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

Trial Summary

What is the purpose of this trial?

The main purposes of this study are to (1) measure the effect of CBD/CBD-A on pain symptoms, pain intensity, pain unpleasantness, and skin sensitivity to hot and cold temperatures; and (2) measure the effect of CBD on brain electrical activity with electroencephalography (EEG).

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.

What data supports the effectiveness of the drug CBD for neuropathic pain in spinal cord injury?

Research shows that CBD, a component of cannabis, can reduce chronic pain in animal models of spinal cord injury. It works by interacting with certain receptors in the body, and when combined with another cannabis component, β-caryophyllene, it can enhance pain relief without significant side effects. ^{1 2 3 4 5}

Is CBD safe for humans?

Research suggests that CBD (Cannabidiol) is generally safe for humans, as it does not produce the significant side effects associated with THC (the psychoactive component of cannabis). Studies in animal models have shown that CBD can reduce pain without causing cannabis-like side effects, making it a potentially safer option for managing neuropathic pain. ^{1 3 5 6 7}

How does the drug CBD differ from other treatments for neuropathic pain in spinal cord injury?

CBD is unique because it reduces neuropathic pain by decreasing oxidative stress and increasing antioxidant defenses, without the psychoactive side effects associated with THC, another cannabis component. It also shows potential for safe and effective pain relief when delivered directly to the spinal area, unlike many systemic treatments. ^{1 5 8 9 10}

Research Team

Eva Widerstrom-Noga, PhD, DDS

Principal Investigator

University of Miami

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

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

Combined non-psychoactive Cannabis components cannabidiol and β-caryophyllene reduce chronic pain via CB1 interaction in a rat spinal cord injury model. [2023]

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

Peripherally injected canabidiol reduces neuropathic pain in mice: Role of the 5-HT1A and TRPV1 receptors. [2023]

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

Cannabis constituent synergy in a mouse neuropathic pain model. [2021]

4. Switzerland 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. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model. [2021]

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

The Cannabidiol Analog PECS-101 Prevents Chemotherapy-Induced Neuropathic Pain via PPARγ Receptors. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats. [2022]

9. England 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. [2022]

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

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. [2022]