Cannabinoids for Sickle Cell Disease

(CRISP Trial)

Overseen By Susanna Curtis, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Cannabinoids

Disqualifiers: Psychosis, Suicidality, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

A randomized, double blind, study of dronabinol as a palliative agent in the treatment of pain, inflammation, and other complications of sickle cell disease (SCD).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on a sickle cell disease modifying therapy or using opioids for pain, you must be on a stable dose for at least 3 months. You will need to abstain from cannabis during the study.

What evidence supports the effectiveness of the drug Dronabinol for treating pain in sickle cell disease?

Research shows that cannabinoids, like Dronabinol, are used by some people with sickle cell disease to relieve pain and improve mood. Additionally, Dronabinol has been found to reduce pain intensity and increase satisfaction in patients with chronic pain, suggesting potential benefits for sickle cell disease pain management. ^{1 2 3 4 5}

Is the use of cannabinoids like Dronabinol generally safe for humans?

Dronabinol, a cannabinoid, has been studied for safety and is generally considered safe with mild-to-moderate side effects like dry mouth, dizziness, and headache, which are usually temporary. More research is needed to fully understand its side effect profile, but current data suggests these effects are acceptable compared to the potential benefits. ^{3 5 6 7 8}

How does the drug Dronabinol differ from other treatments for sickle cell disease?

Dronabinol, a synthetic form of THC (the active component in cannabis), is unique because it offers potential pain relief for sickle cell disease without the risks associated with smoking cannabis or using opioids, which are the standard pain treatments. It is administered in a controlled dosage form, which may provide more consistent and safer pain management compared to unregulated cannabis products. ^{1 3 4 6 9}

Research Team

Susanna Curtis, MD, PhD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

Adults over 18 with Sickle Cell Disease (SCD) who are not pregnant or nursing, and have been on a stable dose of pain medication for at least three months. Participants must not use cannabis regularly, have no history of psychosis or active substance abuse, and agree to avoid cannabis during the first 8 weeks of the study.

Inclusion Criteria

One urine toxicology negative for cannabinoids within 30 days of randomization

I am older than 18 years.

I have been diagnosed with sickle cell disease.

Exclusion Criteria

No daily cannabis use

No diagnosis of active substance use disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dronabinol or placebo for 8 weeks, with dosage individualized per patient. Initial titration from 5mg bid to a minimum dose of 2.5 mg bid to a maximum dose of 10 mg bid.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of inflammation markers and quality of life outcomes.

4 weeks

Treatment Details

Interventions

• Dronabinol
• Placebo

Trial Overview The trial is testing Dronabinol, a cannabinoid medication, against a placebo to see if it can reduce pain and inflammation in people with SCD. The study randomly assigns participants to either the drug or placebo group without them knowing which one they're getting.

Participant Groups

Group I: Dronabinol Experimental Treatment 1 Intervention

BID for 8 weeks. Dosage will be individualized per patient. In days 1-4 of the study each patient will be titrated from 5mg bid to a minimum dose of 2.5 mg bid to a maximum dose of 10 mg bid depending on patient preference.

Group II: Placebo Placebo Group 1 Intervention

A placebo comparator

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a survey of 58 patients with sickle cell disease, 42% reported using marijuana in the past two years, primarily for medicinal purposes, highlighting a potential demand for legal access to medical marijuana for this condition.

Following the inclusion of sickle cell disease as a qualifying condition for medical marijuana in the state, 44 patients requested certification, suggesting that legal access could reduce illicit use and associated risks for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marijuana Use in Adults Living with Sickle Cell Disease. Roberts, JD., Spodick, J., Cole, J., et al.[2020]

Adults with sickle cell disease (SCD) who use cannabis daily report worse pain episode severity compared to non-daily users, indicating that those with more severe pain may be more inclined to use cannabis for relief.

Despite experiencing more severe pain, daily cannabis users had significantly fewer hospital admissions and emergency room visits compared to others with similar disease severity, suggesting that cannabis use may be associated with reduced healthcare utilization in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints. Curtis, SA., Brandow, AM., DeVeaux, M., et al.[2021]

In a study of 86 young adults with sickle cell disease, 36% reported using cannabis in the past year primarily to relieve pain and reduce anxiety, indicating a significant interest in cannabinoids for symptom management.

Most participants experienced side effects related to sedation and mood changes, but a majority (58%) were open to participating in further research on cannabis as a medicinal option for pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis use in sickle cell disease: a questionnaire study. Howard, J., Anie, KA., Holdcroft, A., et al.[2022]

In a study involving 30 patients on opioids for chronic pain, dronabinol (synthetic THC) was found to significantly reduce pain intensity and increase treatment satisfaction compared to a placebo, indicating its potential as an effective adjuvant treatment.

The extended Phase II trial showed that titrated doses of dronabinol provided significant pain relief and reduced pain bothersomeness, although side effects were dose-related, suggesting careful monitoring is needed when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. Narang, S., Gibson, D., Wasan, AD., et al.[2013]

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

Cannabis products are increasingly used by patients with Sickle Cell Disease (SCD) for pain management, especially as concerns about opioid use and its adverse effects grow.

This review highlights the need for caution regarding the reliability of cannabis products, as many may be unvalidated or adulterated, posing health risks to vulnerable patients seeking pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease. Argueta, DA., Aich, A., Muqolli, F., et al.[2020]

In a double-blind crossover trial involving 13 patients with chronic upper motor neuron syndrome, low-dose Nabilone (1 mg per day) significantly reduced spasticity-related pain compared to placebo, demonstrating its efficacy in this challenging condition.

Nabilone was found to be safe, with only mild side effects reported, making it a viable treatment option for patients who do not respond well to conventional pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. Wissel, J., Haydn, T., Müller, J., et al.[2018]

In a pilot study involving 27 adults with sickle cell disease and chronic pain, inhaled cannabis did not significantly reduce overall pain levels compared to a placebo, although it did show a notable effect on improving mood-related interference.

Participants reported no significant differences in treatment-related side effects or opioid use between the cannabis and placebo treatments, suggesting that inhaled cannabis may be safe but not more effective for pain relief in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial. Abrams, DI., Couey, P., Dixit, N., et al.[2020]

Cannabinoids, particularly nabiximols and Epidiolex®, have shown significant therapeutic benefits for conditions like chronic pain, spasticity in multiple sclerosis, and refractory epilepsy, indicating their potential as effective medical treatments.

Pharmaceutical companies are focusing on non-smokable delivery methods for cannabinoids to ensure consistent dosing and targeted effects, which could enhance their efficacy in treating various chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine. Urits, I., Borchart, M., Hasegawa, M., et al.[2020]

References

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

Marijuana Use in Adults Living with Sickle Cell Disease. [2020]

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

Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Cannabis use in sickle cell disease: a questionnaire study. [2022]

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

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]

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

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]

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

Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. [2018]

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

Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine. [2020]