However, these effects of WIN on body weight were transitory, as the difference in females did not persist into adulthood. For the behavioral assessments, female subjects were overall more resistant to the long-term effects of adolescent drug exposure. Group differences were only found in the sucrose consumption test, in which the moderate dose WIN females exhibited decreased natural reward consumption compared to the control females. However, differences from the control were not found with the female nicotine and WIN co-exposure condition for sucrose consumption, suggesting that the presence of nicotine ameliorated the actions of WIN on reward circuitry during the adolescent period. In contrast, adolescent exposure to a low dose of WIN had no effect on physiological or behavioral measures, either alone or in the presence of nicotine, for both males and females. Taken together, these findings demonstrate that while adolescent cannabinoid agonist exposure at a moderate dose exerts variable effects on both physiological and behavioral measures in males and females, co-administration of nicotine surprisingly counteracted some of these effects by normalizing to control levels.While prior studies have examined the effects of adolescent exposure of either nicotine or WIN alone on later behaviors, the current findings represent the first examination of the effects of co-exposure during mid-adolescence and subsequent long-term effects on adult behavior. This age range was selected based on the correlation to human adolescence with higher levels of experimentation and more recurrent patterns of drug consumption than that found in younger individuals. With regard to nicotine alone, opposing effects have been found in male Sprague-Dawley rats with increased depression-associated behaviors, vertical outdoor farming but no difference in anxiety-associated behaviors, during adulthood.
However, these behavioral differences were only found at higher nicotine doses approximately twice that administered in the current study. Chronic exposure approaches with a mini pump or nicotine patch at higher doses have also demonstrated decreased exploratory activity, decreased food consumption under anxiety-related conditions, and deficits in contextual condition to shock-associated cues in Sprague-Dawley rats. In mice, adolescent exposure to high dose mini pump has also been shown to disrupt contextual fear condition, but not cued fear conditioning. However, since studies have shown that of those adolescents age 12–17 who smoke, the majority smoke one or less than one cigarette per day, the current studies focused on a rewarding dose with once daily exposure as an investigative goal. Thus, the lack of difference in the behavioral measures with nicotine exposure in the current studies may be attributed to this relatively lower dose administered. Along these lines, it should be noted that this dose was selected based on the rewarding effects of doses in this range, as assessed with the brain reward threshold measure, and behavioral effects elicited in adolescent mice, and thus, the current results have particular relevance to experimental patterns of drug consumption found in youth. With adolescent cannabinoid agonist exposure, findings derived from prior rat studies have been somewhat variable. In one study, adolescent male and female rats treated with the cannabinoid agonist, CP 55,940, exhibited overall increased time on the open-arm of the elevated plus maze, but these effects were not maintained when examining males and females independently, suggesting these differences may have been confounded by baseline differences between the sexes. Since CP 55,940 has high affinity for both the CB1 and CB2 receptors, as well as GPR55, the lack of differences within each sex for drug condition may also have been due to actions on alternate signaling pathways or differences in agonist actions. Interestingly, male Sprague-Dawley rats treated with WIN, the CB1 and CB2 specific agonist, during adolescence exhibited increased depressive-like behaviors in the forced swim and sucrose consumption tests. In our mouse studies, we did not find any differences in these measures with the low dose of WIN and opposing effects at the moderate dose of WIN, indicating that species differences in metabolism and/or genetic heritability factors likely mediate the effects of cannabinoids on adolescent neuro development.
Finally, adolescent WIN exposure has also been found to increase palatable food intake and alter attribution of incentive salience for food reward in adult male Long Evans rats. The increase in natural reward-related effects with adolescent exposure is consistent with our findings at the moderate WIN dose in mice, suggesting cannabinoid exposure during adolescence similarly alters brain reward pathways to enhance subsequent responsiveness to natural reward. Interestingly, Schoch and colleagues also demonstrated increased expression of the endocannabinoids anandamide and oleoylethanolamine in the nucleus accumbens only during a food restricted state with adolescent WIN exposure in rats . Thus, dependent on the availability of food and level of satiety, changes in neural systems regulating reward-related behaviors may be differentially affected in the presence of cannabinoids. Along these lines, it is interesting to note that in the current study, mice were at a satiated level during sucrose consumption, during which time the opposing differences were found in males and females exposed to adolescent WIN. However, during conditions of food restriction, such as during operant food training in the current study, group differences only emerged for males in the reversal task. Thus, altered endocannabinoid signaling may account for this effect during the food restricted state, whereas other mechanisms likely underlie the behavioral differences observed in the anxiety and natural reward-related measures. Cannabinoid and nicotinic acetylcholine receptors exhibit overlapping expression within brain regions implicated in reward-related and affective behaviors, including the prefrontal cortex, ventral tegmental area, nucleus accumbens, medial habenula, interpeduncular nucleus and hippocampus. On the cellular level, both receptors types are expressed on presynaptic terminals and function to modulate release of various neurotransmitters. For instance, with acute administration, both drugs increase extracellular dopamine in the nucleus accumbens and prefrontal cortex , and adolescent cannabinoid or nicotine exposure have also been shown to affect cholinergic, serotonergic and noradrenergic signaling mechanisms. Thus, in consideration of the effects of nicotine and cannabinoids on several neurotransmitter systems and the behavioral findings from the current studies, future studies will need to dissect the differential impact of single or co-drug exposure during adolescence on neural signaling mechanisms. In conclusion, activation of cannabinoid receptors with or without nicotine led to differential sex-specific effects on anxiety- and reward-related behaviors during adulthood. Together, these studies provide evidence that adolescent exposure to drugs of abuse may lead to alterations in affective and cognitive behaviors during adulthood. These data support the conclusion that consumption of cannabis by youth may alter later cognitive function, and thus, policy approaches should be considered to discourage and/or restrict substance use by this vulnerable population.The United States is experiencing an epidemic of lung injury associated with youth electronic cigarette use, or vaping ; in 2018, 20.8% of U.S. high school students reported currently using e-cigarette.
E-cigarette products such as Juul, a popular device that delivers nicotine and flavors,* are used by students at schools, including in classrooms and bathrooms.† Use of flavored e-cigarettes by youths has become an increasing concern . A recent analysis of the National Youth Tobacco Survey showed that among high school students who currently used e-cigarettes, the percentage who used flavored e-cigarettes increased from 65.1% in 2014 to 67.8% in 2018 . In 2018, 8.1% of high school students currently smoked cigarettes, and 45.7% of those students smoked menthol cigarettes. In addition, 7.6% of high school students currently smoked cigarillos, little cigars, or cigars, 43.6% of whom used flavored varieties of these products . Many youths also use cigars to make marijuana blunts , and some use manufactured disposable cannabis products . Waste from e-cigarette products can contain plastics, nicotine, heavy metals, other chemical toxins, and hazardous lithium-ion batteries . The toxicity of combustible tobacco product waste from cigarettes is well established . Cannabis product waste can include plastics, metals, electronic components, and batteries. A garbology study of environmental contamination from e-cigarette product waste, combustible tobacco product waste, and cannabis product waste was conducted using a purposively selected, nonrandom sample of 12 public high schools with a total enrollment of 18,831 students in Alameda, Contra Costa, Marin, and San Francisco counties in California. Using 2016 data from the National Center for Education Statistics,rolling grow table researchers stratified schools by the percentages of students from low-income families .At each school, researchers systematically scanned the student parking lots and exterior school perimeter areas once during July 2018–April 2019 to collect all e-cigarette product waste, combustible tobacco product waste, and cannabis product waste found on the ground. Overall, 893 waste items were collected, including 172 e-cigarette product waste items . Almost all Juul or Juul-compatible pods and caps were found at schools with predominantly middle- and upper-income student populations. Among 74 Juul or Juul-compatible color-coded flavor caps, 73 were from flavored pods other than tobacco flavor. Overall, 47 pod caps were from mintflavored and other menthol-flavored pods. Additional scans were conducted at one upper-income area school beginning 3 months after Juul Laboratories announced it was removing flavors from retail distribution. These additional scans yielded 127 mint, 20 mango, four fruit Juul or Juul-compatible pod caps, and three yellow Juul-compatible caps. At four high schools with populations composed predominantly of lower-income African-American and Latino students, eight e-cigarette product waste items were collected, in addition to 71 little cigar or cigarillo plastic wrappers and mouthpieces, 94% of which were from flavored products.Across all schools, 620 cigarette butts were collected, including 403 from recently smoked cigarettes that were identifiable. Among these, 168 were menthol.
At low, middle, and upper-income schools, identifiable menthol butts accounted for 60%, 38%, and 28%, respectively, of all identifiable cigarette butts. Fourteen cannabis product waste items were found, including vaporizer pens, cartridges, and packaging from high-potency pineapple- and lemon-flavored cannabis oil concentrate vaporizer cartridges. E-cigarette waste and combustible tobacco product waste contaminate the Bay Area high schools studied and confirm use of these products by high school students. Cannabis product waste represents an emerging issue. The large proportions of flavored products identified in this study are consistent with findings from other studies showing high prevalence rates of flavored e-cigarette and combustible tobacco product use among U.S. youths. Further research and actions at national, state, and community levels are needed to inform policy making to reduce youth access to and use of tobacco products, including e-cigarettes, and cannabis products. Youth use of flavored tobacco products, including mint and all other mentholated flavors, is of particular concern. Likewise, measures are needed to eliminate environmental contamination from e-cigarette, combustible tobacco product, and cannabis product waste in and around schools. Schools can engage students in garbology projects to identify existing and new use of these products and to raise awareness about their hazardous health and environmental impacts.As the legalization of cannabis becomes prevalent in the United States, effects from its abuse will result in an increase in emergency department visits.1 We have witnessed a growing trend in our community ED among adolescents abusing a highly potent form of marijuana, butane hash oil . BHO is a concentrated form of tetrahydrocannabinol that is created by using liquid butane as a solvent to extract THC from marijuana plants. As butane is highly flammable, reports of burns and explosions have been reported from the synthesis and use of BHO. A popular trend called “dabbing” involves heating the concentrated oil and inhaling the resultant vapors. These vapors contain very high concentrations of THC, as high as 90% pure. Adolescents may use e-cigarette devices to abuse BHO as a delivery device. Such devices are easily concealed and produce almost no odor, thus leading to the potential for abuse at school and in the home.2,3 Previous case reports have shown BHO abuse may lead to agitation along with neurotoxicity and cardiotoxicity.Since THC may activate serotonin receptors and inhibit serotonin reuptake, its abuse in high concentrations may mimic serotonin syndrome.We present two cases of adolescents with recent “dabbing” use who exhibited signs and symptoms of serotonin syndrome.A 17-year-old female presented to a large community ED by emergency medical services from her home for CoxHealth System, Department of Emergency Medicine, Springfield, Missouri CoxHealth System, Department of Pharmacy, Springfield, Missouri a possible seizure. EMS providers had witnessed agitation, altered mental status, tachycardia, muscle stiffness and tremors in the limbs, and administered 10 milligrams of midazolam intranasally. History was obtained from the EMS providers and the patient’s parents who were present in the room. The patient had been taking sertraline 50 mg daily and had also been prescribed a short course of cyclobenzaprine 5 mg every eight hours, as needed, for “muscle aches.” According to the parents, the patient had taken “a few” but stopped the cyclobenzaprine as it was not effective.