About a third of participants reported that they sometimes or regularly reduced their opioid medication when using cannabis. However, the prevalence of opioid discontinuation was not significantly different between daily or neardaily marijuana users and non-users. To date, data on self-reported improvement of symptoms has not been substantiated by studies that have monitored opioid and marijuana use. More research on this topic is clearly needed. Nonetheless, our findings suggest that even if objective measures do not support that marijuana is sub-stitutive for opioid use, patients perceive that marijuana use has reduced their opioid use. Perhaps the commercialization of marijuana and the favorable media coverage surrounding the health effects of marijuana are fostering such a perception. More research including clinical trials on the efficacy of cannabis in pain management with the inclusion of patient-centered outcomes is needed to shed light on the role of marijuana on pain management. Our study has several limitations that deserve comment. Our study was a cross-sectional survey of a relatively small number of respondents with a history of marijuana use and opioid use within the past year. Our survey question provided a limited number of examples of opioid medications , so it is possible that we did not identify all opioid users. Although our survey specifically asked about the use of opioids for pain, it is possible that we captured individuals who were using opioids for other reasons such as opioid use disorder. Likewise, it is possible that respondents may be using marijuana for reasons other than pain. Thus, we cannot conclude with certainty that patients are using marijuana as an alternative to opioids for pain per se. We also relied on respondents’ retrospective judgment regarding reduction or cessation of opioid use attributable to marijuana use. Thus, our findings could also be limited by recall bias, although this was minimized by restricting the sample to those who used opioids within the past year. Under reporting of substitution could have occurred,microgreen grow rack particularly in states in which marijuana has not been legalized.There is widespread belief that, unlike tobacco smoke, marijuana smoke is benign.

While the psychoactive substance in marijuana is tetrahydrocannabinol rather than nicotine, marijuana smoke is still the result of biomass combustion and contains many of the same toxins as tobacco smoke,including fine particles that cause cardiovascular morbidity and mortality.Tobacco secondhand smoke alone is responsible for 50 000 deaths in the United States each year, with 46 000 from cardiovascular disease,and implementation of laws prohibiting smoking in public places and workplaces is followed by drops in hospital admissions for acute myocardial infarction, other cardiac events, stroke, and pulmonary diseases.However, due to the illegality of marijuana, it has been difficult to prospectively study the effects of marijuana smoke, and the rare secondhand marijuana smoke studies have focused on whether exposed people test positive on drug tests.The increasing number of states legalizing medicinal and recreational marijuana, and increasing potential for corporate expansion within the cannabis industry,make it important to understand the health consequences of secondhand exposure to marijuana smoke. Vascular health can be evaluated by measuring arterial flow mediated dilation , the extent to which arteries vasodilate in response to increased blood flow.FMD ensures sufficient blood flow to peripheral tissues and the heart. FMD is quantified in humans by ultrasound as the percent vasodilation of the brachial artery in response to restoration of blood flow after transient occlusion.Brachial artery FMD is a well established clinical prognostic indicator of endothelial function that correlates with endothelium-dependent vasodilation of the coronary arteries and other measures of cardiovascular health.Decreased brachial FMD correlates with adverse cardiovascular outcomes that are increased by cigarette smoke, including myocardial infarction and atherosclerosis.FMD is impaired in tobacco smokers relative to nonsmokers.People who report frequent SHS exposure exhibit poor FMD even when smoke is not present during the testing, and a 30-minute exposure to SHS at real-world levels impairs FMD in humans.The nicotine in tobacco is not responsible for the entire adverse effect of tobacco smoke on FMD,and vasodilatory function is also impaired by diesel exhaust and by smoke from incense and candles.These observations, along with the similar chemical composition of tobacco and marijuana smoke,led us to hypothesize that marijuana smoke would also impair FMD.

We developed an animal model that uses micro-ultrasound and a simple reversible surgical occlusion of blood flow to the leg to measure FMD in the femoral arteries of living rats,analogous to the measurement of brachial artery FMD in humans. We extensively validated this technique physiologically and used it to demonstrate age-related changes in the mechanisms underlying FMD,and the beneficial vascular effects of pharmacological preservation of bio-available intracellular nitric oxide.Subsequently, we showed that 30 minutes of tobacco SHS exposure at real-world levels impairs FMD in rats, and that even 1 minute of SHS impairs FMD.We observed similar impairment from exposure to tobacco SHS from little cigars.We, therefore, used this rat model to determine whether marijuana SHS also has adverse effects on the vasculature.Acquisition and possession of marijuana was approved by the Drug Enforcement Agency, the Food and Drug Administration, the Research Advisory Panel of California, and the University of California, San Francisco Office of Environmental Health and Safety. Marijuana cigarettes were supplied by RTI International , contracted through the National Institute on Drug Abuse. Marijuana was from sinsemilla plants with stems removed, and consisted of leaf fragments, small leaves, bracts, and buds, and was grown in the absence of pesticides. The cigarettes were machine rolled with the same dimensions as standard tobacco cigarettes and fit in our cigarette smoking machine without further modification. Upon arrival, marijuana cigarettes were individually wrapped in plastic wrap and numbered, and were stored in airtight containers at 20°C. In accordance with requirements from the Drug Enforcement Agency, the cigarettes were stored in a padlocked freezer with high-security lock and a code deactivated open-door alarm that communicated with the University of California Police Department, physically attached to a heavy Steel case desk, in a controlled-access room outfitted with a solid door with high-security lock, and hinge pins that were non-removable from the outside. Prior to each experiment, marijuana cigarettes were humidified overnight at room temperature by placing them in an airtight container over 50 mL of saturated sodium chloride solution as per instructions on use from RTI, in a locked desk drawer. Logs documenting removal of cigarettes from the freezer and desk were kept as required by the Drug Enforcement Agency. Cigarettes were used within 5 minutes after humidification.We used a modified cigarette smoking system described previously for tobacco SHS experiments.Briefly, the system collects side stream smoke from the burning tip of the cigarette in a 21-L Plexiglas exposure chamber as a ventilator pump simulates human puffing. A Sidepak AM510 personal aerosol monitor , calibrated for cigarette smoke particles and excluding those >2.5 lm, monitors the concentration of respirable suspended particles in the exposure chamber and exhausts back into the chamber. Smoke is collected in the chamber and the cigarette is extinguished, and excess smoke is then vented from the chamber to obtain the desired starting concentration. Air in the chamber is mixed with a small fan. The wall of the chamber contains a gasket through which the nose of an anesthetized rat is inserted to breathe the smoky air. Because the system requires the cigarette to be extinguished before exposure of the rat,ebb and flow flood table adsorption of smoke particles to surfaces in the exposure chamber causes a continued progressive decrease in the levels over time; thus, most of the exposure occurs over the first several minutes. Tobacco cigarettes were smoked according to standard conditions.

Marijuana cigarettes were smoked using the same protocol, with the exception that the puff duration was 1 s for our initial 30-minute exposure experiment due to an instrument calibration error discovered afterward. The difference between a 1-s puff and a 2-s puff is not expected to have a substantial effect on the side stream smoke generated. For each experiment, a single cigarette was lit, smoked for 3 minutes, and extinguished, and particle concentration in the exposure chamber was adjusted until the desired RSP starting concentration was reached . At that time, an individual anesthetized rat, after baseline FMD measurement, was exposed for the specified duration and was then returned to the ultrasound system for post smoke FMD measurement. Negative controls consisted of the same duration of exposure to non-smoky air in the exposure chamber. As in our tobacco study,it took roughly 10 minutes after the end of the exposure period to prepare the rat for an initial post exposure FMD measurement. For some experiments, we measured FMD again 30 minutes later to evaluate recovery.Our hypothesis that FMD is impaired by combustion products common to smoke from burned plant material raises the question of whether FMD is impaired by smoke from burned rolling paper, rather than the tobacco or marijuana. The question is relevant because some people smoke marijuana in pipes. We tested the hypothesis that impairment is dependent on paper smoke by assembling marijuana cigarettes in which the paper was replaced by a fine stainless steel mesh to mimic the properties of rolling paper, which is ventilated. In a confirmatory group of 4 rats, FMD was significantly impaired to a similar extent as that by regular marijuana cigarettes . Since these mesh cigarettes were prepared using the THC-free marijuana, the results confirm that FMD is impaired by SHS from marijuana lacking both THC and rolling paper.Because most of the exposure during our 30-minute period occurred during the first 10 minutes, the question remained of whether a very brief exposure impairs FMD. We previously reported that tobacco SHS exposure for 1 minute at the high restaurant level impairs FMD,34 so we repeated that experiment with marijuana SHS at comparable particle concentration. FMD was substantially decreased by 1 minute of marijuana SHS with and without THC . Measurement of pre-occlusion baseline diameter revealed that the marijuana SHS directly induced vasodilation, even with the THC-free marijuana. This result was in contrast to our previous experiment in which rats were exposed to 30 minutes of declining RSP levels that fell to roughly zero before post exposure FMD was measured, with no observed smoke-induced vasodilation. To reconcile this apparent contradiction, we exposed another group to marijuana SHS and waited a total of 25 minutes after the 1-minute exposure before measuring FMD. This allowed the baseline vasodilation to subside, but FMD still decreased , confirming that 1 minute of marijuana SHS exposure causes endothelial dysfunction that persists beyond any transient vasodilatory effects of the marijuana. All cannabinoids are missing from the THC-free marijuana, and we did not observe significant baseline vasodilation after 1 minute of tobacco SHS in our previous report34 . The identity of the noncannabinoid vasodilator in marijuana is unknown.To determine whether the substantial impairment of FMD involved functional or physical inhibition of vascular smooth muscle function, we performed a separate experiment in which FMD was impaired by 1 minute of marijuana SHS as before, and then after impaired FMD was confirmed, an intravenous bolus of nitroglycerin was injected to induce endothelium-independent vasodilation. This injection caused vasodilation even while FMD was still impaired, as confirmed by a subsequent FMD measurement after the nitroglycerin effect had subsided . Therefore, the impairment of FMD by marijuana SHS was mediated by an endothelium-dependent mechanism, not a direct effect on the smooth muscle of the vessel wall.There is growing awareness that marijuana use in general may lead to cardiovascular complications, an effect normally ascribed to THC, but little attention has been paid specifically to the effects of the generic biomass combustion components. Our inclusion of control groups exposed to SHS from marijuana lacking cannabinoids confirms that THC was not required for the impairment of FMD. Similarly and notably, the finding that FMD is impaired by exposure to marijuana SHS, which is chemically similar to tobacco SHS but does not contain nicotine, confirms that the decrease in FMD caused by tobacco SHS is not dependent on nicotine. Together, our results demonstrate that in rats, FMD is impaired by 1 or more constituents of smoke not specific to marijuana or tobacco, either the products of combustion or other generic plant chemicals that persist after combustion.