Suicides with marijuana toxicology by year and overall suicide by year data are displayed in Figure 5.Cannabis has been associated with adverse social outcomes which may impact EDs and patient health. The large cohort study of Swedish men drafted at age 18-20 and followed to age 40 showed increased risk of unemployment and need for welfare assistance in those using cannabis greater than 50 times . These results were repeated in a longitudinal birth cohort study in New Zealand to 25 years old, which found high levels of cannabis use correlated with statistical significance to poorer educational outcomes, lower income, greater welfare dependence and unemployment, and lower relationship and life satisfaction. This cohort was classified into six levels of cannabis use, and found that as cannabis use increased, the odds ratio of adverse outcome increased. Both of these studies adjusted for confounding factors including socioeconomic background of the family, family functioning and exposure to adversity, exposure to child sexual and physical abuse, childhood and adolescent adjustment, academic achievement in early adolescence, comorbid mental health disorders, and other substance use. A prospective cohort study from upstate New York found that, compared with cannabis nonusers or minimal users , chronic users and users who began use in early adulthood and then tapered off use into later adulthood, had a significantly higher likelihood of unemployment at mean age 43 , even after controlling for covariates. The NASEM review stated that there was a limited level of evidence of impaired academic achievement and education outcomes, cannabis grow systems increased rates of unemployment and/ or low income, and impaired social functioning or engagement in developmentally appropriate social roles.
The report stated that although there was evidence to suggest these outcomes, it was difficult to document a direct link between cannabis use and these outcomes because other variables played a role. Social outcome data for cannabis users specifically in Colorado are currently unavailable and could be an area for further research.A number of review articles on cannabis have described adverse effects on brain imaging. These findings may help establish a mechanistic link between the epidemiological studies on the adverse effects of cannabis. Structural, functional, and chemical changes to the brain have been established. These include both the gray matter and white matter . Structural changes to the brain include reductions in the hippocampus and amygdala volumes in cannabis users. Several studies also identified reductions in volume of specific areas of the prefrontal cortex, as well as functional magnetic resonance imaging studies demonstrating reduced functional connectivity in the prefrontal networks responsible for executive function and the subcortical networks, which process habits and routines. Other fMRI studies show reduced connectivity in the fimbriae of the hippocampus and commissural fibers extending to the precuneus, and suggest that this disturbed brain connectivity in cannabis users may underlie cognitive impairment and vulnerability to psychosis, depression, and anxiety disorders. Multiple other areas of the brain have also been shown to demonstrate changes on fMRI studies in response to cannabis and include the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum. In general, these changes on both structural and functional MRI studies corresponded with frequency of use and earlier age of onset of use. Changes to neurotransmitters in the brain have also been well described in systematic reviews and include disruptions in glutamate, dopamine, N-acetylaspartate, myo-inositol, choline, and γ-aminobutyric acid.
Taken together, these changes may underlie the clinical features being observed in observational and epidemiological studies demonstrating increases in psychosis, impulsivity, depression, anxiety, suicidality, decreases in cognition, IQ, and executive function, abnormalities in habits, routines, decision making capacity, and deficits in learning, memory, attention, and social interaction. Cannabis use has also been associated with abuse of other illicit substances. According to the NASEM report, there is a moderate level of evidence of a statistical association between cannabis use and the development of substance dependence and/or substance abuse disorder for alcohol, tobacco, and illicit drugs. Multiple cohort studies have demonstrated these results. Four separate discordant twin studies have found that the twin who used marijuana was more likely to use other substances even after controlling for environmental and genetic influences.53-56 Although some studies reported that medical cannabis has resulted in improvements in opiate-related deaths, Colorado has had an increase in poisoning and deaths from opiates and methamphetamines since 2010, with the highest in 2017. These rates have increased nationwide as well and the influence of cannabis in Colorado is difficult to discern. Nevertheless, the increase in overdose deaths in Colorado is alarming. These data are shown in Figure 6.25 Although animal studies do not consistently translate to human effects, rat studies can provide some mechanistic clues. After exposure to tetrahydrocannabinol , rats have an increased behavioral sensitization response to not only THC but also opiates and nicotine. Studies also demonstrate that these behavioral changes in rats correspond to neuronal activity changes in mesolimbic dopamine neurons in the ventral tegmental area and nucleus accumbens and that cross tolerance results with exposure to morphine, amphetamines, and cocaine. Repeat morphine self-administration has been shown to be significantly lower in CB1 knockout mice and opiate withdrawal symptoms significantly less when the knockout mice are administered naloxone.
Dependence rates are reported at one in 10 among those who ever use cannabis, one in six among adolescent users, and one in three among daily users. Withdrawal symptoms may include anxiety, insomnia, appetite disturbance, and depression. These symptoms are sufficient to impair everyday functioning and are markedly attenuated by doses of an oral cannabis extract. Cannabinoid hyperemesis syndrome has been well described in the literature. The symptoms of CHS include significant nausea, violent vomiting, and abdominal pain in the setting of chronic cannabis use. Cardinal diagnostic characteristics include regular cannabis use, cyclic nausea and vomiting, and compulsive hot baths or showers with resolution of symptoms after cessation of cannabis use. CHS patients present similarly to cyclic vomiting syndrome patients with the exception that cannabis use is required to make the diagnosis. Following legalization, the prevalence of cyclic vomiting presentations to Denver Health and the University of Colorado Hospital increased 1.92-fold from 41 per 113,262 ED visits from a year prior to marijuana liberalization to 87 per 125,095 ED visits a year following marijuana liberalization . Patients with cyclic vomiting in the post-liberalization period were more likely to have marijuana use documented than patients in the pre-liberalization period . These patients often are evaluated with multiple imaging studies, lab work, endoscopies, and admissions to the hospital as well as antiemetic treatment. These studies are often non-diagnostic and treatment is often ineffective. This may also influence ED crowding. Traffic fatalities with blood or urine drug screens positive for cannabinoids have sharply risen across Colorado. Total fatal motor vehicle collisions in Colorado had been decreasing from a high of 677 in 2002 to a low of 407 in 2011 but then began increasing each year since then to 600 in 2017. Total MVCs mirror this trend. The NASEM review found substantial evidence of a statistical association between cannabis use and increased risk of MVCs. CDPHE found substantial evidence that recent marijuana use by a driver increases his or her risk of a MVC and that the higher the blood THC level, the higher the risk of MVC. The use of alcohol and marijuana together increases risk of impairment and MVC more than either substance alone. For less-than-weekly marijuana users, using marijuana containing 10 milligrams of THC is likely to impair the ability to safely drive, bike, or perform other safety-sensitive activities. A typical marijuana cigarette, or joint, contains 60-115 mg of THC. A systematic review of observational studies and meta analysis for acute cannabis consumption and MVC risk found that driving under the influence of cannabis was associated with a significantly increased risk of MVCs compared with unimpaired driving , ebb and flow tables especially for fatal collisions . However, a recent study of crash fatality rates after recreational marijuana legalization in Washington and Colorado found changes in motor vehicle crash fatality rates were not statistically different from those in similar states without recreational marijuana legalization. This was, however, only after further statistical regression analysis . Initial data demonstrated that after legalization, motor vehicle crash fatality rates increased by a mean of +0.1 fatalities per billion vehicle miles traveled in Washington and Colorado, and decreased by a mean of -0.5 fatalities per billion vehicle miles traveled in the control states each year. The effect of cannabinoids on the cardiovascular system is complex and an area of ongoing research. Of concern to practicing emergency physicians is ST-segment elevation myocardial infarctions and acute stroke presentations with a close temporal relationship with cannabis use, which have been documented in multiple case reports in otherwise young, healthy, male patients. The NASEM summary found there was a limited level of evidence of a statistical association between acute cannabis use and triggering an acute myocardial infarction , ischemic stroke, or subarachnoid hemorrhage. The WHO review states: “There is evidence that cannabis use can trigger coronary events. Recent case reports and case series suggest that cannabis smoking may increase cardiovascular disease risk in younger cannabis smokers who are otherwise at relatively low risk.” CDPHE found moderate evidence that marijuana use increases risk of ischemic stroke in individuals younger than 55 years of age and limited evidence that acute marijuana use increases risk of myocardial infarction. The main case crossover study cited for the AMI findings demonstrated that the risk for AMI associated with cannabis use during the hour preceding symptoms of AMI was elevated 4.8 times over baseline .
This risk was substantially reduced following that hour. A review of nationwide inpatient sample data from 2010 to 2014 demonstrated a 32% increase in inpatient admissions for primary diagnosis of myocardial infarction and secondary diagnosis of cannabis use disorder . The overall mean age of patients was 41 years old. These patients also had longer lengths of stay, higher hospitalization costs, and higher levels of morbidity due to AMI following hospitalization than non-cannabis users. In a study reviewing secondhand marijuana smoke exposure, the authors found that one minute of exposure substantially impaired endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco secondhand smoke. The pathophysiological basis of these events is not fully understood and a full discussion is beyond the scope of this review. In short summary, it may encompass a complex interaction between exogenous cannabinoids and the endocannabinoid system, autonomic nervous system, oxidative stress, direct cellular effects on the endothelium, and pro-coagulant effects. Exposure to THC causes activation of the sympathetic nervous system and inhibition of the parasympathetic nervous system. These effects include elevated heart rate, serum norepinephrine levels, elevated supine blood pressure, and increases in left ventricular systolic function. Smoking results in decreasing oxygen delivery to the heart and other vital organs and may be further compromised by increasing carboxyhemoglobin levels. The impaired myocardial oxygen demand-to-supply ratio following cannabis smoking has been shown to reduce the time to onset of symptoms during exercise in patients with stable angina. Direct effects of cannabis on blood vessels are complex due to the differing compounds in cannabis and the functional properties of the blood vessels examined. Studies are inconsistent regarding the effects on vasoconstriction and dilation. Cannabis has been consistently shown to produce vasodilation with resultant orthostatic hypotension, but it has also been implicated in vasoconstrictive arteritis mechanisms. A large review article suggested that there are three phases in cardiovascular parameters affected by the endocannabinoid system and that different chemical constituents of the cannabis plant have varying effects at different target organs, which may account for the differences. Transient vasospasm and reduction in cerebral blood flow are well described and may underlie changes in coronary, cerebral, and peripheral arterial systems leading to end organ ischemia. Myocardial blood flow has been shown to correlate inversely with circulating plasma levels of endocannabinoids. Cannabis has also been shown to be a potent source of cellular oxidative stress through formation of reactive oxygen species, and this may contribute to endothelial dysfunction and promote regional arterial vasospasm. THC has also recently shown a dose-dependent procoagulant effect. This ex vivo observation has been supported by reports of thrombotic coronary artery occlusion in young individuals without underlying atherosclerosis. There are also cannabinoid receptors on the surface of platelets and THC has been shown to increase the surface expression of glycoprotein IIb–IIIa and P selectin in a concentration-dependent manner resulting in platelet activation. Figure 7 summarizes these effects.Marijuana smoking leads to adverse pulmonary outcomes.