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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dronabinol, a cannabis-derived substance, to determine its effectiveness in relieving pain and inflammation for people with sickle cell disease. Participants will receive either dronabinol or a placebo for eight weeks. The trial aims to discover if dronabinol can ease living with sickle cell disease by reducing pain and other complications. It seeks participants with sickle cell disease who experience pain disrupting their daily lives. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that dronabinol is likely to be safe for humans?

Research suggests that dronabinol, a medication derived from cannabis, might alleviate pain and swelling in sickle cell disease (SCD). However, results remain mixed. Some studies indicate that cannabinoids, the active ingredients in cannabis, are generally safe and do not worsen SCD symptoms.

One study with 23 participants found inhaled cannabis to be safe and more effective than a placebo for pain relief, implying that dronabinol might also be well-tolerated. Although many people with SCD use cannabis for pain relief, solid proof of its effectiveness specifically for SCD is lacking.

Overall, current research suggests dronabinol appears safe, but more studies are needed to confirm this for sickle cell disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike the standard treatments for sickle cell disease, which typically include hydroxyurea and blood transfusions, dronabinol introduces a new approach by using cannabinoids. Dronabinol is derived from cannabis and targets the endocannabinoid system, which may help in managing pain—a major challenge in sickle cell disease. Researchers are excited about the potential of dronabinol because it offers a different mechanism of action, focusing on pain relief and inflammation, which could improve quality of life for patients without the side effects commonly associated with opioids.

What evidence suggests that dronabinol might be an effective treatment for sickle cell disease?

Research has shown that cannabinoids, like dronabinol, may help reduce pain and swelling. In this trial, participants will receive either dronabinol or a placebo to evaluate its effectiveness for sickle cell disease (SCD). Although direct proof of dronabinol's efficacy for SCD is lacking, studies on similar cannabis-based treatments suggest potential benefits. For instance, inhaled cannabis proved more effective than a placebo in relieving pain for adults with SCD. In animal studies, THC (a component of dronabinol) reduced pain sensitivity in mice with SCD without affecting mood or cognition. This suggests dronabinol could help manage pain and discomfort in people with sickle cell disease. ^{1 2 5 6 7}

Who Is on the Research Team?

Susanna Curtis, MD, PhD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10676238

Dronabinol for the reduction of chronic pain and inflammation ... Over one third of people with SCD say they use cannabis for pain relief, but there is currently no evidence to support this use. Further, there is no evidence ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05519111?tab=table

Cannabinoids for the Reduction of Inflammation and Sickle ... A randomized, double blind, study of dronabinol as a palliative agent in the treatment of pain, inflammation, and other complications of sickle cell disease ( ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524178147

Δ9-Tetrahydrocannabinol Alleviates Hyperalgesia in a ... Findings indicate that acute THC administration reduces mechanical and cold hypersensitivity in SCD mice without impacting emotional and cognitive dysfunction.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2768349

Effect of Inhaled Cannabis for Pain in Adults With Sickle ... This randomized clinical trial including 23 participants found that inhaled cannabis was safe. Inhaled cannabis was more effective than inhaled placebo in ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/study-testing-safety-efficacy-cannabinoid-sickle-cell-disease/

New Study to Test Safety and Efficacy of a Cannabinoid ... A new clinical trial testing the safety and efficacy of dronabinol as a palliative agent in patients with sickle cell disease is now open.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5627667/

The Use of Cannabis by Patients with Sickle Cell Disease ... Results: Cannabinoids were found in 144 urine tests from 37 patients and were negative in 126 tests from 35 patients. Males who used cannabis were significantly ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1524904225002012

Cannabis Use for Chronic Pain in Sickle Cell Disease Cannabinoids may help manage SCD pain, though evidence remains mixed. No studies showed exacerbation of SCD symptoms, but safety concerns ...