Cannabidiol + Morphine for Chronic Pain

(CMP Trial)

Overseen By Nareen Sadik, B.S

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Wayne State University

Must not be taking: Past-month medications

Disqualifiers: Psychiatric illness, Substance use, Neurological, Cardiovascular, others

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you've taken medications in the past month that increase study risk, you may be excluded.

What data supports the idea that Cannabidiol + Morphine for Chronic Pain is an effective treatment?

The available research shows that using Cannabidiol (CBD) can help reduce opioid use and improve the quality of life for chronic pain patients. In one study, over half of the patients reduced or stopped using opioids after adding CBD to their treatment, and almost all reported improvements in their quality of life. This suggests that CBD can be an effective alternative to opioids for managing chronic pain. However, the research does not specifically address the combination of Cannabidiol and Morphine for chronic pain, so more studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

What safety data is available for the combination of Cannabidiol and Morphine in treating chronic pain?

The provided research does not directly address the safety data for the combination of Cannabidiol (CBD) and Morphine for chronic pain. However, it includes studies on morphine formulations, such as MST Contin and MorphiDex, which show that morphine is effective for pain management with a side effect profile typical of opioids. Common adverse effects include gastrointestinal and nervous system disorders. The studies suggest that morphine is generally safe when used appropriately, but specific safety data for the combination with CBD is not provided in the research. ^{6 7 8 9 10}

Is the drug Cannabidiol combined with Morphine a promising treatment for chronic pain?

Yes, combining Cannabidiol with Morphine is promising for chronic pain because Morphine is effective in managing moderate to severe pain, and Cannabidiol may enhance its effects, making it a potentially strong option for pain relief. ^{6 11 12 13 14}

What is the purpose of this trial?

The purpose of the proposed study is to investigate the interaction of cannabidiol (CBD) and morphine effects on pain sensitivity. Cannabidiol is a cannabinoid (similar to cannabis, or marijuana) present in marijuana that alters some of the effects of marijuana.

Research Team

Leslie Lundahl, PhD

Principal Investigator

Wayne State University

Eligibility Criteria

This trial is for healthy adults who have smoked cigarettes or marijuana and taken opioids more than three times in their life. They must pass a psychiatric evaluation, substance use history interview, medical exams including blood tests, urinalysis, pregnancy test for females, and an ECG.

Inclusion Criteria

If you have smoked cigarettes (nicotine or marijuana) and taken opioids more than three times in your lifetime, you must report it.

People who want to participate in the study must be in good health; those who are not in good health or have contraindications will be excluded from the study.

I am willing to undergo medical evaluations including blood tests, urine tests, and an ECG.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimental Sessions

Participants undergo three experimental sessions, each separated by at least one week, involving baseline assessments, administration of oral morphine, and smoking sessions with cannabidiol or placebo.

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the experimental sessions

4 weeks

Treatment Details

Interventions

• Cannabidiol
• Immediate-release Oral Morphine Sulfate Tablets

Trial Overview The study is testing how cannabidiol (CBD), a compound found in marijuana that changes its effects, interacts with morphine on pain sensitivity. Participants will take oral morphine sulfate tablets and undergo tests to measure their response to heat and pressure pain.

Participant Groups

Group I: Smoked cannabidiol 9.7% Active Control 2 Interventions

Group II: Smoked cannabidiol 0% Placebo Group 2 Interventions

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?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

Findings from Research

In a study of 177 patients with advanced cancer pain, the THC:CBD extract significantly reduced pain more than placebo, with an average improvement of -1.37 on the pain scale compared to -0.69 for placebo.

The THC extract did not show a significant difference in pain relief compared to placebo, indicating that THC:CBD may be more effective for pain management in patients who do not respond adequately to opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Johnson, JR., Burnell-Nugent, M., Lossignol, D., et al.[2022]

In a follow-up study involving 43 patients with advanced cancer, the long-term use of a THC/CBD oromucosal spray showed significant improvements in pain severity and quality of life without any new safety concerns.

Patients using the THC/CBD spray did not need to increase their dosage over time, indicating that this cannabinoid formulation may provide effective and stable pain relief as an adjuvant therapy for cancer-related pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. Johnson, JR., Lossignol, D., Burnell-Nugent, M., et al.[2022]

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]

In a study of 674 patients with severe neuropathic pain, the oromucosal spray nabiximols (NBX) showed a 55.4% improvement in pain relief compared to a 40.5% improvement with oral dronabinol (DRO), indicating that NBX is more effective for this condition.

NBX also had a better safety profile, with significantly lower rates of treatment-related adverse events (21.1% for NBX vs. 35% for DRO) and fewer discontinuations due to side effects (5.9% for NBX vs. 14.8% for DRO), highlighting its tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry. Ueberall, MA., Essner, U., Vila Silván, C., et al.[2022]

In a post hoc analysis of the SAVANT study, the THC:CBD oromucosal spray (nabiximols) significantly reduced spasticity and pain severity in patients with resistant multiple sclerosis, showing consistent efficacy across various disability and spasticity severity subgroups.

The treatment began to show significant improvements in spasticity and pain scores compared to placebo as early as week 4, indicating that nabiximols can provide rapid relief for patients with moderate to severe spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial. Meuth, SG., Henze, T., Essner, U., et al.[2021]

Oral controlled-release morphine tablets (MST Continus) are effective for treating chronic cancer pain, with studies showing that they provide sufficient pain relief for most patients with opioid-responsive pain.

MST is more convenient for long-term use compared to immediate-release morphine, as it typically requires only twice-daily dosing once patients are stabilized, while maintaining a similar side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled-release morphine (MST Contin) in advanced cancer. The European experience. Hanks, GW.[2019]

MorphiDex, a combination of dextromethorphan and morphine, allows for effective pain control at a significantly lower daily dose of morphine, as shown in a study with 592 patients over 10 months.

Patients reported higher satisfaction with MorphiDex compared to their previous opioid treatments, and the combination may help prevent the development of tolerance to morphine, with most side effects being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine with dextromethorphan: conversion from other opioid analgesics. Chevlen, E.[2019]

In a study involving 24 cancer patients, Kapanol, a once-daily morphine formulation, demonstrated a more stable pharmacokinetic profile with higher minimum plasma concentrations and less fluctuation compared to MS Contin, which is taken every 12 hours.

Despite these pharmacokinetic differences, both Kapanol and MS Contin provided similar levels of pain relief and side effects, indicating that Kapanol is an effective alternative for managing severe cancer-related pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain. Gourlay, GK., Cherry, DA., Onley, MM., et al.[2022]

A survey of 176 physicians in Germany revealed that most rarely observe adverse drug reactions (ADRs) related to opioid replacement therapy (ORT), with methadone being the most frequently associated with ADRs, particularly fatigue, weight gain, and sexual dysfunction.

Despite the occurrence of ADRs, 73.3% of physicians reported never documenting these reactions for ORT, indicating a potential underreporting issue compared to ADRs in general medical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety and adverse drug reaction reporting behavior related to outpatient opioid replacement therapy: Results from a survey among physicians. Gahr, M., Eller, J., Cabanis, M., et al.[2018]

A study involving 28 healthy male volunteers found that the extended release formulation Oramorph SR 30 mg has similar bioavailability to the reference formulation MST Mundipharma Retardtabletten, indicating they can be considered bioequivalent.

Both formulations showed comparable safety profiles, with common side effects including headache, dizziness, nausea, and vomiting, suggesting that Oramorph SR is a safe alternative to the reference product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two morphine extended release formulations after multiple dosing in healthy volunteers. Heinrich-Nols, J., Schug, BS., Evers, G., et al.[2016]

In a follow-up study of 239 patients, transdermal buprenorphine was found to be effective for long-term management of chronic pain, with 90% of participants reporting at least satisfactory pain relief over an average duration of 7.5 months.

The treatment was generally well tolerated, with a high adherence rate of 78.7%, and the most common side effects were mild, including nausea and dizziness, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term management of chronic pain with transdermal buprenorphine: a multicenter, open-label, follow-up study in patients from three short-term clinical trials. Likar, R., Kayser, H., Sittl, R.[2022]

Transdermal buprenorphine was effective in reducing pain intensity by approximately 50% in two patients with refractory complex regional pain syndrome (CRPS).

The treatment was generally safe, with manageable side effects such as application site rash, which was treated with a topical steroid spray.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases. Onofrio, S., Vartan, CM., Nazario, M., et al.[2018]

In a phase III study involving 344 patients with osteoarthritis pain, morphine/naltrexone significantly improved pain management compared to placebo, demonstrating its efficacy in treating moderate to severe chronic pain.

In a 12-month safety study with 465 participants, morphine/naltrexone was well tolerated and provided effective pain relief, with significant improvements in pain scores observed from the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine/naltrexone. Duggan, ST., Scott, LJ.[2021]

Chronic administration of morphine (3 mg/kg bi-daily) significantly reduced pain behaviors in a rat model of cancer-induced bone pain (CIBP) more effectively than a single dose, indicating that continuous treatment may be necessary for better pain management.

Despite the effectiveness of chronic morphine in reducing pain, the study found that certain pathophysiological changes in the dorsal horn of the spinal cord persisted, suggesting that additional therapies may be needed to fully address the underlying nerve changes associated with CIBP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of chronic morphine in a rat model of cancer-induced bone pain: behavior and in dorsal horn pathophysiology. Urch, CE., Donovan-Rodriguez, T., Gordon-Williams, R., et al.[2013]

References

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

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. [2022]

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

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. [2022]

3. 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]

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

Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial. [2021]

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

Controlled-release morphine (MST Contin) in advanced cancer. The European experience. [2019]

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

Morphine with dextromethorphan: conversion from other opioid analgesics. [2019]

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

Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain. [2022]

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

Drug safety and adverse drug reaction reporting behavior related to outpatient opioid replacement therapy: Results from a survey among physicians. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two morphine extended release formulations after multiple dosing in healthy volunteers. [2016]

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

Long-term management of chronic pain with transdermal buprenorphine: a multicenter, open-label, follow-up study in patients from three short-term clinical trials. [2022]

12. England pubmed.ncbi.nlm.nih.gov

The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases. [2018]

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

Morphine/naltrexone. [2021]

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

Efficacy of chronic morphine in a rat model of cancer-induced bone pain: behavior and in dorsal horn pathophysiology. [2013]