Mood disorders may be caused by substance use disorders including methamphetamine (MA) and alcohol use disorders [1]. According to a record from a large treatment centre for substance abuse in Thailand, 40,419 patients received treatment for illicit substance use in 2018, while this number increased to 53,420 in 2022 [2]. In addition, 79.2% of Thais receiving treatment for illicit substance abuse used MA, and 46.39% of all subjects using addictive substances used MA, followed by alcohol (20.18%) [2]. According to information from the 2013 Thai National Mental Health survey, the lifetime and current prevalence of alcoholism are 18.0% and 5.3%, respectively [3].

MA is a derivative of amphetamine that stimulates and energises the user [4], whereas alcohol is a central nervous system depressant [5]. Alcohol use disorder is associated with other substance use disorders and psychiatric disorders, as well as a multitude of adverse health effects. For instance, excessive and long-term alcohol consumption can lead to obesity, hypertension, liver cirrhosis, and cancer if used excessively and continuously [6]. Furthermore, the concurrent use of alcohol and MA may exacerbate the health risks associated with each substance alone [7].

This information shows the importance of examining patterns of alcohol and MA co-use on well-being and suicidal behaviors which are directly associated with alcohol use. Alcohol plays a role as a catalyst for suicidal ideation and behaviors through disinhibition, impulsiveness, and impaired judgment, and is often used as a way to cope with the distress associated with suicidal ideation [8]. Alcohol drinking patterns also predict an increased risk of suicide in those with psychiatric disorders including mood and anxiety disorders [8–14]. Mood and anxiety disorders, suicidal behaviors, and alcohol use are very strongly interrelated phenomena [15–18]. Moreover, MA use and alcohol use disorder are associated with poor health-related quality of life (HR-QoL). For example, long-term use of MA is associated with disabilities and illnesses, including cardiopulmonary disease, cognitive deficits, depression, anxiety, and suicide, which all cause a lowered HR-QoL [19–21]. A few examples among many others, co-occurrence of MA use and alcohol drinking may cause an increased risk of cardiovascular dysfunctions when compared to either drug taken alone [22]. Most clinical trials on MA dependence have excluded alcohol-dependent participants or did not present information on alcohol use [23].

Hence, the aim of this study is to examine the associations between alcohol drinking and MA use among MA users in relation to suicidal behaviors, mood disorders, and HR-QoL. The specific hypotheses are that the severity of alcohol and MA use in MA users are interrelated phenomena that adversely affect HR-QoL and increase suicidal ideation, and which are predicted by a lifetime history of mood disorders.

The results of our study show that in individuals who used MA, there is an inverse association between the severity of current MA and alcohol use and between a lifetime history of alcohol dependence and the severity of MA use. These inverse associations may perhaps be explained by the opposite properties of both drugs, whereby alcohol, a sedative depressant, may counteract the stimulant effects of MA [31]. Moreover, alcohol may inhibit the metabolism of MA as indicated by lowered p-hydroxylated metabolites in the urine of MA users [32]. Thus, it is possible that persons who used MA attenuate their alcohol use in an operant fashion to reduce the adverse effects of their MA use. It is also plausible that patients with alcohol dependence attenuate their MA use to decrease possible interactions between both drugs. Thus, persons who used MA have an increased risk when drinking alcohol to reach intoxication levels [33] as shown in a study that alcohol dependence was a predictor of MA-induced paranoia [34]. The co-use of MA with alcohol increases MA levels and the metabolite amphetamine [35]. In addition, both MA and alcohol stimulate mesocorticolimbic dopaminergic metabolism causing possible synergistic effects [36, 37]. These and other interactions may have undesirable clinical effects including deficits in learning and spatial memory and increased heart rate [35]. It is also plausible that the severity of MA use depends more on internal factors such as substance preference and other personal characteristics rather than on external factors, including preexisting use of alcohol [38].

Here we underscore that these inverse associations observed in our study between the severity of MA and alcohol use do not contradict the well-known comorbidity between both disorders. A recent review indicates that, in persons with MA dependence, the prevalence of alcohol use disorder is 75% [35]. Moreover, some studies report that persons with MA use disorder may have a higher consumption of alcohol or alcohol dependence than those without MA use [32], whereby co-use may mask clinical signs of alcohol intoxication (e.g., sedation) with the risk of developing alcohol toxicity [34]. According to Kirkpatrick et al. [22], MA and alcohol use can augment the pleasurable effects of each other and additionally reduce the negative behavioral effects of each other, indicating that there is a predictable pattern in co-using alcohol and MA. This relationship seems more intense in individuals with low MA dependence severity and individuals with heavier alcohol problems [31]. Although alcohol use is related to a greater risk of MA use on the same day, lagged analyses show no relationships between the previous day’s alcohol use and the risk of MA on the following day after controlling for the previous day’s MA use, or vice versa [39].

Another finding of our study is that the severity of alcohol and MA use, a lifetime history of mood disorders, and female sex predict to a large extent suicidal ideation. This may be explained by findings that alcohol use predisposes towards suicidal behaviors following depressogenic effects of alcohol or greater negative life events following alcohol use [40, 41]. The same authors also proposed that a decrease in problem-solving skills and aggravation of impulsive personality traits, related to serotonin neurotransmission, may be involved [41]. In adolescents, there is also a strong relationship between alcohol-related disorders and suicide attempts as shown in the National Comorbidity Survey [42]. Moreover, psychological autopsy studies report a strong relationship between alcohol use and suicide [42]. Results from meta-analysis studies indicate that drug use and alcohol dependence are largely associated with suicide and that individuals who show heavy alcohol consumption display a five-fold increased tendency towards suicide [43]. There are also reports that injected MA use is accompanied by increased suicidal behaviors [44]. However, Kennedy et al. [45] found that alcohol use is directly associated with a higher risk of suicidal behaviors independent of the use of illicit drugs, while in our study both severity of alcohol and MA use were associated with increased suicidal ideation, although the impact of alcohol use was more important.

In the present study, we found a significant association between mood disorders (lifetime diagnosis) and severity of MA use, but not alcohol use in persons who used MA. These data extend previous findings showing that individuals who use MA injections have significantly more symptoms of depression [46]. Another study found that individuals who abstained from MA have significant reductions in depressive symptoms during treatment [47]. In this respect, it is interesting to note that negative emotionality predicts later substance use disorders in longitudinal studies, which is explained by the effects of negative reinforcement [48]. The current study found that the severity of alcohol use, but not MA use, is greater in males than in females. It is known that men show a greater prevalence of co-occurrence of alcohol and other drug use disorders as compared with women [49]. Male drinkers are more likely to drink high volumes than women, while women are more likely to abstain from alcohol during their lifetime [50].

Finally, the current study found that in persons who used MA, the severity of MA and average alcohol consumption had a strong effect on HR-QoL. These findings extend those of previous papers showing that MA-dependent individuals who completed treatment and continued care have a better HR-QoL [51]. HR-QoL improvement following a residential treatment is shown to correlate with low HR-QoL scores at admission, whereas improvement in physical domain of HR-QoL is related to less alcohol intake and better somatic status [52]. In this respect, Neale [53] reported that drug users have poor physical health expectations and therefore, perceive their health status better than the actual HR-QoL. One study showed that increasing regularity of alcohol use is associated with a better HR-QoL in both male and female subjects [54]. MA use may affect mental and physical HR-QoL through a variety of mechanisms including the induction of side effects such as weight loss, insomnia, mood swings, increased heart rate, delusions, tweaking, cognitive deficits in episodic memory and executive functions, confusion, cardiovascular disorders, inflammation, neuroinflammation, oxidative stress, and increased gut permeability [55–60].

The current study’s findings should be discussed in light of its limitations. First, the study would have been more interesting if we had also assayed biomarkers of MA use and suicidal behaviors, including the cytokine network. Second, it is interesting that females in this group seem to be more prone to suicidal ideation when drinking, however, there are only two female subjects in the high alcohol use disorder group. Third, our finding that high MA use may predict less alcohol use may initially appear puzzling. Nonetheless, we have an overall population of heavy drinkers, and the results presented pertain to heavy alcohol consumption in general. The knowledge gained by amphetamine and cocaine users who consume alcohol more frequently may be applicable to a lower intensity.

In conclusion, the results show that, among MA users, the severity of alcohol use is significantly associated with lowered MA use and male sex, while predicting suicidal ideation but not HR-QoL. The intensity of MA use is the single best predictor of a lowered HR-QoL in MA users and is additionally associated with more suicidal ideation.