:
Alcohol. 2005
Apr;35(3):265-75.
Links
Epidemiologic review of marijuana use and cancer risk.
International Agency for Research on
Cancer, 69008 Lyon, France.
Marijuana is the most commonly used
illegal drug in the United States and is considered by young adults to be the
illicit drug with the least risk. On the other hand, marijuana smoke
contains several of the same carcinogens and co-carcinogens as the tar from
tobacco, raising concerns that smoking of marijuana may be a risk
factor for tobacco-related cancers. We reviewed two cohort studies and 14
case-control studies with assessment of the association of marijuana use and
cancer risk. In the cohort studies, increased risks of lung or colorectal
cancer due to marijuana smoking were not observed, but increased risks of
prostate and cervical cancers among non-tobacco smokers, as well as
adult-onset glioma among tobacco and non-tobacco smokers, were observed. The
14 case-control studies included four studies on head and neck cancers, two
studies on lung cancer, two studies on non-Hodgkin's lymphoma, one study on
anal cancer, one study on penile cancer, and four studies on childhood cancers
with assessment of parental exposures. Zhang and colleagues reported that
marijuana use may increase risk of head and neck cancers in a hospital-based
case-control study in the United States, with dose-response relations for both
frequency and duration of use. However, Rosenblatt and co-workers reported no
association between oral cancer and marijuana use in a population-based
case-control study. An eightfold increase in risk among marijuana users was
observed in a lung cancer study in Tunisia. However, there was no assessment
of the dose response, and marijuana may have been mixed with tobacco. Parental
marijuana use during gestation was associated with increased risks of
childhood leukemia, astrocytoma, and rhabdomyosarcoma, but dose-response
relations were not assessed. In summary, sufficient studies are not available
to adequately evaluate marijuana impact on cancer risk. Several limitations of
previous studies include possible underreporting where marijuana use is
illegal, small sample sizes, and too few heavy marijuana users in the study
sample. Recommendations for future studies are to (1) focus on tobacco-related
cancer sites; (2) obtain detailed marijuana exposure assessment, including
frequency, duration, and amount of personal use as well as mode of use (smoked
in a cigarette, pipe, or bong; taken orally); (3) adjust for tobacco smoking
and conduct analyses on nonusers of tobacco; and (4) conduct larger studies,
meta-analyses, or pooled analyses to maximize statistical precision and
investigate sources of differences in results. Despite the challenges,
elucidation of the association between marijuana use and cancer risk is
important in weighing the benefits and risks of medical marijuana use and to
clarify the impact of marijuana use on public health.
1:
J Clin Pharmacol. 2002
Nov;42(11 Suppl):103S-107S.
Links
Marijuana smoking and head and neck cancer.
Department of Epidemiology, UCLA
School of Public Health, Jonsson Comprehensive Cancer Center, 90095-1772, USA.
A recent epidemiological study showed
that marijuana smoking was associated with an increased risk of head and neck
cancer. Among high school students and young adults, the prevalence of
marijuana use was on the rise in the 1990s, with a simultaneous decline in the
perception that marijuana use is harmful. It will be a major public health
challenge to make people aware of the harmful effects of marijuana smoking, when
some people view it as the illicit drug with the least risk. The carcinogenicity
of delta9-tetrahydrocannabinol (THC) is not clear, but according to laboratory
studies, it appears to have antitumor properties such as apoptosis as well as
tumor-promoting properties such as limiting immune function and increasing
reactive oxygen species. Marijuana tar contains similar carcinogens to tar from
tobacco cigarettes, but each marijuana cigarette maybe more harmful than a
tobacco cigarette since more tar is inhaled and retained when smoking marijuana.
More molecular alterations have been observed in bronchial mucosa specimens of
marijuana smokers compared to nonsmokers. Field cancerization may be occurring
on the bronchial epithelium due to marijuana smoking exposure. Several case
studies were suggestive of an association of marijuana smoking with head and
neck cancers and oral lesions. However, in a cohort study with 8 years of
follow-up, marijuana use was not associated with increased risks of all cancers
or smoking-related cancers. Further epidemiological studies are necessary to
confirm the association of marijuana smoking with head and neck cancers and to
examine marijuana smoking as a risk factor for lung cancer. It will also be of
interest to examine potential field cancerization of the upper aerodigestive
tract by marijuana and to explore marijuana as a risk factor for oral
premalignant lesions.
PMID: 12412843 [PubMed - indexed for MEDLINE]
Marijuana use and increased risk of squamous cell
carcinoma of the head and neck.
Department of Epidemiology, University
of California at Los Angeles School of Public Health, and Jonsson Comprehensive
Cancer Center, 90095-1772, USA. zfzhang@ucla.edu
Marijuana is the most commonly used
illegal drug in the United States. In some subcultures, it is widely perceived
to be harmless. Although the carcinogenic properties of marijuana smoke are
similar to those of tobacco, no epidemiological studies of the relationship
between marijuana use and head and neck cancer have been published. The
relationship between marijuana use and head and neck cancer was investigated by
a case-control study of 173 previously untreated cases with pathologically
confirmed diagnoses of squamous cell carcinoma of the head and neck and 176
cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and
1994. Epidemiological data were collected by using a structured questionnaire,
which included history of tobacco smoking, alcohol use, and marijuana use. The
associations between marijuana use and head and neck cancer were analyzed by
Mantel-Haenszel methods and logistic regression models. Controlling for age,
sex, race, education, alcohol consumption, pack-years of cigarette smoking, and
passive smoking, the risk of squamous cell carcinoma of the head and neck was
increased with marijuana use [odds ratio (OR) comparing ever with never users,
2.6; 95% confidence interval (CI), 1.1-6.6]. Dose-response relationships were
observed for frequency of marijuana use/day (P for trend <0.05) and years of
marijuana use (P for trend <0.05). These associations were stronger for subjects
who were 55 years of age and younger (OR, 3.1; 95% CI, 1.0-9.7). Possible
interaction effects of marijuana use were observed with cigarette smoking,
mutagen sensitivity, and to a lesser extent, alcohol use. Our results suggest
that marijuana use may increase the risk of head and neck cancer with a strong
dose-response pattern. Our analysis indicated that marijuana use may interact
with mutagen sensitivity and other risk factors to increase the risk of head and
neck cancer. The results need to be interpreted with some caution in drawing
causal inferences because of certain methodological limitations, especially with
regard to interactions.
PMID: 10613339 [PubMed - indexed for MEDLINE]
1: J
Natl Cancer Inst. 1998 Aug 19;90(16):1198-205.
Links
- Comment in:
-
J Natl Cancer Inst. 1998 Aug 19;90(16):1182-4.
Histopathologic and molecular alterations in bronchial
epithelium in habitual smokers of marijuana, cocaine, and/or tobacco.
Department of Pathology, University of
California, Los Angeles, USA. sbarsky@ucla.edu
BACKGROUND: Tobacco smoking has been
observed to cause molecular alterations in bronchial epithelium that antedate
the development of lung carcinoma. The rising prevalence of marijuana and
cocaine use among young adults in the United States prompted us to investigate
whether similar molecular and histopathologic alterations occur in habitual
smokers of marijuana and/or cocaine who may or may not also smoke tobacco.
METHODS: Bronchoscopy was performed in 104 healthy volunteer subjects, including
28 nonsmokers and 76 smokers of one or more of the following substances:
marijuana, tobacco, and/or cocaine. Bronchial mucosa biopsy specimens and
brushings were analyzed for histopathologic changes, for immunohistopathologic
expression of intermediate or surrogate end-point markers that are linked to an
increased risk of cancer (Ki-67 [a marker of cell proliferation], epidermal
growth factor receptor, p53, Her-2/neu [also known as erbB-2 and ERBB2],
globular actin, and abnormal DNA ploidy). Reported P values are two-sided.
RESULTS: Smokers of any one substance or of two or more substances exhibited
more alterations than nonsmokers in five to nine of the 10 histopathologic
parameters investigated (all P < .05), and they exhibited more molecular
abnormalities than nonsmokers. Differences between smokers and nonsmokers were
statistically significant (all P < or = .01) for Ki-67, epidermal growth factor
receptor, globular actin, and DNA ploidy. There was general agreement between
the presence of molecular abnormalities and histopathologic alterations;
however, when disagreement occurred, the molecular abnormalities (e.g., Ki-67
and epidermal growth factor receptor) were more frequently altered (all P < or =
.01). CONCLUSIONS: These findings suggest that smoking marijuana and/or
cocaine, like tobacco smoking, exerts field cancerization effects on bronchial
epithelium, which may place smokers of these substances at increased risk
for the subsequent development of lung cancer.
PMID: 9719080 [PubMed - indexed for MEDLINE]
1: J Clin
Pharmacol. 2002 Nov;42(11 Suppl):71S-81S.
Links
Respiratory and immunologic consequences of marijuana
smoking.
Deportment of Medicine, UCLA School of
Medicine, 90095-1690, USA.
Habitual smoking of marijuana has a
number of effects on the respiratory and immune systems that may be clinically
relevant. These include alterations in lung function ranging from no to mild
airflow obstruction without evidence of diffusion impairment, an increased
prevalence of acute and chronic bronchitis, striking endoscopic findings of
airway injury (erythema, edema, and increased secretions) that correlate with
histopathological alterations in bronchial biopsies, and dysregulated growth of
the bronchial epithelium associated with altered expression of nuclear and
cytoplasmic proteins involved in the pathogenesis of bronchogenic carcinoma.
Other consequences of regular marijuana use include ultrastructual abnormalities
in human alveolar macrophages along with impairment of their cytokine
production, antimicrobial activity, and tumoricidal function. Cannabinoid
receptor expression is altered in leukocytes collected from the blood of chronic
smokers, and experimental models support a role for delta9-tetrahydrocannabinol
in suppressing T cell function and cell-mediated immunity. The potential for
marijuana smoking to predispose to the development of respiratory malignancy is
suggested by several lines of evidence, including the presence of potent
carcinogens in marijuana smoke and their resulting deposition in the lung, the
occurrence of premalignant changes in bronchial biopsies obtained from smokers
of marijuana in the absence of tobacco, impairment of antitumor immune defenses
by delta9-tetrahydrocannabinol, and several clinical case series in which
marijuana smokers were disproportionately over represented among young
individuals who developed upper or lower respiratory tract cancer. Additional
well designed epidemiological and immune monitoring studies are required to
determine the potential causal relationship between marijuana use and the
development of respiratory infection and/or cancer.
PMID: 12412839 [PubMed - indexed for MEDLINE]
1:
Monaldi Arch Chest Dis. 2005 Jun;63(2):93-100.
Links
Smoked marijuana as a cause of lung injury.
Division of Pulmonaiy & Critical Care
Medicine, Department of Medicine, David Geffen School of Medicine, UCLA, Los
Angeles, CA 90095-1690, USA. dtashkin@mednet.ucla.edu
In many societies, marijuana is the
second most commonly smoked substance after tobacco. While
delta9-tetrahydrocannabinol (THC) is unique to marijuana and nicotine to
tobacco, the smoke of marijuana, like that of tobacco, consists of a toxic
mixture of gases and particulates, many of which are known to be harmful to the
lung. Although far fewer marijuana than tobacco cigarettes are generally
smoked on a daily basis, the pulmonary consequences of marijuana smoking may
be magnified by the greater deposition of smoke particulates in the lung due to
the differing manner in which marijuana is smoked. Whereas THC causes modest
short-term bronchodilation, regular marijuana smoking produces a number of
long-term pulmonary consequences, including chronic cough and sputum,
histopathologic evidence of widespread airway inflammation and injury and
immunohistochemical evidence of dysregulated growth of respiratory epithelial
cells, that may be precursors to lung cancer. The THC in marijuana could
contribute to some of these injurious changes through its ability to augment
oxidative stress, cause mitochondrial dysfunction, and inhibit apoptosis. On the
other hand, physiologic, clinical or epidemiologic evidence that marijuana
smoking may lead to chronic obstructive pulmonary disease or respiratory cancer
is limited and inconsistent. Habitual use of marijuana is also associated with
abnormalities in the structure and function of alveolar macrophages, including
impairment in microbial phagocytosis and killing that is associated with
defective production of immunostimulatory cytokines and nitric oxide, thereby
potentially predisposing to pulmonary infection. In view of the growing interest
in medicinal marijuana, further epidemiologic studies are needed to clarify the
true risks of regular marijuana smoking on respiratory health.
PMID: 16128224 [PubMed - indexed for MEDLINE]
1:
Clin Rev Allergy
Immunol. 1997 Fall;15(3):243-69.
Links
Marijuana. Respiratory tract effects.
Division of Pulmonary and Critical
Care Medicine, University of California at Davis, Sacramento 95817, USA.
Daily marijuana smoking has been
clearly shown to have adverse effects on pulmonary function and produce
respiratory symptomatology (cough, wheeze, and sputum production) similar to
that of tobacco smokers. Based on the tobacco experience, decrements in
pulmonary function may be predictive of the future development of chronic
obstructive pulmonary disease (COPD). However, in the absence of
alpha-1-antitrypsin deficiency, the habitual marijuana-only smoker would likely
have to smoke 4-5 joints per day for a span of at least 30 yr in order to
develop overt manifestations of COPD. The mutagenic/carcinogenic properties of
marijuana smoke are also well-established. The potential for induction of
laryngeal, oropharyngeal, and possibly bronchogenic carcinoma from marijuana has
been documented by several case reports and observational series. Despite this,
a relative risk ratio for the development of these tumors has not yet been
quantified. Based on a higher frequency of case reports for upper airway cancer
compared to bronchogenic carcinoma, marijuana smoking may have a more
deleterious effect on the upper respiratory tract. However, this hypothesis
remains speculative at best, pending confirmation by longitudinal studies.
PMID: 9358987 [PubMed - indexed for MEDLINE]
1: J Clin
Pharmacol. 2002 Nov;42(11 Suppl):64S-70S.
Links
Cardiovascular consequences of marijuana use.
Kaiser Permanente Medical Care
Program, Division of Research, Oakland, California 94612, USA.
This review describes what is known about
effects of marijuana and cannabinoids in relation to human physiological and
disease outcomes. The acute physiological effects of marijuana include a
substantial dose-dependent increase in heart rate, generally associated with a
mild increase in blood pressure. Orthostatic hypotension may occur acutely as a
result of decreased vascular resistance. Smoking marijuana decreases exercise
test duration in maximal exercise tests, increases the heart rate at submaximal
levels of exercise. Tolerance develops to the acute effects of marijuana
smoking and delta9-tetrahydrocannibol (THC) over several days to a few weeks.
The cardiovascular responses that occur in response to THC are mediated by the
autonomic nervous system, with recent findings also demonstrating that the human
cannabinoid receptor system plays a role in regulating the cardiovascular
response. Although several mechanisms exist by which marijuana use might
contribute to the development of chronic cardiovascular conditions or acutely
trigger cardiovascular events, there are few data regarding marijuana/THC use
and cardiovascular disease outcomes. A large cohort study showed no association
of marijuana use with cardiovascular disease hospitalization or mortality.
However, acute effects of marijuana use include a decrease of the time until the
onset of chest pain in patients with angina pectoris; one study has shown that
marijuana may trigger the onset of myocardial infarction. Patients who have
coronary heart disease or are at high risk for the development of CHD should be
cautioned about the potential hazards of marijuana use as a precipitant for
clinical events. Research directions might include more studies of
cardiovascular disease outcomes and relationships of marijuana with
cardiovascular risk factors, studies of metabolic and physiologic effects of
chronic marijuana use that may affect cardiovascular disease risk, increased
understanding of the role of the cannabinoid receptor system in cardiovascular
regulation, and studies to determine if there is a therapeutic role for
cannabinoids in blood pressure control or for neuroprotection after stroke.
PMID: 12412838 [PubMed - indexed for MEDLINE]
Related Links
1: Circulation. 2001 Jun
12;103(23):2805-9.
Links
Triggering myocardial infarction by marijuana.
Institute for the Prevention of
Cardiovascular Disease, Cardiovascular Division, Department of Medicine, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
mmittlem@caregroup.harvard.edu
BACKGROUND: Marijuana use in the age
group prone to coronary artery disease is higher than it was in the past.
Smoking marijuana is known to have hemodynamic consequences, including a
dose-dependent increase in heart rate, supine hypertension, and postural
hypotension; however, whether it can trigger the onset of myocardial
infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial
Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute
myocardial infarction an average of 4 days after infarction onset. We used the
case-crossover study design to compare the reported use of marijuana in the hour
preceding symptoms of myocardial infarction onset to its expected frequency
using self-matched control data. Of the 3882 patients, 124 (3.2%) reported
smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of
myocardial infarction symptoms. Compared with nonusers, marijuana users were
more likely to be men (94% versus 67%, P<0.001), current cigarette smokers (68%
versus 32%, P<0.001), and obese (43% versus 32%, P=0.008). They were less likely
to have a history of angina (12% versus 25%, P<0.001) or hypertension (30%
versus 44%, P=0.002). The risk of myocardial infarction onset was elevated 4.8
times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes
after marijuana use. The elevated risk rapidly decreased thereafter.
CONCLUSIONS: Smoking marijuana is a rare trigger of acute myocardial infarction.
Understanding the mechanism through which marijuana causes infarction may
provide insight into the triggering of myocardial infarction by this and other,
more common stressors.
PMID: 11401936 [PubMed - indexed for MEDLINE]
1:
Rev Epidemiol Sante Publique. 2000 Oct;48(5):473-83.
Links
[Cannabis and cancer]
[Article in French]
Unite d'Epidemiologie pour la
Prevention du Cancer, Centre International de Recherche sur le Cancer, 150,
cours Albert Thomas, 69372 Lyon Cedex 8, France.
Several publications have recently
suggested a relationship between cannabis use and certain types of cancer.
We gathered information on the latest findings on the subject. A manual and
computerized bibliographic search on cannabis and cancer was conducted. In users
under 40 years of age, cannabis is suspected to increase the risk of
squamous-cell carcinoma of the upper aerodigestive tract, particularly of the
tongue and larynx, and possibly of lung. Other tumours being suspected are non-lymphoblastic
acute leukaemia and astrocytoma. In head and neck cancer, carcinogenicity was
observed for regular (i.e. more than once a day for years) cannabis smokers.
Moreover, cannabis increases the risk of head and neck cancer in a dose-response
manner for frequency and duration of use. Interaction was observed with
cigarette smoking and alcohol use. Delta9-THC seems to have a specific
carcinogenic effect different from that of the pyrolysis products.
Epidemiological studies are needed as soon as possible to provide data on the
European and French situation. Information on the possible risks of a regular
use of cannabis should be a priority.
PMID: 11084527 [PubMed - indexed for MEDLINE]
