Irvine, Calif., July 17, 2020 – Cannabis appears to be a safe and potentially effective treatment for the chronic pain that afflicts people with sickle cell disease, according to a new clinical trial co-led by University of California, Irvine researcher Kalpna Gupta and Dr. Donald Abrams of UC San Francisco. The findings appear in JAMA Network Open.
Clinical trial co-led by UCI professor is first of its kind to use gold-standard methods
“Pain causes many people to turn to cannabis and is, in fact, the top reason that people cite for seeking cannabis from dispensaries,” Gupta said. “We don’t know if all forms of cannabis products will have a similar effect on chronic pain. Vaporized cannabis, which we employed, may be safer than other forms because lower amounts reach the body’s circulation. This trial opens the door for testing different forms of medical cannabis to treat chronic pain.”
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A pilot study performed by our group investigated the analgesic potential of vaporized cannabis in SCD patients ( <"type":"clinical-trial","attrs":<"text":"NCT01771731","term_id":"NCT01771731">> NCT01771731) . Twenty-three patients with SCD-related chronic pain receiving opioids completed a randomized double-blind placebo-controlled crossover trial, inhaling vaporized cannabis or placebo during two separate five-day inpatient sessions that were separated by a 30-day washout period. Vapors were collected in-house by vaporizing cannabis containing 4.4% THC and 4.9% CBD, obtained from the National Institute on Drug Abuse. The crossover design allowed for each patient to serve as their own control. Pain was assessed throughout each treatment period along with pain interference measures. The crossover-pain difference between cannabis and placebo treatment was negative for each treatment day indicating a decrease in pain with cannabis treatment; however, this decrease was not statistically significant. Additionally, pain levels were generally lower in patients given cannabis when compared to those given placebo, but this difference was also not statistically significant. As each five-day study period progressed, patients given cannabis reported that pain interfered less with activities, including walking and sleeping, with a statistically significant decrease in interference with mood. Importantly, this study showed that vaporized cannabis is well-tolerated and significantly improves “mood” in SCD patients with chronic pain. The lack of significant adverse effects in this study encourages further investigation into the use of cannabis-based interventions including CBD to treat chronic SCD pain in prospective trials with a larger cohort over a longer duration .
A 2017 retrospective analysis of patients with SCD indicated that patients using cannabis, confirmed by urinalysis, had higher frequency of VOCs . This study comprised 37 SCD patients that tested positive for a THC metabolite and 35 that tested negative. Notably, patients who tested positive admitted to smoking cannabis as their route of administration. Additionally, cannabis users had significantly higher use of benzodiazepine, cocaine, and phencyclidine compared to non-users. The use of other illicit compounds may potentiate the negative effects associated with cannabis use in this retrospective analysis. In addition, cannabis users had significantly fewer visits to the clinic and increased hospital admissions compared to non-users; the lack of regular treatment and increased disease severity may also represent contributing variables that are difficult to control. Priapism, mortality, and other SCD co-morbidities were not different between groups . Opioid-induced hyperalgesia and tolerance to specific opioids has been suggested to lead to cannabinoid and phencyclidine use in an individual with SCD . The reason for using cannabis in this patient was that pain relief was inadequate with Percocet. After switching to morphine, his urine showed the presence of phencyclidine, which provided him better pain relief than morphine. These studies highlight the inadequacy and changing needs of patients with persistent and/or VOC pain in SCD leading to cannabis use and perhaps of other drugs that they can get to find relief.
There is a strong need for randomized, placebo-controlled studies to accurately determine the effects of specific cannabinoids on SCD. Such studies require special attention to not only cannabis dosing and route of administration (e.g., smoked, vaporized, given as an oromucosal spray), but also to the chemical composition of cannabis plants due to existence of variable cannabinoid contents in cannabis plants . Access to cannabis for research purposes remains a major roadblock in the U.S. and many parts of the world despite increasing preclinical evidence suggesting that it may be a valuable strategy for treating otherwise difficult to manage pain, which may be the case in SCD [19,119]. Research funding allocation for cannabis’s safe use in disease-specific manner is needed to prevent the cannabinoid epidemic before it is too late. Given the growing body of evidence supporting the potential benefits of cannabinoids for the treatment of pain in adults, but the lack of randomized, placebo-controlled studies evaluating their use in treating SCD pain, this area of research deems high significance in order to develop more effective therapeutic options requiring more effective management of sickle pain [145,146].
6.4. Juvenile Use of Cannabis in SCD
1 Hematology/Oncology, Department of Medicine, University of California, Irvine, CA 92868, USA; [email protected] (D.A.A.); [email protected] (A.A.); [email protected] (F.M.); [email protected] (H.C.)
Evidence of human use of the Cannabis sativa L. plant in rituals and medicine dates back millennia . In 1970, cannabis was classified as a Schedule 1 drug in the United States (U.S.), and it was deemed to have no known medical use and a high potential for abuse . Despite the prohibition of cannabis in the U.S. and many European countries, there has been steady progress in studying its constituents for their beneficial effects in many conditions [11,12,13]. An analysis of cannabis use among people using opioids for chronic pain management reported greater pain relief with cannabis than with opioids used alone in a national survey of adults in the U.S. . In addition, emerging evidence suggests that prescriptions for opioids and deaths attributed to opioid use have declined in states that have made medicinal cannabis legal [15,16,17].
6.7. Cannabis Use in Sickle Cell Trait (SCT)
2 Department of Hematology, Oncology, and Transplantation, University of Minnesota, Twin Cities, MN 55455, USA; [email protected]
In a retrospective observational study on 9350 patients 18 years and older admitted for acute ischemic stroke (AIS) who underwent urine drug screening screening, 18% tested positive for cannabis . Among cannabis users unadjusted risk ratio showed a 50% decrease in risk of AIS. However, upon adjusting for SCD, cardiovascular disease, diabetes, cigarette smoking, ethnicity, age, race, etc., the effect was lost. Many limitations in this study included dosage and duration of cannabis use, but it does not show any adverse effect of cannabis on AIS. These findings are important because stroke is one of the major comorbidities of SCD.