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Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes.

Introduction

As most people are aware, marijuana is the most widely used illicit drug in the world. 1 Cannabis is the second most smoked substance, after tobacco. In the past few years, recreational use of cannabis (‘weed’, ‘dope’, ‘grass’, ‘spliff’, ‘toke’, ‘hash’, ‘hemp’, ‘bud’, ‘ganja’ and many others) has had increasing media attention and, with legislation in various countries being relaxed, it appears likely that there will be an increase in exposure generally. However, we still know very little about the long-term effects of smoking cannabis on the respiratory system and on health in general.

Cannabis comes from a flowering plant, native to central Asia and the Indian sub-continent. The genus includes three different species—Cannabis sativa, Cannabis indica and Cannabis ruderalis. They produce two major active compounds, delta-9-tetrahydrocannabinol (d-9-THC) and cannabidiol (CBD); however, they contain 60 cannabinoids and over 400 compounds in total. 2 THC is the psychoactive compound, but it is modulated by CBD. The C. sativa-dominant strains have higher THC content, whereas the C. indica-dominant strains have higher CBD content. 2 The C. ruderalis-dominant strains contain even lower THC concentrations than the C. indica-dominant strains. 3 There is also ‘skunk-like’ cannabis, named for its smell, containing very high THC concentrations. 4

Experimentally, the acute bronchodilator effect 5,6 and analgesic properties 7–9 of inhaled cannabis are well described. Acute bronchodilatation is due to THC. 4 However, as cannabinoids can have partial agonist, or even antagonist, effects, little is known about differences in airway effects from different strains of cannabis containing varying concentrations of cannabinols.

Evidence that chronic cannabis users have an increased incidence of respiratory symptoms such as chronic cough, sputum production, dyspnoea, hoarse voice and chest tightness has been reviewed recently. 6,10 As marijuana smoke contains many of the same compounds as, and shares similar properties with, cigarette smoke, respiratory symptoms would be expected. 11,12

Methodological difficulties

There are obvious inherent difficulties in studying the long-term use of illicit substances. Examining dose–response is confounded by the problem of quantifying cannabis use—the measurement of ‘joint-years’ has inherent difficulties. One joint-year is defined as 365 joints smoked. However, because of the wide variety and strengths of marijuana in a joint, 13,14 as well as the varying amounts that individuals put into a joint, this measure differs markedly between individuals. Reproducibility of joints in the same individual is not well defined. Furthermore, most studies use self-reported joint-years to quantify use; this may be inaccurate owing to the legality of cannabis use, recall bias and alteration of behaviour by its observation.

Another major consideration is the variety of ways that cannabis can be smoked, which alter the characteristics of the smoke inhaled. Using a water bong, e.g., decreased the concentration of inhaled carcinogenic compounds. 11,15 Recent evidence has suggested that using a vapouriser to smoke cannabis may reduce pulmonary complications. 16 Otherwise, there have been no peer-reviewed studies examining the effects of differing methods of smoking cannabis on lung health .

Cannabis and tobacco tend to be smoked differently. Typically, cannabis is smoked without a filter, to a shorter butt length, and the smoke is at a higher temperature. Furthermore, cannabis smokers inhale more deeply, hold their breath for longer and perform a Valsalva manoeuvre at maximal breath-hold. 17–19

Some smokers make joints with marijuana leaves alone, 20 whereas others usually smoke ‘spliffs’ containing both cannabis and tobacco leaves. 21 This varies from one country to another. Cannabis users are also more likely to concurrently smoke tobacco, separately, making it difficult to disentangle the effects of cannabis itself on the lungs.

Effects of tobacco smoking

The effects of cigarette (tobacco) smoking on lung health are well known. They include symptoms of cough, sputum production (which when marked constitutes chronic bronchitis), wheeze and shortness of breath. Spirometric changes such as a progressive, largely irreversible decrease in forced expiratory volume in 1 s (FEV1) and FEV1 divided by forced vital capacity (FVC)−FEV1/FVC ratio occur. This ratio is the most reliable measure of airflow obstruction. These changes may be accompanied by air-trapping within the lungs, measured physiologically (as increased total lung capacity (TLC) or residual volume (RV) or the ratio RV/TLC) or radiologically, on chest X-ray, etc. Chronic persistent, progressive airway narrowing, damage to the alveoli (emphysema) and effects on small airways (investigated with more sophisticated methods, beyond the scope of this review), in varying proportions, comprise the condition chronic obstructive pulmonary disease (COPD). As cannabis was thought to affect the lungs in similar ways to tobacco, it was logical to use spirometric measurements to detect the adverse health effects of marijuana. However, with concurrent tobacco smoking, it is difficult to separate changes due to cannabis from those due to tobacco.

The general paucity of data, the evolving nature of available marijuana (newer, stronger forms, modes of inhalation, etc) and the important confounding factor of tobacco use have led to different interpretations of the health impact of marijuana by the public as well as within the research and medical community. The purpose of this review is to assess current knowledge of the chronic effects of cannabis smoking on respiratory function and the progression of pulmonary disease as well as to identify potential directions for future research.

Methods

MEDLINE/PubMed (NLM), Scopus (Elsevier) and Science Citation Index Expanded (Web of Science) databases were searched for English-language peer-reviewed articles from 1 January 1968 to 6 June 2015. These were refined by the following search terms: ‘marijuana smoking lung’, ‘cannabis smoking lung’, ‘marijuana smoking pulmonary’ and ‘cannabis smoking pulmonary’. This method yielded 256 articles.

These initial 256 results were reduced to 114 peer-reviewed articles, as the other 142 were not published in peer-reviewed journals. The remaining 114 articles were individually screened by title and abstract, looking for measurements of pulmonary function and long-term cannabis use in humans. Case reports and case series were omitted. The final count contained 19 articles fitting all the above criteria. Each article was then individually appraised, with the main findings and conclusions tabulated.

An additional search was also conducted for English-language peer-reviewed articles, as above, containing the following search terms: ‘cannabis bullous lung’, ‘cannabis bullae lung’, ‘cannabis pneumothorax’ ‘bong lung’, ‘marijuana bullous lung’, ‘marijuana bullae lung’ and ‘marijuana pneumothorax’. This yielded 69 articles, which were individually screened by title and abstract for articles relating to bullous lung disease in marijuana smokers. Case reports and case series were included in this search, and the final count contained 18 articles.

Results

Simple lung function measurements

The results of these 19 studies are summarised in Table 1 . A total of 11 studies were cross-sectional, 20,22–31 and 8 were observational cohort studies. 21,32–38 Eighteen out of 19 studies included spirometric measurements in chronic marijuana smokers. 20–29,31–35,37–39 The results from these studies varied; eight studies found no significant changes in FEV1/FVC ratio, 23,24,26–29,32,35 whereas six studies found a significant decrease in FEV1/FVC in chronic marijuana-only smokers compared with that in controls, with 0.5–1.9% reduction. 20–22,34,37,38 The remaining studies also varied in their findings, but suggested that simply measuring the FEV1/FVC ratio does not accurately reflect the pulmonary effects of chronic marijuana use.

Table 1

Author (year) Subjects (n) Tobacco control Results
Cruickshank 23 60 No No significant differences found between cannabis smokers and control with respect to FEV1 and FVC.
Tashkin et al. 28 74 Yes No differences in spirometry results compared with those in matched and unmatched controls. A significant increase was noted in Raw and decrease in sGaw compared with those in both controls. Although not signficant, FVC was raised compared with that in both controls.
Hernandez et al. 24 23 No Spirometry results of marijuana smokers were not significantly different from those of controls. There was also no significant difference in bronchial reactivity to histamine compared with controls.
Tilles et al. 31 68 Yes Cannabis smoking with or without tobacco smoking was associated with a reduction in TLco (74% predicted±20%, P<0.05). In marijuana and marijuana plus tobacco smokers, both FEV1 and FVC were significantly increased compared with that in non-smokers.
Bloom et al. 22, a 990 Yes There was a significant increase in respiratory symptoms of phlegm and wheeze, but not cough or shortness of breath, in non-tobacco cigarette smokers whether or not they had ever smoked tobacco cigarettes. There was a significant decrease in FEV1/FVC compared with that in controls. There was no significant change in FEV1 in any non-tobacco-smoking category.
Tashkin et al. 29 446 Yes Smokers of marijuana and/or tobacco had significantly increased rates of chronic cough, wheeze and sputum production. There was an increase in Raw and decrease in sGaw in male marijuana smokers but not in tobacco smokers. FEV1 and FVC of marijuana smokers were not significantly different from those of controls.
Sherrill et al. 34 856 Yes Non-tobacco smoking was associated with chronic cough (OR=1.73), chronic phlegm (OR=1.53) and wheeze (OR=2.01). There was a significant reduction in FEV1 and FEV1/FVC ratios with previous non-tobacco smoking but not with current smoking.
Sherman et al. 27 63 Yes Macrophage oxidant release, small airway integrity and alveolar gas exchange were similar in both non-smokers and marijuana smokers. There was no significant difference in lung function measurements between marijuana-only smokers and non-smokers. Marijuana and tobacco concurrent smokers showed a decrease in FEV1/FVC and TLco.
Tashkin et al. 30 542 Yes No significant difference in AHR to metacholine was found in non-smokers and marijuana smokers without tobacco. Logistic regression showed a significant response to metacholine with marijuana smoking, however. No dose–response relationship was found between AHR and lifetime marijuana use.
Tashkin et al. 36 394 Yes Although tobacco smoking showed an FEV1 decline in men, marijuana smoking was not associated with FEV1 decline in either gender.
Taylor et al. 38, a 1037 Yes After controlling for tobacco, cannabis users had an increase in wheezing, exercise-related shortness of breath, nocturnal wakening with chest tightness and morning sputum production (P<0.05). Cannabis users had decreased FEV1/FVC compared with non-smokers. There was no significant increase in AHR in tobacco or cannabis users.
Taylor et al. 37, a 1037 Yes After stratifying by use of cannabis, at each age increasing cannabis use was associated with a decline in FEV1/FVC. After adjustments for other co-variates, cannabis as a predictor was only marginally significant (P<0.09).
Moore et al. 26 6728 Yes Marijuana use was significantly associated with chronic bronchitis symptoms, coughing on most days, phlegm production, wheezing and chest sounds without a cold. After adjustment for confounders, cannabis smoking was not associated with an FEV1/FVC ratio <70% (P=0.99).
Aldington et al. 20 339 Yes Both cannabis and tobacco-smoking groups showed a reduction in FEV1/FVC. Tobacco reduced FEV1, whereas cannabis smoking had no effect on FEV1. Tobacco smoking was associated with macroscopic emphysema by CT, but not cannabis-only smoking.
Tan et al. 35 878 Yes Marijuana-only smokers had no significant increase in risk for COPD as defined by symptoms and spirometry. However, concurrent use of tobacco and marijuana produced an increased risk for respiratory symptoms and COPD.
Hancox et al. 32 1037 Yes After adjustment for tobacco, cannabis exposure was associated with increased FVC and TLC, but there was no significant association with FEV1 or FEV1/FVC. Cannabis was associated with increased Raw and lower sGaw.
Pletcher et al. 33 5119 Yes Marijuana exposure was non-linearly associated with lung function, unlike tobacco (P<0.001). Lifetime marijuana exposure showed an increase in FEV1 over time at up to 7 joint-years and declining thereafter. FVC was significantly elevated even in heavy users up to 20 joint-years (P<0.001). Both FEV1 and FVC were increased at all exposure levels compared with those in controls.
Kempker et al. 25 7716 Yes For cannabis smokers with 1–5 and 6–20 joint-years, there was no association with an FEV1/FVC<70% (OR=1.1). Those with over 20 joint-years did (OR=2.1). Use of marijuana in the past month was associated with increased FVC (0.13±0.03%, P=0.0001) for each additional day but no decrease in FEV1.
Macleod et al. 21 500 Yes Cannabis and tobacco use together was associated with increased cough, sputum production and wheeze. After adjustment for tobacco use, age, gender and deprivation, each additional joint-year of cannabis was associated with 0.3% increase in the prevalence of FEV1/FVC<70%.

Abbreviations: AHR, airway hyper-responsiveness; CT, computerised tomography; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; sGaw, specific airway conductance; Raw, airway resistance; TLco, transfer factor of the lung for carbon monoxide.

All studies reporting a significant decrease,

1.5%, in FEV1/FVC ratio in marijuana smokers published incomplete data; in particular, most omitted the absolute results for FVC alone. However, two of these studies reported no significant effect on FEV1 in chronic cannabis use. 20,22 Sherrill et al. 34 in a follow-up survey of a random, stratified, cluster sample of the Tucson population, aged 15–60 years (n=856 who had at least two measurements), found a reduction in FEV1/FVC of −1.9±0.7% and in FEV1 of −142±44 ml only in previous marijuana smokers, with a nonsignificant decrease of −0.5±0.6% in current marijuana smokers. 22 Surprisingly, in 1,239 of the same subjects, tested on at least one occasion, FEV1/FVC was reduced by 0.5±0.6% and FEV1 increased by 58 ml. However, in a population-based cohort born in 1972 and 1973 in Dunedin, New Zealand (n=1,037), Hancox et al. showed no significant association between chronic marijuana use and change in FEV1 or FEV1/FVC at age 32 but found an increased FVC. 32 Subsequently, both Pletcher et al., in a longitudinal study over 20 years, recruited in 1985, examining Coronary Artery Risk Development In 5115 young Adults, and Kempker et al., in a cross-sectional study of 7,716 US adults from the National Health And Nutrition Examination Study cohort 2007–2008 and 2009–2010 surveys, reported similar findings as had Tilles et al. previously, although with a much smaller sample size (n=15 women). 25,31,33 Pletcher et al., reported that FEV1 and FVC were 36 and 59 ml greater in cannabis users, with >10 joint-years’ smoking history, than in non-smoking controls. 33 Kempker 27 showed no effect on FEV1/FVC up to 20 joint-years but over 20 joint-years was associated with a 2.1-fold risk for FEV1/FVC ratio <70%, accounted for by a significant increase in FVC and no significant reduction in FEV1. 25 Interestingly, Tashkin et al. 29 reported a nonsignificant increase in both FEV1 and FVC in a convenience sample of 144 heavy marijuana smokers compared with other smoking groups, and in another study, in the same subjects, 39 found that heavy habitual marijuana use, over a period of 8 years, was not associated with a decline in FEV1. Taken together, this information suggests that, although in some cases FEV1/FVC decreases by

1.5% in chronic users, this may relate more to an increase in FVC rather than to a reduction in FEV1. This represents a major difference from the effects of tobacco smoking. The possibility that the effect on FEV1 is due to selection of people with higher FEV1 (because those with lower values do not smoke or do not continue to smoke cannabis) cannot be excluded in some of the studies.

Effects of dose and duration of exposure

Four studies found a dose-related response to marijuana exposure. 20,21,25,33 Using ANCOVA, Aldington et al. (n=75 with a mean of 54.2 joint-years) found that, for every joint-year of smoking, there was a decrease in FEV1/FVC of 0.019%. Changes due to chronic cannabis use (per joint-year) were also found in specific airway conductance (−0.0017%), functional residual capacity (+0.0013%) and TLC (+0.002%) but not in FEV1 (unfortunately FVC was not reported). From this, they estimated that one pack-year of tobacco was equivalent to 4.1–7.9 joint-years of cannabis smoking (alternatively 1 joint of cannabis was equivalent to 2.5–5 cigarettes) in causing airflow obstruction. 20 This was echoed by MacLeod et al., who found a 0.3% increase in the prevalence of COPD (defined by FEV1/FVC<0.70) for each additional joint-year in marijuana and tobacco concurrent smokers (n=252) in their sample of 500 subjects recruited from a general practice in Edinburgh, Scotland. It is important to note that subjects in this study were eligible for recruitment only if they reported significant tobacco or cannabis use, defined as at least 5 pack-years and/or 1 joint-year, with none of their participants smoking exclusively cannabis. 21 Contrary to previous studies, Pletcher et al. (n=795 in Coronary Artery Risk Development In 5115 young Adults) noted that lifetime marijuana exposure was associated with an increase in FEV1 up to 7 joint-years with a decline thereafter at a slope of −2.2 ml/joint-year, although FEV1 was still nonsignificantly higher than in controls at all exposure levels (by 36 ml at >10 joint-years lifetime exposure). 33 FVC, even after 20 joint-years, was still significantly raised by 59 ml. In both cases, however, FVC and FEV1 had a non-linear relationship with marijuana, which again differs from that of tobacco smoking. 33 Kempker et al. calculated in 855 cannabis smokers that, for each additional joint-year smoked, there was no significant change in FEV1 %predicted (0.02 + 0.02), whereas FEV1/FVC decreased by −0.03±0.01% (P=0.02), accounted for by a significant increase in FVC 0.07+0.02% (P=0.004). 25

There is evidence that current use of marijuana may influence spirometric measurements. Sherrill et al. 34 reported that only former cannabis smokers (n=856) had decreased FEV1/FVC ratios, with no significant change in current smokers. In support, Kempker et al. found that use of cannabis in the past month was associated with an increased FVC for each additional day, with no FEV1 decrease. 25 Eight of the 19 studies reported no criteria for abstinence from marijuana before spirometric testing. 21,22,24,34,37–39 Strictly this confounds interpretation, making it difficult to distinguish acute from chronic effects of marijuana as acute bronchodilator effects of d-9-THC can be seen 2–3 h after inhalation 6,40 and up to 6 h after oral ingestion. 5

Other measures of lung function

Very few studies have examined more sophisticated measurements of lung physiology. Aldington et al. found a very small increase in plethysmographic TLC of 0.14 l in cannabis users in a convenience sample from the Greater Wellington region, New Zealand, which was supported by similar findings by Hancox et al., who reported an increase of just 0.03 l with an increase of 0.01 l in functional residual capacity and RV. 32 Tilles et al. also found that marijuana smokers (n=15) had a TLC of 108±15% of predicted, which was significantly raised. 31 Increased RV may indicate early signs of small airway dysfunction and air-trapping; however, it is not a very specific measure of small airway disease. 41 Conversely, results from Tashkin et al. 28,29 (n=74 and n=144) showed no significant changes in multiple measures of small airway function (FEV25–75%, closing volume, closing capacity, RV) between chronic cannabis smokers and non-smoking controls.

Three studies also reported an association of chronic cannabis smoking with increased airway resistance (0.03–0.38 cm H2O/l/s) 28,29,32 and four studies found reduced specific airway conductance (0.007–0.07 ml/s/cm H2O/l). 20,28,29,32 There was no association of these changes with change in lung volume. 32 Central airway secretions or inflammation or oedema would be a potential explanation.

In studies measuring carbon monoxide transfer factor (TLco), two small studies (n=28 and n=15) found a significant decrease in TLco with chronic concurrent marijuana and tobacco use down to 65±15% of predicted. 27,31 However, these studies did not find a significant reduction in TLco with marijuana-only use. Three other larger studies also found no significant decrease. 20,29,32

Airway responsiveness was measured in three studies. 24,30,38 Hernandez et al. studied 23 subjects from Texas, including six marijuana smokers, using histamine to measure bronchial responsiveness but found no difference in PD50 sRaw (dose of histamine causing a 50% increase in specific resistance, sRaw) in marijuana smokers compared with controls, whereas asthmatics showed significant hyper-reactivity to histamine. Larger studies by Tashkin et al., in a convenience sample of 113 out of 542 subjects, and by Taylor et al., in a sample of cannabis-dependent 21-year olds (n=91), from 943 members of the Dunedin birth cohort (n=1037), measured metacholine responsiveness as the provocative dose causing a 20% reduction in FEV1 (PC20). They found no significant difference in the number of marijuana-only smokers who had a positive PC20 metacholine compared with that in non-smokers. However, it is important to note that, after logistic regression to control for the effect of tobacco and cocaine, Tashkin et al. found that concurrent smokers of marijuana and tobacco had a significant association with hyper-responsiveness to metacholine.

The relationship between tobacco and marijuana together on lung function is complex and somewhat controversial. Sherman et al. reported a reduction in FEV1/FVC and TLco in a marijuana and tobacco-smoking group (n=13) but no change in the marijuana-alone group (n=19). 27 Tan et al. in a sample of 878 people over 40 years of age in Vancouver, Canada, also found a significant increase in respiratory symptoms in the marijuana and tobacco-smoking group but not in the marijuana-only group. 35 However, three other studies have reported no additive effects on lung function of chronically smoking both marijuana and tobacco. 30,37,39

Respiratory symptoms

Eight out of nine studies, which quantified respiratory symptoms, reported an increase in respiratory complaints with odds ratios (ORs) of up to 2.98 compared with non-smoking controls. 20–22,26,28,29,34,38 Respiratory symptoms recorded included increased incidence of cough, sputum production, shortness of breath and wheeze. Taylor et al. also reported significant increases in exercise-related shortness of breath (OR 1.65), nocturnal wakening with chest tightness (OR 1.72) and morning sputum production (OR 2.44) in a birth cohort of 1,037 subjects at 21 years of age. 38 These ORs were even higher if casual cannabis users were excluded. However, in a cross-sectional study of 6,728 subjects gathered from the National Health And Nutrition Examination Study survey, which was conducted between 1988 and 1994, there was no association with shortness of breath (OR 1.29, P=0.26) compared with non-smoking controls after adjusting for age, although they did find an increase in cough, phlegm, wheezing and chronic bronchitis symptoms with similar OR to tobacco users, which is interesting as in this sample marijuana users were, on average, 10 years younger than tobacco smokers. 26 Marijuana users (n=414) were included in the sample if they had smoked more than 100 cannabis cigarettes in total and had at least 1 day of use in the previous month; they were not asked about the frequency of use or overall exposure above 100 cigarettes. In addition to these nine studies, Hancox et al. also found an association between cannabis and morning cough, sputum production and wheeze compared with non-smokers. 42

It was observed that cannabis smoke produces large airway epithelial damage, oedema, erythema and increased secretions with goblet cell hyperplasia, 43 loss of ciliated epithelium and squamous metaplasia on biopsy. There is also evidence of additive bronchial epithelial damage in combined cannabis and tobacco smokers. 44

Effect of quitting cannabis smoking

Examining the effect of quitting is another approach to determining the effect of smoking cannabis. The effect of quitting cigarette (tobacco) smoking is well known. 45–47 Unfortunately, there are only two studies available of quitting cannabis. Tashkin reported that in a convenience sample of 299 young adults, including 95 regular cannabis-only smokers, 71 cannabis and tobacco concurrent smokers and 49 tobacco-only smokers, those who became non-smokers of both substances had no increased risk for chronic bronchitis compared with never smokers at a mean of 9.8 years of follow-up. 29,48 However, those who continued smoking either substance had an increased risk for chronic bronchitis over the follow-up period. Hancox et al. analysed data from a well-characterised, population birth cohort of 1,037 subjects followed from birth to age 38 years with symptomatic assessment at 18, 26, 32 and 38 years of age. 42 Frequent cannabis users numbered 157, 162, 138 and 99 compared with 540, 487, 608 and 703 non-users at different time points. There were significant reductions in morning cough, sputum production and wheeze, but not shortness of breath on exertion in the 26, 52, 54 and 50 quitters compared with continuing smokers, whether of cannabis alone or cannabis and tobacco. Furthermore, symptoms in the quitters were reduced to levels similar to those in never users. Sherill et al. reported that the risk for respiratory symptoms in previous non-tobacco smokers reduced to normal after quitting, but a significant reduction in FEV1, FEV1/FVC and Vmax50 persisted in previous cannabis smokers, although it was not present in current cannabis smokers. 34

Bullous lung disease and emphysema

Characteristic, peripheral, cystic changes on high-resolution computed tomography scan are often found in patients who are (probably heavy) cannabis smokers, 49 although the specificity and rate of occurrence of these findings are unclear. Only one cross-sectional study, recruited from the Greater Wellington area, measured radiological changes, reporting an increase in rates of macroscopic emphysema in tobacco smokers (16% in tobacco±cannabis n=183), but not in cannabis-only smokers (1.3% of 75). 20 However, the cannabis smokers showed a significant increase in low-density lung regions compared with tobacco smokers, and this was interpreted as a result of airflow obstruction and hyperinflation rather than microscopic emphysema.

Aside from the above-mentioned study, 7 case series and 10 case reports were also found, including a total of 56 marijuana smokers presenting with bullous lung disease (often with pneumothorax) with concurrent tobacco smoking present in all but 3 cases. The results of these studies are summarised in Table 2 . One case report was excluded because of being included in a subsequent case series. 50,51 The majority of subjects in these cases were heavy smokers of marijuana, although it is quite difficult to compare usage as the units of measurement varied. Seven case series and six case reports had predominantly upper lobe involvement (2 with Vanishing Lung Syndrome, VLS), and one case report had predominantly lower lobe bullae. For those with upper lobe involvement, the majority had peripheral emphysema. Lung function was measured in four case series, with the majority of cases having normal lung function results.

Table 2

Author (year) Subjects (n) Mean age Marijuana smoking Tobacco smoking (pack-years) Results
Feldman et al. 71 1 24 14–28 g/week for 10 years 14 Spontaneous pneumothorax. Microscopy showed ruptured bulla, serosal adhesions and focal atelectasis
Johnson et al. 49 4 38 2 joints/week to 3 joints/day 3–15 Bilateral upper zone peripheral bullae in all four cases. One with paraseptal and two with apical bullous emphysema
Rawlins et al. 72 2 29 Yes a Yes a Bilateral giant lung bullae and severe upper lobe emphysema
Thompson et al. 73 3 39 ‘Moderate’ for 10 years to ‘heavy’ for 24 years 9–20 Large upper lobe bullae
Phan et al. 74 1 26 10 pipes a day for 5 years 1 Bilateral cystic and bullous changes in lower lobes. Microscopy showed fibrosis and macrophage infiltration
Beshay et al. 75 17 27 53 joint-years 0–25 Multiple apical bullae or bullous emphysema in upper lobes. Histology showed macrophages
Hii et al. 51 10 41 11–149 joint-years 1–27 Asymmetrical bullae peripherally and centrally in upper and mid zones.
Reece 76 1 56 10 cigarettes per day for 25 years >1 Mixed tobacco and cannabis in joint. Multiple giant lung cysts on CT scan, no lobe predominance.
Gao et al. 77 1 23 Yes a None Cystic fibrosis. Bilateral large upper lobe bullae. Recurrent pneumothorax
Allen 78 1 18 1 oz weekly for 4 years 3 Bilateral apical bullae up to 3 cm. Histology showed emphysematous changes with pigmented macrophages and DIP-like changes.
Shah et al. 79 1 27 ‘Heavy’ use for 10 years 20 Large left apical bulla and right apical blebs. CT scan following chest drain of pneumothorax
Sood et al. 80 1 33 ‘Off and on’ for 10 years 15 VLS on the left side shown on chest X-ray and CT scan
Gargani et al. 81 2 41 Yes a NA to 39 One patient had left apical bullae, the other had right upper and middle lobe bullae. In both patients, one bulla contained Aspergillus
Golwala 82 1 25 24 joint-years 1 Bilateral bullae with upper lobe predominance. Previous untreated sarcoidosis but no current clinical/radiological features
Tashtoush et al. 83 1 65 ‘Heavy ’ use for 20 years None Poorly controlled AIDS and previous IV heroin use. Bilateral large lung bullae characteristic of VLS
Fiorelli et al. 84 8 30 7 joints per week to 6 joints per day 15–40 Eight of 13 marijuana smokers with spontaneous pneumothorax had bullae on CT scan. Six had paraseptal bullae and two had upper lobe involvement
Cary et al. 85 1 48 86 joint-years 25 Bilateral upper and mid zone bullous disease. Air fluid level seen on left lung bulla. Sputum grew only Candida; no clinical signs of infection.

Abbreviations: CT, computerised tomography; DIP, desquamative interstitial pneumonia; IV, intravenous; VLS, vanishing lung syndrome.

Cannabis and lung cancer

Currently, the evidence regarding an association of cannabis smoking and lung cancer is inconclusive. 52,53 Some studies have found precancerous histological changes in bronchial biopsies of marijuana smokers. 44,54 However, epidemiological studies have not found a definite association. A pooled analysis of 6 case–control studies with a total of 2,159 lung cancer cases and 2,958 controls found little or no association between cannabis smoking and lung cancer; the overall pooled OR was 0.96 for habitual versus non-habitual smokers. 55 Another large retrospective cohort study of 64,855 subjects found no increased risk for cancer after 8.6 years, although their subjects were relatively young even after follow-up. 56 Other epidemiological studies have reported associations with lung cancer with heavier marijuana use. A 40-year longitudinal cohort study in 49,321 Swedish conscripts found that those who smoked cannabis >50 times had a twofold risk of developing lung cancer. 57 Although this study is large, there are significant flaws in its methodology that limit the conclusions that can be drawn. The subjects were only assessed for tobacco and cannabis use at the time of conscription with no information on use patterns before conscription and the 40 years after conscription. A small case–control study in 403 subjects (79 lung cancer patients including 14 heavy cannabis users) also found, after adjusting for tobacco, an increased risk for lung cancer for each joint-year smoked, although not in the 2 lowest tertiles. 58 However, owing to the small number of cases (n=14) and controls (n=4), it is highly likely that relative risk estimates are inflated.

Discussion

Although there are clear inconsistencies between these 19 studies, which may relate to subjects studied as well as methodology, we can nevertheless draw various conclusions regarding the effects of cannabis on lung function. Cannabis smokers usually also smoke tobacco, either concomitantly or separately. This makes it difficult to disentangle the effects of the two. Quantification of cannabis use compounds the difficulty of dose–response studies. Although studies consistently show the effects of cannabis on symptoms (chronic bronchitis), there are mixed reports regarding airflow obstruction. The larger cross-sectional and observational cohort studies have found no association with reduced FEV1/FVC. Self-selection (where subjects with a tendency to airway narrowing reject cannabis smoking) cannot be excluded. However, more recent, larger studies have found that chronic cannabis users have an increased FVC alone, or in conjunction with an increased FEV1. 32,33 A larger rise in FVC compared with FEV1 could also contribute to previous observations of a decreased FEV1/FVC ratio. 33

This contrasts with the reduced FEV1 and FEV1/FVC ratio (indicating airflow obstruction) consistently associated with cigarette smoking and COPD. The cause of the raised FVC in chronic marijuana smokers is unclear. It has been suggested that it might be because of training of respiratory muscles by the characteristic inhalation techniques employed by marijuana smokers. 19,59,60 However, other evidence that training can increase FVC by this amount in humans is scant. 61 Bronchodilatation of small airways can increase FVC, e.g., by up to 300 ml or 8.6% of predicted after inhaled salbutamol 100 μg. 62 An acute bronchodilator effect of cannabis is well described; in three studies, marijuana was shown to increase FEV1 by 150–250 ml above baseline. 6 Relative preservation of FEV1 (36 ml greater in marijuana smokers, with >10 joint-years of exposure, compared with that in controls) as found by Pletcher could relate to a bronchodilator effect, as suggested by Kempker et al. 25

The lack of a defined marijuana abstinence period complicates interpretation of spirometric results. Current cannabis smokers had higher FVC values in studies of Kempker 25 and Sherrill et al. 34 Against this, tachyphylaxis to the bronchodilator effect would be anticipated, and in studies in asthmatics acute bronchodilatation lasted only about 2–6 h. The small but consistent increases in airway resistance, and reduction in airway conductance, 28,29,32 suggest small effects on central airways, which may be explained by airway secretions, inflammation or oedema.

Another speculative, potential explanation for the absence of chronic airflow obstruction with cannabis smoking may relate to the well-documented anti-inflammatory and immunomodulatory effect of THC 63 —e.g., impairment of functional activity of stimulated alveolar macrophages (antimicrobial and respiratory burst, impaired cytokine production and nitric oxide production) 27,64–66 thought to be critical in COPD pathogenesis. 67–69

The clinical relevance of all this is unclear. COPD resulting from an inflammatory response in the airways to tobacco smoking is a major epidemic, currently the sixth leading cause of death worldwide and projected to be the fourth leading cause of death by 2030. Chronic marijuana smokers, who often also smoke tobacco, present with similar chronic respiratory symptoms but do not appear to develop airflow obstruction and COPD.

Future studies

In general, more information is required on cannabis smoking and the lung. The difficulties with joint-years as the measure of exposure have been mentioned. The observation that chronic marijuana smokers generally buy and keep track of their supply in grams suggests that grams per year may have advantages for both clinicians and researchers. It has been reported that the amount of cannabis purchased each month, and the intensity of the high afterwards, predicted respiratory symptoms independently of frequency of use. 70 Although this will not overcome the problems with self-reporting illegal substance use, it may serve as a better measure of standardisation than joint-years.

Further research is necessary to clarify the relationship between respiratory symptoms and lung function. Further studies are needed to address acute bronchodilatation as a possible confounding factor in studies on chronic airflow obstruction. Serial examination of the bronchodilator effect of cannabis to look for tachyphylaxis would be of interest. More research into the effects of cannabis on the pathogenesis of COPD in relation to small airway inflammation, cytokine production and macrophage involvement is needed as well.

Other measures of airflow obstruction, including airway resistance, plethysmographic lung volumes and particularly measurements of small airways function, including imaging studies, are required. The priority is to understand why tobacco and cannabis smoking both cause chronic bronchitis yet have different effects on lung physiology. The pharmacological and pathophysiological basis of this needs to be established.

More work is needed in quitters of cannabis smoking, including motivations to quit, the effect on respiratory symptoms and lung function and bronchoscopic biopsy studies, to examine the effects on goblet cell hyperplasia and other histological findings.

Conclusions

This review clearly shows that chronic marijuana smoking is associated with respiratory symptoms and increase in FVC. The mechanisms for these effects and the differences from the effects of tobacco remain unclear. More work needs to accurately measure cannabis use as well as measure all aspects of respiratory health, particularly breathlessness and exercise tolerance. More importantly, however, there needs to be larger, longer-term studies with marijuana smokers who do not smoke tobacco.

There is clear evidence that marijuana causes similar symptoms to tobacco smoking (chronic bronchitis) and produces similar large airway pathological features. There is some evidence that the combination of tobacco and marijuana is additive. Tobacco unequivocally causes chronic airflow obstruction and COPD but only in a minority of smokers. Cannabis smoking, however, produces an increase in FVC and the reason(s) for this are unclear and require elucidation. Taking a more detailed history with regard to cannabis smoking and other illicit inhalational drugs should be part of the standard respiratory assessment of all patients, which would also support better epidemiological data collection for future studies, particularly in the primary care population.

Marijuana and the lung: hysteria or cause for concern?

Increasing cannabis use and legalisation highlights the paucity of data we have on the safety of cannabis smoking for respiratory health. Unfortunately, concurrent use of tobacco among marijuana smokers makes it difficult to untangle individual effect of marijuana smoking. Chronic cannabis only smoking has been shown in large cohort studies to reduce forced expiratory volume in 1 s/forced vital capacity via increasing forced vital capacity in chronic use contrary to the picture seen in tobacco smoking. The cause of this is unclear and there are various proposed mechanisms including respiratory muscle training secondary to method of inhalation and acute anti-inflammatory effect and bronchodilation of cannabis on the airways. While cannabis smoke has been shown to increase symptoms of chronic bronchitis, it has not been definitively shown to be associated with shortness of breath or irreversible airway changes. The evidence surrounding the development of lung cancer is less clear; however, preliminary evidence does not suggest association. Bullous lung disease associated with marijuana use has long been observed in clinical practice but published evidence is limited to a total of 57 published cases and only one cross-sectional study looking at radiological changes among chronic users which did not report any increase in macroscopic emphysema. More studies are required to elucidate these missing points to further guide risk stratification, clinical diagnosis and management.

Key points

Cannabis smoking has increased and is likely to increase further with relaxation of legalisation and medicinal use of cannabinoids.

Chronic marijuana smoking often produces symptoms similar to those of chronic tobacco smoking such as cough, sputum production, shortness of breath and wheeze.

Cessation of marijuana smoking is associated with a reduction in respiratory symptoms and no increased risk of chronic bronchitis.

Spirometry changes seen in chronic marijuana smokers appear to differ from those in chronic tobacco smokers. In chronic marijuana smokers there is an increase in FVC as opposed to a definite decrease in FEV1.

Multiple case series have demonstrated peripheral bullae in marijuana smokers, but no observational studies have elucidated the risk.

There is currently no clear association between cannabis smoking and lung cancer, although the research is currently limited.

Educational aims

To update readers on legalisation of recreational and medicinal cannabis.

To summarise the evidence base surrounding the respiratory effects of inhaled marijuana use.

To provide clinicians with an understanding of the main differences between cannabis and tobacco to be able to apply this to patient education.

To highlight common respiratory problems among cannabis users and the need for recreational drug history taking.

Abstract

Chronic cannabis smoking develops a different respiratory picture compared to tobacco. The mechanism behind this is unclear; however, given the increasing prevalence and legalisation it is important to keep in mind the differences in clinical practice. http://ow.ly/kcv930l1sG1

Cannabis is the most widely used illicit substance, and the second most widely smoked, in the world. Cannabis refers to products of the cannabis plant including marijuana (the flowers and tops of the plant; bud) and the resin (hash). Other terms in common use include “weed”, “dope”, “grass”, “hemp”, “ganga”, “reefer”, “spliff”, “toke” and “blunt”.

Although alcohol, caffeine and tobacco indulgence are more widespread, illicit recreational drug use polarises opinion more. Cannabis is seen as harmless on the one hand and as a gateway to hard drug use on the other. Dependence is associated with cannabis use disorder which is increasing in prevalence. Cannabis as a public health issue has risen up the political agenda. With an aim to disrupt an illicit industry funding organised crime, Canada began regulating tetrahydrocannabinol (THC) content in July 2018 in an attempt to improve safety and protect the young. Not surprisingly, there are vocal critics and cries for much more research [1].

As healthcare professionals, we deal with tobacco all the time but we also need to know about the respiratory effects of marijuana to be able to advise our patients and colleagues. This brief review aims to summarise what is known and how concerned we should be, particularly with regards to the lungs.

The cannabis genus includes three species: Cannabis sativa, Cannabis indica and Cannabis ruderalis. Each species contains varying concentrations of the two major psychoactive compounds: delta-9-THC and cannabidiol [2]. The concentrations of psychoactive compounds in recreational marijuana also vary over time, with concentrations higher now than they were 50 years ago due to selective breeding. Positive psychoactive effects of cannabis include euphoria and relaxation [3]. However, negative psychological side-effects range from anxiety to psychosis [3]. Commonly available high potency cannabis, dubbed skunk (based on its distinct smell), is associated with a high risk of psychosis due to its high concentration of delta-9-THC [2, 3].

Pharmacology

The high number of cannabinoids recognised (perhaps over 90) means that cannabis pharmacology is necessarily complex; and a full discussion is not warranted here.

Traditional CB1 receptors, belonging to the G-protein coupled family, were identified in 1988 and cloned in 1990. The concept of an endogenous cannabinoid system was developed after the discovery of an endogenous arachidonic acid metabolite ligand (N-arachidonylethanolamide (anadamide) and subsequently a much more selective agonist 2-arachidonylglycerol). delta-9-THC and synthetic derivatives are CB1 agonists. The CB2 receptor subtype was originally described in differentiated myeloid cells and shows 44% amino acid homology with CB1 but a distinct, though similar, binding profile. Five classes of cannabinoid compounds show activity at CB1 and CB2 receptors with minor selectivity for the agonists delta-9-THC and cannabidiol but major selectivity (>1000-fold) and nanomolar affinity shown by antagonists [4]. Other cannabinoid receptor subtypes have been postulated but not confirmed [5].

Cannabis use is increasing

Recent data from the 2016 Crime Survey for England and Wales on drug misuse suggest that around 2.1 million adults have used cannabis in the past year [6]. In addition, one-third of those surveyed thought it was acceptable for people of their own age to use cannabis occasionally. These figures are unsurprising given the global shift in attitudes towards cannabis and the growing number of countries relaxing legislation on both medical and recreational marijuana use (table 1).

Increasing legalisation of cannabis

Epidemiology

While we know that marijuana use is increasing, legality remains a major problem for epidemiological studies. In the UK, it is a class B drug meaning it is illegal for UK residents to possess cannabis in any form.

Cannabis can be smoked in a variety of ways, usually without a filter and burned at a higher temperature, and with users generally holding their breath for longer periods of time, compared to tobacco smokers [2]. Joints can be made using just cannabis leaves or can be mixed with tobacco in spliffs. Many cannabis users also concurrently smoke tobacco cigarettes. Routes of administration vary by geographical region as well, with European countries mostly smoking spliffs while the Americans largely smoke cannabis only joints [7]. Aside from joint smoking, users may also use water bongs, pipes and, more recently, vaporisers [7, 8].

It follows that the long-term health effects of marijuana smoking are less understood compared to traditional cigarette smoking.

Chronic respiratory effects

Tobacco smoking is well known to increase the risk of chronic bronchitis, emphysema and small airways disease (all components of chronic obstructive pulmonary disease; COPD), as well as the development of various forms of lung cancer. It might be expected that chronic cannabis smoking would have similar sequelae considering that the contents and properties of tobacco and cannabis smoke are similar [2]. However, observational studies tell a different story.

Symptoms

Respiratory symptoms such as cough, sputum production and wheeze are increased in current cannabis users [2, 9, 10]. Importantly, associations with shortness of breath were not found in larger studies [9, 10]. This suggests that cannabis smoke causes chronic bronchitis in current smokers but not shortness of breath or irreversible airway damage.

This is supported by studies examining the effect of quitting marijuana smoking. They show a significant reduction in morning cough, sputum production and wheeze compared to those who continue to smoke [2, 10]. Quitters also had no increased risk for developing chronic bronchitis compared with nonsmokers at follow-up 10 years later [2, 10].

Vaping cannabis is increasingly popular among young adults [8]. While we don’t know the long-term respiratory health effects of e-cigarette use, for either tobacco or cannabis, it has been suggested that vaping may reduce the symptoms associated with smoking [8].

Lung function

COPD is conventionally diagnosed when a patient has an irreversible reduced forced expiratory volume in 1 s (FEV1) compared with forced vital capacity (FVC) on spirometry. Several large, recently published observational studies (table 2) have reported that long-term marijuana only users have an increase in their FVC with little or no change in FEV1, even after 20 joint-years of smoking (1 joint-year is equivalent to 365 joints per year) [2, 27, 29]. A reduced FEV1/FVC ratio due to increased FVC clearly differs from the classical spirometric changes seen in tobacco smoking. The cause of this increase in FVC is unclear. Respiratory muscle training by the breath-holding techniques used during marijuana smoking has been proposed as a cause; however, there is little evidence that training can increase FVC [2, 30]. Additional lung function measurements have only been examined in smaller studies [2]. Very small changes in total lung capacity have been reported in several studies. Small effects on specific airways conductance and resistance have been interpreted as consistent with central airways inflammation. The transfer factor of the lung for carbon monoxide has been reported to be reduced only in smokers of cannabis and tobacco. Interestingly marijuana use within 0–4 days of lung function measurement showed a 13% reduction in exhaled nitrous oxide, though the clinical manifestation of this acute effect is unknown [29].

Summary of observational studies on marijuana exposure and lung function

Acute airway effects of cannabis

Experimentally, the acute bronchodilator effect of inhaled cannabis is well described as an effect of THC [2]. However, since cannabinoids can have partial agonist, or even antagonist, effects little is known about differences in airway effects from different strains of cannabis containing varying concentrations of cannabinols.

We do not know why cannabis smoking does not produce COPD. Possible explanations include a persistent bronchodilator effect (offsetting airway narrowing) or anti-inflammatory or immunomodulatory effects of THC [2].

Bullous lung disease

Bullous lung disease, usually presenting with pneumothorax, is widely recognised as a possible consequence of marijuana smoking. However, while well-established anecdotally, there is actually a paucity of relevant data [2]. As of 2018, there have been seven case series and 11 case reports published. A total of only 57 individual cases were described. Concurrent tobacco smoking was recorded in all but four of the cases. Patient details are summarised in table 3. The majority were heavy marijuana users, up to 149 joint-years. Most of the cases had predominantly upper lobe involvement with added peripheral emphysema and most presented with pneumothorax, presumably due to rupture of a bulla. They are therefore not representative of the general marijuana smoking population. We have found only a single cross-sectional study (n=339) looking at radiological changes among marijuana smokers in New Zealand [23]. Interestingly they reported an increase in macroscopic emphysema in tobacco smokers compared with nonsmokers but not in cannabis only smokers. Low-density lung regions on high-resolution computed tomography in cannabis smokers were interpreted as hyperinflation rather than microscopic emphysema. This is in contrast to a case series of 10 patients which found asymmetrical bullous changes on CT among chronic marijuana smokers but with normal spirometry and chest radiographs [37]. A study looking at smoking status and the presence of emphysematous computed tomography changes of spontaneous pneumothorax patients found no difference in emphysema prevalence among tobacco smokers and tobacco plus cannabis smokers (there were no cannabis only smokers); however, concurrent smokers were significantly younger [49]. While the authors have suggested that cannabis added to tobacco leads to emphysema at a younger age, there are too many confounders such as the subject population, to come to a definitive conclusion.

Summary of cannabis-associated bullous lung disease case reports

Various mechanisms have been proposed to explain an observed association [2, 23]; the main one relating to breath-holding techniques employed during smoking, resembling a Valsalva manoeuvre. It is suggested that this could precipitate barotrauma increasing bulla formation and predisposing to pneumothorax. There is currently no direct evidence for this hypothesis.

It is possible that the lack of published data on bullous lung disease in marijuana smokers relates to its widespread recognition and familiarity. However, it is difficult to draw any firm conclusions on an association, its frequency, other epidemiological characteristics, mechanisms, etc. More studies, preferably prospective series, are required to gather epidemiological data. It falls to health professionals to recognise possible cognitive bias, and to fully investigate pneumothorax and bullous disease rather than simply relating it to drug history.

Lung cancer

The clear association of tobacco smoking and lung cancer and the similar carcinogens present in burning cannabis plant material have long raised the possibility of an association of marijuana use and lung cancer. Furthermore, premalignant changes in bronchial biopsies from marijuana smokers have been shown histologically [2]. However, as with chronic lung disease, there is currently little evidence of a definite link. A Swedish cohort study of almost 50 000 army conscripts reported a two-fold increased risk of lung cancer among marijuana smokers, compared with nonsmokers after 40 years. Unfortunately, and critically, smoking history was only assessed at the time of conscription and there was no data on smoking status before conscription or in the 40 years afterwards [50]. A pooled analysis of six case–control studies found no increased risk of cannabis compared to non-habitual smokers [51]. Other epidemiological studies investigating cancer risk suffered from methodological limitations including small sample sizes or short follow-up [2].

We do not know why cannabis smoking does not appear to be carcinogenic. Various factors might contribute, e.g. potential anti-inflammatory and anti-neoplastic properties of THC and other cannabinoids [52].

Pneumonia

Cannabis has been shown to have immunosuppressive effects on alveolar macrophages and to cause loss of ciliated bronchial epithelium [53]. An increased incidence of pneumonia in cannabis users might be expected. One cross-sectional study surveyed current marijuana users regarding a diagnosis of pneumonia within the previous 12 months and found no increased risk compared to nonsmokers [9]. Otherwise, we have found only isolated case series and studies on immunocompromised patients [53]. Such cases include invasive aspergillosis from spores which were found in contaminated leaves and Pseudomonas associated with bong smoking [54, 55].

Interstitial lung disease

Reports of cannabis-associated interstitial lung disease are few and far between. There are occasional reports of eosinophilic pneumonia (as with smoking generally) and a case of pneumoconiosis associated with talc-adulterated marijuana [52].

Medical use of cannabis

Medical use of cannabis by mouth/orally dates back to 2737 BC in China [56]. Raw herbal cannabis, cannabis oil extracts including products prepared in a pharmacy (magistral preparations), and cannabinoids are all used. There has been increasing recent interest with wide acceptance and authorisation of use of herbal preparations in many European countries and even more widespread authorisation of oral cannabinoid medications in most European countries and the USA and Canada (table 4). The most accepted indications include chronic pain, spasticity in multiple sclerosis, certain rare epilepsy syndromes, and chemotherapy-induced nausea and vomiting [57]. There has also been experimental evidence in the anti-neoplastic effect of cannabinoids [19], as well as in palliative care. It has been recommended in a large variety of other conditions and for improving sleep quality including in obstructive sleep apnoea, although with limited evidence [58].

Licensed cannabinoid medication

Conclusions

The long-term respiratory effects of cannabis differ from traditional tobacco smoking; however, we do not know why and this may be a fruitful area for research. We need to know more about cannabis pharmacology and anti-inflammatory and anti-cancer effects as well as endocannabinoids. Cannabis use has been increasing and is likely to increase more but this should not foster hysteria. Chronic cannabis use is associated with chronic bronchitis but an increase in FVC with no change in FEV1 and not with COPD. The clinical implications and causes of these spirometric changes are currently unknown. Larger prospective longitudinal studies are needed, in particular comparing spirometric changes with bullous/emphysematous changes on high-resolution computed tomography scans. Monitoring symptoms among cannabis users, particularly breathlessness, is paramount. Reducing or eliminating cannabis smoking benefits patients suffering from symptoms of cough and phlegm.

Detailed inhalational drug history taking should be part of the standard assessment of patients in both primary and secondary care. This could support better epidemiological data collection and also foster better patient communication about respiratory and psychological health risks. No medicinal role for cannabinoids has been established as regards the lungs and more research is needed relating to safety.

Is Vaping Marijuana Safe? Deaths and Lung Disease Linked to E-Cigs Call That Into Question

V aping THC may be behind many of the serious lung diseases that have been tied to e-cigarette use––raising concerns about an increasingly popular way of consuming marijuana, which many consumers view as a relatively safe habit.

Up to 450 people have developed illnesses and at least four people have died after using e-cigarettes, Centers for Disease Control and Prevention (CDC) officials said on a call with reporters Friday. While the CDC and Food and Drug Administration (FDA) have not found a device, product or substance that is linked to all cases, a paper published Friday in the New England Journal of Medicine suggests that many sick individuals vaped THC, a compound in marijuana, before developing an illness, either instead of or in addition to nicotine. CDC and public-health officials confirmed this finding.

The investigation threatens to shatter many people’s perceptions of marijuana as safe and natural, an opinion that has gained steam as the drug is legalized in more and more states. A 2018 Gallup poll found that Americans largely view both marijuana and e-cigarettes as less harmful than cigarettes, and that more than 40% of respondents thought marijuana was “not too” or “not at all” harmful. But a growing number of illnesses apparently tied to vaping THC may change some users’ minds—and remove the health halo that often surrounds vaping.

The recent illnesses have surprised Ziva Cooper, research director of the University of California Los Angeles Cannabis Research Initiative. “If you had called me a month ago and asked me about the risks of vaporizing relative to smoking, I would have had a very different answer based on the literature thus far,” Cooper says. “This is an issue that deserves immediate attention.”

E-cigarettes work by heating substances—most often liquid nicotine, but also marijuana flowers or compounds suspended in oils—into aerosols that can be inhaled. Although it’s a source of debate, this process is thought to be healthier than traditional smoking, since burning substances such as tobacco or marijuana creates byproducts that can harm the lungs and overall health. Cooper says a handful of studies on vaping cannabis have suggested that using e-cigarettes is less harmful to the lungs than smoking marijuana.

Perhaps in part because of that belief, vaping marijuana has grown increasingly popular. In Colorado—the poster child of legal marijuana use—there was a 78% increase in the number of marijuana concentrates (a category that includes vape products) sold to consumers from 2017 to 2018, according to state Department of Revenue data. (Marijuana flowers still make up a larger share of the total market, the data shows––but the proportion is changing as concentrate sales rise.)

And it’s not just legal users who are vaping marijuana: About 13% of high school seniors said they had in a federal survey released in December 2018. And the CDC has specifically warned consumers against using “bootleg” vape pen cartridges.

By 2022, U.S. cannabis concentrates sales, driven by vaping products, are projected to hit $8.4 billion—only slightly less than sales of marijuana flowers, according to a report from marketing firm Arcview, which focuses on the cannabis industry.

It’s likely that the processing of THC, rather than the compound itself, is the cause of recent lung issues, says Jacob Borodovsky, an epidemiologist at Washington University School of Medicine in St. Louis who has studied vaping. To produce vape pen liquid, THC is suspended in an oil solution that often also includes chemicals to alter the flavor or consistency of the mixture, which users then heat and inhale. “If I had to bet money on whether or not THC is causing these lung-related issues, I wouldn’t put it on the THC compound itself,” Borodovsky says. “I would put it on the way in which the THC is prepared and delivered.”

Since the regulatory process for vape oils is “pure chaos right now,” it’s hard to know which chemicals have been added, and even if what’s on the label is accurate, he says. The FDA, for example, has issued multiple warnings to companies making inaccurate claims about the contents of products containing CBD, another compound in marijuana.

The FDA is now testing more than 100 product samples used by patients who developed lung diseases after vaping, in an effort to find out exactly what’s in them and what could be causing illnesses. New York state health officials on Thursday pointed to vitamin E acetate, an unauthorized additive in some marijuana vape pods, as a focus of their investigation. But on Friday, an FDA spokesman said, “No one substance, including Vitamin E acetate, has been identified in all of the samples tested” by the agency.

The spokesperson added: “Importantly, identifying any compounds that are present in the samples will be one piece of the puzzle but will not necessarily answer questions about causality.”

While the FDA attempts to stop cannabis products from making health claims, it does not regulate THC vaping products––in part because marijuana remains illegal under federal law. And though some states require companies to submit to random independent testing of their products, Borodovsky says, there’s little oversight before something goes to market—and even less for the “black and gray market companies” that have popped up as the industry has grown. “Just because it says lab-tested on the label, don’t believe that,” he says.

Products that contain less than 0.3% THC do not fall under Drug Enforcement Administration purview. And those that contain more are subject to a byzantine regulatory system that can prevent even scientists from studying their contents.

Since marijuana is classified as a Schedule I drug under federal law, the same category as heroin and LSD, researchers need special permission to work with it, and they’re limited to studying products that come from the only facility approved to grow marijuana for research: the University of Mississippi, which traditionally doesn’t produce things like vape oils and edibles. “We cannot study [some] products that are available to the public, which is a significant barrier to understanding the public-health implications,” Cooper, the UCLA cannabis researcher, says.

As the investigation into lung diseases continues, the CDC is advising consumers to “consider not using e-cigarettes,” and particularly avoid products that have been altered or purchased on the street.

Cooper agrees that people should be careful, and notes that plants may be a safer alternative to more processed products. “There’s enough concern for there to be a general statement that people should be very cautious about vaping,” she says. “It’s safer, if you’re going to vape, to go with plant product with a known device.”