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Objective: This study investigated patterns of the simultaneous use of alcohol, tobacco and cannabis among young polydrug users, and whether use of one substance might be a cue for use of another and associations with the severity of substance dependence.

Methods: The study focused on 3 subsamples from the ongoing Swiss Cohort Study on Substance Use Risk Factors (C-SURF, N=5,990). It used 12 months of data on alcohol/tobacco co-users, alcohol/cannabis co-users and tobacco/cannabis co-users (N=2,660, 1,755 and 1,460 respectively. Simultaneous use, numbers of symptoms of substance dependence, and hazardous use of alcohol, tobacco and cannabis were assessed. The effect of simultaneous polydrug use (SPU) on the numbers of symptoms of substance dependence was tested using analysis of variance.

Results: Polydrug use was most common as SPU, and less common as non/occasional SPU. Moreover, when participants started to use one substance while using another, the severity of substance dependence was more strongly associated with the triggered substance than with cue.

Conclusions: This study highlights the necessity to take SPU into account. First, SPU rather than separate drug use was the most common pattern for polydrug users. Second, frequent SPU was associated with increased numbers of symptoms of substance dependence compared to non/occasional SPU. Furthermore, SPU may reveal the severity of substance use dependence, when substance use is triggered by a cue substance. For these reasons, SPU should be a serious cause for concern for prevention and intervention purposes.

Alcohol; Cannabis; Cue reactivity; Simultaneous polydrug use; Symptoms of substance dependence; Tobacco

Use of a single drug is very rare among drug users [1-4]. A common form of polydrug use (i.e. the use of more than one drug) is simultaneous polydrug use (SPU), which refers to the use of two or more substances at the same time, on a single occasion [5]. SPU remains an understudied topic, despite it being a widespread substance use pattern [6-8] which carries more health, social and mental-related consequences than other forms of non-simultaneous polydrug use [9]. Indeed, studies often focus on use of single drugs even though these drugs are often used together. More research is needed about related risks and consequences of SPU [10], even for the most common substances (alcohol, tobacco and cannabis). Furthermore, little is also known about the potential for substance use dependence of SPU in comparison with non-SPU, especially among young adults. This study investigated this topic.

Some studies have reported increased consequences and adverse effects of simultaneous alcohol and cannabis use [10-12], such as later substance-related problems (relational, academic, health) and dependence [13-15]. Others studies have shown that simultaneous use of tobacco and cannabis increased the risk of cannabis abuse and dependence [16,17]. Studies dealing with alcohol and tobacco co-use have shown that current smoking status predicts alcohol dependence [18,19], but these studies did not focus specifically on simultaneous use of alcohol and tobacco. Moreover, to our knowledge, no study has investigated different kinds of SPU. For example, one can smoke while drinking (i.e. alcohol use triggers tobacco use: start to smoke while drinking) or drink while smoking (i.e. tobacco use triggers alcohol use: start to drink while smoking). Substance users can show a pattern of use including either one of these simultaneous uses (e.g. smoking while drinking, but not drinking while smoking), or both. These aspects of substance use can be understood using the cue-reactivity model [20]. In this conditioning model of addiction, people with a substance dependence are highly susceptible reactive to cues from earlier use (e.g. environmental cues, such as a place, or physical cues, such as smell or sight). The ingestion of another psychoactive substance may also be a cue for the alternate substance [21]. Drobes [22] showed that alcohol cues promote cravings to smoke and that smoking cues trigger cravings to drink alcohol. However, this is true for drinkers who were alcoholic smokers, but not for nonalcoholic smokers, for whom smoking cues did not promote cravings to drink alcohol. Thus, encouragement to use a substance because another acts as a cue may reveal dependence to triggered substance. Nevertheless, to our knowledge, no studies have investigated how or whether people are more dependent to substances when their use has been triggered by a cue substance. Moreover, neither cannabis use as a cue for the use of other substances, nor cannabis use triggered by a cue substance has yet been studied.

The present study looked at the 3 most commonly used substances � alcohol, tobacco and cannabis and its aims were thus twofold. We investigated the patterns of SPU and the relationships between the severity of alcohol, tobacco and cannabis dependence and different kinds of SPU. We hypothesized that: a) the severity of substance dependence is most common with SPU, and less common with non/occasional SPU, and b) that the severity of substance dependence is more strongly associated with the substance that is triggered by the cue substance.

Sample

Alcohol use

Tobacco use

Cannabis use

Simultaneous polydrug use

Descriptive statistics were first computed to examine the patterns of non/occasional, partial and cross-simultaneous use for each polydrug use pairing. Multiple analyses of variance (ANOVA type III for unbalanced data) with pairwise post-hoc comparisons (Tukey’s honest significant difference test) were then performed to assess the differences between the 4 groups in each polydrug use pairing on the number of symptoms of substance dependence. Six models were tested in total. In each of the 3 subsamples, one model was tested for each of the related symptoms of dependence (e.g. alcohol and nicotine dependence for the subsample of alcohol/tobacco users). We performed multiple ANOVA because we adjusted results for hazardous use, as level of use may affect substance dependence. A Bonferroni correction was performed in post-hoc comparisons to keep the type I error rate at 5%. All analyses were performed using SPSS 21 software.

Table 2 summarizes the descriptive statistics. Combining alcohol/tobacco was more common than combining alcohol/cannabis, or combining tobacco/cannabis (respectively 42.4%, 28.9% and 23.9% of the whole sample). Non/occasional SPU was quite uncommon (11.6% for alcohol/tobacco users; 32.4% for alcohol/cannabis users; 28.1% for tobacco/cannabis users). Cross-simultaneous use was more frequent for alcohol/tobacco (49.4%), whereas drinking while using cannabis or smoking was more frequent for alcohol/cannabis users (35.7%) and tobacco/cannabis users (38.8%). Using cannabis while drinking or smoking was the least common pattern (12.8% of the alcohol/cannabis users, and 6.0% of the tobacco/cannabis users).

The number of symptoms of dependence and disorder were low for all the 3 SPU subsamples. However, all 3 subsamples revealed hazardous use at non negligible prevalence rates, especially for alcohol use (range across the 3 subsamples: alcohol: 63.1%�69.5%; tobacco: 45.5%�49.8%; cannabis: 31.3%�35.1%).

Number of symptoms of substance dependence according to the SPU pairing

This study investigated the SPU of 3 pairings of widely used substances: alcohol, tobacco and cannabis. It aimed to explore SPU patterns and the relationships between different kinds of SPU and severity of substance dependence.

First of all, SPU seems to be a usual drug use pattern among young adults, especially for combinations of alcohol with another substance. Cross-SPU and partial forms of SPU were more frequent than non/occasional SPU for all 3 combinations of substance pairings. As reported in previous studies, frequent SPU seemed to be the most common pattern of polydrug use [6-8]. Furthermore, different kinds of SPU were distinguished with regard to each subsample pairing. Alcohol and tobacco were often cues triggering cannabis use (35.7% and 38.8%), whereas alcohol and tobacco accompany each other (cross-SPU) for almost half of the alcohol and tobacco users. Cannabis as a cue triggering alcohol or tobacco use was a less common pattern (12.8% and 6.0% of participants, respectively). This result seemed consistent with the pathway that goes from licit drugs (alcohol, tobacco) to cannabis use [28-32].

The polydrug pairing users showed different numbers of symptoms of substance dependence according to their patterns of simultaneous use. First, cross-SPU participants showed a higher number of symptoms of substance dependence than other forms (non/occasional SPU or partial SPU), except in 4 cases out of 18. That is, participants who frequently used substances simultaneously were more dependent on them than participants who reported other forms of SPU, and this was independent of the level of use of each substance, as we adjusted for hazardous use. This result was consistent with our first hypothesis, a), which supposed that the severity of polydrug dependence is most common with SPU rather than with non/occasional SPU. This result replicated those reported for alcohol and cannabis co-use [13-15], tobacco and cannabis co-use [16,17], and alcohol and tobacco co-use [18,19], even these results did not specifically focused on SPU.

However, frequent SPU was not necessarily synonymous with an increased number of symptoms of substance dependence compared to more occasional SPU. When the participants started to use one substance while using another (partial forms of SPU), the number of symptoms of substance dependence was higher for the substance that was triggered by the cue, as reported in the cue-reactivity model [20]. For example, the number of symptoms of nicotine dependence was higher among users who started to smoke while drinking (alcohol cue triggered tobacco use), than for users who never or occasionally used these 2 substances at the same time, but the number of symptoms of alcohol dependence in this group did not differ from the number of symptoms of occasional/non SPU users. Thus, severity of substance dependence was not only related to the frequent versus non/occasional SPU, but also to the kind of SPU. People who light a cigarette while drinking (alcohol cue triggered tobacco use) may be more addicted to nicotine than people who poured themselves a drink while smoking (smoking cue triggered alcohol use). When the use of one substance was triggered by the use of a first one, the need to start using the second one seemed related to the severity of dependence to this substance. It is possible that the more participants were dependent on a substance, the more they felt the craving to start using it while using a cue substance. These results were highlighted among alcoholic smokers (i.e. alcohol-dependent users), for whom smoking cues trigger cravings to drink alcohol [22]. Data are scarce for the other substances. Previous studies did not focus on substance dependence and substance use as a cue, but on craving and other cues such as visual ones (e.g. pictures of glasses of beer or cigarette packs). For example, for alcohol cue and cravings to smoke, Carpenter et al. [33] showed that daily smokers reported a higher response to alcohol visual cue rather than occasional smokers. Polydrug use has been well studied for alcohol and tobacco use [34], and we know that cigarette smoking increases during alcohol self-administration and vice versa [35]. For cannabis and alcohol, a study reported higher craving to use cannabis among cannabis users when they were presented a visual stimulus related to alcohol (not controlling for baseline craving) [36]. For cannabis use as a cue for nicotine dependence, we only know that cannabis use is a predictor of nicotine dependence, according to the reverse gateway theory [37]. Indeed, studies with cannabis cue are very rare [38]. This study filled in the gap for substance use as a cue for polydrug dependence for the couple of substance alcohol/cannabis and tobacco/cannabis. Therefore, the specific type of partial SPU may be an indicator of severity of substance dependence, and further investigations will be necessary to explore this assumption. This result was consistent for all 3 polydrug use pairings and was related to the severity of dependence, except for the number of symptoms of alcohol dependence: When alcohol/tobacco users drank while smoking (smoking cue triggered alcohol use), they did not have more symptoms of alcohol dependence than users who smoked while drinking (alcohol cue triggered tobacco use). However, they did have more symptoms of alcohol dependence than non/occasional simultaneous users. These results were consistent with our second hypothesis, b), which suggested that the severity of substance dependence is more strongly associated with the triggered substance than by the cue substance.

This study has some limitations. The first was that we assessed frequent SPU versus non/occasional SPU instead of presence of SPU versus absence of SPU. Indeed, it was difficult to assess presence versus absence, because SPU was the most common pattern among polydrug users (67.6%âÂ?Â?88.4% of frequent SPU) and total absence of SPU was rare. Thus, this assessment was not able to show the “pure” effect of presence of SPU versus absence of SPU. The second limitation was the study’s cross-sectional design. It was impossible to show whether more frequent SPU leads to an increased severity of substance dependence, or whether more frequent SPU was a consequence of the severity of substance dependence. Further longitudinal studies are needed to verify the hypothesis of SPU’s harmful effects (i.e. SPU worsened substance dependence). A third limitation was that no women could be included. This study is largely representative of men, but further investigations will be needed to know if women show the same patterns of SPU and substance dependence. Indeed, previous studies showed that polydrug use was higher among men than women (see for example Font-Mayolas et al. [39]). It is also the case for SPU [40]. Concerning cue reactivity, results are inconsistent. Some studies reported that women seemed more sensible to cues [33], others reported that men were [41], whereas others did not find any difference [42]. More investigations are needed on this topic. Finally, a last shortcoming was that at age 20, the participants were more likely to still engage in experimental substance use rather than dependent substance use. For example, withdrawal seems rare among youth. On the opposite, young people are likely to experiment tolerance and hazardous use [43]. To avoid misinterpretations and use of an inaccurate diagnose [44], we used the whole continuum of severity instead of a threshold. Indeed, studies reported that the total information provided by the dependence criteria was comparable among younger and older adults [45].

This study provided insight into the patterns of simultaneous polydrug use. Two results highlighted the necessity of taking SPU into account. First, frequent SPU was the most common pattern for young polydrug users and few of them never or occasionally used substance pairings at the same time. Second, a frequent SPU was associated with increased severity of substance dependence compared to non/occasional SPU. For both these reasons, SPU should be a serious concern for drug use prevention and intervention purposes. Moreover, the kind of partial SPU (i.e. one substance is a trigger for a second one) should be considered, as the level of use of a substance, triggered by a cue, reveals the severity of dependence to that substance.

SPU is a common pattern of drug use among young polydrug users. A frequent SPU was associated with increased severity of substance dependence compared to non/occasional SPU. When a substance is a trigger for a second one, it reveals the severity of dependence to that second substance.

Swiss National Science Foundation FN 33CS30_139467.