CBD for Brain Inflammation and Pain Sensitization

Overseen By Rajiv Radhakrishnan, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Any medications

Disqualifiers: Metal in body, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

15 Participants Needed

Trial Summary

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

Yes, you must stop taking any current medications to participate in this trial.

What data supports the effectiveness of the drug Cannabidiol (CBD) for brain inflammation and pain sensitization?

Research shows that Cannabidiol (CBD) has anti-inflammatory and pain-relieving properties, as seen in studies with animals experiencing inflammatory pain and neuropathic pain. Additionally, CBD is noted for its potential benefits in inflammatory conditions, making it a promising option for treating brain inflammation and pain sensitization. ^{1 2 3 4 5}

Is CBD safe for human use?

Research suggests that CBD is generally safe for humans, with studies indicating excellent tolerability even at high doses. However, more clinical trials are needed to confirm its safety across different conditions. ^{1 2 3 4 6}

How is the drug CBD unique in treating brain inflammation and pain sensitization?

CBD is unique because it targets neuroinflammation by inhibiting glial cells, which are involved in maintaining pain, and it does so without causing intoxication, unlike other cannabis components. This makes it a novel option for reducing brain inflammation and pain sensitization. ^{1 2 4 7 8}

What is the purpose of this trial?

This study aims to examine the effect of cannabidiol (CBD) pre-treatment on brain microglial activation in healthy human subjects. Secondarily, this study aims to examine the effect of cannabidiol (CBD) pre-treatment on central pain-sensitization in healthy human subjects.

Research Team

Rajiv Radhakrishnan, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for healthy men and women aged 18-55 with no significant medical or neurological illnesses. Participants must not be using any medications, have metal implants that could interfere with MRI scans, or be pregnant or lactating.

Inclusion Criteria

Able to provide written informed consent

I do not have any major health or brain conditions.

Within the annual permissible radiation exposure

Exclusion Criteria

I am currently taking medication.

You have metal objects inside your body.

Pregnancy or lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive cannabidiol (CBD) or placebo pre-treatment to examine effects on microglial activation and central pain-sensitization

10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Cannabidiol

Trial Overview The study tests how cannabidiol (CBD) affects brain inflammation and pain sensitivity in healthy people. It involves CBD pre-treatment followed by PET scans using [11C]PBR28 to measure microglial activation and a low-dose lipopolysaccharide challenge.

Participant Groups

Group I: CBD Active Control 3 Interventions

Group II: Placebo Placebo Group 3 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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

In a study involving 32 dogs with canine atopic dermatitis, treatment with a mix of CBD and CBDA significantly reduced pruritus (itchiness) scores at 14 and 28 days, indicating its potential effectiveness in alleviating itching associated with the condition.

However, there was no significant improvement in the overall severity of skin lesions as measured by the CADESI-04 score, suggesting that while CBD/CBDA may help with itching, it does not address the skin lesions themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis. Loewinger, M., Wakshlag, JJ., Bowden, D., 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]

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 randomized placebo-controlled trial involving 20 patients with Crohn's disease, cannabidiol (CBD) was found to be safe with no observed side effects, but it did not show any significant beneficial effects on disease activity after 8 weeks of treatment.

Despite the lack of efficacy, the study suggests that the ineffectiveness of CBD could be due to factors such as the small dosage used, the limited number of participants, or the need for a combination with other cannabinoids, indicating that further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial. Naftali, T., Mechulam, R., Marii, A., et al.[2022]

CBDA-ME, a stable form of cannabidiolic acid, demonstrated significant anti-hyperalgesic effects in male rats with chronic neuropathic pain, suggesting its potential as an effective treatment for pain management.

The study found that the anti-nociceptive effects of CBDA-ME were not observed in female rats, indicating possible sex-based differences in response to this cannabinoid, which warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain. Zhu, YF., Linher-Melville, K., Niazmand, MJ., et al.[2021]

Cannabidiol (CBD) shows strong potential as an effective treatment for multiple sclerosis (MS) in animal models, particularly for its anti-inflammatory and immunosuppressive properties, with excellent tolerability even at high doses.

However, clinical evidence in humans is limited and often negative, suggesting a need for more studies with optimized dosing and better-defined efficacy endpoints to fully understand CBD's effects in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. Furgiuele, A., Cosentino, M., Ferrari, M., et al.[2023]

This phase II clinical trial will assess the effects of cannabidiol (CBD) on neuroinflammation in 80 adults with chronic low back pain over 4 weeks, using advanced imaging techniques to measure changes in glial activation.

The primary goal is to determine if CBD reduces levels of the 18 kDa translocator protein (TSPO), a marker of neuroinflammation, compared to a placebo, potentially offering a new therapeutic approach for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a phase II, double-blind, randomised controlled trial of cannabidiol (CBD) compared with placebo for reduction of brain neuroinflammation in adults with chronic low back pain. Pike, CK., Kim, M., Schnitzer, K., et al.[2023]

Cannabidiol (CBD) has shown potential therapeutic effects for pain and inflammation, but the evidence is inconclusive due to variations in study methods, including different routes of administration and types of pain assessed, with most studies involving small participant numbers.

Positive results were consistently observed in studies focusing on the effects of CBD on arthritis, suggesting it may be particularly beneficial for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Cannabidiol in Inflammation: A Review of Pre-clinical and Clinical Findings. Sklenárová, M., Šíma, M., Slanař, O.[2023]

References

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

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis. [2022]

2. 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]

3. 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]

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

Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain. [2021]

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

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Study protocol for a phase II, double-blind, randomised controlled trial of cannabidiol (CBD) compared with placebo for reduction of brain neuroinflammation in adults with chronic low back pain. [2023]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

Effects of Cannabidiol in Inflammation: A Review of Pre-clinical and Clinical Findings. [2023]