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Effects of cannabis on pulmonary structure, function and symptomsSarah Aldington, Mathew Williams, Mike Nowitz, Mark Weatherall, Alison Pritchard, AmandaMcNaughton, Geoffrey Robinson, Richard Beasley. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thorax 2007;0:1–7. doi: 10.1136/thx.2006.077081 Background: Cannabis is the most widely used illegal drug worldwide. Long-term use of cannabis is known tocause chronic bronchitis and airflow obstruction, but the prevalence of macroscopic emphysema, the dose-response relationship and the dose equivalence of cannabis with tobacco has not been determined.
Methods: A convenience sample of adults from the Greater Wellington region was recruited into foursmoking groups: cannabis only, tobacco only, combined cannabis and tobacco and non-smokers of eithersubstance. Their respiratory status was assessed using high-resolution CT (HRCT) scanning, pulmonaryfunction tests and a respiratory and smoking questionnaire. Associations between respiratory status and See end of article for cannabis use were examined by analysis of covariance and logistic regression.
authors' affiliations Results: 339 subjects were recruited into the four groups. A dose-response relationship was found between cannabis smoking and reduced forced expiratory volume in 1 s to forced vital capacity ratio and specific Correspondence to: airways conductance, and increased total lung capacity. For measures of airflow obstruction, one cannabis Professor Richard Beasley, joint had a similar effect to 2.5–5 tobacco cigarettes. Cannabis smoking was associated with decreased lung Medical Research Institute of density on HRCT scans. Macroscopic emphysema was detected in 1/75 (1.3%), 15/92 (16.3%), 17/91 New Zealand, P O Box 10055, Wellington 6143, (18.9%) and 0/81 subjects in the cannabis only, combined cannabis and tobacco, tobacco alone and non- New Zealand; Richard.
smoking groups, respectively.
Conclusions: Smoking cannabis was associated with a dose-related impairment of large airways function Received 28 December 2006 resulting in airflow obstruction and hyperinflation. In contrast, cannabis smoking was seldom associated with Accepted 6 June 2007 macroscopic emphysema. The 1:2.5–5 dose equivalence between cannabis joints and tobacco cigarettes for adverse effects on lung function is of major public health significance.
Cannabis is used by an estimated 160 million people 75years.1011 Subjects were sent a single page postal ques- worldwide.1 Concerns regarding its pulmonary effects tionnaire seeking demographic, respiratory and smoking arose from the observation that it is qualitatively similar history data. Those who completed and returned their ques- to tobacco, with the exception of their respective tetrahydro- tionnaires were invited to undertake a detailed interviewer- cannabinol (THC) and nicotine components.2 This observation administered questionnaire and investigative modules. Owing led to a series of cross-sectional and longitudinal studies which to the inadequate number of subjects who smoked cannabis in showed that long-term cannabis smoking results in chronic this random population sample, it was necessary to recruit a bronchitis3–5 and airflow obstruction with impaired large convenience sample for the study (see fig E1 in the online airways function.6 However, other studies have failed to find supplement available at http://thorax.bmj.com/supplemental).
an effect of cannabis smoking on lung function.7 These studies The results therefore pertain only to the convenience sample.
were limited by the unavailability of CT scanning to determinethe presence of emphysema which a recent case series suggests Phase II: convenience sample may be associated with cannabis use.8 Importantly, it has not A convenience sample of adults aged 18–70 years was recruited yet been possible to determine the dose-response relationship from the Greater Wellington area using newspaper and radio of long-term cannabis smoking with adverse respiratory effects advertisements and through informal contacts. The stated using objective measures of pulmonary structure and function, purpose of the study was to investigate the health of cannabis or the dose equivalence of cannabis with tobacco consumption.
In this study, lung function tests, high resolution CT scans and detailed questionnaires were used to determine the Smoking categories association between cannabis smoking (with and without Participants were recruited into four smoking categories: (1) tobacco) on pulmonary structure, function and symptoms.
cannabis only; (2) tobacco only; (3) combined cannabis and This study was undertaken in New Zealand because of the high tobacco; and (4) non-smokers of either substance. Inclusion prevalence of cannabis smoking and the infrequent practice of criteria for cannabis smokers and tobacco smokers were a combining cannabis and tobacco.9 lifetime exposure of at least 5 joint-years of cannabis or at least1 pack-year of tobacco, respectively. A joint-year of cannabis METHODSStudy population Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, Phase I: Random sample forced expiratory volume in 1 s; FRC, functional residual capacity; FVC, forced vital capacity; MMEF, maximum mid-expiratory flow; RV, residual Participants in the Wellington Respiratory Survey were volume; sGaw, specific airways conductance; SVC, slow vital capacity; randomly selected from the electoral register, equally distrib- THC, tetrahydrocannabinol; TLC, total lung capacity; TLCO, carbon uted by sex across the five 10-year age groups from 25 to monoxide transfer factor Aldington, Williams, Nowitz, et al was defined as smoking one joint per day for 1 year and a pack- year of tobacco was equivalent to smoking 20 tobacco cigarettes Blood samples were taken from all participants for measure- per day for 1 year. Non-smokers had a lifetime exposure of ment of haemoglobin, carboxyhaemoglobin and a1-antitrypsin ,1 pack-year of tobacco and ,20 joints of cannabis.
levels. A urine sample was collected for measurement of THC Subjects were excluded if they had chronic lung disease and the tobacco metabolite cotinine for the purpose of (such as asthma, chronic bronchitis or cystic fibrosis) diag- validating the subject groups. Atopy was defined by a positive nosed by a doctor before the age of 16, were pregnant, were skin prick test to at least one common allergen or a serum IgE heterozygous or homozygous for a level .100 kU/l.
1-antitrypsin deficiency or they had used a substance of abuse other than cannabis,tobacco and alcohol .12 times in their lifetime. Subjects who claimed to be non-smokers were excluded as controls if they Participants completed a detailed respiratory questionnaire tested positive for urinary THC or cotinine.
incorporating validated questions from the Compendium ofRespiratory Standard Questionnaires (CORSQ).16 Questions Lung function tests were asked to determine smoking history, passive smoking Participants underwent extensive pulmonary function testing exposure, respiratory symptoms, family history, occupation and using two Jaeger Master Screen Body volume constant known respiratory illnesses. Wheeze was defined as a whistling plethysmography units (Masterlab 4.5 and 4.6 Erich-Jaeger, sound in the chest, either high or low pitched, at any time.
Wurtzberg, Germany). Tests performed included forced expira- Cough was considered significant if it occurred more than six tory volume in 1 s (FEV times a day. Phlegm production referred to mucus production forced vital capacity (FVC), maximum mid-expiratory flow (MMEF), slow vital capacity from the chest and excluded mucoid discharge from the nose.
(SVC), total lung capacity (TLC), residual volume (RV), To meet the criteria for chronic bronchitis, phlegm production functional residual capacity (FRC), specific airways conduc- had to occur on most days for at least 3 months of the year for tance (sGaw) and carbon monoxide transfer factor (T two consecutive years. Chest tightness was defined as a tight or function tests were carried out before and after the adminis- heavy feeling in the chest. Passive smoking exposure was tration of 400 mg salbutamol inhaled via a spacer device. T calculated using a modified version of the system used in the Po measurements were corrected for haemoglobin and carboxy- River Delta epidemiological study.17 Exposure was calculated haemoglobin and for lung volume to give the carbon monoxide for home, work and social places by multiplying hours per day6 days per week 6 intensity. The three values were summed transfer coefficient (TLCO/VA). Reference equations were those and multiplied by years of exposure to give a total exposure.
derived by the European Community for Coal and Steel.12 Family history was a dichotomous variable defined as the The lung function tests were conducted in accordance with presence or absence of a first degree relative with a family American Thoracic Society13 14 and European Respiratory history of COPD, asthma, emphysema or chronic bronchitis.
Society15 guidelines and equipment was calibrated daily.
The occupational histories were coded using the New Zealand Subjects were asked to refrain from caffeine and carbonated Standard Classification of Occupations 1999. Occupations drinks for 6 h before testing and smokers were asked to refrain associated with a higher risk of COPD were identified from from tobacco for 2 h and cannabis for 6 h before testing. Short- the literature and subjects were assigned a ‘‘duration at risk'' acting bronchodilators were withheld for 6 h and long-acting value in years. Socioeconomic status was derived from the New bronchodilators for 36 h prior to testing. Testing was not Zealand deprivation score, a composite of nine variables carried out within 3 weeks of a respiratory tract infection.
Ethnicity was derived by priority coding of the responses into three groups; Maori, European and ‘‘other''. The questionnaire Subjects were scanned, without contrast, using a single scanner was administered in a standardised manner by trained (GE Prospeed, General Electrical Medical Systems, YMS, Japan) by two radiographers specifically trained in the study Subjects also completed a detailed questionnaire regarding protocol. Scans were obtained at full inspiration with a breath their lifetime use of cannabis, which was a modified version of hold time of 4.5 s (1 mm thickness high resolution axial images that used in previous studies.6 Information was obtained performed at 1 cm intervals with a 5126512 matrix, kVp 120, regarding amount, frequency, type and method of cannabis use and inhalation characteristics. The most common method The three images obtained at levels 1 cm above the superior of using cannabis in New Zealand is smoking a joint, in which margin of the aortic arch, 1 cm below the carina and 3 cm cannabis is rolled in the form of a cigarette without the addition above the top of the diaphragm were used for measurements of of tobacco.9 If subjects smoked cannabis in a form other than a lung density using a density mask programme. The trachea and joint (eg, pipes or bongs), they were asked to estimate the main stem bronchi were excluded from the measurements of number of cannabis joints to which that would equate. This lung area, and lung tissue was separated from the chest wall conversion allowed cannabis use for all participants to be using a density of 2300 to 21200 Hounsfield Units (HU) to quantified in terms of the total number of joints smoked. If calculate the total area of lung tissue per slice. The area below subjects shared joints they were asked to estimate the 2950 HU was expressed as a percentage of total lung area for proportion of the joint they actually smoked themselves. The that slice (RA950) and as the mean of three slices. The apical total number of joint-years of cannabis smoked was calculated slice of the HRCT scan was analysed as a separate variable as it from the questionnaire. Subjects were additionally asked to has been shown to be a better discriminator between controls calculate how many joints they would obtain per gram of and subjects with chronic obstructive pulmonary disease cannabis. Both questionnaires were piloted before use.
All lung slices were subjectively analysed by two radiologists, Statistical analysis blinded to the patient's smoking history, for the presence and For categorical variables, respiratory symptoms and the severity of emphysema, the type and distribution of any presence of macroscopic emphysema on CT scans, the associa- emphysematous change and any other morphological changes tion between cannabis and tobacco smoking, each treated as in the lung.
categorical predictor variables, and the presence or absence of Pulmonary effects of cannabis Figure 1 Participant flow diagram for inclusion of subjects.
the respiratory symptom and macroscopic emphysema was smokers of each substance is reported, together with how this examined by logistic regression. As well as testing whether each difference was modified for tobacco smokers who also smoked of cannabis or tobacco smoking was associated with the cannabis where an interaction term between cannabis and symptom or CT scan result, adjusted each for the other, an tobacco smoking was significant at p = 0.05. Normality interaction term was assessed to determine if the presence of assumptions were reasonably well met for the analyses.
cannabis smoking altered the association with tobacco smoking As we found that smokers of cannabis and tobacco smoked (ie, if cannabis smoking was an effect modifier as well as a less tobacco than tobacco only smokers, we also carried out confounding variable). With the relatively small number of ANCOVA treating cannabis and tobacco smoking as joint-years subjects we were unable to adjust these associations for the and pack-years, respectively, as detailed in the Methods section.
other variables describing characteristics of the subjects. Odds For these analyses we adjusted for age, sex and height. Type III ratios (ORs) for an association are reported together with 95% sums of squares were again used to evaluate the effect of each confidence intervals. Where an interaction term was significant of cannabis and tobacco smoking adjusted for the other. The at p = 0.05, the effect of smoking cannabis on smokers of coefficients describing these associations show the number of tobacco is also given.
units change in the particular pulmonary function variable for For continuous variables, CT scan findings and pulmonary the amount smoked per extra joint-year for cannabis and pack- function tests, the association between cannabis and tobacco year for tobacco.
smoking was examined by analysis of covariance (ANCOVA),again treated as categorical predictor variables, together with testing for an interaction term between cannabis and tobacco Subject characteristics smoking. These analyses were adjusted for age, sex, height, Four hundred and forty-two volunteers presented to the clinic family history, passive smoking, ethnicity, atopy and years of for screening, 103 of whom did not meet the inclusion criteria, working in an at-risk occupation. Type III sums of squares were leaving 339 for recruitment into the four smoking groups: used to check for the importance of cannabis and tobacco cannabis only (n = 75); combined cannabis and tobacco smoking each adjusted for the other. The adjusted difference (n = 91); tobacco only (n = 92); non-smokers of either sub- between smokers of cannabis or tobacco smokers and non- stance (n = 81) (fig 1). Urine testing confirmed a history of the Table 1 Characteristics of study participants Cannabis + tobacco Mean (SD) age (years) Mean (SD) height (m) Mean (SD) joint-years Mean (SD) pack-years Median (interquartile range) deprivation score (10 = mostdeprived) Aldington, Williams, Nowitz, et al Table 2 High-resolution CT (HRCT), lung function and respiratory symptom findings for thefour groups, classified according to smoking status Cannabis + tobacco HRCTMean (SD) RA950* apical slice (%)Mean (SD) RA950 mean of 3 slices (%)Macroscopic emphysema, Lung functionMean (SD) FEV1/FVC (%) Mean (SD) FEV1 (l) Mean (SD) sGaw (/s.kPa) Mean (SD) TLC (l) Mean (SD) FRC (l) Mean (SD) TLCO/VA (mmol/min/kPa/l)Mean (SD) MMEF (l/min) Respiratory symptomsWheeze, N (%) Chest tightness, N (%) Symptoms of chronic bronchitis, N (%) FEV1, forced expiratory volume in 1 s; FRC, functional residual capacity; FVC, forced vital capacity; MMEF, maximummid-expiratory flow; RV, residual volume; sGaw, specific airways conductance; TLC, total lung capacity; TLCO/VA,carbon monoxide transfer coefficient.
*RA950, relative area of lung occupied by attenuation values lower than 2950 Hounsfield units as a percentage of thetotal lung area.
absence of cannabis or tobacco smoking in the respective In the combined cannabis and tobacco group (n = 91), all control groups. The characteristics of the participants are subjects reported smoking joints as the predominant form of shown in table 1. The mean age of the four groups was similar cannabis consumption. Twenty of these subjects (22%) reported and most of the participants were men. The distribution of adding tobacco to cannabis in the preparation of the joint. In ethnic groups was broadly representative of the distribution in addition to smoking joints, 72 (79%) reported that they had the general population of New Zealand. Socioeconomic status also smoked cannabis by another method such as bongs or was higher in the non-smoking group and the tobacco smoking group than in both cannabis smoking groups.
Cannabis smokers used similar amounts of cannabis whether In the cannabis only group (n = 75), all subjects reported or not they were also tobacco smokers. However, tobacco smoking joints as the predominant form of cannabis consump- smokers who smoked cannabis smoked less tobacco than those tion. Nine of these subjects (12%) reported having previously who smoked tobacco alone, with a difference of 7.4 pack-years added tobacco to cannabis in the preparation of the joint, but in (95% CI 3.4 to 11.4).
none of these subjects was this routine practice. In addition to As cannabis is purchased by weight and supplies are smoking joints, 54 (72%) reported that they had also smoked monitored with care, subjects were able to calculate the cannabis by another method such as bongs or pipes.
number of joints they obtained per gram of cannabis. Theyreported that the most common amount of cannabis purchasedwas a NZ$20 foil of median weight 1.1 g (range 1–5) fromwhich the median number of joints obtained was 3 (range 1–7.5). From these figures it was possible to calculate that the Table 3 Continuous variables: main effects of cannabisand tobacco smoking median amount of cannabis contained in one joint was 0.37 g,with considerable variability between subjects. As a reference, the standard weight of a tobacco cigarette is 1 g.
RA950 apical slice (%) 0.1 (21.4 to 1.6) RA950 mean of 3 slices (%) 20.6 (22.0 to 0.8) –1.1 (–2.6 to 0. 1) –2.5 (–4.0 to –1.1) Associations between cannabis and tobacco use and –0.01 (–0.13 to 0.11) –0.2 (–0.33 to –0.09) measures of pulmonary structure, function and –0.12 (–0.21 to –0.03) –0.08 (–0.17 to 0.01) 0.14 (–0.02 to 0.31) –0.08 (–0.24 to 0.09) Descriptive statistics for cannabis and tobacco use and 0.02 (–0.07 to 0.10) 0.04 (–0.05 to 0.12) 0.11 (–0.04 to 0.26) 0.04 (–0.11 to 0.19) measures of pulmonary structure, function and symptoms are TLCO/VA (mmol/min/kPa/l) –0.01 (–0.05 to 0.03) –0.11 (–0.16 to –0.07) shown in table 2. The statistical analysis of the effects of –4.94 (–19.3 to 9.4) –25.2 (–39.5 to –11.0) cannabis and tobacco use on these respiratory measures aresummarised in table 3. The main effects represent the FEV1, forced expiratory volume in 1 s; FRC, functional residual capacity; FVC, forcedvital capacity; MMEF, maximum mid-expiratory flow; RV, residual volume; sGaw, differences between smokers of cannabis and non-smokers of specific airways conductance; SVC, slow vital capacity; TLC, total lung capacity; TLCO/VA, cannabis, and smokers of tobacco and non-smokers of tobacco, carbon monoxide transfer coefficient.
Pulmonary effects of cannabis Respiratory symptoms (table 3). Tobacco smoking was associated with the presence Wheeze was associated with cannabis smoking, OR 1.3 (1.0 to of macroscopic emphysema (OR 5.7 (95% CI 2.1 to 15.6)) while 1.6), and tobacco smoking, OR 1.4 (1.1 to 1.9) with no evidence cannabis smoking was not (OR 1.0 (95% CI 0.7 to 1.4)). An of an interaction. Chest tightness was associated with cannabis interaction term could not be calculated for macroscopic smoking, OR 1.4 (1.1 to 1.7), but not with tobacco smoking, OR emphysema. In the two tobacco smoking groups (with and 1.1 (0.9 to 1.3). Cough was associated with cannabis smoking, without cannabis) there was no difference in the distribution of OR 1.5 (1.1 to 2.0), and tobacco smoking, OR 1.9 (1.4 to 2.6), emphysema (centrilobular versus paraseptal). The one cannabis however there was evidence of an interaction. The apparent only subject with macroscopic emphysema had a 437 joint-year effect of being a combined cannabis and tobacco smoker was to attenuate this association. For example, in tobacco smokerswho also smoked cannabis the association with cough had an Cannabis and tobacco use as continuous variables OR of 1.0 (0.7 to 1.4), indicating that for combined smokers of Cannabis use, analysed as joint-years, predicted FEV tobacco and marijuana there was no association with cough.
ratio, sGaw, FRC and TLC, but was not associated with FEV Chronic bronchitis, defined as daily sputum production for at least 3 months of the year for greater than 2 years duration, TLCO/VA or MMEF. Tobacco use was also associated with FEV1/ was associated with cannabis use, OR 2.0 (1.4 to 2.7), and FVC ratio, FRC and sGaw but not with TLC. The regression tobacco use, OR 1.6 (1.2 to 2.2). The presence of asthma coefficients describing some of the associations are shown in diagnosed after the age of 16 years was associated with table 4. The interpretation of these coefficients is the number of cannabis use, OR 1.7 (1.0 to 2.9), but not tobacco, OR 1.2 (0.7 to units change for the respiratory response variable per unit change in joint-years of cannabis or pack-years of tobaccosmoked. For example, the FEV1/FVC ratio, expressed as apercentage, decreased by 1.5% for each 10 pack-years of Lung function tests tobacco smoking. One pack-year of tobacco was equivalent to Table 3 shows the main effects of cannabis and tobacco on the 7.9, 4.4 and 4.1 joint-years for the effect on FEV lung function tests. There was no statistically significant sGaw, respectively. As 1 pack-year represents 20 cigarettes per interaction between cannabis and tobacco smoking on TLC day for 1 year, it could be calculated that one joint was and TLCO/VA but, for FEV1/FVC, FEV1, MMEF and sGaw, there equivalent to 2.5–5 tobacco cigarettes for the effect on FEV was a statistically significant interaction. Both cannabis and FVC, FRC and sGaw.
tobacco smoking were associated with a reduction in the FEV1/FVC ratio, but the effect of cannabis was only of marginalstatistical significance. The effect of cannabis smoking in those who smoke tobacco was to attenuate this effect by 0.8% (95% This study has identified the nature and magnitude of the CI –1.8% to 3.4%). Cannabis smoking had no effect on FEV1 but effects of cannabis smoking on respiratory structure, function tobacco smoking reduced it. The effect of cannabis smoking on and symptoms. There was a dose-response relationship of those who smoke tobacco was to attenuate this effect by cannabis smoking with airflow obstruction, impaired large 0.13 litres (95% CI –0.08 to 0.36). Cannabis had no statistically airways function and hyperinflation. For measures of airflow significant effect on MMEF and tobacco smoking reduced it.
obstruction, one joint of cannabis had a similar effect to that of The effect of cannabis on smokers was to attenuate this effect 2.5–5 tobacco cigarettes. In contrast, cannabis smoking was by 14.9 l/s (95% CI –10.5 to 40.2). Cannabis increased TLC with uncommonly associated with macroscopic emphysema, which marginal statistical significance but tobacco had no effect on was present almost entirely in the tobacco smoking groups.
TLC. Neither cannabis nor tobacco had a statistically significant There are several methodological issues relevant to the effect on RV or FRC. Cannabis and tobacco use reduced sGaw, interpretation of the results. The first was the inability to although the effect was of marginal statistical significance for identify a sufficient number of cannabis smokers from the tobacco. Although the interaction term was statistically random population sample. Despite starting with an initial significant, cannabis smoking did not further reduce sGaw in postal questionnaire of 3500 adults, only 19 met the criteria for those who smoked tobacco (–0.02 (95% CI –0.18 to 0.14)). For smoking at least 5 joint-years with no other illegal drug use and TLCO/VA (adjusted), cannabis had no effect while tobacco no chronic respiratory disorder such as asthma in childhood. It smoking reduced this measurement.
was apparent that it was not possible to use a randompopulation sample for a study of this nature and, as previously,6 High-resolution CT scanning a convenience sample was used. While this approach incurred Cannabis smoking was associated with an increased percentage the risk of selection bias by preferentially attracting people of low density lung tissue both on the apical slice and the mean concerned about their respiratory health, this applies equally to of the three slices but tobacco smoking showed no such all subject groups. We applied strict exclusion criteria for other association and there was no evidence of an interaction illegal drug use due to their potential respiratory effects.18 Thismeant that many potential participants were ineligible,particularly the heaviest cannabis users who were more likely Table 4 Regression coefficients for association between to have used other drugs. As a result, these criteria preferen- selected lung function variables and cannabis and tobacco tially excluded such heavy users, suggesting that the effects observed may represent a conservative estimate.
Cannabis association Tobacco association 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 –0.019 (–0.033 to –0.0048) –0.15 (–0.20 to –0.096) lung function.19 The requirement for cannabis smokers to have –0.0017 (–0.0026 to –0.0009) –0.007 (–0.01 to –0.004) a history of at least 5 joint-years was based on the data that one 0.0013 (–0.00013 to 0.0027) 0.0057 (0.0005 to 0.0109) 0.002 (0.0004 to 0.004) –0.0006 (–0.006 to 0.005) cannabis joint results in three to five times higher levels ofcarbon monoxide and tar deposition, respectively,20 thereby FEV1, forced expiratory volume in 1 s; FRC, functional residual capacity; FVC, forced achieving an a priori equivalence between the lower limit of vital capacity; sGaw, specific airways conductance; TLC, total lung capacity.
cannabis and tobacco smoking levels. It also ensured that Aldington, Williams, Nowitz, et al experimental users who did not smoke cannabis habitually ing in the twofold increased prevalence of chronic bronchitis.
were excluded.
These findings are unlikely to be due to pre-existing disease as Cannabis remains illegal in New Zealand although partici- subjects were excluded if they had chronic lung disease pants were willing to volunteer under the assurance of strict diagnosed by a doctor before the age of 16 years.
confidentiality. All subjects in the groups with no cannabis or Another novel finding was the effect of cannabis smoking— no tobacco use had negative samples for THC or cotinine, but not tobacco smoking—on lung density, which has been demonstrating the honest reporting of the subjects in this proposed as a marker of emphysema.29 30 However, we and regard. A further problem is that cannabis use is often difficult others have observed that decreased lung density may not be to quantify precisely due to smokers sharing joints, different specific to emphysema10 31–34 and correlates more closely with inhalation techniques and different ways of smoking cannabis markers of airflow obstruction and hyperinflation.11 As a result, including joints, pipes and bongs. In order to standardise use, we have interpreted our lung density findings as being subjects were asked to estimate the ‘‘joint equivalent'' used by predominantly due to the effect of cannabis smoking on these methods to enable cannabis use to be expressed as joint- airflow obstruction and hyperinflation rather than causing years of use. In our community the median amount of cannabis emphysema. This interpretation is consistent with our finding in a joint was 0.37 g, although there was considerable that macroscopic emphysema was present almost entirely in variability in the amount of cannabis in joints prepared by the tobacco smoking groups. Furthermore, tobacco—but not different subjects. By comparison, the average amount of cannabis use—was associated with a significant reduction in tobacco in a commercial cigarette of standard length is 1 g.
TLCO, the most specific lung function measure of emphysema in Although the calculation of joint-years was based on subjects with airflow obstruction.35 Thus, while a case series has subjects' self-reports, there is evidence that cannabis use is shown that heavy cannabis smoking may cause macroscopic more accurately reported than other drugs21 and self-reports emphysema at a young age with a characteristic apical have been shown to correlate well with urinary THC levels.22 paraseptal pattern,8 our findings would suggest that this is Influential factors in increasing the validity of self-reported not a common complication with the amount of cannabis drug use include privacy, anonymity and credibility of the smoked in New Zealand. Importantly, it suggests that cannabis study. Every effort was made to create a relaxed and does not cause emphysema when smoked in sufficient confidential environment to increase the accuracy of reporting, quantities to cause airflow obstruction, hyperinflation andchronic bronchitis.
and all subjects gave informed consent.
Finally, we observed that, whereas cannabis smokers used The practice of combining cannabis and tobacco within a similar amounts of cannabis whether or not they were tobacco joint is relatively uncommon in New Zealand.9 In our sample of smokers as well, tobacco smokers who used cannabis smoked cannabis only smokers, 12% had combined their cannabis with less tobacco than those who smoked tobacco alone. Similarly, a tobacco on some occasions although it was not routine practice study from the USA reported that, whereas cannabis users in any of these subjects. As a result, the small quantities of more often smoked tobacco, they were less likely than never tobacco used by cannabis only smokers were unlikely to cannabis users to be heavy long-term users of tobacco, as significantly affect the results.
defined by a level of .30 pack-years.36 However, this lesser As this study was exploratory, caution must be used in amount of tobacco in combined users did not result in reduced interpreting the presence or absence of associations. In adverse respiratory effects compared with tobacco only smokers particular, we analysed a number of measures of pulmonary because of the additional effects of the cannabis use.
structure, function and symptoms without any adjustment for In conclusion, these findings suggest that the predominant the inflation of type I error that may ensue. For some variables effects of cannabis on pulmonary structure, function and where we failed to find associations, this may reflect a relative symptoms are in causing the symptoms of wheezing, cough, lack of statistical power for any individual analysis.
chest tightness and sputum production, large airways obstruc- The most important finding was that one joint of cannabis tion and hyperinflation, but not emphysema. The dose was similar to 2.5–5 tobacco cigarettes in terms of causing equivalence of 1:2.5–5 between cannabis joints and tobacco airflow obstruction. This dose equivalence is consistent with the cigarettes in causing airflow obstruction is of major public reported 3–5-fold greater levels of carboxyhaemoglobin and tar inhaled when smoking a cannabis joint compared with atobacco cigarette of the same size.20 This pattern is likely torelate to the different characteristics of the cannabis joint and the way in which it is smoked. Cannabis is usually smoked The authors thank the subjects who participated in the study and without a filter23 and to a shorter butt length,24 and the smoke is Denise Fabian, Avrille Holt, Patricia Heuser, Eleanor Chambers, Andrew a higher temperature. Furthermore, cannabis smokers inhale Kingzett-Taylor and the radiology and administrative staff of Pacific more deeply,20 hold their breath for longer20 and perform the Radiology Ltd for their contribution to this study.
Valsalva manoeuvre at maximal breath hold.25 Our findings have extended previous observations that the Further data are given in fig E1 in the online principal physiological impairment with long-term cannabis supplement available at http://thorax.bmj.com/ smoking is on large airway function6 by demonstrating a dose- response relationship for sGaw. Similarly, a dose-responserelationship was observed with measures of airflow obstructionand hyperinflation which are a consequence of the large airways impairment. Previous research has shown that this Authors' affiliations large airways impairment is probably due to the inflammation Sarah Aldington, Mathew Williams, Alison Pritchard, Amanda and oedema that occurs in the tracheobronchial mucosa of McNaughton, Geoffrey Robinson, Richard Beasley, Medical ResearchInstitute of New Zealand, Wellington, New Zealand cannabis smokers,26 as well as mucus hypersecretion.27 It is well Mike Nowitz, Pacific Radiology, Wakefield Hospital, Wellington, and recognised that an increase in airway resistance leads to Wellington School of Medicine and Health Sciences, Wellington, New hyperinflation.28 These effects are also likely to contribute to the increased prevalence of symptoms of wheezing, cough and Mark Weatherall, Wellington School of Medicine and Health Sciences, sputum production associated with cannabis smoking, result- Wellington, New Zealand Pulmonary effects of cannabis 17 Simoni M, Carrozzi L, Baldacci S, et al. Characteristics of women exposed and unexposed to environmental tobacco smoke (ETS) in a general population sample Funding was provided by the New Zealand Ministry of Health, the Hawke's of North Italy (Po River Delta epidemiological study). Eur J Epidemiol Bay Medical Research Foundation and GlaxoSmithKline (UK).
Competing interests: None.
18 Tashkin D. Airway effects of marijuana, cocaine, and other inhaled illicit agents.
Curr Opin Pulm Med 2001;7:43–61.
19 Lange P, Parner J, Vestbo J, et al. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med 1998;339:1194–2000.
20 Wu T, Tashkin D, Djahed B, et al. Pulmonary hazards of smoking marijuana as 1 United Nations Office on Drugs and Crime. World Drug Report 2006;1.
compared with tobacco. N Engl J Med 1988;318:347–51.
2 Hoffmann D, Brunnerman D, Gori G, et al. On the carcinogenicity of marijuana 21 Hser Y-I, Maglione M, Boyle K. Validity of self-report of drug use among STD smoke. Recent Advances Phytochem 1975;9:63–81.
patients, ER patients, and arrestees. Am J Drug Alcohol Abuse 1999;25:81–91.
3 Bloom J, Kaltenborn W, Paoletti P, et al. Respiratory effects of non-tobacco 22 Martin G, Wilkinson D, Kapur B. Validation of self-reported cannabis use by cigarettes. BMJ 1987;295:1516–8.
urine analysis. Addict Behav 1988;13:147–50.
4 Taylor R, Fergusson D, Milne B, et al. A longitudinal study of the effects of 23 Rickert W, Robinson J, Rogers B. A comparison of tar, carbon monoxide and PH tobacco and cannabis exposure on lung function in young adults. Addiction levels in smoke from marijuana and tobacco cigarettes. Can J Public Health 5 Sherrill D, Krzyzanowski M, Bloom J, et al. Respiratory effects of non-tobacco 24 Tashkin D, Gliederer F, Rose J, et al. Tar, CO and THC delivery from the 1st and cigarettes: a longitudinal study in general population. Int J Epidemiol 2nd halves of a marijuana cigarette. Pharmacol, Biochem Behavior 6 Tashkin D, Coulson A, Clark V, et al. Respiratory symptoms and lung function in 25 Birrer R, Calderon J. Pneumothorax, pneumomediastinum and habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, pneumopericardium following Valsalva's maneuver during marijuana smoking.
smokers of tobacco alone and non smokers. Am Rev Respir Dis NY State J Med 1984;84:619–20.
26 Sarafian TA, Magallanes JA, Shau H, et al. Oxidative stress produced by 7 Tashkin D, Simmons M, Sherrill D, et al. Heavy habitual marijuana smoking does marijuana smoke. Am J Respir Cell Mol Biol 1999;20:1286–93.
not cause an accelerated decline in FEV 27 Gong H, Fligiel S, Tashkin D, et al. Tracheobronchial changes in habitual, heavy 1 with age. Am J Respir Crit Care Med smokers of marijuana with and without tobacco. Am Rev Respir Dis 8 Johnson M, Smith R, Morrison D, et al. Large lung bullae in marijuana smokers.
28 Pellegrino R, Brusasco V. On the causes of lung hyperinflation during 9 Wilkins C, Girling M, Sweetsur P, et al. Cannabis and other illicit drug trends in bronchoconstriction. Eur Respir J 1997;10:468–75.
New Zealand, 2005. Auckland: Massey University, 2005.
29 Gevenois P, de Maertelaer V, de Vuyst P, et al. Comparison of computed density 10 Marsh S, Aldington S, Williams M, et al. Utility of lung density measurements in and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care the diagnosis of emphysema. Respir Med 2007;101:1512–20.
11 Marsh S, Aldington S, Williams M, et al. Physiological associations of 30 Gevenois P, de Vuyst P, de Maertelaer V, et al. Comparison of computed density computerized tomography lung density: a factor analysis. Int J COPD and microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care 12 Quanjer P, Dalhuijsen A, van Zomeren B. Standardization of lung function tests.
31 Mishima M, Hirai T, Itoh H, et al. Complexity of terminal airspace geometry Report of the Working Party for Standardization of Lung Function Tests.
assessed by lung computed tomography in normal subjects and patients with European Community for Coal and Steel. Bull Eur Physiopathol Respir chronic obstructive airways disease. Proc Natl Acad Sci USA 1999;96:8829–34.
32 Newman K, Lynch D, Newman L, et al. Quantitative computed tomography 13 American Thoracic Society. Standardization of spirometry: 1994 update.
detects air trapping due to asthma. Chest 1994;106:105–9.
Am J Respir Crit Care Med 1994;152:1107–36.
33 Biernacki W, Redpath A, Best J, et al. Measurement of CT lung density in patients 14 American Thoracic Society. Single-breath carbon monoxide diffusing capacity with chronic asthma. Eur Respir J 1997;10:2455–9.
(transfer factor): recommendations for a standard technique. Am J Respir Crit 34 Mitsunobu F, Mifune T, Ashida K, et al. Influence of age and disease severity on Care Med 1995;152:2185–98.
high resolution CT lung densitometry in asthma. Thorax 2001;56:851–6.
15 Coates A, Peslin R, Rodenstein D, et al. ERS/ATS workshop report series: 35 Pellegrino R, Viegi G, Brusasco V, et al. ATS/ERS Task Force: Standardisation of Measurement of lung volumes by plethysmography. Eur Respir J lung function testing. Interpretative strategies for lung function tests. Eur Respir J 16 Pistelli F, Viegi G, Carrozzi L, et al. Appendix 3: Compendium of respiratory 36 Rosenblatt KA, Daling JR, Chen C, et al. Marijuana use and risk of oral standard questionnaires for adults (CORSQ). Eur Respir Rev 2001;11:118–43.
squamous cell carcinoma. Cancer Res 2004;64:4049–54.

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