Cannabinoids for Pain Management and Neuroprotection

Recruiting at 1 trial location

Overseen By Jyotpal Singh

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Regina

Must not be taking: Steroids

Disqualifiers: Female, Neurological conditions, Cardiac, 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: 8

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must list any prescription medications you are taking. You cannot use cannabis-based therapy within 2 months before the study or during the study.

What data supports the effectiveness of the drug for pain management and neuroprotection?

Research shows that THC and CBD, components of cannabis, can reduce pain in animal models of nerve injury and chemotherapy-induced pain. In humans, a THC/CBD spray has shown some promise in reducing pain and improving sleep quality in patients with multiple sclerosis, although results were mixed and further studies are needed. ^{1 2 3 4 5}

Is the use of cannabinoids like CBD and THC generally safe for humans?

Cannabinoids such as CBD and THC have been studied for safety, showing that CBD can cause side effects like sleep disturbances and potential drug interactions, while THC may cause psychoactive effects. Both have been used in clinical settings, but careful monitoring is recommended due to potential adverse effects and interactions with other medications. ^{1 3 5 6 7}

How does the cannabinoid drug for pain management and neuroprotection differ from other treatments?

This cannabinoid drug, which includes THC and CBD, is unique because it can be delivered directly to the spine (intrathecal delivery), providing effective pain relief without the typical side effects associated with systemic administration. This targeted approach enhances its potency and safety compared to oral or systemic treatments. ^{1 8 9 10 11}

What is the purpose of this trial?

The goal of this open-label, placebo-controlled, dosage escalation study is to learn about the safety of a Cannabis/Hemp Isolate Extract in normal healthy adults engaged in elite contact sport competition. The main question it aims to answer is: • Are cannabis/hemp-based products with high CBD safe, well-tolerated and without adverse physiological and psychological dysfunction, when administered on a daily basis? Participants will: * be given CBD and a placebo. The placebo will be taken for 2 weeks prior to starting the CBD. Participants will start on a low dose of CBD, beginning at 5 mg CBD/kg body mass, which will be increased by 5 mg/kg every 2-weeks until 30 mg CBD/kg body mass is taken; * have blood samples taken to analyse how much CBD is used in the body and for how long it lasts in the body (pharmacokinetics and pharmacodynamics); * have saliva samples collected for genetic analysis; * undergo testing sessions, which will include psychological and health questionnaires, equipment to record signals from the brain and heart, and safety laboratory tests.

Research Team

Patrick Neary

Principal Investigator

University of Regina

Payam Dehghani,

Principal Investigator

Saskatchewan Health Authority - Regina Area

Eligibility Criteria

This trial is for healthy adults who play elite contact sports. They should be interested in exploring the effects of a Cannabis/Hemp Isolate Extract with high CBD content on pain management and neuroprotection from concussion. Participants must not have any health conditions that exclude them from safely taking part.

Inclusion Criteria

I have no history of stroke or heart issues.

Not habitual recreational users of cannabis (i.e., <1 day/week) or tobacco users

I am a healthy male aged 18-35 and compete in contact sports.

Exclusion Criteria

I am female.

I can attend regular assessments and take daily medication.

Allergy or known intolerance to any of the compounds within the study preparation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo

Participants take a placebo for 2 weeks prior to starting the CBD regimen

2 weeks

1 visit (in-person)

Dose Escalation Treatment

Participants start on a low dose of CBD, beginning at 5 mg CBD/kg body mass, increased by 5 mg/kg every 2 weeks until 30 mg CBD/kg body mass is taken

12 weeks

7 visits (in-person) every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabis/Hemp Isolate Extract

Trial Overview The study tests the safety of escalating doses of Cannabis/Hemp Isolate Extract, starting at 5 mg CBD per kg body mass up to 30 mg/kg. It's an open-label, placebo-controlled study where participants first take a placebo then switch to CBD while undergoing various tests and sample collections.

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

When participants start the CBD, they will be started on a low dose of CBD, beginning at 5 mg CBD/kg body mass, and then increased by 5 mg/kg every 2-weeks until 30 mg CBD/kg body mass is taken.

Who Is Running the Clinical Trial?

University of Regina

Lead Sponsor

Trials

59

Recruited

9,100+

My Next Health Inc.

Collaborator

Trials

1

Recruited

40+

National Football League (NFL)

Collaborator

Trials

1

Recruited

40+

Findings from Research

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 mouse model of chemotherapy-induced neuropathic pain, both CBD and THC were effective in reducing mechanical sensitivity, with low doses of each showing a synergistic effect when combined.

CBD demonstrated the ability to alleviate pain from oxaliplatin-induced neuropathy, while THC was effective against vincristine-induced pain, suggesting that combining these cannabinoids could enhance treatment options for chemotherapy-related nerve pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single and combined effects of &#916;9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain. King, KM., Myers, AM., Soroka-Monzo, AJ., 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]

In a phase III study involving 339 multiple sclerosis patients with central neuropathic pain, the THC/CBD oromucosal spray (Sativex) did not meet the primary endpoint of responder analysis at week 14, showing only a slight difference in response rates compared to placebo (50% vs. 45%).

However, during the randomized-withdrawal phase, the THC/CBD spray significantly delayed treatment failure, with only 24% of patients on the spray failing treatment compared to 57% on placebo, indicating potential long-term benefits of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. Langford, RM., Mares, J., Novotna, A., et al.[2022]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

A new liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was successfully developed to accurately identify and quantify THC and CBD in olive oil, showing linearity and low imprecision over a range of concentrations.

The extraction efficiency of THC and CBD from olive oil can be significantly improved by optimizing the extraction temperature, with a 2°C increase leading to a notable rise in extraction percentages for both cannabinoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil. Morini, L., Porro, G., Liso, M., et al.[2018]

Pre-clinical studies suggest that cannabidiol (CBD) has neuroprotective effects and may benefit patients with neurodegenerative diseases like Alzheimer's, Parkinson's, and multiple sclerosis, but more robust clinical trials are needed to confirm these findings.

Recent clinical studies indicate that CBD may be effective in treating refractory epilepsy in children and young adults, showing promise as an alternative for patients who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological Aspects of Medical Use of Cannabidiol. Mannucci, C., Navarra, M., Calapai, F., et al.[2022]

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]

Cannabidiolic acid (CBDA) demonstrated significant anti-hyperalgesia and anti-inflammatory effects in a rat model when administered before inflammation, indicating its potential as a more potent alternative to cannabidiol (CBD).

The study found that combining low doses of CBDA and THC, which were ineffective alone, resulted in enhanced anti-hyperalgesia and reduced inflammation, suggesting a synergistic effect between these compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cannabidiolic acid and &#8710;9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain. Rock, EM., Limebeer, CL., Parker, LA.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Single and combined effects of &#916;9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain. [2021]

3. 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]

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil. [2018]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Neurological Aspects of Medical Use of Cannabidiol. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. Germany pubmed.ncbi.nlm.nih.gov

Effect of cannabidiolic acid and &#8710;9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain. [2018]