The results of this study showed that, compared to the cisgender population, transgender individuals have a greater probability of current use of tobacco and specific substances and of having consumed any substance over their lifetimes. In relation to tobacco, we found that the use of cigarettes, cigars, or e-cigarettes was higher among transgender individuals compared to their cisgender peers [31]. In a study that included 350 transgender people, 64% reported having used tobacco, 23% had perceived their use as problematic at some point in their lives, and 13% believed their use was currently problematic [46]. Indeed, previous studies have highlighted the structural discrimination suffered by the transgender population as one of the factors motivating their increased tobacco consumption, suggesting that this consumption is related to the desire of this populace to reduce their perceived stress levels [47].

In addition to structural discrimination, part of the transgender group is also regularly exposed to situations of social exclusion, marginalisation, and sex work in which drug use (mainly tobacco use) is very frequent [48]; these situations are more likely to occur in the group of transgender women compared to transgender men. This led some studies to explore intragroup differences, which indicated a higher prevalence of tobacco use among transgender men compared to transgender women [31]. Other work described the opposite, with a higher risk of tobacco and other drug use found among the group of transgender women [49]. However, still other studies pointed towards heterogeneity between the general transgender population and the cisgender men group, with an increased prevalence of tobacco use among these aforementioned groups compared to the female cisgender group [48].

All these discrepancies mean that more intragroup studies of the transgender population compared to the cisgender population will be required to assess the association between the experience of discrimination and the use of tobacco. In our study, the prevalence of consumption was higher, while in the other study, the age of consumption onset was earlier in the transgender group, often in the early stages of adolescence [50]. These data, which point to greater vulnerability of the group as the result of the discrimination they are subjected to, tended to homogenise in adulthood because of the increased concern for health and a desire to stop consuming among this population [51]. Of note, when we considered tobacco use disorder in this current study, we found no differences between the transgender and cisgender groups, although the small number of studies included in this analysis meant that our confidence in the reliability of this result was poor.

Regarding substance use, our results coincided with other studies indicating that transgender people have a higher prevalence of substance use than cisgender people [23,35,52]. Specifically, one study estimated that transgender students were twice as likely as their cisgender peers to use cocaine or amphetamines and three times as likely to abuse inhalants [35].

Another problem was the misuse of prescription drugs, which was associated with lower self-esteem, greater discrimination based on gender identity, and increased self-reported symptoms of anxiety, depression, and somatic distress [53]. Moreover, this misuse was more frequent in binary transgender men and non-binary individuals, compared to binary transgender women [54]. Indeed, 24% of transgender women reported misuse of prescribed medications, in particular highlighting the use of analgesics (21.2%), anxiolytics (14.4%), stimulants (12.5%), and sedatives (8.7%) [53].

The factor most strongly associated with abuse, especially in the case of prescription opioids and tranquilisers, was the age at which the first medication had been prescribed, with transgender students being twice as likely to abuse analgesics compared to their cisgender peers [35,55]. However, no differences were found in this study between transgender and cisgender people in terms of general substance use or substance use disorder. These results contradict previous studies showing that transgender people were more likely to suffer from a substance use disorder, specifically with amphetamines, cocaine, or cannabis [52,56,57]. Nonetheless, our analyses included a small number of studies; therefore, the results must be interpreted with caution.

Several hypotheses have been proposed about the reasons for this relationship between substance use and identifying as transgender. One of the most accepted of these is the minority stress theory [58,59,60], which considers that the stigma, prejudice, discrimination, and harassment these individuals regularly receive from society could favour the appearance of depression, anxiety, or suicidal ideation, given that the prevalence of these disorders is higher in this group compared to their cisgender peers [61,62,63]. Thus, the use of substances would arise as a response to this discomfort and as a product of both internal factors (self-stigma, expectations of rejection, and non-conformity with self-image) and external factors (interpersonal and structural discrimination) [23,64].

Furthermore, the scarcity of specific resources aimed at the transgender demographic, as a consequence of institutional discrimination, would act as a trigger for consumption in this context [65,66,67]. In this sense, other studies indicate that substance abuse is linked to symptoms of depression in transgender women [68], increased stigma [69], and being a victim of transphobic discrimination [70]. Moreover, the risk of violence victimisation has also been significantly associated with substance misuse [55], especially in students who identify themselves as transgender or male. [71].

Another hypothesis to explain the higher prevalence of substance abuse among transgender individuals considers consumption as an emotional regulation strategy or a maladaptive coping mechanism to deal with traumatic experiences [41,67]. Some studies concluded that the presence of trauma in the biography of transgender individuals is decisive, given that, for example, more than half of transgender women consumers report having experienced some type of trauma in their lives [69]. In fact, compared to the cisgender population, young people from sexual minorities are more likely to have been victims of child abuse [46].

It is also interesting to consider the impact of psychiatric comorbidities on illicit substance use as a possible moderator. Most papers included in our analysis did not explore this relationship, but there is evidence that transgender people suffer a high prevalence of mental health disorders, highlighting anxiety [72], depression, self-harm, and suicidal ideation [73]. Previous studies carried out in the cisgender population demonstrated the impact that psychiatric comorbidities have on substance abuse, increasing the severity of addiction and functional impairment [74]. Although there are no specific studies focused on dual disorders in transgender individuals, the prevalence of psychiatric comorbidities in this population led us to hypothesize that substance abuse could be modulated by these diseases, being more severe and requiring a comprehensive approach that integrates or improves coordination between substance abuse and mental health care systems [74].

The most unexpected result of this present study was that there were no differences in the probability of presenting alcohol use or alcohol use disorder between cisgender and transgender people. In contrast, previous studies have postulated that one of the toxic substances with the greatest presence among the transgender population is alcohol [46,51,56]. Indeed, 60.4% of this population reported consuming alcohol regularly, and 24.3% reported having drunk excessively in the last 30 d [70]. In addition, it has been shown that transmasculine people are more likely to report binge drinking compared to transfeminine individuals, with this finding being linked to sex work in both cases [75].

Among transgender women, binge drinking was significantly higher in those who used amphetamines, had depressive symptoms, dropped out of school because of their gender identity, or had experienced verbal abuse [8]. In this sense, those who experience sexual abuse are also three times more likely to use cocaine, and those who had made suicide attempts had a higher risk of using marijuana [69]. To explain this divergence, it is important to remember that alcohol is also one of the drugs with the greatest presence in general society [76]. For example, in the USA (where most of the studies included in this work had been conducted), more people aged over 12 y had used alcohol in the year prior than any other drug or tobacco product, and alcohol use disorder was the most common type of substance use disorder [77].

The fact that no differences in the probability of presenting alcohol use or alcohol use disorder were found between cisgender and transgender people could perhaps be explained because of (1) the factors described in the previous paragraph, (2) the large sample size of our study, and (3) the enormous disproportion between the transgender and cisgender groups in the studies we considered, with the latter meaning that transgender people accounted for less than 1% of our sample. Thus, it is possible that the difference in prevalence of each individual study would have been insufficient to reach statistical significance when the combined probabilities were calculated. Another reason for this discordant result could be that the statistical difference found in these studies was not clinically significant. A debatable issue is that we considered binge and heavy drinking as abuse, and therefore, we included it in alcohol use disorder. We did this because we considered that a consumption of this entity is practically impossible not to cause some negative consequence, so we differentiated it from the use of alcohol, which would be a moderate consumption limiting intake to two drinks or less in a day for men and one drink or less in a day for women.

The fact that several studies were in populations from sexual and gender minorities may have also influenced the results, meaning that the prevalences would have been more similar than if they had been compared to the general cisgender population. Regarding alcohol use disorder, many of the studies we considered included samples of young people in which it may have been too early for the disorder to have established. In spite of all the above, our favourite hypothesis is that as the rights of sexual and gender minorities advance and the stigma decreases, the prevalence of consumption will gradually equalise between cisgender and transgender people.

As limitations of this study, the main is the heterogeneity between the studies we included with respect to their populations (students, general population, sexual and gender minorities, sexual workers), cohort age (a minimum of 29% of the sample was under the age of 18), consumption type (current use, lifetime use, abuse, and dependence) and how to evaluate it, and substances evaluated. The heterogeneity and sensitivity analysis and the low number of studies in some of the analysis and categories did not allow the analysis of specific subgroups, but the influence of variables such as age, sample type, and other identities is an open question. Likewise, the search terms used could have left studies referring to a specific substance out of the results. The fact that these terms were in English probably influenced that all the studies were in that language and, except for two, the rest were carried out in North America (most of them in the United States). Nonetheless, no publication bias was detected, and the sensitivity and subgroup analyses indicated that the results were robust. Another limitation was the small number of studies included in three of the analyses, which meant that we did not have reliable results regarding general substance use, tobacco use disorder, or substance use disorder. Furthermore, in some studies, we had to calculate the OR directly from the data, and so, this figure had not been adjusted for other relevant variables in these cases. However, we considered that the adjusted ORs would probably have been smaller than those we found, and so, the result regarding alcohol would have likely remained the same. The lifetime substance use analysis could be less informative due to the inclusion of tobacco and alcohol; however, the sensitivity analysis indicated that excluding these studies would not substantially change the result. Another limitation is that the quantity and frequency of use were not assessed.

Finally, the transgender and cisgender populations were directly compared without segregation, according to the sex assigned at birth, sexual orientation, or the binary–non-binary variable. We performed the analysis in this way to obtain a first quantitative synthesis of the difference between the transgender and cisgender populations and because, otherwise, even less data would have been available in some of our analyses. The availability of this quantitative synthesis is precisely the strong point of this current study. However, in order to obtain more information in this regard and perform intragroup analyses, as several of the articles included in this study did (29, 36–38, 40, 41, 44), future studies should always report segregated results. Moreover, it would also be interesting to promote studies in the general population specifically focused on the transgender population, not only as part of the 2SLGBTQIA+ collective.

Taking these limitations into account, our data indicated that, compared to cisgender people, transgender individuals had a higher risk of presenting tobacco and substance use, but they did not differ in terms of alcohol use or alcohol use disorder. Two conclusions follow from this. First, although transgender participants were more likely to use tobacco and substances, this probability was not much higher than that of cisgender individuals. Indeed, this difference reached a ratio of only 2:1 when the data that generated heterogeneity in the consumption of specific substances were eliminated. In addition, there were no differences for alcohol use or for any substance use disorder. Thus, we would like to think that, as the stigma suffered by this population progressively reduces, consumption will also decrease. In turn, this could reduce the prejudice and stigma of considering this population as people who use drugs and as “addicts”.

Second, although our study did not test it, hypothetically, the greater probability of tobacco and substance use among transgender individuals may constitute an emotional regulation strategy or a maladaptive coping mechanism in the face of traumatic experiences. This strategy could also respond to minority stress caused by stigma, prejudice, discrimination, and bullying. However, the desire to reduce substance use was similar between transgender and cisgender people, with transgender individuals reporting a greater need for help and being more likely to seek it [78]. The problem is that detoxification and drug dependency treatment centres are designed to serve cisgender heterosexual populations, and so, apart from exposing themselves to stigmatic and prejudiced attitudes, transgender people also face heteronormative barriers in structural and programmatic elements [79].

Thus, specialised substance abuse interventions must take gender minorities into consideration, and the professionals delivering them must have sufficient training to provide this demographic with appropriate care by, for example, considering the influence of minority stress [65]. This is especially important for prevention, as our findings showed that transgender people do not have higher odds of substance use disorder, but rather are more likely to use substances, especially at younger ages (since much of the sample was middle/high school students). It is critical to address addiction prevention in relation to sexual identity, lived experiences, related stressors, social and cultural contexts [64], and risky sexual behaviours [56]. To do this, anti-discrimination and stigmatisation policies must be implemented, and substance abuse prevention and treatment services should be adapted to be inclusive of the 2SLGBTQIA+ community. More research will be required to explore the barriers to accessing specialised services that transgender individuals experience. This would allow researchers to understand the specific needs of this population and develop preventive interventions and adapted treatments [24,80]. To ensure that substance abuse treatment services are inclusive, it would perhaps be advisable to register gender identity and to design specific interventions for this demographic.