2013 literature review said: "unfortunately, methodological limitations in many of the reviewed studies, including selection bias, small sample size, limited generalizability, and lack of adjustment for tobacco smoking, may limit the ability to attribute cancer risk solely to marijuana use." reviewing studies adjusted for age and tobacco use, they said there was a risk of lung cancer even after adjusting for tobacco use, but that the period of time over which the risk increases is uncertain. a 2013 review which specifically examined the effects of cannabis on the lung concluded "indings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use, although evidence is mixed concerning possible carcinogenic risks of heavy, long-term use." in 2013 the international lung cancer consortium found no significant additional lung cancer risk in tobacco users who also smoked cannabis. nor did they find an increased risk in cannabis smokers who did not use tobacco. they concluded that "ur pooled results showed no significant association between the intensity, duration, or cumulative consumption of cannabis smoke and the risk of lung cancer overall or in never smokers." they cautioned that "ur results cannot preclude the possibility that cannabis may exhibit an association with lung cancer risk at extremely high dosage." the same authors supported further study, and called attention to evolving means of cannabis consumption: "specifically, respiratory risks may differ with the use of water pipes and vaporizers or with consuming oral preparations." cannabis smoke contains thousands of organic and inorganic chemicals, including many of the same carcinogens as tobacco smoke. a 2012 special report by the british lung foundation concluded that cannabis smoking was linked to many adverse effects, including bronchitis and lung cancer. they identified cannabis smoke as a carcinogen and also said awareness of the danger was low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. they said there was an increased risk from each cannabis cigarette due to drawing in large puffs of smoke and holding them. cannabis smoke has been listed on the california proposition 65 warning list as a carcinogen since 2009, but leaves and pure thc are not. head and neck a 2015 review found no association between head and neck cancer and lifetime cannabis smoking. respiratory effects cannabis sativa from vienna dioscurides, 512 ad a 2013 literature review by gordon and colleagues concluded that inhaled cannabis is associated with lung disease, although tashkin's 2013 review has found "no clear link to chronic obstructive pulmonary disease". smoking cannabis has been linked to adverse respiratory effects including: chronic coughing, wheezing, sputum production, and acute bronchitis. it has been suggested that the common practice of inhaling cannabis smoke deeply and holding breath could lead to pneumothorax. in a few case reports involving immunocompromised patients, pulmonary infections such as aspergillosis have been attributed to smoking cannabis contaminated with fungi. the transmission of tuberculosis has been linked to cannabis inhalation techniques, such as sharing water pipes and 'hotboxing'. of the various methods of cannabis consumption, smoking is considered the most harmful; the inhalation of smoke from organic materials can cause various health problems (e.g., coughing and sputum). isoprenes help to modulate and slow down reaction rates, contributing to the significantly differing qualities of partial combustion products from various sources. reproductive and endocrine effects main article: cannabis and male fertilty male cannabis use has been associated with reduced fertility and decreased sperm counts. initial epigenetic studies have shown that male cannabis use cause widespread dna methylation changes in sperm, resulting in lower rates of fertilization and higher rates of miscarriage. sperm dna methylation alterations from cannabis extract exposure are evident in the offspring of rats. this is important as prenatal cannabis exposure has been associated with neuropsychiatric disorders, and rates of autism have increased in the u.s., particularly in states where cannabis is legal. main article: cannabis in pregnancy a study released by the national academies of sciences, engineering, and medicine cited significant evidence for a statistical link between mothers who smoke cannabis during pregnancy and lower birth weights of their babies. cannabis consumption in pregnancy is associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring. although the majority of research has concentrated on the adverse effects of alcohol, there is now evidence that prenatal exposure to cannabis has serious effects on the developing brain and is associated with "deficits in language, attention, areas of cognitive performance, and delinquent behavior in adolescence". a report prepared for the australian national council on drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy as it may interact with the endocannabinoid system. mortality no fatal overdoses associated with cannabis use have ever been reported. due to the small number of studies that have been conducted, the evidence is insufficient to show a long-term elevated risk of mortality from any cause. motor vehicle accidents, suicide, and possible respiratory and brain cancers are all of interest to many researchers, but no studies have been able to show a consistent increase in mortality from these causes.