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.
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