Cannabidiol for Sickle Cell Disease

(SPICE Trial)

Overseen By Susanna Curtis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: SCD modifying therapy

Must not be taking: Cannabinoids

Disqualifiers: Psychosis, Substance use disorder, others

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, 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 before joining the study.

What data supports the effectiveness of the drug Cannabidiol for Sickle Cell Disease?

Cannabidiol (CBD) has shown potential benefits in reducing inflammation, as seen in a study on Crohn's Disease, and has been effective in managing spasticity in multiple sclerosis when combined with THC. These findings suggest that CBD might help with symptoms related to inflammation and pain, which are common in Sickle Cell Disease. ^{1 2 3 4 5}

Is cannabidiol (CBD) generally safe for human use?

Cannabidiol (CBD) is generally well tolerated in humans, but it can cause some side effects like diarrhea, sleepiness, and changes in liver function. It may also interact with other medications, so it's important to monitor these interactions carefully. Serious side effects are rare but can include liver issues and pneumonia, especially when used with other medications. ^{1 3 6 7 8}

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

Cannabidiol (CBD) is unique for sickle cell disease as it is derived from cannabis and is being explored for its potential to reduce pain and inflammation, unlike traditional treatments that focus on managing symptoms like anemia and preventing complications. CBD's novel mechanism of action involves interacting with the body's endocannabinoid system, which is different from the mechanisms of standard treatments. ^{9 10 11 12 13}

What is the purpose of this trial?

Randomized, placebo-controlled, double masked, dose finding study of twice daily cannabidiol given at 3 dose levels, 200mg, 400mg, and 600mg, compared to placebo for 4 weeks.

Research Team

Susanna Curtis

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults over 18 with Sickle Cell Disease who can consent to research, have low pain interference scores, and don't use cannabis. They must not be pregnant or nursing and agree to birth control if applicable. Stable doses of opioids for pain or SCD therapies are required.

Inclusion Criteria

Able to consent for research

Baseline score of 60 or lower on the ASCQ-Me 7-day pain interference domain

One urine toxicology negative for cannabinoids within 30 days of randomization

Exclusion Criteria

No known intolerance to cannabinoids

No history of psychotic episode, psychosis, or active suicidality

Not a daily cannabis user

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive twice daily cannabidiol at 3 dose levels or placebo for 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Cannabidiol

Trial Overview The trial is testing the effects of cannabidiol (CBD) at different doses (200mg, 400mg, and 600mg) versus a placebo in managing symptoms of Sickle Cell Disease over four weeks. It's randomized and double-masked so neither participants nor researchers know who gets CBD or placebo.

Participant Groups

Group I: Cannabidiol 200 mg Active Control 1 Intervention

Twice daily 200 mg cannabidiol

Group II: Cannabidiol 400 mg Active Control 1 Intervention

Twice daily 400 mg cannabidiol

Group III: Cannabidiol 600 mg Active Control 1 Intervention

Twice daily 600 mg cannabidiol

Group IV: Placebo Placebo Group 1 Intervention

Twice daily matching placebo

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

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]

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

In a study of 50 patients with multiple sclerosis, the combination of THC and CBD was effective in reducing spasticity in 80% of cases, suggesting it could be a beneficial alternative treatment for this symptom.

The treatment had an acceptable safety profile, with adverse effects reported in a minority of patients, including dizziness and somnolence, indicating that while some side effects occurred, they were manageable and did not outweigh the benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. Lorente Fernández, L., Monte Boquet, E., Pérez-Miralles, F., et al.[2022]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

In a study involving 40 children with drug-resistant epilepsy, cannabidiol was found to have a manageable safety profile, with the most common side effect being somnolence, which resolved in most cases.

Caregivers reported subjective improvements in their children's overall health, although the study's open-label design means that it's unclear if these benefits were directly due to cannabidiol treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for treating drug-resistant epilepsy in children: the New South Wales experience. Chen, KA., Farrar, M., Cardamone, M., et al.[2020]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

References

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

2. 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]

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

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. [2022]

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

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study. [2020]

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

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

7. Australia pubmed.ncbi.nlm.nih.gov

Cannabidiol for treating drug-resistant epilepsy in children: the New South Wales experience. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Treatment of hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine (2-CdA): identification of parameters predictive of adverse effects. [2019]

11. Poland pubmed.ncbi.nlm.nih.gov

[Clinical pharmacology of 2-chlorodeoxyadenosine (Cladribine)]. [2013]

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

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine. [2017]

13. Germany pubmed.ncbi.nlm.nih.gov

Teniposide is not effective in chronic lymphocytic leukemia. [2019]