Q: Can cannabis use cause lung cancer like smoking tobacco does?

Thanks for your question! Cannabis, or marijuana, is the second most widely smoked substance in our society after tobacco in cigarettes. Smoking cigarettes is the number one risk factor for lung cancer, according to the Centers for Disease Control and Prevention (CDC), but the truth is, we don’t really know the risk associated with cannabis use. The increasing legal acceptance of recreational and medical cannabis use makes understanding the health consequences of cannabis an urgent concern. It is important to understand whether cannabis use, or the mode of cannabis use, is associated with lung cancer and other health problems.

The short answer – Cannabis use does not increase risk of lung cancer.

The very quick answer is that there is little evidence to suggest that smoking cannabis causes lung cancer.

A recent meta-analysis—that is, a study of other studies—pooled data from 6 different case-control studies across four different countries (U.S., Canada, U.K, and New Zealand), resulting in the examination of data from 2,159 lung cancer cases and 2,985 controls¹ Zhang, L. R. et al. Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium. Int J Cancer136, 894-903, doi:10.1002/ijc.29036 (2015). https://www.ncbi.nlm.nih.gov/pubmed/24947688. To determine the association between smoking cannabis and developing lung cancer, the authors calculated a pooled odds ratio (OR) and 95% Confidence Interval (CI). That sounds a bit technical, so I will try to explain:

• The OR represents the probability of an event occurring given a particular exposure divided by the probability of the event occurring in the absence of exposure. For us, the event is lung cancer and the exposure is cannabis.
• The 95% CI is the interval of values within which we are 95% sure the actual OR exists. In other words, if, based on our research we measure an OR of 0.76, with a 95% CI of 0.7-0.8, we can be 95% sure that the actual OR is somewhere between 0.7 and 0.8, though it might not be exactly 0.76, which is what we measured in our sample population.
• An OR = 1 indicates that there is an equal chance of getting lung cancer given exposure to cannabis as there is of not getting cancer; in other words, cannabis use does not affect the probability of developing lung cancer. An OR > 1 means that the exposure increases the probability of the event occurring, while an OR < 1 means that exposure decreases the probability of the event occurring.

Zhang et al reported that the overall pooled odds ratio (OR) for habitual versus nonhabitual or never users of cannabis was 0.96, with a 95% CI of 0.66–1.38¹Zhang, L. R. et al. Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium. Int J Cancer136, 894-903, doi:10.1002/ijc.29036 (2015). https://www.ncbi.nlm.nih.gov/pubmed/24947688. In other words, the measured OR was <1, and we can be 95% sure that the actual OR falls somewhere between 0.66 and 1.38. For comparison, the odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was measured at 40.4, with a 95% CI of 21.8-79.6² Stellman, S. D. et al. Smoking and lung cancer risk in American and Japanese men: an international case-control study. Cancer Epidemiol Biomarkers Prev10, 1193-1199 (2001). https://www.ncbi.nlm.nih.gov/pubmed/11700268.

Other epidemiological studies that have examined cancer rates in smokers of cannabis similarly failed to find a significant association between smoking cannabis and cancer³ Huang, Y. H. et al. An epidemiologic review of marijuana and cancer: an update. Cancer Epidemiol Biomarkers Prev24, 15-31, doi:10.1158/1055-9965.EPI-14-1026 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25587109⁴ Sidney, S., Quesenberry, C. P., Jr., Friedman, G. D. & Tekawa, I. S. Marijuana use and cancer incidence (California, United States). Cancer Causes Control8, 722-728 (1997). https://www.ncbi.nlm.nih.gov/pubmed/9328194⁵ de Carvalho, M. F. et al. Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies. Arch Oral Biol60, 1750-1755, doi:10.1016/j.archoralbio.2015.09.009 (2015). https://www.ncbi.nlm.nih.gov/pubmed/26433192. The conclusion we can draw, then, is that there is little evidence to suggest that smoking cannabis increases the risk of developing lung cancer.

Is there a difference between cigarette smoke and cannabis smoke?

Tobacco smoke and cannabis smoke contain some of the same harmful chemicals and carcinogens, including vinyl chlorides, phenol, reactive oxygen species, acetaldehyde, carbon monoxide, hydrogen cyanide, and various polycyclic aromatic hydrocarbons (PAH)⁶ Hoffmann D., B. K. D., Gori G.B., Wynder E.L. . in Recent Advances in Phytochemistry. (ed Runeckles V.C.)  63-81 (Springer, 1975).⁷ Moir, D. et al. A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two machine smoking conditions. Chem Res Toxicol21, 494-502, doi:10.1021/tx700275p (2008). https://www.ncbi.nlm.nih.gov/pubmed/18062674⁸ Owen, K. P., Sutter, M. E. & Albertson, T. E. Marijuana: respiratory tract effects. Clin Rev Allergy Immunol46, 65-81, doi:10.1007/s12016-013-8374-y (2014). https://www.ncbi.nlm.nih.gov/pubmed/23715638⁹ Wu, T. C., Tashkin, D. P., Djahed, B. & Rose, J. E. Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med318, 347-351, doi:10.1056/NEJM198802113180603 (1988). https://www.ncbi.nlm.nih.gov/pubmed/3340105. Some studies have suggested that, compared with tobacco smoking, cannabis smoking may involve inhalation of approximately three times the amount of tar and the retention of one third more of the inhaled tar in the respiratory tract⁹Wu, T. C., Tashkin, D. P., Djahed, B. & Rose, J. E. Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med318, 347-351, doi:10.1056/NEJM198802113180603 (1988). https://www.ncbi.nlm.nih.gov/pubmed/3340105. Furthermore, tar from cannabis smoking has been found to have higher concentrations of benzo(a)pyrene, a carcinogenic PAH, than tobacco tar⁶Hoffmann D., B. K. D., Gori G.B., Wynder E.L. . in Recent Advances in Phytochemistry. (ed Runeckles V.C.)  63-81 (Springer, 1975)..  

Still, the epidemiological evidence suggesting a link between smoking marijuana and different forms of cancer is lacking¹Zhang, L. R. et al. Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium. Int J Cancer136, 894-903, doi:10.1002/ijc.29036 (2015). https://www.ncbi.nlm.nih.gov/pubmed/24947688³Huang, Y. H. et al. An epidemiologic review of marijuana and cancer: an update. Cancer Epidemiol Biomarkers Prev24, 15-31, doi:10.1158/1055-9965.EPI-14-1026 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25587109⁴Sidney, S., Quesenberry, C. P., Jr., Friedman, G. D. & Tekawa, I. S. Marijuana use and cancer incidence (California, United States). Cancer Causes Control8, 722-728 (1997). https://www.ncbi.nlm.nih.gov/pubmed/9328194⁵de Carvalho, M. F. et al. Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies. Arch Oral Biol60, 1750-1755, doi:10.1016/j.archoralbio.2015.09.009 (2015). https://www.ncbi.nlm.nih.gov/pubmed/26433192.

How can this be true? It is important to note that the mode of action of nicotine in cigarette smoke is very different from the mode of action of cannabinoids in cannabis smoke. In other words, the two substances have different pharmacology; they act on different receptors on cells in the body and have different biological consequences.

For one example, a family of proteins in our bodies, called cytochrome P450 enzymes (CYP), are activated by chemicals in cigarette smoke and break down the PAHs found in cigarette smoke, thereby releasing cancer-causing agents into our bodies. PAHs are also found in marijuana smoke, but in this case, the active ingredient in marijuana may suppress CYP enzymes, preventing this cancer-causing process¹⁰ Roth, M. D. et al. Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 by marijuana smoke and delta (9)-tetrahydrocannabinol. Am J Respir Cell Mol Biol24, 339-344, doi:10.1165/ajrcmb.24.3.4252 (2001). https://www.ncbi.nlm.nih.gov/pubmed/11245634.

As another example, it has been shown that nicotine promotes the development of blood vessels that are important for tumor growth¹¹ Heeschen, C. et al. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat Med7, 833-839, doi:10.1038/89961 (2001). https://www.ncbi.nlm.nih.gov/pubmed/11433349. Cannabinoids, on the other hand, have been shown to suppress tumor growth¹² Galve-Roperh, I. et al. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med6, 313-319, doi:10.1038/73171 (2000). https://www.ncbi.nlm.nih.gov/pubmed/10700234.

So, does that mean smoking cannabis isn’t harmful?

What I’ve said so far, however, does not mean that smoking cannabis is completely harmless. Previous studies have shown precancerous abnormalities in the tissue of the respiratory tracts of cannabis smokers¹³ Fligiel, S. E. et al. Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco. Chest112, 319-326, doi:10.1378/chest.112.2.319 (1997). https://journal.chestnet.org/article/S0012-3692(15)52997-8/abstract¹⁴ Gong, H., Jr., Fligiel, S., Tashkin, D. P. & Barbers, R. G. Tracheobronchial changes in habitual, heavy smokers of marijuana with and without tobacco. Am Rev Respir Dis136, 142-149, doi:10.1164/ajrccm/136.1.142 (1987). https://www.ncbi.nlm.nih.gov/pubmed/3496818. Moreover, studies have reported higher rates of chronic cough or sputum, wheezing, and shortness of breath in frequent smokers of marijuana, as well as increased incidence of acute bronchitis¹⁵ Tashkin, D. P. Effects of marijuana smoking on the lung. Ann Am Thorac Soc10, 239-247, doi:10.1513/AnnalsATS.201212-127FR (2013). https://www.ncbi.nlm.nih.gov/pubmed/23802821. So while smoking marijuana does not likely cause cancer, it can cause some injury to the respiratory system. It is possible that other forms of cannabis (edibles, oils, topical creams, etc) consumption could minimize these risks, but the research on this is slim. To illustrate, a search on the database for scientific journal articles, Pubmed, for “edible cannabis” yielded one result. A search for “smoking cannabis,” on the other hand yielded 155 results (on Pubmed, as-of 10/21/2019). And these forms of cannabis consumption may carry their own risks¹⁶ Russell, C., Rueda, S., Room, R., Tyndall, M. & Fischer, B. Routes of administration for cannabis use – basic prevalence and related health outcomes: A scoping review and synthesis. Int J Drug Policy52, 87-96, doi:10.1016/j.drugpo.2017.11.008 (2018). https://www.ncbi.nlm.nih.gov/pubmed/29277082.

What’s the bottom line?

Currently, smoking cannabis does not appear to increase risk of cancer, but may cause some respiratory symptoms. More research is needed to determine whether alternative methods of cannabis consumption can mitigate these risks. As cannabis use becomes more “normal,” rigorous research is needed to evaluate its long-term benefits or consequences on overall health.