bs_bs_banner HORIZONS REVIEW doi:10.1111/j.1360-0443.2012.03837.x The co-occurring use and misuse of cannabis and tobacco: a reviewadd_3837 1221..1233 Arpana Agrawal1, Alan J. Budney2 & Michael T. Lynskey1 Department of Psychiatry,Washington University School of Medicine, Saint Louis, MO, USA1 and Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA2 ABSTRACT Aims Cannabis and tobacco use and misuse frequently co-occur. This review examines the epidemiological evidence supporting the life-time co-occurrence of cannabis and tobacco use and outlines the mechanisms that link these drugs to each other. Mechanisms include (i) shared genetic factors; (ii) shared environmental influences, including (iii) route of administration (via smoking), (iv) co-administration and (v) models of co-use. We also discuss respiratory harms associated with co-use of cannabis and tobacco, overlapping withdrawal syndromes and outline treatment implica- tions for co-occurring use. Methods Selective review of published studies. Results Both cannabis and tobacco use and misuse are influenced by genetic factors, and a proportion of these genetic factors influence both cannabis and tobacco use and misuse. Environmental factors such as availability play an important role, with economic models suggesting a complementary relationship where increases in price of one drug decrease the use of the other. Route of administration and smoking cues may contribute to their sustained use. Similar withdrawal syndromes, with many symptoms in common, may have important treatment implications. Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking. Conclusions There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general. There is an urgent need for research to identify the underlying mechanisms and harness their potential etiological implications to tailor treatment options for this serious public health challenge. Keywords Cannabis, co-administration, genetics, marijuana, nicotine, policy, tobacco, treatment. Correspondence to: Arpana Agrawal, Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, CB 8134, St Louis, MO 63110, USA. E-mail: [email protected] Submitted 26 August 2011; initial review completed 17 October 2011; final version accepted 16 January 2012 INTRODUCTION past month use in 2010 [3]. In Australia, while popula- tion trends also indicate a similar increase from 9.1% in According to the Centers for Disease Control (CDC), 2007 to 10.3% in 2010, recent cannabis use appears to tobacco kills more people world-wide than human immu- have declined in youth since 1998 [7]. Despite cross- nodeficiency virus (HIV), tuberculosis and malaria com- national variations in rates of use, cannabis smoking has bined [1,2]. One in five deaths in the United States are been and continues to be associated with adverse effects attributable to cigarette smoking [1], and more than on school, employment, relationships, cognitive process- 27.4% of the United States population aged 12 years and ing, mental health, health (primarily respiratory) and older reported past month use of a tobacco product, pri- health-care utilization [8]. Independently, each of these marily cigarette smoking, in 2010 [3]. Cannabis (mari- psychoactive substances is associated, to varying degrees, juana) remains the most commonly used illicit drug in with considerable morbidity [9,10]. However, given these most developed nations [4]. Rates in the United States associated harms, what is perhaps most alarming is have been stable [5], with recent trends indicating a slight that the use of cannabis and tobacco (primarily as increase, especially in youth [6]. Compared with 2002, tobacco cigarettes) co-occurs frequently across the when 6.2% of those aged 12 years and older in the United life-span [11,12]. In this review we discuss life-time States reported past month cannabis use, 6.9% reported co-occurrence, which indicates the use and misuse of © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction Addiction, 107, 1221–1233 1222 Arpana Agrawal et al. Figure 1 Overview of mechanisms con- tributing to the life-time co-occurrence of cannabis and tobacco use cannabis and tobacco at any point (and not necessarily 70 at the same time). Discussion of the implications of 60 57.9 Cigarette smoker simultaneous use (i.e. used on the same occasion) and 50 Never smoked tobacco co-administration (e.g. mulling: adding tobacco to can- 40 nabis joints; or blunts: rolling cannabis in cigar paper) is also presented.The extent of and mechanisms underlying 30 the co-occurring use of these psychoactive substances, Prevalence (%) 20 11.9 the consequences and the treatment implications remain 10 research questions of considerable interest. Figure 1 pro- 2.5 0.3 0 vides an overview of these various mechanisms: we Ever use cannabis Cannabis Use Disorder discuss (i) the epidemiology of life-time co-occurrence of 100 cannabis and tobacco use; (ii) the mechanisms underly- 90 90 ing life-time co-occurring use, including shared genetic Ever used cannabis 80 Never used cannabis and environmental factors and economic factors; (iii) 70 route of administration as a contributing factor; (iv) res- 60 piratory complications associated with co-occurring use; 50 46.8 (v) overlapping withdrawal features; and (vi) treatment 40 30 approaches for smokers with cannabis problems and Prevalence (%) 19.1 cannabis users with nicotine dependence. 20 10 5.5 0 EPIDEMIOLOGY Ever smoked tobacco Nicotine dependent Figure 2 shows the extent of life-time co-occurring can- Figure 2 Prevalence of cannabis use, cigarette smoking, cannabis nabis and tobacco use in the United States, based on data use disorders (past 12 months) and nicotine dependence (based on the Fagerström Test of Nicotine Dependence [127]) in those aged collected by the National Household Survey on Drug Use 12 and older from the 2009 National Household Survey of Drug and Health (NSDUH) in 2009 (estimated using available Use and Health (NSDUH) [5]. For instance, 57.9% of cigarette data: http://www.icpsr.umich.edu/icpsrweb/SAMHDA/ smokers (including former smokers) report ever using cannabis studies/29621; accessed 2 March 2012; archived at compared with 11.9% of those who have never smoked cigarettes. http://www.webcitation.org/65rnDa1WO). In the US Nicotine dependence based on Fagerstrom Test for Nicotine population aged 12 years and older, life-time prevalence Dependence. Both cannabis use disorder (abuse/dependence) and of cigarette smoking was 60.6% for females and 69.3% nicotine dependence are recent for males. Cannabis use was reported by 37.1% of females cannabis users (versus 46.8% of non-users) reported and 46.4% of males. Importantly, 57.9% of cigarette being cigarette smokers at some point during their life- smokers (compared with 11.9% of non-smokers) time. Similarly elevated rates of recent (not lifetime) nico- reported a life-time history of cannabis use while 90% of tine dependence in cannabis users and cannabis use © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction Addiction, 107, 1221–1233 Cannabis and tobacco review 1223 disorders in cigarette smokers are noted (Fig. 2). Addi- growing evidence for reverse gateways reflects increasing tionally, both disorders co-occur, with 4.9% (versus ease of access to cannabis relative to cigarettes, the sale 1.2%) of those with past month nicotine dependence of which to minors may now be more stringently moni- reporting past year cannabis use disorders and 37.5% tored, remains to be investigated. (versus 12.9%) of those with cannabis use disorders meeting criteria for nicotine dependence. Escalation of use in reverse gateways While gateways and reverse gateways have referred traditionally to substance initiation, there is also over- MECHANISMS OF CO-OCCURRING USE whelming support for associations between cannabis use As indicated in Fig. 2 and the literature [13], most can- and escalation of tobacco involvement. In the study by nabis users report a life-time history of cigarette smoking. Patton and colleagues [22], daily cannabis use was asso- Cigarette smoking, however, is reported commonly in ciated with a 3.6-fold increase in nicotine dependence. users of a variety of illicit psychoactive drugs (e.g. in In data from the United States, cannabis use was associ- NSDUH, more than 90% of cocaine and methamphet- ated with a more rapid transition into daily smoking and amine users report cigarette smoking). None the less, the nicotine dependence [25,26]. co-occurring use of cannabis and tobacco may extend Based on these epidemiological trends, there has been beyond the mechanisms underlying general co-use of increasing research into the factors that contribute to substances. In the following sections, we describe evi- co-occurring use and misuse of cannabis and tobacco. dence accumulating from the literature on the putative Perhaps the strongest and most consistent contributor mechanisms connecting cannabis and tobacco use; an to co-occurring cannabis and tobacco use are shared overview may be found in Fig. 1. genetic influences. Gateways and reverse gateways Shared genetic predispositions A gateway drug (which is used prior to other drugs) Individual differences in tobacco use (or smoking initia- is distinguished by sequence, association (use