Cannabinoids for Sickle Cell Disease
(CRISP Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Icahn School of Medicine at Mount Sinai
Must not be taking: Cannabinoids
Disqualifiers: Psychosis, Suicidality, Pregnancy, others
Prior Safety Data
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.
12345Is 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.
35678How 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.
13469Eligibility 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.
+10 more
Exclusion Criteria
No daily cannabis use
No diagnosis of active substance use disorder
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DronabinolExperimental Treatment1 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: PlaceboPlacebo Group1 Intervention
A placebo comparator
Dronabinol is already approved in United States, United States, Australia, 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 Australia as Marinol 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mount Sinai HospitalNew York, NY
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Who Is Running the Clinical Trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Marijuana Use in Adults Living with Sickle Cell Disease. [2020]Introduction: Legal access to marijuana, most frequently as "medical marijuana," is becoming more common in the United States, but most states do not specify sickle cell disease as a qualifying condition. We were aware that some of our patients living with sickle cell disease used illicit marijuana, and we sought more information about this. Materials and Methods: We practice at an urban, academic medical center and provide primary, secondary, and tertiary care for ∼130 adults living with sickle cell disease. We surveyed our patients with a brief, anonymous, paper-and-pen instrument. We reviewed institutional records for clinically driven urine drug testing. We tracked patient requests for certification for medical marijuana. Results: Among 58 patients surveyed, 42% reported marijuana use within the past 2 years. Among users, most endorsed five medicinal indications; a minority reported recreational use. Among 57 patients who had at least one urine drug test, 18% tested positive for cannabinoids only, 12% tested positive for cocaine and/or phencyclidine only, and 5% tested positive for both cannabinoids and cocaine/phencyclidine. Subsequent to these studies, sickle cell disease became a qualifying condition for medical marijuana in our state. In the interval ∼1.5 years, 44 patients have requested certification. Conclusion: Our findings and those of others create a rationale for research into the possible therapeutic effects of marijuana or cannabinoids, the presumed active constituents of marijuana, in sickle cell disease. Explicit inclusion of sickle cell disease as a qualifying condition for medical marijuana might reduce illicit marijuana use and related risks and costs to both persons living with sickle cell disease and society.
Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints. [2021]Introduction: Previous studies have shown that cannabis use is common in adults with sickle cell disease (SCD), and that many patients report using cannabis to treat pain. Methods: We performed a cross-sectional study of adults with SCD and compared daily users of cannabis with others using validated patient-reported measures of pain and quality of life as well as opioid and health care utilization. Results: Daily cannabis users with SCD had worse pain episode severity scores than others (56.7 vs. 48.8, p=0.02) yet had 1.8 fewer annual admissions (p=0.01) and 1.2 fewer annual emergency room (ER) visits (p=0.01), and similar amounts of opioids dispensed to others after matching for age, gender, SCD genotype, hydroxyurea use, and pain impact scores. Conclusions: We show that people with SCD with more severe pain crisis are more likely to use daily cannabis, yet have lower rates of hospital admission and ER use as compared with others with similar disease severity and pain impact. Randomized controlled trials should be performed.
Cannabis use in sickle cell disease: a questionnaire study. [2022]Cannabinoids are increasingly being considered for the management of various painful conditions, and could be considered as an option for treating acute pain in sickle cell disease (SCD). The objective of this study was to determine the extent of use of cannabis in the community for pain and other symptom relief, and its side effects during self-administration in patients with SCD. Patients attending Central Middlesex Hospital in London were invited to complete a structured self-administered anonymous questionnaire. Eighty-six young adults with HbSS, HbSC and HbSbetathalassaemia disease (median age 30 years) participated in the study. Results showed that 31 (36%) had used cannabis in the previous 12 months to relieve symptoms associated with SCD. The main route in all but two patients was by smoking. The main reasons for use were to reduce pain in 52%, and to induce relaxation or relieve anxiety and depression in 39%. Symptoms related to sedation and mood effects were reported in 77% of patients. The majority of patients (58%) expressed their willingness to participate in studies of cannabis as a medicine. We conclude that research in the use of cannabinoids for pain relief in SCD would be both important and acceptable to adult patients.
Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals, Brussels, Belgium), a synthetic Delta(9)-THC (tetrahydrocannabinol), in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized, single-dose, double-blinded, placebo-controlled, crossover trial in which subjects were randomly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three, 8-hour visits. Baseline self-report measures, hourly ratings of pain intensity, pain relief, pain bothersomeness, treatment satisfaction, mood, side effects, and blood serum levels were obtained. Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids. Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo. No differences in benefit were found between the 20 mg and 10 mg doses. In the Phase II trial, titrated dronabinol contributed to significant relief of pain, reduced pain bothersomeness, and increased satisfaction compared with baseline. The incidence of side effects was dose-related. Overall, the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain.
The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.
Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease. [2020]Pain in Sickle Cell Disease (SCD) is a major comorbidity and unique with acute pain due to recurrent and episodic vaso-occlusive crises as well as chronic pain, which can span an individual's entire life. Opioids are the mainstay treatment for pain in SCD. Due to recent health crises raised by adverse effects including deaths from opioid use, pain management in SCD is adversely affected. Cannabis and its products are most widely used for pain in multiple conditions and also by patients with SCD on their own. With the availability of "Medical Cannabis" and approval to use cannabis as medicine across majority of States in the United States as well as over-the-counter preparations, cannabis products are being used increasingly for SCD. The reliability of many of these products remains questionable, which poses a major health risk to the vulnerable individuals seeking pain relief. Therefore, this review provides up to date insights into available categories of cannabis-based treatment strategies, their mechanism of action and pre-clinical and clinical outcomes in SCD. It provides evidence for the benefits and risks of cannabis use in SCD and cautions about the unreliable and unvalidated products that may be adulterated with life-threatening non-cannabis compounds.
Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. [2018]About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from disabling spasticity-related pain not sufficiently correctable by conventional treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit in the treatment of pain in patients with multiple sclerosis (MS). The question arose whether synthetic cannabinoids with lower potential for psychotropic side effects could be effective as well. To evaluate the safety and efficacy of low dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on spasticity-related pain a placebo-controlled double-blind crossover trial was performed.11 out of 13 included patients completed the study. The 11-Point-Box-Test showed a significant decrease of pain under Nabilone (p
Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial. [2020]Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown.
An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine. [2020]Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy. Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism. Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions. The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well. Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.