THC + CBD for Opioid Use Disorder and Chronic Pain

Overseen By Julia V. Meyerovich, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Methadone

Must not be taking: Benzodiazepines, Other opioids

Disqualifiers: Cannabis use disorder, Liver dysfunction, Neurological conditions, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

147 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of THC and CBD (cannabinoids found in cannabis) can reduce pain and opioid cravings in individuals with opioid use disorder (OUD) who also experience chronic pain. Participants will take either a low dose, a higher dose, or a placebo (a harmless pill with no active ingredients) to compare effects. The trial targets individuals with chronic low back pain that affects daily life and who are on stable methadone therapy. Participants should have tried cannabis at least once and be willing to follow study procedures. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you can only participate if you are on a stable dose of certain medications for at least three months. If you take medications that affect pain, like NSAIDs or certain antidepressants, you need to be on a consistent dose.

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

Earlier studies have generally found dronabinol, a type of THC, to be well-tolerated. However, some participants experienced side effects such as dizziness, dry mouth, tiredness, nausea, headaches, and drowsiness. These side effects commonly occur with cannabinoid treatments.

Research has shown that dronabinol might help reduce pain and allow some people to use less pain medication, including opioids. While these results are promising, it's important to remember that researchers are still studying this treatment for safety and effectiveness. Always consult a healthcare provider to understand the benefits and possible side effects for your situation. ^{1 2 3 4 5}

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

Researchers are excited about the combined THC and CBD treatment because it targets both opioid use disorder and chronic pain through a novel mechanism. Unlike traditional treatments that often rely on opioids or non-opioid pain relievers, this approach utilizes cannabinoids, which may offer pain relief and reduce opioid cravings without the same risk of addiction. THC and CBD work together to balance psychoactive effects and enhance therapeutic benefits, potentially offering a safer alternative to current options. Additionally, using dronabinol, a synthetic form of THC, allows for precise dosing, which could improve the consistency and safety of treatment outcomes.

What evidence suggests that this trial's treatments could be effective for opioid use disorder and chronic pain?

Research has shown that combining THC and CBD might help treat chronic pain and reduce opioid cravings. THC can ease pain, while CBD might lower the urge to use opioids. Studies suggest that CBD can also reduce some of THC's side effects, such as feeling high. Other research indicates that cannabis might work as well as opioids for pain relief, with fewer people discontinuing treatment. Overall, using THC and CBD together appears to be a balanced way to manage pain and reduce opioid cravings. Participants in this trial will receive different doses of Dronabinol, a form of THC, to evaluate its effects on chronic pain and opioid use disorder. ^{5 6 7 8 9}

Who Is on the Research Team?

Joao P. De Aquino, M.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with both opioid use disorder (OUD) and chronic pain who are currently on methadone therapy. It aims to see if THC and CBD can help reduce their pain and cravings for opioids.

Inclusion Criteria

Provision of signed and dated informed consent form

For females of reproductive potential: use of highly effective contraception and agreement to use during study participation and for additional 2 weeks after last test session

I am willing and able to follow all study requirements.

Exclusion Criteria

Currently lactating

Allergy or serious adverse reaction to cannabis or its constituent cannabinoid

Allergy or serious adverse reaction to Butylated Hydroxytoluene (BHT)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single doses of THC and CBD in a double-blind, placebo-controlled, crossover design across three test sessions

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiovascular effects and adverse events

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Combined THC and CBD

Trial Overview The study tests the effects of two different doses of combined THC and CBD (600mg, 300mg) against a placebo, which has no active ingredients, to determine if they can alleviate symptoms of OUD and chronic pain.

How Is the Trial Designed?

Group I: Dronabinol 5mg Active Control 3 Interventions

Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 5 mg Dronabinol across all three test sessions

Group II: Dronabinol 10mg Active Control 3 Interventions

Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 10 mg Dronabinol across all three test sessions

Group III: Placebo 0mg Placebo Group 3 Interventions

Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 0 mg Dronabinol across all three test sessions

Combined THC and CBD is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Medical Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in European Union as Medical Cannabis for:

• Spasticity associated with multiple sclerosis
• Nausea and vomiting associated with chemotherapy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The novel combination cannabinoid medication (1:1 THC/CBD) was well tolerated in a phase I study involving 9 patients with chronic non-cancer pain, with most adverse events being mild, such as euphoric mood and headache.

While there were no significant changes in pain severity, improvements in pain interference, mood, and some sleep parameters were noted, suggesting potential benefits that warrant further investigation in a larger randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study. Bonomo, Y., Norman, A., Collins, L., et al.[2022]

In a study of 800 patients with severe chronic pain, the oromucosal spray containing THC and CBD resulted in a significant average symptom relief improvement of 39% after 12 weeks, with particularly strong effects observed in patients with neuropathic pain.

The treatment was generally well-tolerated, with 19.9% of patients reporting mild side effects, such as increased appetite and changes in taste, and only 4% discontinuing due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry. Ueberall, MA., Essner, U., Mueller-Schwefe, GH.[2020]

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]

Combination THC/CBD medicines are effective for chronic pain, particularly neuropathic and inflammatory pain, and have a good safety profile compared to opioids, with low potential for dependence.

CBD-only medications show substantial effectiveness for stress and moderate effectiveness for anxiety and insomnia, but should be used cautiously in patients with a history of depression or psychosis, as they may exacerbate these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions. Henson, JD., Vitetta, L., Hall, S.[2022]

Medical cannabis can effectively reduce chronic pain and, when used alongside prescription opiates, can lead to lower opiate usage and fewer side effects for patients.

Cannabinoids may help prevent tolerance and withdrawal symptoms from opiates, and they could also assist in treating problematic substance use, suggesting that better access to medical cannabis could mitigate the harms associated with opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain. Lucas, P.[2012]

In a study of 2,112 adult patients with chronic pain, 92.5% reported improvement in their primary symptoms after using cannabis-based oral formulations, indicating high efficacy as an adjuvant treatment.

The majority of patients experienced minimal side effects, with 71.7% reporting none, and the most common mild side effects, such as somnolence and dizziness, tended to decrease over time, suggesting that these formulations are safe for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. Moreno-Sanz, G., Madiedo, A., Hernandez, P., et al.[2022]

Medical cannabis and cannabinoids are increasingly recognized for their efficacy in managing chronic pain, with various preparations available that differ in their THC:CBD ratios.

Despite the popularity of the 'entourage effect' theory, systematic studies have not supported the idea that other cannabis plant constituents enhance pain treatment, and there is a lack of well-conducted comparisons between different cannabis products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Cannabis, Cannabidiol and Other Cannabinoids in Chronic Pain. The Perspective of Physicians. Köstenberger, M., Nahler, G., Jones, TM., et al.[2023]

In a mouse model of neuropathic pain, both THC and CBD were effective in reducing pain when administered orally, but THC also caused side effects at similar doses, indicating a limited therapeutic window.

The combination of THC and CBD did not enhance pain relief compared to THC alone when taken orally, but it did increase the risk of side effects, suggesting that CBD may offer a safer alternative for treating neuropathic pain despite its lower efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model. Mitchell, VA., Harley, J., Casey, SL., et al.[2021]

In a study of 100 chronic pain patients using medical cannabis, 93% reported a decrease or cessation of opioid use after starting cannabis, indicating its potential efficacy in reducing reliance on opioids.

However, 10% of participants, particularly younger individuals, met the criteria for cannabis use disorder, highlighting the need for careful evaluation of risk factors like age and depression before prescribing medical cannabis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and benefit of cannabis prescription for chronic non-cancer pain. Zloczower, O., Brill, S., Zeitak, Y., et al.[2022]

Citations

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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 ...

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Cannabis for medical use versus opioids for chronic non- ... Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.

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Clinical Approach to Medical Cannabinoid Use in Chronic ... CBD may work synergistically to improve THC's analgesia and attenuate its psychoactive/cognitive side effects.1,3,9 Data shows that a THC:CBD ...

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Cannabinoids in Chronic Pain Management: A Review of ... They demonstrated a reduction in opioid doses and a reduction in maximum pain intensity, as rated on a numeric rating scale, from an mean of 8.7 to 4.9 in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06454669?term=tetrahydrocannabinol&aggFilters=status:rec%20enr%20act&viewType=Table&rank=4

Dronabinol as an Adjunct for Reducing Pain The impact of cannabinoid treatments on pain in human volunteers has been evaluated for: 1) experimentally induced acute pain, 2) acute postsurgical pain, and 3 ...

8. nature.com nature.com/articles/s41386-021-01007-4

Within-subject, double-blinded, randomized, and placebo ... Together these data suggest that dronabinol may enhance the analgesic effects of a low dose of hydromorphone, indicative of possible opioid- ...

9. academic.oup.com academic.oup.com/painmedicine/article/23/8/1409/6519324

Effectiveness and Tolerability of Dronabinol Use in Patients ... Treatment effects observed with DRO were large enough for more than half of patients to reduce at least one pain medication, such as opioid analgesics or NSAIDs ...