Airway inflammation and emphysema are more common in marijuana smokers than cigarette smokers, according to a study published in Radiology. Researchers said the difference may be due to the way that marijuana is smoked and the fact that marijuana smoke enters the lungs unfiltered.
Marijuana is one of the most widely used psychoactive substances in the world and the most-commonly smoked substance after tobacco. Its use has increased in recent years amid legalization of recreational marijuana in Canada and many states in the U.S. The growing use has created an urgent need for information on marijuana’s effects on the lungs, something that is currently lacking.
“We know what cigarettes do to the lungs,” said study author Giselle Revah, MD, a cardiothoracic radiologist and assistant professor at the University of Ottawa in Ottawa, Canada. “There are well researched and established findings of cigarette smoking on the lungs. Marijuana we know very little about.”
Pulmonary emphysema in (A, B) marijuana and (C, D) tobacco smokers. (A) Axial and (B) coronal CT images in a 44-year-old male marijuana smoker show paraseptal emphysema (arrowheads) in bilateral upper lobes. (C) Axial and (D) coronal CT images in a 66-year-old female tobacco smoker with centrilobular emphysema represented by areas of centrilobular lucency (arrowheads). (Murtha, et al.)
https://doi.org/10.1148/radiol.212611 © RSNA 2022
Higher Incidence May Be Partially Related to Lack of Filtering
Three-quarters of the marijuana smokers had emphysema, a lung disease that causes difficulty with breathing, compared with 67% of the tobacco-only smokers. Only 5% of the non-smokers had emphysema. Paraseptal emphysema, which damages the tiny ducts that connect to the air sacs in the lungs, was the predominant emphysema subtype in marijuana smokers compared to the tobacco-only group.
Airway inflammation was also more common in marijuana smokers than non-smokers and tobacco-only smokers, as was gynecomastia, enlarged male breast tissue due to a hormone imbalance. Gynecomastia was found in 38% of the marijuana smokers, compared with 11% of the tobacco-only smokers and 16% of the controls.
The researchers found similar results among age-matched subgroups, where the rates of emphysema and airway inflammation were again higher in the marijuana smokers than the tobacco-only smokers.
There was no difference in coronary artery calcification between age-matched marijuana and tobacco-only groups.
Dr. Revah said the results were surprising, especially considering that the patients in the tobacco-only group had an extensive smoking history.
“The fact that our marijuana smokers—some of whom also smoked tobacco—had additional findings of airway inflammation/chronic bronchitis suggests that marijuana has additional synergistic effects on the lungs above tobacco,” she said. “In addition, our results were still significant when we compared the non-age-matched groups, including younger patients who smoked marijuana and who presumably had less lifetime exposure to cigarette smoke.”
The reasons for the differences between the two groups is likely due to several factors. Marijuana is smoked unfiltered, Dr. Revah noted, while tobacco cigarettes are usually filtered. This results in more particulates reaching the airways from smoking marijuana.
In addition, marijuana is inhaled with a longer breath hold and puff volume than tobacco smoke.
“It has been suggested that smoking a marijuana joint deposits four times more particulates in the lung than an average tobacco cigarette,” Dr. Revah said. “These particulates are likely airway irritants.”
The higher incidence of emphysema may also be due to the way that marijuana is smoked. Full inhalation with a sustained Valsalva maneuver, an attempt at exhalation against a closed airway, may lead to trauma and peripheral airspace changes.
More research is needed, Dr. Revah said, with larger groups of people and more data on how much and how often people are smoking. Future research could also look at the impact of different inhalation techniques, such as through a bong, a joint or a pipe.
“It would be interesting to see if the inhalation method makes a difference,” Dr. Revah said.
For More Information
This study has identified the nature and magnitude of the effects of cannabis smoking on respiratory structure, function and symptoms. There was a dose-response relationship of cannabis smoking with airflow obstruction, impaired large airways function and hyperinflation. For measures of airflow obstruction, one joint of cannabis had a similar effect to that of 2.5–5 tobacco cigarettes. In contrast, cannabis smoking was uncommonly associated with macroscopic emphysema, which was present almost entirely in the tobacco smoking groups.
There are several methodological issues relevant to the interpretation of the results. The first was the inability to identify a sufficient number of cannabis smokers from the random population sample. Despite starting with an initial postal questionnaire of 3500 adults, only 19 met the criteria for smoking at least 5 joint-years with no other illegal drug use and no chronic respiratory disorder such as asthma in childhood.
It was apparent that it was not possible to use a random population sample for a study of this nature and, as previously,6 a convenience sample was used. While this approach incurred the risk of selection bias by preferentially attracting people concerned about their respiratory health, this applies equally to all subject groups. We applied strict exclusion criteria for other illegal drug use due to their potential respiratory effects.18
This meant that many potential participants were ineligible, particularly the heaviest cannabis users who were more likely to have used other drugs. As a result, these criteria preferentially excluded such heavy users, suggesting that the effects observed may represent a conservative estimate.
The requirement for tobacco smokers to have a history of at least 1 pack-year was based on the data that tobacco smokers need to smoke in excess of this amount to develop abnormal lung function.19 The requirement for cannabis smokers to have a history of at least 5 joint-years was based on the data that one cannabis joint results in three to five times higher levels of carbon monoxide and tar deposition, respectively,20 thereby achieving an a priori equivalence between the lower limit of cannabis and tobacco smoking levels. It also ensured that experimental users who did not smoke cannabis habitually were excluded.
Cannabis remains illegal in New Zealand although participants were willing to volunteer under the assurance of strict confidentiality. All subjects in the groups with no cannabis or no tobacco use had negative samples for THC or cotinine, demonstrating the honest reporting of the subjects in this regard. A further problem is that cannabis use is often difficult to quantify precisely due to smokers sharing joints, different inhalation techniques and different ways of smoking cannabis including joints, pipes and bongs.
In order to standardise use, subjects were asked to estimate the “joint equivalent” used by these methods to enable cannabis use to be expressed as joint-years of use. In our community the median amount of cannabis in a joint was 0.37 g, although there was considerable variability in the amount of cannabis in joints prepared by different subjects. By comparison, the average amount of tobacco in a commercial cigarette of standard length is 1 g.
Although the calculation of joint-years was based on subjects’ self-reports, there is evidence that cannabis use is more accurately reported than other drugs21 and self-reports have been shown to correlate well with urinary THC levels.22 Influential factors in increasing the validity of self-reported drug use include privacy, anonymity and credibility of the study. Every effort was made to create a relaxed and confidential environment to increase the accuracy of reporting, and all subjects gave informed consent.
The practice of combining cannabis and tobacco within a joint is relatively uncommon in New Zealand.9 In our sample of cannabis only smokers, 12% had combined their cannabis with tobacco on some occasions although it was not routine practice in any of these subjects. As a result, the small quantities of tobacco used by cannabis only smokers were unlikely to significantly affect the results.
As this study was exploratory, caution must be used in interpreting the presence or absence of associations. In particular, we analysed a number of measures of pulmonary structure, function and symptoms without any adjustment for the inflation of type I error that may ensue. For some variables where we failed to find associations, this may reflect a relative lack of statistical power for any individual analysis.
The most important finding was that one joint of cannabis was similar to 2.5–5 tobacco cigarettes in terms of causing airflow obstruction. This dose equivalence is consistent with the reported 3–5-fold greater levels of carboxyhaemoglobin and tar inhaled when smoking a cannabis joint compared with a tobacco cigarette of the same size.20 This pattern is likely to relate to the different characteristics of the cannabis joint and the way in which it is smoked. Cannabis is usually smoked without a filter23 and to a shorter butt length,24 and the smoke is a higher temperature. Furthermore, cannabis smokers inhale more deeply,20 hold their breath for longer20 and perform the Valsalva manoeuvre at maximal breath hold.25
Our findings have extended previous observations that the principal physiological impairment with long-term cannabis smoking is on large airway function6 by demonstrating a dose-response relationship for sGaw. Similarly, a dose-response relationship was observed with measures of airflow obstruction and hyperinflation which are a consequence of the large airways impairment. Previous research has shown that this large airways impairment is probably due to the inflammation and oedema that occurs in the tracheobronchial mucosa of cannabis smokers,26 as well as mucus hypersecretion.27 It is well recognised that an increase in airway resistance leads to hyperinflation.28 These effects are also likely to contribute to the increased prevalence of symptoms of wheezing, cough and sputum production associated with cannabis smoking, resulting in the twofold increased prevalence of chronic bronchitis. These findings are unlikely to be due to pre-existing disease as subjects were excluded if they had chronic lung disease diagnosed by a doctor before the age of 16 years.
Another novel finding was the effect of cannabis smoking—but not tobacco smoking—on lung density, which has been proposed as a marker of emphysema.29 30 However, we and others have observed that decreased lung density may not be specific to emphysema10 31–34 and correlates more closely with markers of airflow obstruction and hyperinflation.11 As a result, we have interpreted our lung density findings as being predominantly due to the effect of cannabis smoking on airflow obstruction and hyperinflation rather than causing emphysema. This interpretation is consistent with our finding that macroscopic emphysema was present almost entirely in the tobacco smoking groups. Furthermore, tobacco—but not cannabis use—was associated with a significant reduction in TLCO, the most specific lung function measure of emphysema in subjects with airflow obstruction.35 Thus, while a case series has shown that heavy cannabis smoking may cause macroscopic emphysema at a young age with a characteristic apical paraseptal pattern,8 our findings would suggest that this is not a common complication with the amount of cannabis smoked in New Zealand. Importantly, it suggests that cannabis does not cause emphysema when smoked in sufficient quantities to cause airflow obstruction, hyperinflation and chronic bronchitis.
Finally, we observed that, whereas cannabis smokers used similar amounts of cannabis whether or not they were tobacco smokers as well, tobacco smokers who used cannabis smoked less tobacco than those who smoked tobacco alone. Similarly, a study from the USA reported that, whereas cannabis users more often smoked tobacco, they were less likely than never cannabis users to be heavy long-term users of tobacco, as defined by a level of >30 pack-years.36 However, this lesser amount of tobacco in combined users did not result in reduced adverse respiratory effects compared with tobacco only smokers because of the additional effects of the cannabis use.
In conclusion, these findings suggest that the predominant effects of cannabis on pulmonary structure, function and symptoms are in causing the symptoms of wheezing, cough, chest tightness and sputum production, large airways obstruction and hyperinflation, but not emphysema. The dose equivalence of 1:2.5–5 between cannabis joints and tobacco cigarettes in causing airflow obstruction is of major public health significance.
Further data are given in figs E1 and E2 in the online supplement available at http://thorax.bmj.com/ supplemental.