Cannabinoids + Anti-inflammatory Diet for Neuropathic Pain

(CATNP Trial)

Overseen By Alexandria Roa Agudelo

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eldon Loh, MD

Must not be taking: Cannabinoids

Disqualifiers: Psychotic disorder, Convulsive disorders, Substance abuse, Cardiac dysfunction, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find better ways to manage neuropathic pain, the nerve pain that can occur after a spinal cord injury. Researchers are testing whether an anti-inflammatory diet and nabilone (a medication derived from cannabis) can help reduce pain and improve daily function. Participants will try either a diet change, a pill, or both for four weeks, with some receiving placebos (inactive treatments) for comparison. Those who have experienced ongoing neuropathic pain following a spinal cord injury for over a year might be a good fit. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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

You need to stop taking any cannabinoids or cannabinoid medications at least 1 month before the study. Other pain medications should be stable for at least 1 month before joining the study.

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

Research has shown that an anti-inflammatory diet can reduce pain and improve overall well-being. Consuming foods like fish, leafy greens, and nuts often leads to less pain and stress. This suggests the diet is safe and may benefit those with chronic pain.

Nabilone, a synthetic drug similar to cannabis, has been used to manage chronic pain. Research indicates it is generally well-tolerated. Some individuals have reported minor side effects like drowsiness or dizziness, but these are usually not serious. This suggests that nabilone can be a safe option for reducing pain.

Both the diet and nabilone are under study to determine if they work better together. Based on current knowledge, they appear to be promising and safe options for individuals dealing with nerve pain after a spinal cord injury. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuropathic pain because they offer a unique combination of dietary and pharmaceutical approaches. Unlike standard treatments, which often include medications like antidepressants and anticonvulsants, this approach combines an anti-inflammatory diet with Nabilone, a synthetic cannabinoid. The anti-inflammatory diet aims to reduce pain by eliminating foods that may cause inflammation, while Nabilone potentially provides pain relief through cannabinoid receptors in the body. This dual approach could offer a more holistic way to manage neuropathic pain, targeting both inflammation and nerve pain pathways.

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

Research has shown that an anti-inflammatory diet can reduce pain and improve overall well-being. Studies have linked this diet to less long-term pain and better physical health. It can also boost mood and enhance sleep quality. In this trial, some participants will follow an anti-inflammatory diet.

Regarding nabilone, studies indicate it effectively manages nerve pain. Specifically, research found that nabilone reduced pain and improved sleep in patients with diabetic nerve pain. Another study showed it improved pain and quality of life for those with ongoing pain conditions. In this trial, some participants will receive Nabilone capsules.

This trial will compare the effects of the anti-inflammatory diet and nabilone, both individually and in combination, to placebo options. Together, the anti-inflammatory diet and nabilone offer promising options for reducing nerve pain, potentially providing relief beyond current treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Eldon Loh, MD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

David Ditor, MD

Principal Investigator

Brock University

Are You a Good Fit for This Trial?

Adults over 25 with a stable spinal cord injury for at least a year, experiencing neuropathic pain. They must not be pregnant or planning pregnancy, have used cannabinoids recently, or have certain medical conditions like liver issues or psychotic disorders. Stable dosing of other pain meds is required and they must agree to use birth control.

Inclusion Criteria

Signed informed consent obtained prior to any study-related activities

I have had a spinal cord injury for over a year, with no worsening in the last 6 months.

You must have a body mass index (BMI) between 18 and 40.

Exclusion Criteria

My liver function tests are significantly abnormal.

I am not pregnant, breastfeeding, nor planning to become pregnant during the study and for three months after.

I have conditions that could affect the assessment of my nerve pain after a spinal cord injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an anti-inflammatory diet or a placebo diet, and nabilone or a placebo for 4 weeks

4 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

Visits may be in-person or over the phone

What Are the Treatments Tested in This Trial?

Interventions

• Anti-inflammatory diet
• Nabilone Capsules
• Placebo capsules
• Placebo diet

Trial Overview The trial tests if an anti-inflammatory diet and Nabilone capsules can reduce neuropathic pain in those with spinal cord injuries better than placebo alternatives. Participants will follow the assigned diet and take either Nabilone or placebo capsules for four weeks.

How Is the Trial Designed?

Group I: Anti-inflammatory diet and Nabilone capsules Active Control 2 Interventions

Capsules will be 0.5mg nabilone. Participants will take up to 8 capsules per day for a maximum dose of 4mg of nabilone per day. This meal plan will eliminate foods that have been established as pro-inflammatory (e.g. processed foods, refined sugars, refined wheat products, etc.) as well as foods that are commonly associated with even mild intolerances (e.g. cow's milk) and those that negatively impact cardiovascular health (e.g. hydrogenated oils, alcohol, coffee, refined sugars and wheat, trans fats, processed foods). In their place, the meal plan will consist of foods with established anti-inflammatory properties (e.g. (Oily fish, lean poultry, dark leafy greens, cruciferous vegetables, nuts, whole grains, most kinds of berries, etc).

Group II: Placebo diet and Nabilone capsules Active Control 2 Interventions

Capsules will be 0.5mg nabilone. Participants will take up to 8 capsules per day for a maximum dose of 4mg of nabilone per day.

Group III: Anti-inflammatory diet and placebo capsules Active Control 2 Interventions

This meal plan will eliminate foods that have been established as pro-inflammatory (e.g. processed foods, refined sugars, refined wheat products, etc.) as well as foods that are commonly associated with even mild intolerances (e.g. cow's milk) and those that negatively impact cardiovascular health (e.g. hydrogenated oils, alcohol, coffee, refined sugars and wheat, trans fats, processed foods). In their place, the meal plan will consist of foods with established anti-inflammatory properties (e.g. (Oily fish, lean poultry, dark leafy greens, cruciferous vegetables, nuts, whole grains, most kinds of berries, etc).

Group IV: Placebo diet and placebo capsules Placebo Group 2 Interventions

Participants taking the placebo diet and capsules

Who Is Running the Clinical Trial?

Eldon Loh, MD

Lead Sponsor

Trials

1

Recruited

140+

Ontario Neurotrauma Foundation

Collaborator

Trials

24

Recruited

1,100+

Published Research Related to This Trial

Cannabis-based medicinal products, particularly those with a 1:1 ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD), were found to have the highest benefit-safety score (79 out of 100) for treating chronic neuropathic pain compared to other medications, indicating their potential effectiveness and safety.

Even when accounting for reduced pain relief and quality of life scores, THC/CBD and THC maintained a better benefit-safety balance than traditional non-cannabinoid treatments, highlighting the need for further research into cannabinoids for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products. Nutt, DJ., Phillips, LD., Barnes, MP., et al.[2022]

A systematic review and meta-analysis of 12 studies involving natural compounds (nutraceuticals) showed significant reductions in neuropathic pain symptoms, including thermal hyperalgesia and mechanical allodynia, in animal models.

The findings suggest that nutraceuticals could be an effective option for managing persistent neuropathic pain, highlighting their potential clinical relevance in pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis on the Role of Nutraceuticals in the Management of Neuropathic Pain in In Vivo Studies. Ilari, S., Proietti, S., Russo, P., et al.[2023]

In a case series of five patients with various neuropathic pain conditions, treatment with high doses of omega-3 fatty acids (2400-7200 mg/day) resulted in significant pain reduction and improved function, lasting up to 19 months after starting treatment.

No serious adverse effects were reported, suggesting that omega-3 fatty acids may be a safe and beneficial option for managing neuropathic pain, warranting further research through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids for neuropathic pain: case series. Ko, GD., Nowacki, NB., Arseneau, L., et al.[2022]

A review of 17 randomized controlled trials found that phytocannabinoid treatments, particularly those containing THC alone, showed the most promise for relieving neuropathic pain, with significant pain relief reported in several studies.

While THC/CBD combinations showed some pain reduction, the evidence was less consistent, and studies focusing on CBD alone did not demonstrate significant analgesic effects, suggesting that THC is the more effective component for treating neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phytocannabinoids for the Treatment of Neuropathic Pain: A Scoping Review of Randomised Controlled Trials Published Between 2012 and 2023. Lewis, M., Baroutian, S., Hanning, SM.[2023]

This systematic review aims to evaluate the effectiveness of cannabinoids and cannabis-based medicines in managing pain by analyzing preclinical studies involving animal models of tissue damage, inflammation, or neuropathy.

The review will use standardized mean difference meta-analysis to summarize the antinociceptive effects, helping to identify the strengths and weaknesses of current research and guide future studies in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protocol for the systematic review and meta-analysis of studies in which cannabinoids were tested for antinociceptive effects in animal models of pathological or injury-related persistent pain. Soliman, N., Hohmann, AG., Haroutounian, S., et al.[2022]

In a randomized, double-blind trial involving 145 patients with peripheral neuropathic pain, neither cannabidiol (CBD), tetra-hydro-cannabinol (THC), nor their combination showed any significant pain relief compared to placebo after 8 weeks of treatment.

The study found that all treatment groups had similar or worse pain scores compared to placebo, indicating that cannabinoids may not be effective for patients who have not responded to previous treatments for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment. Zubcevic, K., Petersen, M., Bach, FW., et al.[2023]

Medical cannabis effectively alleviated severe diabetic neuropathic pain and helped reverse muscular emaciation in a patient with a history of heroin abuse, demonstrating its potential as a treatment option for neuropathic pain.

The tetrahydrocannabinol (THC) component of medical cannabis not only provided pain relief but also increased appetite, contributing to weight gain and improved muscle mass, highlighting its dual benefits in managing diabetic neuropathic cachexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis alleviates neuropathic pain and reverses weight loss in diabetic neuropathic cachexia in a previous heroin abuser. Naccache, DD.[2022]

Combining low doses of the MAGL inhibitor JZL184 and the COX inhibitor diclofenac effectively reduced neuropathic pain in mice, showing a synergistic effect on mechanical allodynia and an additive effect on cold allodynia.

The analgesic effects of this combination were primarily mediated through CB1 receptors, suggesting that this dual inhibition approach could provide effective pain relief with fewer side effects compared to traditional NSAIDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice. Crowe, MS., Leishman, E., Banks, ML., et al.[2018]

Dietary bioactive compounds like ginger, curcumin, and omega-3 fatty acids have shown promise in reducing neuropathic pain (NP) and related neuroinflammation, as demonstrated in cellular and animal studies.

These compounds may work by enhancing neuron survival and reducing neuronal hyperexcitability through various mechanisms, including activation of cannabinoid and opioid receptors, suggesting a potential alternative to traditional opioid treatments for NP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioactive compounds for neuropathic pain: An update on preclinical studies and future perspectives. Shen, CL., Castro, L., Fang, CY., et al.[2023]

In a study of 2,741 patients in Denmark, cannabis-based medicines (CBM/MC) showed potential benefits for individuals with neuropathic pain, including reduced use of gabapentin and fewer hospital days compared to matched controls.

However, while CBM/MC users with neuropathic pain did not reduce their opioid use, the treatment did not demonstrate efficacy for patients with other pain disorders, indicating a specific benefit for neuropathic pain only.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis-based medicines and medical cannabis for patients with neuropathic pain and other pain disorders: Nationwide register-based pharmacoepidemiologic comparison with propensity score matched controls. Hjorthøj, C., La Cour, P., Nordentoft, M., et al.[2022]

Nabilone, a synthetic cannabinoid approved for severe nausea and vomiting from chemotherapy, shows promise as an adjunctive therapy for various pain conditions, including cancer pain and fibromyalgia, with small but significant reductions in pain reported across multiple studies.

The safety profile of nabilone is generally favorable, with common side effects like euphoria and drowsiness, but severe adverse reactions are rare, and its potential for abuse is considered low, making it a viable option as a third-line treatment according to some clinical guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabilone for the Management of Pain. Tsang, CC., Giudice, MG.[2016]

The systematic review analyzed 40 studies on dietary interventions and supplements for chronic neuropathic pain, finding that while some supplements like alpha-lipoic acid and vitamin D may be beneficial for diabetic peripheral neuropathy (DPN), there is insufficient evidence to recommend any supplements for chemotherapy-induced peripheral neuropathy (CIPN).

Conflicting results were noted for several supplements, with some, like acetyl-l-carnitine, potentially being ineffective or harmful, highlighting the need for further research to clarify their roles in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review. Frediani, JK., Lal, AA., Kim, E., et al.[2023]

Cannabinoid drugs have shown moderate effectiveness in reducing chronic neuropathic pain, especially in patients who do not respond well to traditional treatments, according to recent clinical studies.

While cannabinoids have comparable side effects to existing pain medications, their psychoactive effects limit dosage, highlighting the need for new formulations that minimize these side effects for better pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids for the treatment of neuropathic pain: clinical evidence. Ashton, JC., Milligan, ED.[2008]

Citations

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The effect of an anti-inflammatory diet on chronic pain We found a correlation between increased anti-inflammatory food intake and improved physical characteristics, stress, and pain in the patients we assessed.

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A Systematic Review of Dietary Lifestyle Interventions for ... Lastly, Torlak and colleagues (2020) found that an intermittent high protein/Mediterranean diet also resulted in significant improvements in NP on VAS and LANSS ...

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A Personalized Mediterranean Diet Improves Pain and ... The DIET group showed an improvement in most of the fibromyalgia parameters, including the disability scores, fatigue, and anxiety. Conclusions.

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Chronic Pain Relief: Nutrition and Mitochondrial Health Studies suggest that anti-inflammatory Mediterranean-style diets may not only reduce risk of inflammatory arthritis25 but may also help reduce ...

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Anti-Inflammatory Diet for Chronic Pain | Foods That Help ... While diet won't cure pain, it can lower inflammation and reduce flare-ups. Patients often report better sleep, improved mood, and increased ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1526590023005278

Proinflammatory Dietary Intake Relates to Pain Sensitivity ... Higher scores in the HEI-2015 represent more beneficial diets and are related to an anti-inflammatory diet and lower Dietary Inflammatory Index (DII) scores.

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Study Details | NCT04057456 | Cannabinoids and an Anti- ... Nabilone and an anti-inflammatory diet are two novel treatments that may be beneficial for managing Neuropathic Pain (NP) after Spinal Cord Injury (SCI).