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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabidiol (CBD), a compound in cannabis, affects brain inflammation and pain sensitivity. Researchers aim to determine if CBD can reduce activation in brain cells called microglia, which contribute to inflammation and pain. Participants will receive either CBD or a placebo (inactive substance) to compare effects. The trial suits healthy individuals without significant medical conditions and not currently taking any medications. As an Early Phase 1 trial, this research focuses on understanding how CBD works in people, offering participants a chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that cannabidiol (CBD) is likely to be safe for humans?

Past studies have shown that cannabidiol (CBD) is generally safe for people. Research confirms that most individuals tolerate CBD well. When side effects occur, they are usually mild, such as fatigue or changes in appetite. Importantly, extensive evidence from studies conducted before and after human testing supports CBD's safety, reinforcing its general safety for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain inflammation and pain sensitization, which often include non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, cannabidiol (CBD) offers a unique approach. CBD is derived from cannabis plants and is known for its anti-inflammatory and pain-relieving properties without the psychoactive effects of THC. Researchers are excited about CBD because it interacts with the body's endocannabinoid system, potentially reducing inflammation and altering pain perception pathways in a way that traditional medications do not. This could lead to effective symptom relief with fewer side effects, making it a promising alternative for patients seeking new options.

What evidence suggests that cannabidiol might be an effective treatment for brain inflammation and pain sensitization?

Research has shown that cannabidiol (CBD), which participants in this trial may receive, might help reduce inflammation in the brain, known as neuroinflammation. Studies have found that CBD can lower this type of inflammation. It also has properties that relieve pain and reduce inflammation, potentially making it useful for treating pain. Some research suggests that CBD can decrease anxiety by affecting certain parts of the brain. These findings indicate that CBD could be helpful for brain inflammation and pain. However, more research is needed to fully understand these effects. ^{3 6 7 8 9}

Who Is on the Research Team?

Mohini Ranganathan, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10823027/

Cannabidiol and brain function: current knowledge and future ... Taken together, these results suggest that CBD can reduce anxiety, and that this is related to its effects on activity in limbic and paralimbic brain areas. 3.3 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1043661825004128

Cannabidiol and Beta-Caryophyllene: chronic ... Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9486315/

Study protocol for a phase II, double-blind, randomised ... The principal aim of this trial is to evaluate whether CBD, compared with placebo, affects neuroinflammation, as measured by TSPO levels.

4. mdpi.com mdpi.com/1424-8247/17/11/1438

Cannabidiol (CBD): A Systematic Review of Clinical and ... CBD could be an effective and safe treatment in reducing pain due to its analgesic and anti-inflammatory properties.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521689620300458

7 Use of cannabidiol (CBD) for the treatment of chronic pain Many of the studies compare CBD with its psychoactive counterpart, THC, and have yielded analgesic effects that have not fully been understood.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9028607/

The current understanding of the benefits, safety, and ... In addition, a considerable amount of safety evaluation data on CBD have derived from pre-clinical and clinical studies during the development of the CBD ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0074774224000680

Cannabidiol and pain Understanding CBD's role in pain management continues to evolve, with animal studies providing evidence that CBD achieves its analgesic effects through ...

9. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1328885/full

Cannabidiol and brain function: current knowledge ... The potential effectiveness of CBD in reducing chronic pain is considered but also in reducing the symptoms of various brain disorders such as epilepsy, ...