Cannabis for Chronic Headaches

(CAN-CHA Trial)

Recruiting at 2 trial locations

Overseen By Lauren Kelly

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Manitoba

Must not be taking: Opioids, Antipsychotics, Barbiturates, others

Disqualifiers: Post-concussion headache, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 16 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Chronic headaches are a major cause of disability among adolescents. Cannabis products have supported the management of headaches in adults and may play a role in pediatric chronic pain. We propose a multisite, open-label, tolerability study conducted across three centers in Canada of Cannabidiol-enriched Cannabis Herbal Extract in adolescents (ages 14 to 17 years old) with chronic headaches. The study includes a one month baseline assessment, four months of escalating treatment doses and a weaning period. Our primary outcome is tolerability defined as the number and severity of reported adverse events.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, such as opioids, antipsychotics, and muscle relaxants, as they are listed in the exclusion criteria. The protocol does not specify a washout period, but it's important to discuss your current medications with the study team.

What data supports the effectiveness of the drug CBD50 plus for chronic headaches?

While there is no direct evidence for CBD50 plus in treating chronic headaches, cannabidiol (CBD), a component of this drug, has been shown to help control seizures in epilepsy, suggesting it may have potential benefits for other neurological conditions. ^{1 2 3 4 5}

Is cannabidiol (CBD) generally safe for humans?

Cannabidiol (CBD) is generally considered safe for humans, but some people may experience side effects like sleepiness and diarrhea. Rarely, it can cause skin rashes or interact with other medications, such as lithium, leading to increased side effects. ^{1 6 7 8 9}

How does the drug CBD50 plus differ from other treatments for chronic headaches?

CBD50 plus, which includes cannabidiol (CBD), is unique because it targets migraine-related pain through a complex signaling mechanism without causing typical cannabis-like side effects. Unlike other treatments, it reduces inflammation and pain in specific brain areas involved in migraines, offering a novel approach to managing chronic headaches. ^{1 3 10 11 12}

Research Team

Lauren E Kelly, PhD

Principal Investigator

University of Manitoba

Eligibility Criteria

Adolescents aged 14-17 with chronic migraines for over three months, who haven't found relief from other treatments like certain antidepressants or anticonvulsants. They must not have specific medical conditions that could interfere with the study, be willing to avoid pregnancy and recreational cannabis use, and commit to additional psychological and physiotherapy support.

Inclusion Criteria

I am willing to participate in psychology and physiotherapy sessions during the trial.

I've tried other treatments like antidepressants or gabapentinoids, but they didn't work or caused side effects.

I have been diagnosed with chronic migraine for over three months.

Exclusion Criteria

As per the investigator judgement, the participant is not an ideal candidate due to a personal issue or medical condition that is likely to impede in the successful completion of the study

I have had headaches after a concussion or experience new daily headaches.

Participants who are pregnant or breast/chest-feeding or plans to become pregnant within the study period or within three months of interventional product discontinuation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a one month baseline assessment to document initial headache frequency, anxiety, sleep quality, mood, and pain intensity

4 weeks

1 visit (in-person)

Treatment

Participants receive escalating doses of Cannabidiol-enriched Cannabis Herbal Extract over four months

16 weeks

Monthly visits (in-person)

Weaning

Participants gradually reduce the dosage of the study medication

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CBD50 plus
• LGP1:20
• MPL-001

Trial Overview The CAN-CHA Trial is testing a Cannabidiol-enriched Cannabis Herbal Extract (MPL-001) in teens with chronic headaches. Over four months, participants will receive escalating doses of this treatment after a one-month observation period, followed by weaning off the drug. The main focus is on how well they tolerate it.

Participant Groups

Group I: Cannabidiol-enriched Cannabis Herbal Extract Experimental Treatment 1 Intervention

CBD50 plus

CBD50 plus 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

Approved in European Union as Epidyolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Approved in Canada as Sativex for:

• Central neuropathic pain in multiple sclerosis
• Cancer-related pain

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

The Canadian Collaborative for Childhood Cannabinoid Therapeutics

Collaborator

Trials

3

Recruited

580+

SickKids Foundation

Collaborator

Trials

10

Recruited

2,200+

The Canadian Collaborative for Childhood Cannabinoid Therapeutics (C4T)

Collaborator

Trials

1

Recruited

20+

Findings from Research

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

Epidiolex™, a purified form of cannabidiol (CBD), shows promise in controlling seizures in Dravet syndrome, with its mechanism linked to the mitochondrial glycine cleavage system, specifically the GcvH1 protein.

CBD appears to regulate methionine levels by inhibiting its synthesis, which is altered in Dravet syndrome and associated with seizure activity, suggesting a novel metabolic pathway involved in its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. Perry, CJ., Finch, P., Müller-Taubenberger, A., et al.[2021]

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., et al.[2021]

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

Epidiolex® (CBD) is effective for treating epilepsy in patients over 2 years old, but it can interact with other medications, as seen in a case where it contributed to lithium toxicity in a patient with Lennox-Gastaut syndrome.

After discontinuing lithium due to toxicity, the patient improved and remained seizure-free on CBD and two other antiseizure medications, highlighting the importance of monitoring drug interactions when adding CBD to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Drug Interactions Between Cannabidiol and Lithium. Singh, RK., Dillon, B., Tatum, DA., et al.[2020]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

Epidiolex® (cannabidiol) is an FDA-approved medication for treating epilepsy associated with Lennox-Gastaut and Dravet syndromes, showing promise for treatment-resistant epilepsy.

A case study of a 23-year-old female revealed a delayed skin rash related to Epidiolex®, highlighting the need to monitor for potential side effects even when they are rare in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex-induced skin rash. Singh, J., Antimisiaris, MF.[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 study using male Sprague Dawley rats, cannabidiol (CBD) was found to effectively reduce migraine-related pain by decreasing trigeminal hyperalgesia and lowering levels of pain-related markers like CGRP and IL-6, indicating its potential as a therapeutic option for migraine relief.

CBD was shown to penetrate key brain areas involved in migraine pain without accumulating, and it did not affect anxiety or motor behavior, suggesting a favorable safety profile for its use in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine. Greco, R., Francavilla, M., Demartini, C., et al.[2023]

In a study of 107 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), cannabidiol (CBD) was found to be effective as an add-on therapy, with a notable 30% of LGS patients and 21% of DS patients achieving a 50% reduction in seizure frequency after 12 months.

The treatment was well-tolerated, with a retention rate of 63% at 12 months, although 31% of patients experienced adverse events, primarily somnolence and gastrointestinal issues, indicating that while CBD is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome. Nabbout, R., Arzimanoglou, A., Auvin, S., et al.[2023]

References

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

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. [2021]

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

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

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

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

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

Drug-Drug Interactions Between Cannabidiol and Lithium. [2020]

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

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. [2021]

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

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. [2020]

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

Epidiolex-induced skin rash. [2021]

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. England pubmed.ncbi.nlm.nih.gov

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome. [2023]