The coexistence in an individual of an addictive disorder and a mental disorder in a specific period of time is frequent, and is called dual pathology (DP)
[28]. Thus, DP occurs in patients with symptoms that fit the criteria for two different psychiatric disorders, one of them being an addiction. DP is underdiagnosed and poorly treated
[41]; in fact, it is not officially recognized in the DSM or CIE nomenclature. However, the term dual pathology is similar to other more commonly used terms, such as dual diagnosis, comorbid or co-occurring disorder or psychiatric comorbidity
[41]. The prevalence of DP is high, with 65–85% of addicts in treatment that report having another psychiatric disorder
[42] and about 45% of psychiatric patients that report having an addiction
[43]. Scientific evidence supports the link between disorders present in DP; therefore, access to a single multidisciplinary care model that integrates and coordinates the mental health network and the addiction network is advocated, enabling personalized bio-psycho-social treatments that do not leave any addict unassisted
[26][27].
Among all the psychiatric pathologies related to cannabis use, psychosis has been the most widely studied. In an international study with volunteers from 11 locations in Europe and Brazil, it was observed that the probability of developing a psychotic syndrome among daily cannabis users was two to three times higher than in non-users, while in those who used high-potency cannabis, it was one to six times higher than in non-users. This study also highlights the positive relationship between the use of cannabis with higher than 10% THC levels and the development of certain types of psychosis
[45]. Not all studies are so categorical in their conclusions, as there are other predisposing factors, such as genetics or childhood trauma
[46]. However, increasing evidence indicates a high risk of developing psychosis after frequent cannabis use, especially with high THC levels
[24][40]. Both natural and synthetic cannabinoid use in young people has been associated with the occurrence of transient and dose-dependent positive and negative schizophrenic symptoms in healthy individuals not at risk for schizophrenia. However, in adolescents who do present such risk factors, they would cause an earlier onset (between 2 and 6 years of age) and a worse prognosis in the development of schizophrenia
[23].
3. Gender Differences in the Development of Psychotic, Depressive and Anxious Symptoms Associated with Cannabis Use
The interest in incorporating the gender perspective in dual pathology is quite recent
[27]. Some reviews have examined the roles that the interaction between gender and cannabis use have on the development of psychosis
[4][53]; however, recently, Prieto-Arenas and Díaz
[54] have performed a systematic review on clinically based research evidence of gender differences in the development of psychotic, depressive and anxious symptoms associated with cannabis use. That systematic review was performed on the main databases (PubMed and Web of Science) following PRISMA guidelines on clinical studies published until December 2020. The most important findings to date from the reviewed studies on gender differences in the association between cannabis use and the psychiatric symptomatology described below are summarized in
Table 1.
Table 1. The most important findings to date from the human literature on gender differences in the association between cannabis use and the development of psychotic, depressive and anxious symptoms. M: male; F: female; CUD: cannabis use disorder.
Reviewing the human literature that evaluates the association between cannabis use and the development of psychopathologies, some studies show that cannabis use increases the risk of first-episode psychosis and the development of psychosis more in men than in women
[4][53][55], a fact that could be attributed to the greater polyconsumption that men perform
[56]. However, when the substance consumed is a synthetic cannabinoid, the risk increases in both sexes
[57]. We must bear in mind that these designed drugs have higher levels of THC, which has been related to the appearance of psychiatric comorbidity
[24][29]. However, gender differences are not so conclusive when it comes to the effects of cannabis on the age of onset of psychosis. While some studies relate the use of cannabis with an earlier start of first-episode psychosis in both sexes, without finding gender differences
[5][53][58][59], other studies find that the use of this drug reduces the age of onset of psychosis more in women than in men
[4][60][55][61], eliminating the gender differences observed in general in the age of onset of psychotic disorders
[58].
Thus, cannabis use, whether recreational or compulsive, has been related to the appearance of symptoms of psychosis in both the adolescent
[62][20] and young population
[63], and in subjects with risk factors for the development of psychosis
[64]. In a nonclinical population of university students, women reported greater intensity of psychotic experiences associated with cannabis use than men
[63]. Women with risk factors for the development of psychosis also presented a greater severity of general psychiatric pathology related to the consumption of this drug
[64]. However, in this same population, male users exhibited a greater severity of negative psychotic symptoms
[64].
On the other hand, women diagnosed with a CUD also showed more psychotic and depressive symptoms than men of the same age range (23–25 years), although there was no relationship between the frequency of cannabis use and the age of onset of symptoms
[20]. In addition, it should be noted that after one year of treatment, men with CUD significantly reduced their use of cannabis, while women did not
[65].
Among patients with first-episode psychosis, cannabis use has been observed to worsen psychological, social and work activity in men, while the opposite result was surprisingly found in women
[21]. This finding could be due to the lower number of women being evaluated in the study; therefore, more in-depth research is needed to fully understand this fact
[54].
In contrast, in patients with a cannabis-induced psychotic disorder, it is men who have a greater severity of general psychopathology, in addition to a greater intensity and prevalence of positive symptoms
[66], while women show more negative symptoms
[65]. This coincides with two reviews in which it is concluded that cannabis use in men increases the manifestation of psychotic symptoms and hospitalizations
[4][55]. However, other studies do not find these gender differences in first-episode psychosis patients, finding a similar severity of clinical symptoms and length of hospitalization period in both sexes
[3][21]. It should be noted that with the use of synthetic cannabis, the levels of agitation in women with psychotic pathology increase compared to those of men
[57].
In summary, we can affirm that all the studies demonstrate the existence of an association between the use of cannabis and the appearance of psychotic symptoms. However, despite gender differences being observed, they are not always confirmed by all studies, depending mainly on the population studied
[54]. It seems that female cannabis users would manifest a greater intensity of psychotic symptoms and general psychiatric pathology in both the previously asymptomatic population and people with a problematic use of cannabis
[62][20][63][64]. Therefore, cannabis use appears to be a higher risk factor for women than men, and is associated with a worse prognosis of schizophrenia
[53] and CUD
[65] in women. On the other hand, although male cannabis users with first-episode psychosis showed a worse quality of life
[21], there were no gender differences in the severity of clinical symptoms
[3][21]. Nonetheless, when cannabis has already induced a psychotic disorder, it is men who show a greater severity of general psychopathology
[66].
Cannabis use has generally been associated with depressive symptoms
[51]. However, while some studies have shown that women present this cannabis-related symptomatology to a greater extent than men
[67], others do not find such differences
[61][63]. Therefore, this association should be specified, since some studies focus on gender differences found in the development of depressive symptoms, others in major depression and others in suicidal ideation
[54].
The increase in the frequency of cannabis use is predictive of depressive symptoms in adolescents of both sexes
[68][69], although more significantly in women
[68][69][70], who show greater psychological distress than men
[71]. These results coincide with the fact that women present more depression in the general population
[7][8]. On the other hand, other studies indicate that cannabis use is a predictor of depressive symptoms with a greater severity only in men
[72][73], which is maintained over the years
[74]. This would explain why cannabis use has been seen to increase the probability of developing episodes of major depression in males
[75]. This notwithstanding, gender differences between cannabis abuse and major depression have not yet been found
[71].
Among subjects with cannabis misuse, men show more depressive symptoms at younger ages (19–20 years), while women show higher depressive and somatization symptoms
[76][62][70][77][78] at later ages (23–25 years)
[20]. Probably, these gender differences in the age of onset of depressive symptoms are due to the fact that men start consumption earlier in life
[56].
It has also been described that women with risky cannabis use show a higher possibility of suicide than men in late adolescence
[76]. However, men manifest a greater probability of suicidal ideation when increasing the frequency of consumption
[61][79], and the gender differences disappear when the sample is extended to the general population
[79]. On the other hand, although no relationship has been found between the risk of suicide and the age of onset in the development of CUD in any sex
[76], a relationship has been observed between the suicidal history and the onset of cannabis use in women
[61]. This is in keeping with the fact that the main reason for consumption reported by women is to relax and reduce stress, probably using cannabis as self-medication
[21][20].
Additionally, female cannabis users with first-episode psychosis or diagnosed psychosis have shown greater dysphoria and depression than men
[65][64][66]. However, among psychotic males who use cannabis daily, two trends have been found according to age.
While it is observed that the increase in the frequency of consumption reduces the probability of suicide attempts in the youngest, when the age range increases (35–64 years), there is a relationship between daily consumption and a greater number of suicide attempts compared to non-users [80]. This change in the direction of the relationship between use and suicide in men could be the result of differences between the acute and chronic effects produced by cannabis [31].
Finally, there are few studies that relate cannabis use to the development of anxious symptomatology, as most studies focus on assessing anxiety as a risk factor for its use. In general, women have the highest levels of anxiety and related disorders among adolescents [20][70], the general population [20][64][67][81], and psychiatric patients [76][66][77][78], with the biggest gender differences found in late adolescents [20]. Specifically, it has been described that the men and women with low stress tolerance are those who show the most problems related to cannabis use, and in particular women who use the drug as a stress-coping mechanism [82], in a manner similar to that previously commented upon [21][20]. Hence, a positive relationship has been found between cannabis abuse and generalized anxiety disorder in women in the general population, while men showed a negative relationship with panic disorder [81]. In addition, women manifest greater anxiety than men in the periods of abstinence [61][83]. As observed with depression, Foster et al. [76] found no relationship between the age of onset of CUD and anxiety problems.
In conclusion, the scientific evidence reveals the existence of gender differences in psychiatric symptoms associated with cannabis use, although the direction of such differences is not always clear [54]. A lack of information in studies about variables such as the THC level in the cannabis used, the frequency of use or the age of onset of cannabis use makes it difficult to know the causes for the conflicting results. Besides, few studies consider the specific characteristics of women diagnosed with dual pathology, although all the data indicate a higher prevalence of drug-associated pathologies and a worse prognosis in women [27]. For this reason, it is necessary to delve deeper into this issue and address gender differences to create more individualized prevention strategies and more effective treatment for dual disorders related with cannabis abuse.