Tashkin et al measured FEV1 serially in 255 habitual male and female smokers of marijuana and/or tobacco and nonsmokers of either substance on up to seven occasions at intervals of $ 1 year over a total period of up to 8 years. Random effects models were used in men and women separately to estimate mean rates of decline in FEV1 and to compare these rates between smokers of marijuana or tobacco alone, smokers of both substances, and nonsmokers of either substance. Smoking marijuana was not found to be associated with greater declines in FEV1 than nonsmoking nor was a relationship seen between the daily number of marijuana joints smoked and rate of decline in FEV1. In contrast, smoking tobacco had a significant effect on FEV1 decline in men in a dose-responsive manner. Findings are illustrated in Figure 3. Hancox et al performed serial lung function measurements in 779 members of a birth cohort in Dunedin, New Zealand, at 18, 21, 26, and 32 years of age. They assessed changes in FEV1, FVC, and FEV1/FVC associated with tobacco and marijuana smoking using regression analyses and estimates of both joint-years and pack-years as predictors, adjusting for sex and height at 32 years of age, changes in height between 15 and 32 years of age, and concomitant tobacco or marijuana use. The results are shown in Table 3. Among marijuana smokers, FVC increased significantly over time, whereasFEV1 showed a non significant increase and FEV1/FVC exhibited a non significant decline. In contrast, among tobacco smokers, FEV1 and FEV1/FVC both showed significant declines, whereas FVC showed no change.The smoke contents of marijuana cigarettes contain the same procarcinogenic components, including the very potent human carcinogen, benzpyrene, found in tobacco smoke.Bronchial biopsies obtained from heavy, habitual marijuana smokers have shown the same widespread histopathologic epithelial abnormalities noted in tobacco smokers, including squamous metaplasia and cellular disorganization,that are widely thought to be precancerous.
Immunohistologic examination of bronchial biopsies from marijuana smokers has shown higher levels of the protein products of oncogenes, including Ki67 and EGFR,whereas laryngeal cancer specimens from marijuana smokers have been shown to exhibit increased expression of oncoproteins compared both with tobacco smokers and nonsmokers.A few older epidemiologic studies from North Africa have shown a positive association with lung cancer; however,greenhouse rolling racks the common practice of admixing marijuana and tobacco within the same cigarette in these societies precludes disentangling the effects of marijuana from those of tobacco. A population-based cohort study of men 18 to 20 years of age conscripted into the Swedish military in 1969 to 1970 tracked these men until 2009 for incident lung cancer cases using linked nationwide medical registries.Cox regression was used to assess the relationship between lifetime use of marijuana self-reported at the time of conscription and risk of subsequent lung cancer diagnosis over the ensuring 40 years, adjusting for tobacco use also up to only 18 to 20 years of age.The hazard ratio for lung cancer was significantly positive in relation to lifetime marijuana use of > 50 times. However, because neither marijuana nor tobacco use was determined after the baseline assessment, the authors were unable to adjust for true lifetime use of tobacco, a crucially important residual confounder.Several investigators have demonstrated a tumor suppressive effect of THC and other cannabinoids on a variety of malignancies, including lung, in both cell culture systems and animal models, as previously reviewed by Bifulco et al and Velasco et al.These findings appear to reflect antiproliferative, proapoptotic, and antiangiogenic properties of THC that might counteract the tumor-initiating or tumorpromoting effects of the carcinogens contained with the smoke of marijuana. A large cohort study of health plan participants in Northern California failed to show an increased risk of tobacco-related cancers in association with self-reported marijuana use.A pooled analysis of six well-designed case-control studies of the association between habitual marijuana smoking and lung cancer that totaled 2,159 cases and 2,985 control subjects did not find any increased risk of lung cancer in association with marijuana use.Only one of the six studies included in the pooled analysis showed a significantly positive association between lung cancer and marijuana use, mainly in the heaviest marijuana use tertile, but the latter tertile included only four matched control subjects, making the estimates of risk imprecise.
Marijuana smoking might predispose to lower respiratory tract infection in at least three ways. First, the destruction of ciliated epithelium in the large central airways and the associated hyperplasia of mucus-secreting surface epithelial cells demonstrated in bronchial biopsies of habitual marijuana smokers may lead to increased production of mucus in the face of a diminished capacity to cleanse the lung of the excess mucus because of ciliary loss, thereby providing a substrate for potentially pathogenic microbial organisms colonizing the lower respiratory tract.Second, the immunosuppressive effect of THC leading to impairment of the bactericidal and fungicidal activity of AMs,further compromises the lung’s defense against microbial infection. Finally, marijuana has been shown to be frequently contaminated with Aspergillus fumigatus and potentially pathogenic gram-negative bacteria.Therefore, introduction of these microorganisms into the lung in the face of marijuana-related impairment in the lung’s host defense provides another possible mechanism for increasing the risk of pneumonia. The possible association of marijuana with an increased risk of pneumonia is supported by older case reports of Aspergillus pneumonia in smokers of marijuana immunocompromised by AIDS,chronic granulomatous disease,bone marrow transplantation,renal transplantation, or lung cancer treated with chemotherapy.In addition, a cluster of five patients with cavitary TB who used a marijuana water pipe was reported in Australia in 2003, followed by another report from Australia 10 years later of three additional cases of open cavitary TB in marijuana bong users.In these cases, it is not clear whether the spread of TB infection was because of close contact with patients with cavitary TB who might have shared a water pipe to smoke marijuana and/or to marijuana-related impairment in the lung’s defense against infection. Although a few older epidemiologic studies have suggested that marijuana use might be a significant independent risk factor for opportunistic infection in individuals who are HIV positive,an early analysis of data from the Multi-center AIDS Cohort Study failed to find evidence that marijuana was a risk factor for progression of individuals who are HIV positive to full-blown AIDS.Further preliminary analysis of the possible association of marijuana use with pneumonia risk using the Multi-center AIDS Cohort Study data set updated to 2013 has not shown a significant association of marijuana use with increased risk of either community-acquired or opportunistic pneumonia in either the HIV-negative or HIV-positive members of the cohort, after adjustment for tobacco, age, and among the individuals who are HIV positive, cluster of differentiation 4 cell counts and viral load.
A long-standing observation in clinical and epidemiological research into substance use has been that users of one drug typically do not limit their use to a single substance. For example, alcohol and tobacco are commonly used by the same person and often in the same setting, as are tobacco and marijuana. Though the synergistic effects of these particular drugs have been suggested as a potential explanation , another interesting possibility is that individuals have an underlying liability to drug use within and across different pharmacological classes. Support for this notion has been shown for both licit and illicit drugs in a variety of populations and drug use phenotypes. As poly-substance use is associated with problematic use and reduced treatment efficacy , identifying informative precursors to the onset of abuse and dependence remains a priority. Among the variety of factors that have been examined as an early indicator of later, more problematic use patterns, how someone experiences a drug , is one of the most interesting. Subjective experiences are thought to reflect individual differences in the pharmacological effects of a drug. Factor analytic studies of these experiences frequently yield two main factors: pleasant or positive and unpleasant or negative. Positive subjective experiences often include euphoria, relaxation, and feeling less inhibition. Negative subjective experiences include nausea,vertical grow difficulty inhaling, dizziness and sadness. Though weakly correlated , users of a drug sometimes report both positive and negative experiences. Alcohol, tobacco, and marijuana are the most commonly used licit and illicit drugs. Studies examining the subjective experiences to these drugs have generally found that how a person responds to a particular drug is predictive of more problematic use of the same drug. For example, dependent cigarette users more frequently endorse positive experiences than regular smokers and moderate-to-heavy drinkers report experiencing greater stimulant-like effects to alcohol than lighter drinkers. A similar relationship has been demonstrated for marijuana use. Although results are mixed, negative experiences to tobacco and marijuana have also been positively associated with problematic use. For alcohol consumption, low levels of response, primarily measured using negative subjective effects, have been associated with an increased risk of an alcohol use disorder as lower thresholds to the sedative effects of alcohol protected against developing abuse later in life.In particular, subjective experiences to a variety of drugs are correlated and can predict levels of involvement for substances in other pharmacological classes. This observation has been shown for pleasurable experiences of alcohol and tobacco where both drugs were predictive of current alcohol use in a college aged sample. Further, marijuana use has been shown to increase a sense of “liking” among non-smokers whereas alcohol has no effect on the subjective experiences of cigarettes. Lastly, greater rates of alcohol dependence and illicit drug use have been observed among high marijuana users as defined by greater rates of sensitivity to positive and negative subjective experiences. Though additional studies are needed, these cross-drug results indicate that how a person responds to a drug is predictive of how they will respond to other drugs. In this report we detail findings from a study of subjective experiences to alcohol, tobacco, and marijuana in a sample of young adults participating in the Colorado Center for Antisocial Drug Dependence. Subjective experiences were collected from both clinical and community participants using a questionnaire developed by Lyons et al.. Our analyses were designed to address three questions. First, how do positive and negative subjective experiences across alcohol, tobacco, and marijuana compare? Second, to what extent do subjective experiences to alcohol,tobacco, and marijuana overlap? Lastly, to what degree do subjective experiences to one drug associate with more problematic use behaviors for a different drug?Participants were drawn from the Colorado Center on Antisocial Drug Dependence [CADD] and consisted of 3853 participants between the ages of 11 and 30 years old and included both community and clinical participants. Our community-based sample was drawn from those participating in the Colorado Twin Registry , Colorado Adoption Project , with clinical controls drawn from the Colorado Adolescent Substance Abuse Family Study. Our clinical sample was drawn from adolescents in treatment for substance abuse and delinquency as a part of the ASA study. Additional clinical participants were drawn from an adjudicated sample from the Denver metropolitan area. Siblings of the clinical subjects were also included. All participants in the current study met one or more of the following criteria: they had consumed at least six drinks in their lifetime, had used tobacco daily for at least one month, or had used marijuana six or more time in their lifetime.Patterns of alcohol, tobacco and marijuana use, abuse and dependence symptomatology were collected using the Composite International Diagnostic Interview-Substance Abuse Module. Abuse and dependence status as defined by the Diagnostic and Statistical Manual of Mental Disorders was determined using scoring algorithms based on whole life substance related problems. Retrospective subjective experiences were collected using a 23- item questionnaire developed by Lyons et al.. The original Lyons questionnaire was comprised of 23 items. As discussed in Zeiger et al. , due to the CADD interview length the original Lyons questionnaire was shortened after wave 1; a factor analysis was conducted on the Lyons questionnaire and 10 items with lower or mixed loadings were dropped. Subsequently, most subjects received the shortened 13-item questionnaire, thus these analyses were conducted on the 13-item response set from all subjects.