether cannabidiol (CBD) can reduce craving and relapse in individuals with opioid use disorder (OUD).

5. journals.sagepub.com journals.sagepub.com/doi/10.1089/can.2018.0052?icid=int.sj-full-text.similar-articles.4

Cannabinoids, Pain, and Opioid Use Reduction For example, cannabis products with higher ratios of CBD:THC are associated with fewer cognitive and psychiatric negative consequences. ... combination of CBD ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10411365/

Cannabidiol as a Harm Reduction Strategy for People Who ... The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7720894/

Safety Considerations in Cannabinoid-Based Medicine - PMC Cannabinoid-based medicines are associated with safety risks which should be assessed in the context of potential therapeutic benefits.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2949875923000814

Differential effect of cannabis use on opioid agonist ... In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a ...

9. committees.parliament.uk committees.parliament.uk/writtenevidence/99392/pdf/

DMC0041 - Evidence on Drugs policy: medicinal cannabis Sativex (a 1:1 ratio spray of THC extract and CBD extract) caused 71% of patients to experience symptomatic relief of chemotherapy-induced nausea and vomiting ...