More than half (57.9%) of the people who had used opiates for a long time in our study were diagnosed with an opiate use disorder. Opiate users with an OUD diagnosis were relatively younger than those without OUD and had started using at an earlier age. Other factors associated with OUD included living in rural areas, having low socioeconomic status and having a lower BMI. Younger and more educated opiate users, and those who smoked cigarettes, were more likely to have severe OUD. Individuals with OUD had higher psychological distress scores compared with opiate users without such diagnosis. Patterns of opiate use were also different between individuals with and without OUD: opiate users with OUD used higher doses and were more likely to increase their dose during the follow-up, and OUD diagnosis was more common in those using opiates orally instead of smoking.
Our study confirms that the widespread consumption of opiates has led to OUD and is a major health problem in this population; given the 17% prevalence of opiate use among all the GCS participants, the overall prevalence of lifetime OUD in the GCS is estimated at about 10% (17%×57.9%). This is while in the U.S., the prevalence of OUD has been estimated at around 0.7% in people aged 25 years and above (31), and in the Netherlands, the prevalence of opioid use disorder other than heroin was reported 0.0056% (32, 33). The rates in our study were even higher than the results of the 2011 Iranian Mental Health Survey which showed a prevalence of 3.02% for opiate use in the past year, and 2.23% for OUD (18). However, unlike that survey, we studied lifetime prevalence which is naturally higher compared with the past year definition used in the survey. Another explanation may be related to the geographic distribution of opiate use. The prevalence of opiate use in Iran follows a geographic pattern and the provinces in the south and northeast (where our study was conducted) have higher rates compared to other regions of the country. Also, it might be related to the age of participants. We investigated people between 40 to 75 years, while the 2011 national study was conducted on 15 to 64 years group. Lifetime prevalence of OUD increases overtime.
In Iran, opium is sometimes considered a “soft drug” due to its widespread use, but the fact that almost three out of five long-term opium users were clinically diagnosed as having an OUD is in contrast with this notion. OUD is associated with poor mental health and a number of important psychological comorbidities. Opiate use increases the risk of mood disorders, suicide attempts, and violent behavior (34–36). Other substance uses and severe mental disorders are commonly associated with OUD (37). Mood and anxiety disorders may precede the substance use and may even be the cause of abuse, making the diagnosis and treatment even more complex (34, 38). People with psychological comorbidities are more prone to seek a substance to resolve their undesirable psychological symptoms (39). Our study did not include an assessment of these mental comorbidities, but we screened for psychological distress using a validated questionnaire. K10 were first developed to screen for more recent non-specific symptoms of serious mental disorders, i.e. anxiety disorders, mood disorders, and psychotic disorders (26, 40). People with higher psychological distress are more likely to seek outpatient mental health care, be under psychological treatment in the future, and have higher mortality (27, 28). Nearly 32% of opiate users in this study had psychological distress, and individuals with OUD were twice more likely to have psychological distress after adjusting for opiate use patterns. In a study from Nepal, half of all kinds of substance users in drug rehabilitation centers had psychological distress (41). Similar findings have also been reported for cannabis and nonmedical use of prescription opioids (42, 43).
Opium consumption is a known carcinogen (44), and recent studies have found that it can increase the risk of premature mortality from different causes (12, 45–47). These risks increase with the dose and duration of use, putting users with OUD at an even greater risk. Opium users have also been shown to be exposed to very high levels of lead, probably as a result of opium adulterations to increase weight. Lead exposure among users is dose-dependent and is seen mainly among those who used opium orally (48). Lead is a probable carcinogen and a risk factor for cardiovascular diseases, and users with OUD are more likely to have high blood lead levels due to their longer and higher use. Moreover, in our study people with OUD were more likely to take opium orally in both periods and keep their habit of eating opiates. Oral consumption is easier than inhalation, and enables the heavy user to consume opiates regardless of time and location. These hazards are aggravated by the fact that the most common OUD symptoms in our population of opiate users were withdrawal symptoms and repeated (failed) attempts to quit or control use, meaning that a large proportion of these long-term users will continue using for a long time, maybe for the rest of their lives.
Certain groups of opiate users were at increased risk of developing OUD in our study. Opiate users with OUD were on average younger than those without it, because they may live shorter, and had started using at an earlier age. In the U.S., National Epidemiologic Study on Alcohol and Related Conditions reported similar finding and suggested implementing programs to prevent the initiation of opioid use with an emphasis on younger age groups (49). A comparative study on three cohorts of Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) reported higher odds of nonmedical prescription opioid use and use disorder in Millennials (50, 51). Younger individuals become dependent to a substance faster than the older age groups (52). Besides, coping with social and psychological challenges is one of the proposed reasons for the higher frequency of OUD among younger age groups (53). Prioritizing younger and long-time users for opiate use treatment consultations can slow the upward trend of opiate use disorder in the future.
We showed that rural users and those in lower SES levels were more likely to have OUD than urban users with higher SES scores. Our finding on socioeconomic status was in line with the Iranian household Mental Health survey, in which subjects with higher SES were at lower risk of opioid dependence than those at lower levels (17). Also, the U.S. National Epidemiologic Study on Alcohol and Related Conditions reported incomes at or above 40,000 U.S. dollars as a protective factor for OUD (49). Opium is inexpensive, which makes it affordable for people with low income even in rural areas.
Limitations
We studied a sizeable number of opiate users and evaluated clinical OUD by DSM-5 criteria in a non-clinical setting using a validated questionnaire. The availability of detailed data on the lifetime pattern of opiate use and other lifestyle variables in the context of a prospective cohort study is another strength of this study. Comparing these data in the baseline and after more than 10 years of follow-up enabled us to investigate the impact of changes in opiate use on OUD. However, the OUD questionnaire was only available at the follow-up visit, and we had not assessed OUD at the baseline, which is the main limitation of our study. Assessment of psychological distress was also done at the follow-up. Another limitation of this study was insufficient information on other comorbidities such as depression and anxiety for further adjustment. However, we used Kessler score for evaluating psychologic distress and found it quite useful in a study of a high-risk group. Also, we were not able to investigate some previously proposed OUD risk factors like personal and psychological traits due to lack of data.