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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabidiol (CBD), a compound from marijuana, interacts with morphine to affect pain sensitivity. The study includes smoked CBD, with one group receiving it and another receiving a placebo. Researchers seek participants who have smoked cigarettes or marijuana and have occasionally used opioids. Participants should be in good health without serious mental health issues or other major illnesses. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination treatment.

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.

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

Research has shown that cannabidiol (CBD), one of the treatments under study, is generally well-tolerated. In studies involving individuals with chronic pain, only a small percentage of participants, between 4.3% and 12.9%, discontinued CBD due to side effects, depending on the dose. In comparison, 3.5% stopped when taking a placebo. This suggests that CBD is relatively safe, though some individuals might still experience issues.

For morphine, the other treatment in the study, extensive safety information already exists since it is an approved medication. However, morphine is known to cause side effects such as nausea, drowsiness, or constipation, which can vary among individuals.

Overall, the safety profiles of both CBD and morphine appear promising, but individual experiences may differ. Researchers will closely monitor participants during the study to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cannabidiol and morphine for chronic pain because it could offer a new way to manage pain with potentially fewer side effects. Unlike standard treatments like opioids alone, which can lead to dependence and other serious side effects, cannabidiol (CBD) is derived from cannabis and is known for its anti-inflammatory and pain-relieving properties without the high risk of addiction. This study explores the synergy between CBD and morphine, which might allow for lower doses of opioids, thus reducing their associated risks. By targeting the pain pathways differently, this combination could provide more effective relief for chronic pain sufferers.

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

Research has shown that cannabidiol (CBD) can help manage long-term pain. In this trial, participants will receive either smoked cannabidiol with 9.7% CBD or a placebo with 0% CBD. Studies have found that treatments using cannabis, including CBD, might reduce pain by more than half for people with nerve-related pain. Specifically, inhaling cannabis with CBD relieved pain for 67.2% of patients and completely removed pain for 34.5% within two hours. CBD reduces inflammation, which might also help lessen pain. Overall, CBD is moderately effective in treating different types of long-term pain, including nerve and muscle pain. ^{1 6 7 8 9}

Who Is on the Research Team?

Leslie Lundahl, PhD

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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 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]

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]

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9288157/

Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain in 1750 adult participants with neuropathic pain showed that cannabis-based medicine might help achieve >50% pain relief (primary outcome) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11940634/

Cannabinoids in Chronic Pain Management: A Review of the ... Evidence suggests that cannabinoids provide moderate efficacy in managing neuropathic pain, fibromyalgia, cancer-related pain, and multiple sclerosis-related ...

3. mdpi.com mdpi.com/2035-8377/17/9/141

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse ... Inhaled cannabis containing 6% THC and 11% CBD relieved pain in 67.2% of patients and eliminated pain completely in 34.5% within two hours, significantly ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02683018?tab=table

Investigation of Cannabis for Chronic Pain and Palliative ... Among these is cannabidiol, which does not produce subjective effects, but has been shown to have potent anti-inflammatory effects. In addition, there is data ...

5. researchgate.net researchgate.net/publication/385561312_Efficiency_of_cannabis_and_cannabidiol_in_managing_chronic_pain_syndromes_A_comprehensive_narrative_review

(PDF) Efficiency of cannabis and cannabidiol in managing ... Cannabinoids were most effective in treating chronic secondary headache and orofacial pain, chronic secondary musculoskeletal pain, chronic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12472909/

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse ... Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1524904223001935?utm_source=bkreader&utm_campaign=bkreader%3A%20outbound&utm_medium=referral

Effectiveness of Cannabidiol to Manage Chronic Pain The majority of the studies indicated pain reduction ranging from 42% - 66% with CBD alone and CBD with Tetrahydrocannabinol.

8. jpain.org jpain.org/article/S1526-5900(23)00582-5/fulltext

Cannabidiol (CBD) Products for Pain: Ineffective ... Fifteen of the 16 RCTs were negative: no greater pain-relieving effect for CBD than for placebo. Meta-analyses link CBD to increased rates of serious adverse ...

9. cureus.com cureus.com/articles/343272-a-survey-on-the-use-of-cannabidiol-cbd-isolate-its-perceived-benefits-and-associated-side-effects-among-subjects-with-chronic-pain

A Survey on the Use of Cannabidiol (CBD) Isolate, Its ... Moreover, 56.2% of respondents found relief with 100 mg or less of CBD, with only a few needing to increase the dose to above 1,000 mg (Figure 3) ...