A critical yet unresolved public health issue is whether cannabis smoking can increase the risk of lung cancer. Since marijuana smoke contains many of the same chemicals as tobacco smoke in addition to 60 cannabinoid compounds  it is plausible to raise the hypothesis that it may be carcinogenic. Several lines of evidence justify this concern: marijuana and tobacco smoke contain many of the same potent carcinogens and the condensate from marijuana smoke is even more toxic than that from tobacco smoke . Furthermore, marijuana smoking results in greater delivery of tar to the lungs because it is associated with deeper inhalation and longer breath-holding times, and marijuana cigarettes are unfiltered [7, 22]. In addition, studies looking at bronchial biopsies have demonstrated that marijuana users show inflammation of the airways, but also histological and molecular changes indicative of precancerous changes, similar to those found in tobacco smokers [12, 13, 33]. Marijuana is also widely acknowledged to stimulate the mitogen-activated kinase (MAPK) pathway, which is a major stimulant for developmental and malignant cell growth. Exposure to cannabis was associated with an increased incidence of acute myelomonocytic leukemia (AMML) in the pediatric population after in-utero exposure to cannabis .
Even though there is molecular, cellular, and histopathological evidence for a potential carcinogenic effect of marijuana, the epidemiologic studies yielded inconsistent results.
In a retrospective cohort study, 64,855 examinees aged 15–49 years enrolled in the Kaiser Permanente health maintenance organization in northern California were followed for a mean length of 8.6 years . Former and current users of marijuana failed to show an increased incidence of cancers at all sites after adjusting for tobacco use. Marijuana use was not associated with common tobacco-related cancers or with cancers of the lung, colorectal, melanoma, breast, prostate, and cervix. Among non-smokers of tobacco cigarettes, ever having used marijuana was associated with an increased risk of prostate cancer and a marginally increased risk of cervical cancer. However, the study was limited by the relatively young age of the subjects (average age was 48 years) and a follow-up period that was not long enough to allow for the development of cancer.
Also, a well designed population-based case–control study in Washington state failed to find any increased risk for the development of upper airway cancers in association with marijuana use (RR 0.9; 99 % CI 0.6–1.3) or any trend towards dose response in relation to the frequency and duration of use .
Another large population-based case–control study of 1,212 cancer cases of the upper aero-digestive tract in Los Angeles and 1,040 cancer-free controls also showed no positive association when adjusting for several confounders including nicotine use .
However, a case–control study conducted by Aldington et al. in New Zealand  included 79 cases of lung cancer and 324 controls. Subjects and controls were <55 years old. While marijuana smoking (lifetime use of more than 20 joints) was not associated with a significant increased risk of lung cancer, the subjects in the highest tertile of use (>10.5 joints/year with one joint/year equivalent to smoking 365 joints or filled pipes) had the highest risk RR 5.7 (95 % CI 1.5-21.6) after adjustment for confounders. Using logistic regression, the risk of lung cancer was estimated to increase by 8 % ( 95 % CI 2–15 %) for each joint/year of cannabis smoked after adjustment for confounding variables such as cigarette smoking, occupation, family history, etc. In this study, the association with lung cancer was found only in the third tertile, which contained a small number of patients (14 patients) and there was no dose-dependent relationship noted.
Furthermore, Callaghan et al. , in a population-based cohort study, examined 49,321 men aged 18–20 years old (military conscripts) in Sweden recruited between 1969–1979. The participants were tracked until 2009 (40 years) for incident lung cancer outcome using several Swedish patient registries. The study reported a twofold risk (hazard ratio 2.12, 95 % CI 1.08-4.14) of developing lung cancer over the 40-year follow-up period after statistical adjustment for baseline tobacco and alcohol use, co-existing respiratory conditions, and socio-economical status.
Because case control studies yielded mixed results, several authors presented pooled analyses of smaller studies. Berthiller et al.  presented three case–control studies conducted in Tunisia, Morocco, and Algeria, three areas of cannabis consumption and production. The study included 430 cases (all men) and 778 controls. All cannabis smokers were tobacco users. The study found that there was a 2.4-fold increase in the risk of lung cancer among ever cannabis smokers compared to never users after adjustment for age, tobacco smoking, and occupational exposure. The authors acknowledge the potential of residual confounding by tobacco smoking (tobacco and marijuana are habitually smoked together in that part of the world).
In Tunisia, in a hospital-based case–control study, the risk of lung cancer in prior cannabis users was studied in 149 new lung cancer cases and 188 controls . The odds ratio for the past users of cannabis and lung cancer was 4.1 (95 % CI: 1.9-9.0) after adjustment for age, tobacco use, and occupational exposure. There was no clear dose–response relationship between the risk of lung cancer and the intensity or duration of cannabis use. Because in Tunisia many cannabis smokers mix cannabis with tobacco, tobacco may be a major confounder for these results.
Mehra et al.  published a systematic review of the impact of marijuana smoking on the development of premalignant lung changes and lung cancer. 19 studies entered into analysis from 186 initially identified. The authors found an association of marijuana smoking with increased tar exposure, alveolar macrophage tumoricidal dysfunction, increased oxidative stress, and bronchial mucosa histopathologic abnormalities compared to tobacco smokers and nonsmoking controls. The study did not find a significant association between marijuana use and lung cancer after adjusting for tobacco use. The authors raise the question of methodologic deficiencies in the studies included in the analysis that may have accounted for the results.
Zhang et al.  published a study which included 2,159 lung cancer cases and 2,985 controls pooled from six case-controlled studies within the International Lung Cancer Consortium. There was little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers. The authors however, mention that the possibility of potential adverse effects of heavy consumption could not be excluded.
The epidemiological evidence for an association between cannabis and lung cancer is limited and conflicting. Case series have suggested a causative role for cannabis for lung cancer in young adults. The case–control studies published to date have suggested both the presence and absence of an association, but these studies have been limited by the inability to quantify use, confounded by combined cannabis and tobacco or other substance use, or were undertaken in populations where cannabis use may have serious legal consequences resulting in potential reporting bias and poor response rates.
In addition, the interpretation of the epidemiological data is further limited by the design of these studies: case series represent uncontrolled observations from which causality cannot be inferred. Case–control studies, on the other hand, establish associations, but this again does not represent causation. In some of the studies in which a relationship between marijuana smoking and lung cancer was established, the association was weak and there was no dose–response relationship to strengthen the association.
Just as in the tobacco story, the long time lapse between smoking marijuana and the development of serious respiratory complications attenuates the individual’s perception of risk. As inconclusive as the epidemiological studies might be, prudence should warn individuals that marijuana smoking may result in serious short-term and long-term respiratory complications, potentially as drastic as those caused by tobacco smoke.