CBD for Neuropathic Pain in Spinal Cord Injury

Overseen By Eva Widerstrom-Noga, PhD, DDS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Miami

Must not be taking: Valproate, Strong CYP2C19/3A4 inducers

Disqualifiers: Drug/alcohol abuse, Cannabis use, Severe psychopathology, Significant medical illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how CBD, a compound from cannabis, can reduce pain and improve brain activity in people with spinal cord injuries. Participants will receive either CBD or a placebo (a non-active substance) in different sequences to assess effects on pain levels and brain waves. The trial seeks individuals who have experienced neuropathic pain from a spinal cord injury for at least three months and have previously tried cannabis. Those dealing with moderate to severe pain daily and meeting these criteria might find this trial suitable. As a Phase 1/Phase 2 trial, the research aims to understand how the treatment works and measure its effectiveness in an initial group, offering a chance to contribute to groundbreaking pain management solutions.

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

The trial does not specify if you need to stop taking your current medications, but you cannot use cannabis products or certain other drugs during the study. If you take valproate or strong CYP2C19 and CYP3A4 inducers, you may not be eligible to participate.

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

Studies have shown that using CBD for pain relief in spinal cord injury cases might not always be helpful and can lead to more side effects. Research indicates that while CBD may reduce pain in some animal studies, it can also increase the risk of unwanted symptoms or reactions in people. Prospective trial participants should consider these risks alongside the potential benefits of CBD treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using CBD for neuropathic pain in spinal cord injury because it offers a novel approach compared to current treatments like opioids and anticonvulsants. Unlike these standard treatments, which often come with significant side effects and risk of dependency, CBD is derived from cannabis and is believed to have fewer side effects and lower risk of addiction. It works differently by targeting the endocannabinoid system, which may help modulate pain signals more effectively. This unique mechanism of action has the potential to provide relief for those who haven't found success with traditional pain management strategies.

What evidence suggests that CBD might be an effective treatment for neuropathic pain in spinal cord injury?

Research has shown that CBD (cannabidiol) might help reduce nerve pain in people with spinal cord injuries. An early study found that cannabis and cannabinoids, including CBD, lowered pain levels in these patients. Another study on mice demonstrated that CBD eased nerve pain by affecting certain parts of the spinal cord. Additionally, a review of cannabinoids showed significant improvements in pain and movement in models of spinal cord injury. In this trial, participants will be in one of two groups: one group will receive a one-time dose of CBD/CBD-A followed by a placebo, while the other group will receive a placebo followed by a one-time dose of CBD/CBD-A. These findings suggest that CBD could be a promising option for managing nerve pain. ^{1 3 6 7 8}

Who Is on the Research Team?

Eva Widerstrom-Noga, PhD, DDS

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults aged 18-64 with spinal cord injury who have been experiencing moderate to severe neuropathic pain for at least three months. Participants must not have significant medical illnesses, severe mental health disorders, current substance abuse issues, or be pregnant or breastfeeding without effective birth control.

Inclusion Criteria

My pain level is at least a 4 out of 10.

My neuropathic pain has been evaluated with specific questionnaires.

I have had nerve pain for at least three months.

Exclusion Criteria

I do not have a severe mental health condition like major depression, bipolar, schizophrenia, or PTSD.

I have a serious health condition like diabetes, heart disease, or liver problems.

You are currently misusing drugs or alcohol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time dose of CBD/CBD-A or placebo, followed by a crossover to the other treatment after a two-week period

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in brain electrocortical activity, neuropathic pain symptoms, and sensory function

3 hours post intervention

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CBD

Trial Overview The study tests the effects of Cannabidiol (CBD) on neuropathic pain severity and brain activity in people with spinal cord injuries. It compares CBD's impact on pain symptoms and EEG readings against a placebo.

How Is the Trial Designed?

Group I: Placebo followed by CBD/CBD-A group Experimental Treatment 2 Interventions

Participants in this group will receive a placebo on visit 2, followed by a one time of CBD/CBD-A on visit 3 after a two-week period.

Group II: CBD/CBD-A followed by placebo group Experimental Treatment 2 Interventions

Participants in this group will receive a one time dose of CBD/CBD-A on visit 2, followed by a placebo on visit 3 after a two-week period.

CBD 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?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Consortium for Medical Marijuana Clinical Outcomes Research

Collaborator

Trials

5

Recruited

100+

Published Research Related to This Trial

Targeted spinal delivery of THC and CBD significantly reduces neuropathic pain (allodynia) in a mouse model, with a 1:1 combination showing enhanced effectiveness compared to each compound alone.

Importantly, this method of delivery does not produce the typical side effects associated with THC, suggesting that intrathecal administration could be a safe and effective treatment option for nerve injury-induced pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model. Casey, SL., Mitchell, VA., Sokolaj, EE., et al.[2022]

In a study involving 17 healthy noncannabis users, cannabidiol (CBD) did not consistently improve pain threshold or tolerance in a cold pressor test, and in some cases, it even increased pain ratings compared to placebo.

While CBD was found to be safe and well tolerated, with minor decreases in blood pressure, it showed only modest effects on mood and potential abuse liability, suggesting that its analgesic effects may not be reliable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans. Arout, CA., Haney, M., Herrmann, ES., et al.[2022]

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]

This study investigates the effects of cannabis-based medicine (CBM) on spasticity and neuropathic pain in patients with multiple sclerosis and spinal cord injury, using a double-blind, multicenter design with various cannabinoid formulations (THC, CBD, or a combination) compared to a placebo.

The research aims to provide valuable insights into the efficacy and side effects of these cannabinoids, as well as their pharmacodynamics and pharmacokinetics, which are currently not well understood in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Cannabis-Based Medicine on Neuropathic Pain and Spasticity in Patients with Multiple Sclerosis and Spinal Cord Injury: Study Protocol of a National Multicenter Double-Blinded, Placebo-Controlled Trial. Hansen, JS., Hansen, RM., Petersen, T., et al.[2021]

In a mouse model of neuropathic pain, the combination of low-dose THC and CBD significantly enhanced pain relief, showing a 200-fold increase in potency compared to THC alone, without increasing side effects.

While higher doses of THC and CBD did provide greater pain relief, they also led to side effects similar to those caused by THC alone, indicating that lower doses may be more beneficial for managing pain with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis constituent synergy in a mouse neuropathic pain model. Casey, SL., Atwal, N., Vaughan, CW.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10767995/

A preliminary study evaluating self-reported effects of ... These preliminary results suggest that cannabis and cannabinoids may be effective in reducing neuropathic pain among those with SCI and may help to limit the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12317335/

The Efficacy and Safety of Use of Cannabis and Cannabinoid ... This systematic review examines the efficacy of medical cannabis in pain management within orthopaedic domains, including arthritis pain, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526590025006054

Cannabidiol reduces neuropathic pain and cognitive ... The present study reveals cannabidiol's dual effects in female mice by reducing neuropathic pain through spinal PPARγ and 5-HT 1A receptor activation.

4. nature.com nature.com/articles/s41393-021-00680-y

Systematic review of the impact of cannabinoids on ... Modulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04057456

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).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9096558/

Cannabinoid Use for Pain Reduction in Spinal Cord Injuries The current best evidence suggests that cannabinoids may not be beneficial for pain relief in SCI patients, but they do increase the risks of adverse events.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01555983

Vaporized Cannabis and Spinal Cord Injury Pain This study will demonstrate that vaporized marijuana results in antinociception when compared to placebo in subjects with spinal cord injury.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2590109525000734

Understanding Cannabis Use After Spinal Cord Injury Overall, 42.5% of participants reported cannabis use postinjury, and 37.5% were current users, exceeding the general Canadian population's ...