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Cbd oil sickle cell

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On Day 1 of each admission, subjects will provide blood samples for baseline markers of inflammation and SCD disease progression. They will undergo assessments of pain, mood, and quality of life. At 12 pm on Day 1, they will inhale vaporized study agent (equivalent to 1 cannabis/placebo cigarette) using the Volcano® vaporizer; on Days 2-4 they will inhale study agent at 8 am, 2 pm, and 8 pm, and they will inhale their final dose on Day 5 at 8 am. Subjects will continue their pre-study analgesic regimen while in the study. If additional analgesia is required, supplemental therapy will be administered and the dose recorded. Pain measurements by visual analogue scale will be obtained every 2 hours while subjects are awake. On Day 5 a second set of blood samples for inflammation markers and disease progression will be obtained, and subjects will again complete pain, mood, and quality of life assessments.

Hypotheses are as follows:

Cbd oil sickle cell

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“These trial results show that vaporized cannabis appears to be generally safe,” said Gupta, a professor of medicine on the faculty of UCI’s Center for the Study of Cannabis. “They also suggest that sickle cell patients may be able to mitigate their pain with cannabis – and that cannabis might help society address the public health crisis related to opioids. Of course, we still need larger studies with more participants to give us a better picture of how cannabis could benefit people with chronic pain.”

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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.”

Twenty-three patients with sickle cell disease-related pain completed the trial, inhaling vaporized cannabis or a vaporized placebo during two five-day inpatient sessions that were separated by at least 30 days. This allowed them to act as their own control group.

Opioids are currently the primary treatment for the chronic and acute pain caused by sickle cell disease. But the rise in opioid-associated deaths has prompted physicians to prescribe them less frequently, leaving sickle cell patients with fewer options.

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The study was funded by an Excellence in Hemoglobinopathies Research Award from the NIH’s National Heart, Lung and Blood Institute (grant UO1HL117664).

Researchers assessed participants’ pain levels throughout the treatment period and found that the effectiveness of cannabis appeared to increase over time. As the five-day study period progressed, subjects reported that pain interfered less and less with activities, including walking and sleeping, and there was a statistically significant drop in how much pain affected their mood. Although pain levels were generally lower in patients given cannabis than in those given the placebo, the difference was not statistically significant.

Cbd oil sickle cell

Innumerable medical cannabis preparations are available from “Dispensaries”, but most of them are not validated for their contents and their effectiveness through regulatory analysis and controlled clinical trials, respectively. Majority of Medical cannabis preparations tested either did not contain the labeled contents or had a small % compared to the labeled amount [137,138]. All medical cannabis preparations are not made equal and may have different cannabinoid content and composition. Therefore, the cannabinoid composition specific to the needs of the underlying pathobiology and symptoms needs to be selected for treatment. Outbreaks of coagulopathy from products marketed as cannabinoids but containing long-acting rodenticide raises life-threatening concerns [139]. Commercially available, mislabeled and adulterated cannabis products pose major health risks [137,138,140]. Therefore, awareness and education of individuals regarding potential harms of the adulterated and unreliable cannabis products needs to be raised and users and healthcare providers need to validate the reliability of the contents.

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) [30]. 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 [30].

We gratefully acknowledge the members of the Gupta laboratory for their support and contributions to revision of the manuscript: Christopher Ventura, Hanan Chweih-Vendrame, and Stacy Kiven.

Inflammation, hemolysis, and cell-free hemoglobin in the hypoxic sickle microenvironment cause oxidative stress in SCD [90]. WIN55,212-2, CP55,940 and anandamide exert a protective effect on quinolinic acid-induced mitochondrial dysfunction, reactive oxygen species (ROS) formation and lipid peroxidation in rat striated cultured cells and rat brain synaptosomes [91]. Importantly, in parkin-null, human tau overexpressing (PK-/-/TauVLW) mice, a model of complex neurodegenerative disease, short-term Sativex (Nabiximols, 1:1, THC:CBD preparation) administration significantly reduced intraneuronal monoamine oxidase-related free radicals, increased the ratio of reduced/oxidized glutathione, and improved behavioral and pathological abnormality [92]. Consistent with these observations in other pathologies, cannabinoids may also reduce oxidative stress and pain in SCD.

8. Conclusions

The use of cannabinoids has been associated with poor health outcomes in patients with SCT, characterized by heterozygosity of the sickle allele. Two case studies have indicated priapism in SCT patients who admitted to using cannabis in the days prior to hospital admission. Notably, these individuals admitted to the use of other substances that contribute to priapism, including alcohol and cocaine in the first patient, and alcohol and tobacco in the second patient [117,118]. Therefore, the effect of cannabis in these studies is confounded by the use of other substances, like many other studies.

Cannabis and cannabinoids have been evaluated clinically for their analgesic potential in various disease states, and recently these findings have been described in a systematic review [96]. Studies indicate that smoked cannabis may provide analgesic support in chronic and neuropathic pain, but smoking is associated with its own risks and pathologies; thus, other formulations and routes of administration are also being investigated [97,98,99]. To date, several double-blind placebo-controlled studies have been completed to evaluate the safety and efficacy of oral THC and/or Sativex which delivers a controlled dose of 2.7 mg THC and 2.5 mg CBD per spray [100]. Sativex has also been tested in several pain contexts, including cancer, chronic abdominal pain, multiple sclerosis, brachial plexus injury, and diabetic neuropathy. In a study of chronic abdominal pain, oral THC did not reduce measures of pain, but was well-tolerated and absorbed over a 2-month period [101]. In contrast, Sativex was effective at providing sustained relief of central neuropathic pain in patients with multiple sclerosis on fixed and self-titrating schedules compared to patients receiving placebo [102,103]. Moreover, Sativex improved pain at targeted responder levels and significantly improved sleep in difficult-to-treat neuropathic pain arising from brachial plexus avulsion and allodynia-characterized neuropathic pain [104,105]. The latter study was followed-up with a 52-week open-label trial in which pain relief was maintained without dose increase or toxicity [106]. While promising, these studies must be evaluated critically due to their potential for biases related to sampling [107].

SCD originates from a single point mutation of the beta globin gene of hemoglobin that leads to rigid sickle-shaped red blood cells (RBCs) in a deoxygenated state [47]. The biological underpinnings of pain in SCD remain poorly understood. Pain in SCD may be a direct consequence of avascular necrosis or lower limb ulcers [48,49]. It is known that sickle RBCs cause vaso-occlusion leading to impaired blood and oxygen supply to the organs resulting in end-organ damage and acute, unpredictable and recurrent episodes of pain [1,50,51]. Inflammation, endothelial activation, oxidative stress, ischemia/reperfusion injury, and hemolysis underlie sickle pathobiology, which are further enhanced in the wake of VOCs [52]. The underlying mechanism for how vaso-occlusion leads to pain remains incompletely understood.

6.4. Juvenile Use of Cannabis in SCD

Erythrocyte adhesion, nitric oxide depletion, hemolysis, oxidative stress and inflammation accompany endothelial dysfunction in SCD [93,94]. Endothelial activation causes upregulation of adhesion molecules including selectins, vascular cell adhesion molecule and intercellular adhesion molecule 1, which exacerbate vaso-occlusion and end-organ damage [47]. CB1R and CB2R are widely expressed on vascular smooth muscle cells and endothelium [95]. Both receptors have been widely studied in vascular relaxation and activation of ion channels including potassium, calcium and TRPVs. Antagonistic roles are demonstrated in different settings and disease states with respect to CB1R and/or CB2R. Thus, it is likely that cannabinoids influence endothelial function in a sickle-specific microenvironment.

To date, several other clinical studies involving cannabis, THC preparations, and/or Sativex have been completed in patients with chronic pain arising from various diseases. Results from these studies indicate no effect to mild effect at reducing chronic pain, improving sleep quality, and improving patient-reported quality of life. Side-effects from these studies are also limited, and it appears that low doses are well-tolerated. The results from these studies, however, have not undergone peer review, and thus must be heavily scrutinized before any recommendations can be made. The identifiers for the aforementioned studies follow: <"type":"clinical-trial","attrs":<"text":"NCT01606202","term_id":"NCT01606202">> NCT01606202, <"type":"clinical-trial","attrs":<"text":"NCT00713817","term_id":"NCT00713817">> NCT00713817, <"type":"clinical-trial","attrs":<"text":"NCT00710424","term_id":"NCT00710424">> NCT00710424, <"type":"clinical-trial","attrs":<"text":"NCT01606176","term_id":"NCT01606176">> NCT01606176, <"type":"clinical-trial","attrs":<"text":"NCT01262651","term_id":"NCT01262651">> NCT01262651, and <"type":"clinical-trial","attrs":<"text":"NCT00241579","term_id":"NCT00241579">> NCT00241579.