Allergic Skin Test Reactivity to Marijuana in the Southwest

In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended.     

Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo

Habitual marijuana smoking is associated with inflammation and atypia of airway epithelium accompanied by symptoms of chronic bronchitis. We hypothesized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, might contribute to these findings by impairing cellular energetics and mitochondrial function. To test this hypothesis, we examined particulate smoke extracts from marijuana cigarettes, tobacco cigarettes, and placebo marijuana (0% THC) cigarettes for their effects on the mitochondrial function of A549 cells in vitro. Only extracts prepared from marijuana cigarettes altered mitochondrial staining by the potentiometric probe JC-1. With the use of a cross-flow, nose-only inhalation system, rats were then exposed for 20 min to whole marijuana smoke and examined for its effects on airway epithelial cells. Inhalation of marijuana smoke produced lung tissue concentrations of THC that were 8-10 times higher than those measured in blood (75 +/- 38 ng/g wet wt tissue vs. 9.2 +/- 2.0 ng/ml), suggesting high local exposure. Intratracheal infusion of JC-1 immediately following marijuana smoke exposure revealed a diffuse decrease in lung cell JC-1 red fluorescence compared with tissue from unexposed or placebo smoke-exposed rats. Exposure to marijuana smoke in vivo also decreased JC-1 red fluorescence (54% decrease, P < 0.01) and ATP levels (75% decrease, P < 0.01) in single-cell preparations of tracheal epithelial cells. These results suggest that inhalation of marijuana smoke has deleterious effects on airway epithelial cell energetics that may contribute to the adverse pulmonary consequences of marijuana smoking.     

Promotion as Prevention: Positive Youth Development as Protective against Tobacco,Alcohol, Illicit Drug,and Sex Initiation

The present study was designed to examine the association of positive youth development with the likelihood of tobacco, alcohol, marijuana, hard drug, and sex initiation between 5th and 10th grades. A national, largely middle-class sample of 5,305 adolescents, participating in a longitudinal study funded by the National 4-H Council (although not all participants were enrolled in 4-H or other after-school programs), completed measures of positive youth development (PYD) constructs and of tobacco, alcohol, marijuana, and hard drug use once per year between 5th and 10th grades. At the 9th and 10th grade assessments, adolescents were asked whether they had initiated sexual intercourse and, if so, at what age they had first engaged in intercourse. Although the present sample was somewhat lower risk compared to national averages, survival analysis models indicated that PYD was significantly and negatively associated with the initiation hazards for tobacco use, marijuana use, and sex initiation for girls only, and with hard drug use for both genders. PYD was also positively associated with the odds of condom use across genders. Results are discussed with regard to PYD as a preventive process.     

Carboxy- and oxyhemoglobin in pregnant ewe and fetus after inhalation of marijuana, marijuana placebo and tobacco cigarette smoke

We measured carboxyhemoglobin (HbCO) and oxyhemoglobin (HbO2) percent saturations and blood gases in four near-term pregnant ewes and their fetuses, during and for 6 hours after 9-12 minutes of smoke inhalation from one high-potency marijuana cigarette (M), a marijuana placebo cigarette (P), and a reference tobacco cigarette (T). Maternal HbCO reached maximum levels at or soon after the exposure (M, 2.8%; P, 3.5%; T, 6.3% above baseline) and fell to baseline values by 6 hours. Fetal HbCO rose slowly reaching a plateau at 3 hours (M, 0.7%; P, 1.1%; T, 2.0% above baseline) which was maintained for at least three additional hours. Reductions in maternal and fetal HbO2 after exposure to marijuana placebo and reference tobacco cigarettes reflected these rises in HbCO. After exposure to marijuana cigarettes, however, fetal HbO2 dropped precipitously by 17% of baseline and showed a prolonged rate of return to presmoking HbO2 levels. Although P exposure caused a greater change in HbCO in the fetus than did M, it had a less-profound effect on fetal oxygenation.     

Pulmonary complications of smoked substance abuse.

After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cells in the lungs'' immune defense system. In addition, the available evidence strongly suggests that regularly smoking marijuana may predispose to the development of cancer of the respiratory tract. "Crack" smoking has become increasingly prevalent in our society, especially among habitual smokers of marijuana. New evidence is emerging implicating smoked cocaine as a cause of acute respiratory tract symptoms, lung dysfunction, and, in some cases, serious, life-threatening acute lung injury. A strong physician message to users of marijuana, cocaine, or both concerning the harmful effects of these smoked substances on the lungs and other organs may persuade some of them, especially those with drug-related respiratory complications, to quit smoking.     

Respiratory effects of non-tobacco cigarettes.

Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 9% were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controlled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking. These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.     

Correlates of Marijuana Drugged Driving and Openness to Driving While High: Evidence from Colorado and Washington

Aims

A potential unintended consequence of legalizing recreational marijuana is increased marijuana-related driving impairment. Some states where recreational marijuana is legal have begun implementing interventions to mitigate driving under the influence (DUI) of marijuana, including media campaigns to increase knowledge about DUI laws. However, little is known about the associations between knowledge of DUI laws and marijuana DUI behavior. In this study, we provide new data from a survey of marijuana users in Colorado and Washington to examine associations between marijuana drugged driving and two potential behavioral precursors of marijuana DUI. We also explore other factors that may influence marijuana DUI.

Methods

Data are from an online survey of marijuana users in Colorado and Washington. Respondents who reported any marijuana use in the past 30 days (n = 865) served as the analytic sample. We examined prevalence of two behavioral outcomes: (1) any driving of a motor vehicle while high in the past year and (2) driving a motor vehicle within 1 hour of using marijuana 5 or more times in the past month. Additional outcomes measuring willingness to drive while high were also assessed. Logistic regressions were used to estimate each outcome as a function of two multi-item scales measuring knowledge of the legal consequences of driving high and perceptions that driving while high is not safe. Additional covariates for potential confounders were included in each model.

Results

Prevalence of past-year driving while under the influence of marijuana was 43.6% among respondents. The prevalence of driving within 1 hour of using marijuana at least 5 times in the past month was 23.9%. Increased perception that driving high is unsafe was associated with lower odds of past-year marijuana DUI (OR = 0.31, P < 0.01) and lower past-month odds of driving 5 or more times within 1 hour of using marijuana (OR = 0.26, P < 0.01). Increased knowledge of marijuana DUI laws was also associated with lower odds of each of these outcomes (OR = 0.63, P < 0.01, OR = 0.69, P = 0.02, respectively). Post-estimation Wald tests confirmed the negative associations with marijuana DUI were greater in magnitude for safety perceptions than knowledge of DUI laws. Increased perceptions that driving while high is unsafe was associated with significantly lower willingness to drive after using marijuana while increased knowledge of marijuana DUI laws was not associated with these outcomes.

Conclusions

Despite recent interventions targeting public awareness of the legal consequences of marijuana DUI, our results suggest that knowledge of these laws is a weaker predictor of DUI behavior than perceptions that driving high is unsafe. In addition, safety perceptions predict decreased openness to driving high while knowledge of DUI laws was not associated with openness. These findings suggest that interventions for reducing the incidence of marijuana DUI are likely to be more successful by targeting safety perceptions related to marijuana DUI rather than knowledge of DUI laws. We caution that because these data are limited to an online convenience sample, results may not be generalizable beyond our sample.     

Marijuana: effects on pulse rate, subjective estimates of intoxication and multiple measures of memory

Twelve experienced marijuana users received marijuana cigarettes containing 10 mg Δ⁹-THC or placebo in two experimental sessions each separated by a one week interval. The effects of both treatments on pulse rate, subjective estimates of intoxication, multiple measures of memory including free, serial and delayed recall, final free recall, and recognition memory were assessed. Pulse rate and subjective ratings were elevated significantly following intoxication with active marijuana in comparison to placebo. Each of the three types of recall were significantly reduced following intoxication with marijuana but no differential effects of drug on recall condition were noted. Intrusion errors were elevated on the final free recall test following intoxication but recognition memory was unaffected.     

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.     

Cancer patterns in Canada.

Data from a cross-sectional survey of the health of Ontario children carried out in 1983 were used to provide estimates of the prevalence, patterns and sociodemographic correlates of the use of tobacco, alcohol and illicit drugs (substance use) among adolescents aged 12 to 16 years. Ninety-one percent of selected households participated. The prevalence rates of all categories of substance use, except use of inhalants, increased with increasing age. Among children aged 14 to 16 years the rates for girls were higher than those for boys for all categories of substance use except use of other, nondefined drugs. The prevalence rates of substance use tended to be higher in small urban areas except for use of marijuana (more prevalent in large urban areas) and use of inhalants (more prevalent in rural areas). The strongest evidence of clustering of substance use within families was found for smoking. Children who used less prevalent drugs (e.g., "hard" drugs) also tended to use the more prevalent ones (e.g., marijuana, tobacco and alcohol). Associations between substance use and low socioeconomic status suggested a positive relation with smoking and a negative relation with use of alcohol. The findings highlight the need for preventive programs aimed at specific subgroups in the adolescent population.     

Focus: Sex and Gender Health: Marijuana,the Endocannabinoid System and the Female Reproductive System

Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.     

Neuropsychological effects of marijuana

This study assigned 81 non-naïve subjects, divided into low- and high-dose groups, to four experimental conditions (marijuana/marijuana, marijuana/placebo, placebo/marijuana and placebo/placebo) for two sessions separated by about one week. The low dose was 4.8 mg. Δ⁹-THC followed by 2.4 mg. one hour later. The high dose was 9.1 mg. followed by 4.5 mg. one hour later. A battery of neuropsychological tests was administered.The low dose produced generalized impairment of all mental processes (concept formation, memory, tactile form discrimination and motor function) and the effect was generalized to all modalities. The high dose resulted in more extensive impairment, again generalized.The drug effects noted were explained in terms of generalized impairment of central integrative processes. The effects of marijuana on learning as well as memory were explained in terms of impaired output (recall), but the impairment was transient.     

Reefer Madness: Legal & Moral Issues Surrounding the Medical Prescription of Marijuana

California, Arizona, and several other states have recently legalized medical marijuana. My goal in this paper is to demonstrate that even if one grants the opponents of legalization many of their contentious assumptions, the federal government is still obligated to take several specific steps toward the legalization of medical marijuana. I defend this claim against a variety of objections, including the claims: that marijuana is unsafe, that marijuana cannot be adequately tested or produced as a drug, that the availability of synthetic THC makes marijuana superfluous, and especially that legalizing medical marijuana will increase recreational use by 'sending the wrong message '. I then go on to argue that given the intransigent position of the federal government on this issue, state governments are justified in unilaterally legalizing medical marijuana as an act of civil disobedience.
A large portion of this paper consists of an extensive response to the objection that legalizing medical marijuana will 'send the wrong message '– which I take to be the primary impediment to legalization. This objection basically claims that the consequences of withholding legalization (especially preventing increased recreational use) are superior to those of legalizing medical marijuana. I argue that legalization is justified even if one were to grant both that the harms of legalization outweighed its benefits and that utilitarianism is true. This requires a subtle and somewhat extended discussion of utilitarian moral and political theory.     

Allergenic fungi and actinomycetes in smoking materials and their health implications

Street marijuana, commercial cigarettes and pipe tobaccos were studied for the presence of fungi and actinomycetes associated with hypersensitivity pneumonitis. Aspergillus species and thermophilic actinomycetes were isolated from the smoking materials. In addition, Aspergillus fumigatus spores were isolated from marijuana smoke, indicating the potential hazard involved in developing serious disease. Precipitin antibodies against fungi, particularly Aspergillus, showed a higher prevalence in marijuana smokers, whereas only very few cigarette smokers and nonsmokers demonstrated antibodies to fungi. Cigarette smokers and nonsmokers showed more or less similar prevelance of antibodies against thermophilic actinomycetes.     

The neurophysiological basis of the marijuana experience

Experiments were done with 75 healthy young adults to explore the neurophysiological basis of the acute marijuana intoxication state. Tests included recording the scalp EEG, visual and auditory cerebral evoked-potentials, the CNV, cerebral slow potentials related to certainty of response correctness in auditory discrimination tasks, heart rate, respiration and the galvanic skin response. All variables were recorded over 45 minutes before and 45 minutes after smoking a marijuana cigarette containing either 4.8, 9.1 or less than 0.01 mg. Δ⁹-THC.High doses of marijuana induced a significant decrease in the peak power of the alpha rhythm and an increase in auditory evoked-response latency. The CNV increased in ampiitude after smoking marijuana in low doses and sequential CNVs showed changes consistent with sustained attention but decreased certainty about performance following either low or high dose. Marijuana interfered significantly with performance of the discrimination task itself.     

The effects of chronic marijuana use on circadian entrainment

Animal literature suggests a connection between marijuana use and altered circadian rhythms. However, the effect has not yet been demonstrated in humans. The present study examined the effect of chronic marijuana use on human circadian function. Participants consisted of current users who reported smoking marijuana daily for at least a year and non-marijuana user controls. Participants took a neurocognitive assessment, wore actigraphs and maintained sleep diaries for three weeks. While no significant cognitive changes were found between groups, data revealed that chronic marijuana use may act as an additional zeitgeber and lead to increased entrainment in human users.     

Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys

The acute behavioral effects of marijuana smoke were assessed in rhesus monkeys using a battery of food-reinforced complex operant tasks that included incremental repeated acquisition (IRA, n = 9), conditioned position responding (CPR, n = 8), progressive ratio (PR, n = 8), delayed matching to sample (DMTS, n = 6), and temporal response differentiation responding (TRD, n = 3). Marijuana or placebo smoke was delivered by a specialized face mask 15-min before sessions at exposure levels of 1, 5, 10, and 15 puffs (35cc/puff) or one cigarette smoked to a butt length of approximately 10 mm (approximately 20 puffs). Marijuana smoke caused significant disruptions of performance in all tests except PR after exposure to 10 or more puffs. Generally, response rates decreased or latencies to respond increased. Performance in the PR test was not consistently affected by marijuana exposure. Accuracy of responding was not altered by marijuana smoke at doses lower than those that decreased response rates in the IRA or CPR tests. In the three animals performing under all five schedules, the relative sensitivities for detecting marijuana behavioral effects were DMTS = TRD greater than IRA = CPR greater than PR. These results suggest that performance under operant schedules that are thought to represent some aspect of time perception, short-term memory, learning, motivation, and position discrimination show differential sensitivity to disruption by marijuana smoke, a finding similar to that noted previously for iv THC administration.     

Marijuana exposure in vivo and human lymphocyte chromosomes.

Sequential chromosome examinations of peripheral lymphocte cultures were carried out on 21 adult male volunteers who smoked natural blend marijuana cigarettes containing about 1%, 2%, or no delta9-THC. For a limited number of subjects, blood samples from a single venipuncture were cultured independently in two cytogenetic laboratories, and later the slides were exchaged for re-analysis. There were significant differences between laboratories in the absolute break frequencies recorded. These inter-laboratory differences were demonstrated for both techniques of cell culture and metaphase analysis. Neither laboratory found a statistically significant increase in break frequencies asssociated with marijuana smoking. The present study, therefore, failed to detect a measurable effect of marijuana smoking on chromosomal aberrations in subjects experienced in the use of the drug.     

Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor.

Awareness of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. This paper will review data implicating the cannabinoid CB1 receptor in regulating the behavioral effects of Delta(9)-tetrahydrocannobinol (THC), the primary psychoactive component of cannabis, across a range of species. The behavioral effects that will be discussed include those that directly contribute to the maintenance of chronic marijuana smoking, such as reward, subjective effects, and the positive and negative reinforcing effects of marijuana, THC and synthetic cannabinoids. The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.