Galve-Roperh et al. found that cannabinoids cause a bi-phasic increase in ceramide levels in C6 glioma cells. The first phase of ceramide accumulation occurred within seconds or minutes after cannabinoid administration, which was likely to be a result of stimulus-dependent hydrolysis of sphingomyelin. Two days after the addition of the drug, a second increase in ceramide levels took place, which coincided with the onset of the apoptotic response—probably reflecting an increase in de novo ceramide biosynthesis through the ceramide synthase pathway8 . How these changes in intracellular ceramide intervene in apoptosis is unknown, but the fact that they are synchronized with increases in extracellular signal-regulated kinase and Raf-1 kinase indicates that these three factors may cooperate in mediating cannabinoid-induced glioma cell death. But how likely is it that the discovery of anti-tumor effects of cannabinoids will affect malignant glioma therapy? At present, glioma patients who are subjected to an aggressive, multimodal treatment consisting of surgery, radiation therapy and chemotherapy have a median survival rate of 40–50 weeks9 . This bleak scenario alone should provide sufficient motivation to continue the studies initiated by Galve-Roperh et al. The risk of typical cannabinoid side effects—euphoria, amnesia,rolling flood tables decreased psychomotor performance and hypotension—may be outweighed by therapeutic advantages, and eventually be overcome through the development of selective CB2-selective agonists.CM is a type of behavioral therapy in which individuals are “reinforced,” or rewarded, for evidence of positive behavioral change . CM typically consists of monetary-based rewards or vouchers to reinforce abstinence from the target drug or to encourage retention in pharmacological or psychosocial treatment .
As presented in the Benefit Coverage, Utilization, and Cost Impacts section, with the amount of funding that would be available unknown, CHBRP has purposefully modeled a limited expansion — for only 1,000 beneficiaries — intending to provide two examples that could be scaled larger, depending on the amount of available funds. These two examples, stimulant use disorder and cannabis use disorder, serve as case studies on what the cost and utilization implications would be of Medi-Cal enrollees getting treatment for SUD with and without CM. As presented in the Medical Effectiveness section, evidence varies by SUD regarding the impact of CM. While there is clear and convincing evidence that CM is effective for stimulant use disorder and a preponderance of evidence that CM is effective for cannabis use disorder, these findings are related to outcomes during treatment. For both stimulant use disorder and cannabis use disorder, it is not clear how this may impact results in post treatment abstinence, but there is evidence to suggest that achieving abstinence during treatment is the greatest predictor of long-term recovery. The public health implications of these two simulations are discussed below.This simulation projected that for every 1,000 Medi-Cal enrollees engaged in treatment for stimulant use disorder, there would be 14,400 group counseling appointments and urinalysis tests without CM increasing to 16,800 with treatment including CM. As shown in Table 2, CM would lead to an additional 2,400 group counseling sessions per 1,000 enrollees attended and urinalyses performed. In absence of CM, 40% of the 14,400 urinalyses would be negative for stimulants for a total of 5,760 stimulant-free samples. With the addition of CM, it is expected that 60% of the 16,800 urine samples would be negative for a total of 10,080 negative samples.
Therefore, for every 1,000 Medi-Cal enrollees engaged in treatment for stimulant use disorder using CM, CHBRP would expect to see an increase of 4,320 additional negative urine samples. Therefore, as each negative urine sample represents roughly three days of abstinence, this translates roughly into nearly 13,000 additional stimulant-free days. SUD often involves cycles of relapse and remission, can vary in severity, and often requires ongoing professional treatment, lifestyle changes, and case management . Therefore, although abstinence may not persist post treatment, achieving periods of abstinence is still one goal of treatment, especially considering the best predictor of long-term recovery is abstinence during treatment . In addition, as there is no FDA-approved medication to treat stimulant use disorder, CM to improve treatment engagement and abstinence may be the best treatment option available. Patients addicted to stimulants such as methamphetamine are at higher risk for a range of physical and psychological issues including mental illness, cognitive issues, antisocial behaviors, cardiovascular events, sexually transmitted diseases, and blood-borne infections including HIV and hepatitis B and C, and consequently are at increased risk of death . The rate of amphetamine-related overdose deaths was 5.8/100,000 Californians in 2018 . Methamphetamine has taken over as the leading cause of overdose deaths in California, followed by the rate of all opioid overdose deaths of 5.23/100,000 . In addition, impacts of methamphetamine use are exacerbated by its association with increased violence and crime . Other downstream effects of methamphetamine use include reduced work related productivity and increased family and housing instability. It is possible that the additional 13,000 stimulant-free days among the 1,000 Medi-Cal enrollees in this simulation would lead to reductions in many of these short-term outcomes.The California Opioid Overdose Surveillance Dashboard shows that Blacks had the highest rates of hospitalizations for amphetamine overdose , which were more than double rates of whites , Latinos , Native Americans , and Asians . Yet, Native Americans had the highest amphetamine overdose mortality rates in California in 2018 , followed by Blacks and whites .
Asians had the lowest amphetamine overdose mortality rate at 1.4/100,000 . Disparities by gender existed in the rates of ER visits for amphetamine overdoses and deaths with males being more than twice as likely to have an ER visit for an overdose and more than three times as likely to die from amphetamine overdose .This simulation projected that for every 1,000 Medi-Cal enrollees engaged in treatment for cannabis use disorder in absence of CM, 30% of the 7,200 urinalyses would be negative for cannabis for a total of 2,160 cannabis-free samples. With the addition of CM, it is expected that 45% of the 7,200 urine samples would be negative for a total of 3,240 negative samples. Therefore, for every 1,000 Medi-Cal enrollees engaged in treatment for cannabis use disorder using CM, CHBRP would expect to see an increase of 1,080 additional negative urine samples. Therefore, as each negative urine sample represents roughly seven days of abstinence, this translates roughly into more than 7,500 additional cannabis-free days. The impacts of 7,500 additional cannabis-free days include reductions in risks of psychiatric disorders, impairments in learning and coordination, and lung inflammation/chronic bronchitis, and potential opportunities for improvements in cognitive function and educational and workplace outcomes . There is also a potential for a reduction in ER visits and hospitalizations due to cannabis use disorder.Some interventions in proposed mandates provide immediate measurable impacts , while other interventions may take years to make a measurable impact . When possible, CHBRP estimates the long term effects to the public’s health that would be attributable to the mandate. As presented in the Medical Effectiveness section, there is no research that examines the long term impacts of CM for SUD treatment. For this analysis, CHBRP modeled a 12-week substance use disorder treatment program using contingency management , one for stimulant use disorder and one for cannabis use disorder. It is unclear how many providers would choose to offer CM as part of SUD treatment and how many patients would participate in the long term. In addition,flood and drain tray since there is no research that examines long-term impacts of CM for SUDs treatment on health care utilization, it is not possible to quantify the long-term utilization and cost impacts of SB 110. As with other chronic conditions, effective management of SUDs will require repeated, short-term treatments or longer-term treatment over time. Current practices involve short-term episodic treatments, which have limitations when treating long-term chronic conditions. Of those that achieve long-term recovery, it is estimated that nearly half are able to enter recovery on the first try, 14% have one recurrence, 19% have 2-5 recurrences, and 15% have 6 or more recurrences prior to achieving recovery stability . It is estimated that between 2-5 recovery attempts are made by persons with stimulant use disorder and cannabis use disorder prior to successfully resolving the SUD . Therefore, to the extent that participating in CM treatment programs produce better during treatment abstinence results, this may encourage patients to try to make another recovery attempt in the future, with each attempt making it more likely they will enter long-term recovery. As discussed previously, a key barrier to abstinence for any SUD is patient interest and readiness to abstain. It is possible that the availability of CM will attract more patients to participate in treatment in the first place. In addition, CHBRP anticipates that the demand for treatment of SUDs would continue as relapsed patients attempt abstinence again and first-time initiators would join the pool of patients seeking care. This in turn could contribute to long-term positive public health impacts, as programs become more available and patients become more aware of them over time. However, limited patient readiness for SUD treatment and limited number of providers may remain significant barriers to care. To the extent that SB 110 results in an increase in SUD treatment with CM, and the extent to which this leads to additional quit attempts and long-term abstinence, it is possible SB 110 would contribute to reductions in substance use–related morbidity and mortality.
Sleep disturbance is one of the most prevalent symptoms reported by HIV-infected individuals , with up to 73% reporting significant sleep disturbances . Unlike some other symptoms associated with HIV that typically present during the initial phase of illness , sleep disturbance has been shown to be present over the course of the disease . This is particularly concerning as disturbed sleep has been associated with poorer antiretroviral medication adherence , viral load , greater HIV symptom severity , and higher rates of negative psychological symptoms . While the prevalence and consequences of sleep disturbances among individuals with HIV have been established, relatively little work has investigated malleable factors that may confer greater risk of sleep disturbances for this population. One relevant factor in this area is anxiety sensitivity , a cognitive vulnerability defined as the fear of anxiety, its relevant bodily sensations, and its potential negative social, physical, and mental consequences . AS has unique relations to sleep disturbances and, among individuals with HIV, specifically, has been linked to greater physiological distress, anxiety, and depression symptoms , suicidality , as well as self-reported HIV symptom severity . Unfortunately, there has been little work in terms of understanding whether greater AS might relate to decrements in sleep quality among individuals with HIV. Drawing from the literature more broadly, Vincent and Walker found that, in a sample of adults with chronic insomnia, AS was related to sleep-related impairment, with a trend relation between AS and frequency of medication use, after accounting for general worry and presence of Axis I psychopathology. Babson, Trainor, Bunaciu, and Feldner found that AS interacted with sleep anticipatory anxiety to predict sleep onset latency, after accounting for negative affect, gender, age, cannabis use, nicotine dependence, and alcohol use. In a similar investigation conducted among individuals with panic disorder, Hoge et al. found that after accounting for relevant covariates including age, major depression, and panic disorder severity, individuals with elevated AS reported significantly greater latency to sleep. Taken together, these studies indicated that elevations in AS confer risk for greater sleep disturbances, although these associations appear nuanced in terms of particular aspects of sleep quality, with no research having sought to elucidate these relations for individuals with HIV. Our study sought to explore the incremental association between AS and global sleep quality, as well as to determine differential associations between AS and a variety of facets that comprise global sleep quality, including perceived sleep quality, latency, duration, efficiency, disturbance, medication use, and daytime dysfunction in HIV-infected individuals receiving treatment at community clinics. We sought to explore AS in relation to global sleep impairment and specific components in order to explicate which aspects of sleep interference might be most relevant to AS.