The combustion of this vegetable material into smoke and its inhalation into the lungs is inherently unhealthy. The extent to which an individual can make an informed decision to assume the risks of smoke inhalation can only be gauged by an assessment of the risks and dependence liability associated with the unique chemicals in the plant material. Considerable research has been done on the effects of marijuana smoke on the lungs by Donald Tashkin of UCLA and his colleagues.
A 1987 paper explains the research dilemma.
“Evidence regarding the potential long-term pulmonary consequences of regular marijuana smoking is mixed. Several studies conducted during the past decade on whole animals and isolated cell systems exposed to marijuana smoke, as well as some clinical observations, suggest that marijuana can be harmful to the lung. Conversely, human studies carried out abroad have failed to find any evidence of respiratory dysfunction or disease in long term heavy users of marijuana.”(5)
This study reviewed the history of heavy marijuana smoking on self-reported histories of symptoms of respiratory and pulmonary disease. Tashkin’s findings in this review serve as a baseline for a great deal of his subsequent research; this review established marijuana and tobacco smokers had similar symptoms of respiratory problems.
“A significantly larger proportion of smokers of marijuana and/or tobacco than nonsmokers reported chronic cough, chronic sputum production, more than 1 episode of acute lower respiratory tract illness within the past 3 years (increased cough and sputum lasting more than 3 wk), and wheezing. No significant differences were found when prevalence of these respiratory symptoms was compared across the 3 smoking groups: smokers of marijuana alone, tobacco alone, and marijuana plus tobacco. Breathlessness was reported by relatively few subjects and was similar in frequency across the 4 subject groups, with 1 exception: tobacco smokers reported a higher prevalence of shortness of breath than did marijuana smokers.”(6)
The author’s basic hypothesis is that marijuana smoke, like tobacco smoke, is harmful to the lungs, and that exposure of the lungs to both marijuana and tobacco smoke is even worse. Their findings in this and subsequent studies provide no reason to reject this hypothesis. The public wants to know if marijuana smoking is more or less dangerous for the lungs than tobacco smoking. If one were to insist on a simple answer, that answer would be this: any smoke is damaging to the lungs, and continued exposure to smoke will likely cause lung cancer. However if the public insists on using tobacco smoke as a reference, Tashkin’s research demonstrates that describing marijuana smoke in reference to tobacco smoke is complicated. On a simple numerical scale, in some areas marijuana produces higher indices of risk than tobacco, and in other areas, a lower indication of risk. The conclusion of this 1987 study is as follows.
“We conclude that habitual, heavy marijuana smoking, irrespective of concomitant tobacco smoking, leads to symptoms of chronic bronchitis and an increased frequency of acute bronchitic episodes. In addition, heavy, habitual smoking of marijuana, whether alone or with tobacco, has an adverse effect on large airway function, but marijuana use alone, unlike regular tobacco smoking, has no demonstrable impact on small airways function or on diffusing capacity. The combination of heavy, habitual marijuana and regular tobacco smoking does not appear to worsen chronic respiratory symptoms or lung function abnormalities associated with smoking either substance alone. The implications of these findings with respect to the subsequent development of clinically significant chronic air-flow obstruction in continuing heavy smokers of marijuana is as yet unclear.”(7) (emphasis added)
Marijuana smokers smoke less material by weight per day than tobacco smokers, but they inhale the smoke deeper into their lungs and retain it longer. In a 1988 paper, Tashkin and his colleagues report on their attempts to establish that marijuana smoking delivers a greater quantity of smoke particulates and noxious gases to the lungs than tobacco smoke.
“[M]arijuana smoking resulted in a tar burden to the respiratory tract that was 3.5 to 4.5 times greater than that produced by tobacco smoking in the same subjects. Furthermore, smoking a single marijuana cigarette caused a fourfold greater increment in carboxyhemoglobin saturation than did smoking a single tobacco cigarette.”(8)
“In view of the many similarities in the smoke contents of marijuana and tobacco, it has been argued that habitually smoking a few marijuana cigarettes a day may have a proportionately less harmful long-term effect on the lungs than regularly smoking several times more tobacco cigarettes. This argument assumes that the number of cigarettes smoked is directly proportional to the dose of smoke contents inhaled; however this assumption ignores the ways in which the characteristics of smoking may influence the delivery of the combustion products of cigarettes.”(9)
One reason the authors provide to explain the delivery of greater tar to the lungs is that unlike tobacco cigarettes, marijuana cigarettes do not have filters. Also, they report that the increased carboxy hemoglobin levels are a result of the manner of smoking rather than the carbon monoxide content of the substances. This is very interesting in a public health context, because these factors can be addressed by changes in smoking techniques. Other factors that contribute to the differences in the tar and gas content is the density of the cigarettes. Tobacco cigarettes are tightly packed, providing more filtration. Marijuana cigarettes are comparatively loosely packed, and provide more complete combustion of the smoking material.
In a 1990 review article, Tashkin places these recent findings in perspective.
“It is also noteworthy that most tobacco cigarettes currently in use are filter-tipped and have a relatively low tar content, but marijuana cigarettes do not contain filters and generate about twice as much tar as tobacco per unit of weight, assuming a similar smoking profile. Furthermore, the techniques for smoking marijuana and tobacco differ substantially: on the average, with marijuana the inhalation, or “puff,” volume is about two-thirds larger, the depth of smoke inhalation about 40% greater, and breath holding about four times longer than those characteristics of tobacco smoking. These differences in filtration and smoking technique can result in about a fourfold greater amount of tar delivered to and retained in the lungs from the smoking of marijuana than from a comparable amount of tobacco, thus potentially amplifying the harmful effects of marijuana on the lungs.”(10)
The exposure of the lungs to harmful particulates represents one of two possible health threats provided by marijuana use. The other possible threat is whether or not marijuana smoke affects the lung’s ability to protect itself from harmful bacteria and clean itself of the harmful particulates produced by the smoke.
The results of various studies
“imply that marijuana smoking, like tobacco smoking, impairs the lungs’ defense against microbial invasion, thereby increasing the tendency to respiratory tract infection.”(11)
A 1991 study by this team addressed this second possible health problem. Here is an explanation of the function of alveolar macrophages.
“Alveolar macrophages (AM) are the principle defensive cells of the lung against inhaled particulate matter and have a primary role in the inflammatory responses of the host lung. Therefore, increased numbers of AM in the lungs of cigarette smokers would be anticipated and, in fact, have been observed in the lungs of humans habitually exposed to the irritating fumes and particulates contained in the smoke of tobacco and/or marijuana cigarettes. Because AM are constantly being lost from the lung, their continued replacement would be important in maintaining the health and integrity of the host lung.”(12)
This results of this study is that marijuana smoke stimulated macrophages to action, but not as aggressively as tobacco smoke. Many substances stimulate macrophage production, macrophage cell division is a normal physiological response to foreign particles.
“Overall, the total number of bronchoalveolar lavage (BAL) macrophages that were . . .labeled from either tobacco or marijuana smokers was significantly greater than that obtained from nonsmokers. . .the nonsmoking group had the least number of . . .labeled macrophages (1.01) and the marijuana smokers had the next lowest number of dividing macrophages (2.90). The subjects who smoked tobacco had a nearly 19-fold greater number of . . .labeled macrophages (17.9) compared to non-smokers, and the subjects who smoked both marijuana and tobacco had the second highest number of labeled macrophages (10.5), with a 10-fold increase.”(13) (numbers in parenthesis are x 10-3)
These results illustrate the complexity of arguing that marijuana smoke is more harmful than tobacco smoke. It may even be the case in this area that marijuana smoke mitigates against some of the damage of tobacco smoke. This study contradicted an earlier study by the same team that showed a worse effect of combined marijuana and tobacco smoking on alveolar macrophages.
“Interestingly, it appears that the substance(s) in marijuana smoke may be less stimulatory than the substance(s) in tobacco smoke, and, in fact, our data suggest that marijuana smoke may even inhibit tobacco induced proliferation. The reason for this phenomenon is unclear . . .[and] is based on only six individuals in the combined tobacco- and marijuana-smoking group and may be different with a larger sample.”(14)
The same year Tashkin worked on a study on Pulmonary Alveolar Macrophages (PAM), considered one of the primary defenses the lung has to infection.
“We conclude that marijuana smoking does not alter phagocytic behavior or the respiratory burst of human PAM, but marijuana smoking does decrease the ability of human PAM to destroy ingested Candida albicanus. These findings contrast with the effects of tobacco smoking, which not only decreases the fungicidal activity of human PAM but also increases their respiratory burst.”(15)
However, the authors explain that Candida albicanus (a yeast) is a relatively large organism, and a decreased ability to destroy it may not indicate a decreased ability to destroy bacteria.
“An appropriate question to ask is whether fungistatic or fungicidal activity by PAM bears any relationship to the intracellular killing of bacteria. As opposed to fungi pathogens, bacteria are more likely to be encountered during lung infections of MS or TS. Human PAM from healthy volunteers were recently compared with respect to their ability to ingest and kill Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicanus. (16) Although bacterial killing was complete in 2 [hours], 4-6 [hours]. were needed for PAM to kill a stationary phase, agerminative strain of C. albicanus for PAM.”(17)
Returning to the issue of particulate exposure, Tashkin has also hypothesized in 1991 that “prolonged breathholding characteristics of marijuana smoking enhances THC absorption and possibly the associated rise in heart rate and the level of intoxication.”(18) If long breathholding determines intoxication efficiency, “then it may be difficult to modify this topographic variable in an attempt to reduce the cardiorespiratory hazards of marijuana smoking.”(19) These hypotheses were based on the findings of this study that the longer breathholding of marijuana smokers contributed to the greater exposure to tar and noxious gas quantified in earlier studies. (20)
Tashkin and his research team have also characterized the differences in the delivery of tar, carbon dioxide, and D9-THC from the first and second halves of a marijuana cigarette:
“An important clinical implication of the findings from this study is that smoking fewer marijuana cigarettes down to a shorter butt length to deliver more D9-THC and achieve a greater “high” will also result in the delivery of more tar and carbon monoxide to the smoker’s respiratory tract that the consumption of a comparable amount of marijuana from more cigarettes smoked to a longer butt length. Because of the respiratory irritant and carcinogenic effects of some of the components of marijuana-derived tar, and the adverse effects of inhaled carbon monoxide on oxygen transfer in the lung, transport in the blood and delivery to the tissues, the common practice of smoking marijuana down to a short butt length may augment its potentially harmful effects on cardiorespiratory health.”(21)
“Another of Tashkin’s teams has studied the impact of marijuana smoking on lung macrophage oxidant release, a mechanism that contributes to emphysema. In this study important differences were found between marijuana smoke and tobacco smoke.
“In summary, pulmonary alveolar macrophages recovered from marijuana-only smokers have a spontaneous and stimulated release of oxidants that is equivalent to nonsmoker’s macrophages. This finding coincides with the absences of small-airway dysfunction or diffusion abnormality in both groups of subjects. In contrast, pulmonary alveolar macrophages from tobacco smokers generate more oxidants under basal and stimulated conditions, and tobacco smokers do have demonstrable evidence of small-airways disease.”(22)
Also in 1991, a team led by Gary Huber reported on “Marijuana and Tobacco Smoke Gas-Phase Cytotoxins.”(23) They note that PAM is depressed in vitro, but the results are not replicated in vivo (the same clash of theory and result Tashkin has clarified above.) The primary cytotoxins appear to be water soluble. Furthermore, stale smoke rapidly loses cytotoxic properties. The authors hypothesized that proximal airwaves remove the water-soluble cytotoxic constituents from the gas phase of the smoke. They created a model system that successfully tested this hypothesis.
“These results may explain to a significant degree, the discrepancies that exist in literature between in vitro and in vivo cytotoxicity of marijuana and tobacco smoke. These results also raise the consideration that the potentially injurious effects of water-soluble, gas-phase constituents on alveolar macrophages on lung explants may not be relevant to the health and integrity or the lung of the intact smoker in everyday life.”(24)
Certainly other aspects of marijuana or tobacco smoke may have an adverse effect on macrophages.
“Although the gas-phase cytotoxins have received much of the earlier investigative attention; the data presented herein, however, would appear to render them less suitable culprits.”(25)
In 1992 a team of Tashkin’s explored the effect of THC potency on respiratory functions.
“The present study was carried out to investigate the effects of escalating doses of THC administered in smoked marijuana on the ventilatory and mouth occlusion pressure responses to both hypercapnia [high levels of CO2] and hypoxia [low levels of O2] and on resting minute ventilation and metabolic rate in young, healthy experienced male users of marijuana.”(26)
The study found no effect of THC on ventilation, oxygen consumption, carbon dioxide production, or metabolic rate. The only effects of THC noted were that:
“The habitual marijuana smokers participating in this study exhibited a significant increase in heart rate, subjective intoxication (high), and decrease in airway resistance after smoking the active preparations of marijuana, but not placebo marijuana. These findings are consistent with the known cardioaccelerator, psychotropic, and bronchodilator effects of THC.”(27)
This study used marijuana cigarettes from the National Institute on Drug Abuse of 0, 1.55%, and 2.65% THC. While the authors can not account for the possible effect of tolerance to marijuana, they do argue that the potencies used in their study are relevant to common use of the drug.
“These doses of THC are comparable with those delivered from the recreational smoking of “street” marijuana (500 mg marijuana containing 1 to 6% THC) or the oral ingestion of U.S. Food and Drug Administration-approved synthetic marijuana (7.5 to 22.5 mg) for control of nausea and vomiting due to cancer chemotherapeutic agents. Our results therefore suggest that THC in doses commonly used either recreationally or medicinally neither stimulates nor depresses central or peripheral chemoreceptor-mediated ventilatory drive in habitual users of marijuana.”(28)
In 1993 Tashkin and colleagues studied the effect of marijuana smoke on airway hyperresponsiveness (AHR), a risk factor for development of or a marker of airway injury in individuals susceptible to chronic airflow obstruction. There results:
“In summary, in a convenience sample of 542 nonsmokers and habitual smokers of marijuana, cocaine, and/or tobacco, cocaine had no demonstrable influence on nonspecific AHR, whereas marijuana appeared to have an inconsistent effect and heavy tobacco smoking a modest but statistically significant positive influence in both men and women, independent of the effect of lung function on AHR. Neither marijuana nor cocaine appeared to potentiate the effect on AHR of other smoked substances, including tobacco.”(29)
The fact that several studies indicate that marijuana smoke is not as harmful as tobacco smoke does not change the validity of Tashkin’s original assertion that marijuana smoke is harmful to the human lungs, and that this harm is compounded in individuals who also smoke tobacco.
In a recent editorial, Tashkin argued that:
“Several lines of evidence suggest that marijuana smoking is also associated with an increased risk for the development of respiratory tract malignancy.”(30)
Tashkin explicitly notes that advocates of the legalization of marijuana are wrong when they contend that no evidence exists linking marijuana smoking to serious health effects. Some diseases take a long time to develop, but other respiratory problems do not.
“One might conclude from the dearth of information concerning marijuana-related morbidity [indicating acute respiratory illness such as bronchitis and pneumonia] either that such health effects are too infrequent to be measured or that such effects are occurring at greater than expected frequency but have not been documented because of the lack of a systematic effort to “capture” these events.”(31)
One additional complication created by marijuana’s illegality is that doctors (32) and health care professionals do not ask patients about marijuana use, or patients are reluctant to disclose such use. (33) While the research of Tashkin and others suggests that the harmful effects of marijuana could be minimized through introducing filtration and the idea honest disclosure and discussion with health care professionals to marijuana smokers. This introduces a critical issue which will be discussed in section 6, that is, what public policies will best reduce the harm associated with marijuana use.
Otherwise, the research of Tashkin and others on the effect of marijuana smoke on the lung contributes a great deal to understanding and characterizing the pharmacology of marijuana and its smoke. Marijuana smoke is the primary vehicle that introduces the active ingredients in marijuana into the human body; smoking is the primary route of administration. It is important in understanding the pharmacology of marijuana to distinguish between the effects of the smoke and the effects of the active ingredients, cannabinoids. Furthermore, understanding the absorption of the active ingredients from the smoke is crucial to understanding the effects of the constituent chemicals, the cannabinoids, on the rest of the body.