As many as 600 million people worldwide use betel quid, a mixture of areca catechu nut, betel leaves, and slaked lime. Tobacco is often added to this combination.1 Areca catechu nut is the fourth most commonly used addictive substance in the world after caffeine, nicotine, and alcohol. Arecoline, a nonselective muscarinic agonist, is the primary psychoactive agent in areca catechu nut.2
Betel quid use is endemic to many parts of Asia, and rates of addiction to the substance are increasing in those regions. Regular use of betel quid is associated with several health comorbidities, including oral cancer. In a recent study published in JAMA Psychiatry, researchers sought to “investigate the validity and pattern of [Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)]-defined betel quid use disorder (BUD) and its association with oral potentially malignant disorder among Asian populations.”3
The investigators interviewed 8922 randomly selected community-dwelling adults (4564 women and 4358 men; mean age, 44.2±0.2 years) from 6 betel quid-endemic countries included in the Asian Betel-quid Consortium Study.
Using DSM-5 criteria for substance use disorder (SUD) to assess study participants for BUD, the investigators found that these criteria “showed sufficient unidimensionality to act as a valid measure for BUD.” Betel quid users were classified as follows:
- No BUD: 0 to 1 symptom
- Mild BUD: 2 to 3 symptoms
- Moderate BUD: 4 to 5 symptoms
- Severe BUD: ≥6 symptoms
According to the results, the 12-month prevalence of DSM-5-defined BUD was 18.0% (mild, 3.2%; moderate, 4.3%; and severe, 10.5%). Among current betel quid users, 86.0% were found to have DSM-5-defined BUD (mild, 15.5%; moderate, 20.6; and severe, 50.0%). Compared with non-users, betel quid users were shown to have a substantially greater risk (from 9.6-fold to 35.5-fold) for oral potentially malignant disorder.
In a related editorial article published in the same issue of JAMA Psychiatry, researchers proposed that these study results offer an opportunity to advance the conceptualization of SUD, and they offer suggestions for the further study of BUD.2
BUD symptoms “were associated with other findings expected to precede, co-occur, or be the consequences of [SUD], which supported the validity of BUD,” they wrote. For example, compared with participants without BUD, those with BUD were more likely to have a lower education level and family and friends who used betel quid. In addition, BUD was associated with smoking and alcohol use.
“Perhaps most important was the association of BUD severity with oral potentially malignant disorders, which suggested a serious clinical consequence of BUD over and above the risk conferred by use patterns,” they stated in the editorial. “The existence of multiple antecedent, concurrent, and consequent correlates enhances the validity (ie, the credibility) of BUD in the same way that the number of symptoms of a disorder in a patient increases our confidence in that diagnosis.”
Another noteworthy finding of the study is the variation in use and prevalence patterns among different countries, which aligns with the concept that SUD risk has social and cultural determinants.
The authors further describe 3 important implications of these results:
There is a syndrome that can be labeled as substance abuse, which provides a basis for communication among patients, clinicians, and other stakeholders.
The observed heterogeneity in symptoms of BUD indicates that multiple neurobiologic mechanisms are impaired in those with the disorder. “Identifying the sources or degree of heterogeneity that are relevant to causation or clinical care will be one of the crucial tasks and tests of precision medicine,” according to the investigators.2
As there are multiple causes that may underlie SUD symptoms (such as childhood trauma, genetic predisposition, and stressful life events), multiple causal pathways for SUDs likely exist. There is a need to elucidate “how risk factors interact with one another in each person to lead to the development of SUDs and psychiatric disorders more generally.” Such insight would help to guide prevention efforts and strengthen the foundation of precision medicine.
The researchers point in their editorial to several areas of focus for future research:
- The natural history of BUD, such as predictors of use and transition to BUD
- The stability of BUD symptoms over time
- Consequences of BUD and the extent of functional impairment because “these are crucial determinants in accepting behaviors as evidence of disorder status”
- Comorbidity of BUD with other SUDs or psychiatric disorders and related implications for causal mechanisms, assessment, and treatment
- Studies that connect these epidemiologic observations with clinical and neuroscience research, such as investigating whether associations between specific brain pathways and certain diagnostic criteria in BUD are similar to those of other SUDs
“As we continue to delineate different levels of description and explanation of what an SUD or (more broadly) an addictive disorder is, the questions raised by the study of Lee et al suggest exciting opportunities for nosological research, precision epidemiology, neurobiology, and intervention development,” they concluded. “Iteratively answering those questions should help advance science and, more importantly, improve the health of individuals with substance use disorders and other psychiatric disorders.”
- Centers for Disease Control and Prevention. Betel Quid with Tobacco (Gutka). https://www.cdc.gov/tobacco/data_statistics/fact_sheets/smokeless/betel_quid/index.htm. Updated December 1, 2016. Accessed on March 14, 2018.
- Blanco C, Compton WM, Lopez MF. What is an addictive disorder? JAMA Psychiatry. 2018;75(3):229-230.
- Lee CH, Ko AMS, Yang FM, et al. Association of DSM-5 betel-quid use disorder with oral potentially malignant disorder in 6 betel-quid endemic Asian populations. JAMA Psychiatry. 2018;75(3):261-269.
- Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793-795.