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cbd for sickle cell disease

Neurologically the reason why cannabis increased the frequency of VOCs that required hospitalization may be related to the shift from goal-oriented to habit-oriented behavior caused by cannabis. Cannabinoids exert their action through binding to G-protein receptors located throughout the body. 36 These include CB1 and CB2 receptors. THC binds preferentially to CB1 receptors and CBD binds preferentially to CB2 receptors. CB1 receptors mediate the psychoactive aspects of cannabinoids and CB2 receptors play a role in pain relief. Normally, activity of orbitofrontal cortex (OFC) neurons project to OFC–dorsal striatum (DS) neurons. Activity of the OFC-DS terminals is believed to be necessary for goal-directed behavior. Deletion of CB1 receptors from OFC-DS neurons in mice prevented the shift from goal-directed to habit-directed behavior. 41,42 Accordingly, a herbal cannabis drug that is THC-rich may preferentially activate the CB1 Receptors which, in turn, may promote the shift from goal-oriented to habit-oriented behavior and maximize the psychoactive effects of the drug. In clinical terms, this shift may encourage patients to reflexively seek help in the hospital rather than in the clinic.

Types of SCD were initially determined by solubility testing, hemoglobin electrophoresis in alkaline and acidic media, and thin-layer isoelectric focusing, and later, by high-performance liquid chromatography. Urine samples, collected randomly, were analyzed for the presence of amphetamine, benzodiazepines, opiates, barbiturate, cannabinoid, propoxyphene, methadone, and phencyclidine. The analytical cutoff for amphetamine was 1000 ng/mL; for benzodiazepine and barbiturate 200 ng/mL; for opiates, cocaine, propoxyphene, and methadone 300 ng/mL; for phencyclidine 25 ng/mL; and for cannabinoid 50 ng/mL. (The cannabinoid chemical tested in urine is actually11-nor-9-carboxy-Δ 9 -tetrahydrocannnabinol.) Samples were classified as either positive or negative for cannabinoid.

Conclusion: These data show an unexpected negative effect of cannabis on the frequency of VOCs. This may be due to the effect of cannabis on the brain and/or the severity of the disease in the cannabis users. More controlled studies are needed to clarify these findings.

More recently, there has been popular interest in using cannabis as an analgesic for various types of pain. 20 Medical cannabis is used to treat many indications, a few of which have evidence to support treatment with cannabis and many that do not. 21 There is some evidence supporting the idea that cannabis may reduce symptoms of spasticity associated with multiple sclerosis (MS), 22 HIV/AIDS-related cachexia, 23 and chemotherapy-induced nausea and vomiting. 24 Moreover, cannabis may reduce neuropathic pain 25,26 and possibly some other pain conditions. 22,27,28 However, for the almost 30 other indications for which medical cannabis has been approved across the U.S., the evidence is of very low quality. 28 That cannabis should have “beneficial” effects for conditions as diverse as amyotrophic lateral sclerosis, MS, ulcerative colitis, or posttraumatic stress disorder, 29 which have no common pathophysiology, raises questions about the evidence supporting its use. Furthermore, cannabis is associated with abuse, dependence, psychosis, cognitive deficits, etc. 30–32 Given the advent of the legal status of cannabis, RCTs on the efficacy and safety of cannabis or its constituent cannabinoids are urgently needed. 25,33–35

Discussion

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 younger (p<0.001) than males who did not. Patients who tested positive used benzodiazepines, cocaine, and phencyclidine significantly more often than patients who tested negative. There was no significant difference in the amounts of opioids consumed by users and nonusers of cannabis. The cannabis cohort was seen in the clinic significantly (p<0.05) less often than controls, but hospital admissions were significantly greater in the cannabis group than controls (p<0.05).

The most important finding in this study is that, patients who tested positive for cannabinoid were admitted to the hospital for the treatment of VOCs significantly more often than patients in the control group, and they were seen significantly less often in the clinic. Neither the placebo effect of cannabis nor the expectations of pain reduction by its users were operative in this study. It seems the severity of the disease, the use of cannabis, and the use of other illegal drugs conspired to make the disease worse, which required more hospital admissions. Why this combination makes the disease worse is unknown. A possible reason why the use of cannabis did not decrease the frequency of hospital admissions due to VOC may be the severity of their disease as far as pain is concerned. However, priapism (seven in the positive group, eight in the negative group), mortality (six patients in each group), and other complications of SCD were not significantly different (p>0.05) in both cohorts. Patients who tested positive for cannabinoid seem to be a subgroup of patients with severe SCD associated with constantly increasing transmission of painful stimuli associated with central sensitization, glial activation, and rewiring of the brain. 39 Consequently, these patients constantly seek more legal and illegal medications in search for pain relief. This may explain why these patients used more benzodiazepines, cocaine, and phencyclidine than patients who did not use cannabis. Interestingly the patients with positive urine drug screen for cannabinoid did not use opioids more frequently than the control group.

Frequency of Clinic Visits and Admissions to Emergency Department and Hospital of Patients Positive or Negative for Cannabinoid

Laboratory data

Patients whose urine was positive for cannabinoid were counseled and referred to Psychiatry and/or Addiction Medicine for further management. Repeat testing was negative and remained negative in some patients, but fluctuated between positive and negative for cannabinoid in others.

All patients who tested positive for cannabinoid admitted smoking cannabis on a regular basis and indicated that the reason for doing this was to achieve better pain relief. Other reasons included the desire to achieve relaxation and manage anxiety/depression syndromes. Similar to previous reports, 37,38 males used cannabis more often than females and the use of cannabis was significantly higher in younger males than males in the control group.

Cbd for sickle cell disease

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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.

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.

Clinical trial co-led by UCI professor is first of its kind to use gold-standard methods

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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.

The double-blind, placebo-controlled, randomized trial was the first to employ such gold-standard methods to assess cannabis’s potential for pain alleviation in people with sickle cell disease. The cannabis used in the trial was obtained from the National Institute on Drug Abuse – part of the National Institutes of Health – and contained equal parts of THC and CBD.

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“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.”

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