Cannabidiol for Opioid Use Disorder and Chronic Pain

Overseen By Julia Meyerovich, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must be taking: Methadone, Buprenorphine

Must not be taking: Benzodiazepines, Platelet inhibitors

Disqualifiers: Unstable psychiatric disorders, Recent stressors, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blind, randomized, placebo-controlled cross-over human laboratory study with a duration of approximately 4 weeks, during which participants will come to the testing site for a total of five times: one initial screening session, and four experimental sessions where study medication, Cannabidiol (CBD) will be administered, separated by at least 72 hours to limit carryover effects.

Will I have to stop taking my current medications?

The trial requires that you stay on your current methadone or buprenorphine treatment. However, you cannot participate if you are currently using benzodiazepines or platelet inhibitors. The protocol does not specify other medication restrictions, so it's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Cannabidiol (CBD) for Opioid Use Disorder and Chronic Pain?

Research shows that Cannabidiol (CBD) can reduce inflammation, as seen in studies where it was used to lower cytokine production (proteins that can cause inflammation) in response to various irritants. This suggests that CBD might help with conditions involving inflammation, which could be relevant for chronic pain management. ^{1 2 3 4 5}

Is cannabidiol (CBD) safe for humans?

Research suggests that CBD is generally safe for humans, with studies showing it can be a non-intoxicating alternative to opioids for chronic pain. However, there are concerns about the risk of adulteration in freely available CBD products and potential health hazards for pregnant women. ^{6 7 8 9 10}

How is the drug Cannabidiol (CBD) unique in treating opioid use disorder and chronic pain?

Cannabidiol (CBD) is unique because it is a non-intoxicating component of the cannabis plant that may help reduce opioid use and improve quality of life without the psychoactive effects associated with THC. Unlike traditional opioids, CBD has a better safety profile and may also improve sleep and reduce stress-related triggers for relapse in opioid use disorder. ^{6 7 9 11 12}

Research Team

Joao De Aquino, M.D.

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults aged 18-70 with chronic high-intensity musculoskeletal pain and opioid use disorder, who are stable on opioid maintenance treatment. Participants must be able to consent in English, not have major medical issues or unstable psychiatric conditions, and women must not be pregnant or breastfeeding.

Inclusion Criteria

Capable of providing informed consent in English

You do not meet the criteria for having problems with drugs or alcohol, except for opioid use disorder or tobacco use disorder in the past year.

I have been on a stable dose of my opioid treatment for at least two weeks.

Exclusion Criteria

You have gone through significant emotional stress in the past 6 weeks, as decided by the main doctor in charge.

I am currently taking benzodiazepines or medications like clopidogrel.

You have severe depression or are currently having thoughts of hurting yourself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Treatment

Participants receive oral CBD or placebo during four experimental sessions, with each session separated by at least 72 hours

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment via a phone call

1 week

1 visit (phone call)

Treatment Details

Interventions

• Cannabidiol

Trial Overview The study tests the effects of Cannabidiol (CBD) at different doses (1200mg, 800mg, and 400mg) compared to a saline placebo in managing chronic pain and opioid dependency. It's a double-blind study where neither participants nor researchers know who gets CBD or placebo during four sessions after an initial screening.

Participant Groups

Group I: CBD 400mg Active Control 1 Intervention

CBD 400 mg

Group II: CBD 1200mg Active Control 1 Intervention

CBD 1200mg

Group III: CBD 800mg Active Control 1 Intervention

CBD 800mg

Group IV: Saline Placebo Group 1 Intervention

saline

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

VA Connecticut Healthcare System

Collaborator

Trials

86

Recruited

8,800+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study of 48 patients with chronic beryllium disease (CBD) treated with inhaled corticosteroids (ICS), there was no significant change in pulmonary function over time compared to 68 untreated controls, indicating that ICS may not affect lung function decline.

However, ICS treatment led to significant improvements in symptoms such as cough (58% improvement) and dyspnea (26% improvement), particularly in patients with lower baseline lung function, suggesting that ICS can be beneficial for symptom management in CBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of inhaled corticosteroids on lung function in chronic beryllium disease. Mroz, MM., Ferguson, JH., Faino, AV., et al.[2023]

The COMBO-MS trial is designed to compare the effectiveness of cognitive behavioral therapy (CBT), modafinil, and their combination in reducing fatigue in patients with multiple sclerosis (MS) over a 12-week period, involving random assignment of participants with significant fatigue.

The study aims to determine if combination therapy is more effective than either treatment alone and to explore how factors like depression, sleep disorders, and disease severity may influence treatment outcomes, which could lead to better management strategies for MS-related fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized pragmatic trial of telephone-delivered cognitive behavioral-therapy, modafinil, and combination therapy of both for fatigue in multiple sclerosis: The design of the "COMBO-MS" trial. Kratz, AL., Alschuler, KN., Ehde, DM., et al.[2020]

In a post hoc analysis of the FORWARD study involving severe COPD patients, treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP-FF) resulted in a 35% reduction in exacerbation rates compared to treatment with formoterol fumarate alone.

The findings support the new GOLD 2017 recommendations, suggesting that inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) therapy is a beneficial treatment option for COPD patients who experienced one exacerbation in the previous year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of extrafine beclomethasone dipropionate-formoterol fumarate in COPD patients who are not "frequent exacerbators": a post hoc analysis of the FORWARD study. Singh, D., Vezzoli, S., Petruzzelli, S., et al.[2018]

A review of 35 studies involving cannabidiol (CBD) found that it was well tolerated and effective in treating conditions like epilepsy, with an average effective dose of 15 mg/kg/d leading to significant reductions in seizure frequency or severity.

While CBD showed promise in various medical contexts, including anxiety and psychotic symptoms, many studies with lower doses (around 2.4 mg/kg/d) did not demonstrate positive effects, indicating that effective dosing remains unclear and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of cannabidiol dosing in clinical populations. Millar, SA., Stone, NL., Bellman, ZD., et al.[2023]

The metered dose inhaler (CBD-MDI) formulation of cannabidiol (CBD) was found to be safe for respiratory cells and did not provoke an immune response in alveolar macrophages, indicating its potential for therapeutic use.

CBD-MDI effectively reduced inflammation caused by various stimuli, including viral and bacterial antigens, and showed comparable efficacy to the corticosteroid budesonide, suggesting it may be a viable treatment option for inflammation rather than a preventive measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants. Srichana, T., Chunhachaichana, C., Suedee, R., et al.[2022]

A systematic review of 12 studies involving cannabidiol (CBD) suggests it may be an effective alternative for managing chronic pain, as it is non-intoxicating and does not produce the psychoactive effects associated with THC.

While some studies indicate benefits of CBD for chronic pain, sleep improvement, and quality of life, more clinical trials are needed to establish its efficacy and safety definitively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain: A Systematic Review. Villanueva, MRB., Joshaghani, N., Villa, N., et al.[2022]

A study involving healthy volunteers showed that cannabidiol (CBD) can be safely administered alongside high-potency opioids like fentanyl without causing respiratory depression or cardiovascular issues, indicating its potential safety for further research.

The pharmacokinetics of CBD were consistent, with peak plasma concentrations occurring within a few hours after administration, suggesting that CBD does not interfere with the effects of opioids, laying the groundwork for exploring CBD as a treatment for opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Manini, AF., Yiannoulos, G., Bergamaschi, MM., et al.[2018]

In a study of 28 patients with chronic neck or back pain, a combination of cannabidiol (CBD) and Δ9-THC was found to be well tolerated, with most side effects being mild, such as nausea and fatigue.

Patients experienced significant reductions in pain scores with higher doses (1.0 mL and 1.5 mL twice daily), achieving reductions of 28.8% and 34.1% respectively, indicating the efficacy of this treatment for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study. Glare, P., Chye, R., Bloch, M., et al.[2023]

In an 8-week study involving 97 chronic pain patients who had been using opioids for at least a year, over half (53%) were able to reduce or eliminate their opioid use after adding CBD-rich hemp extract to their treatment regimen.

The majority of patients (94%) reported improvements in their quality of life, with significant enhancements in sleep quality and pain interference, suggesting that CBD may be a promising alternative to opioids for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Capano, A., Weaver, R., Burkman, E.[2020]

Cannabidiol (CBD) shows promise as a treatment for chronic pain and certain forms of epilepsy, with evidence suggesting it can improve quality of life for some patients.

Despite its potential benefits, CBD use carries risks, including the possibility of harmful adulterants in freely available products and potential health hazards for pregnant women and their developing babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Balanced Approach for Cannabidiol Use in Chronic Pain. Argueta, DA., Ventura, CM., Kiven, S., et al.[2021]

A pilot study involving 10 participants with opioid use disorder (OUD) found that a single dose of 600 mg of cannabidiol (CBD) significantly reduced cue-induced craving and attentional bias towards drug-related cues, suggesting it may help in preventing relapse.

These results indicate that CBD could be a promising adjunctive treatment to medications for OUD, like buprenorphine or methadone, by potentially lowering the brain's response to drug-related triggers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial. Suzuki, J., Prostko, S., Szpak, V., et al.[2023]

Cannabidiol (CBD), a non-psychoactive component of cannabis, has not been extensively studied for pain management, and there are currently no approved pharmaceutical products containing CBD alone for this purpose.

The only available pharmaceutical product containing CBD for pain management is nabiximols, which combines CBD with THC, making it challenging to isolate the effects of CBD on pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence. Boyaji, S., Merkow, J., Elman, RNM., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of inhaled corticosteroids on lung function in chronic beryllium disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized pragmatic trial of telephone-delivered cognitive behavioral-therapy, modafinil, and combination therapy of both for fatigue in multiple sclerosis: The design of the "COMBO-MS" trial. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

The efficacy of extrafine beclomethasone dipropionate-formoterol fumarate in COPD patients who are not "frequent exacerbators": a post hoc analysis of the FORWARD study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A systematic review of cannabidiol dosing in clinical populations. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain: A Systematic Review. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A Balanced Approach for Cannabidiol Use in Chronic Pain. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence. [2020]