In a large, nationally representative sample of US adults, we found that: 1) the vast majority of individuals with lifetime dependence on nicotine, alcohol, cannabis or cocaine would remit at some point in their lives; 2) remission from cannabis or cocaine dependence occurred faster than remission from nicotine or alcohol dependence; 3) significant racial-ethnic differences were observed in the cumulative probability of remission from nicotine dependence and cocaine dependence; and, 4) several socio-demographic, psychopathological and drug use-related predictors of remission were shared by at least two substances.
Cumulative probability estimates of remission were high for all the substances assessed, however these estimates should be interpreted with caution given the irregular course of addictions punctuated by remissions and relapses. Social factors, such as the progressive adoption of adult roles and responsibilities [30
] and increased contact with environments in which substance dependence has lower acceptability may exert a powerful influence on the likelihood of experiencing remission. Age-related decreases in impulsivity and other neurodevelopmental changes [31
], increased self-efficacy to abstain, and awareness of the health-related, social, and judicial [32
] consequences of substance use are also likely contributors of remission.
More than two thirds remissions from cannabis and cocaine dependence occurred within the first decade after onset of dependence, whereas only one-fifth of remissions from nicotine dependence and one-third of remissions from alcohol dependence occurred within that period. The differences in the rate of remission across substances may be explained, at least in part, by the speed at which physical, psychological and social adverse consequences manifest after the onset of dependence. For instance, the risk of early cardiovascular adverse consequences is much higher among individuals with cocaine dependence than among those with nicotine or alcohol dependence [33
]. The behavioral disturbances resulting from cannabis or cocaine dependence and their illegal status impose stronger social pressures to remit [15
]. The high availability of alcohol and nicotine environmental cues for their consumption may also contribute to explain the difficulty stopping the use of these substances [35
]. Particularly for nicotine, the immediate perceived benefits from its use, including anxiety and stress reduction, improved performance on a variety of cognitive tasks, and decreased food consumption and metabolism [35
], may initially outweigh the potential perceived harms produced by its chronic use.
Contrasting with results from the National Comorbidity Survey [3
], a lower rate of remission from nicotine dependence was observed in Blacks. Compared to White smokers, Black smokers start smoking later in life, have lower daily nicotine consumption, tend to smoke cigarettes with longer rod length and higher tar and nicotine content (i.e., menthols), and have slower clearance of cotinine and higher intake of nicotine per cigarette.[36
] Furthermore, the reduced access of Blacks and Hispanics to tobacco preventive services [38
], as well as the intensive targeting of these minority groups by tobacco companies [39
], could also help explain the observed racial-ethnic differences in the probability of nicotine dependence remission. Consistent with previous studies [40
], we also found that Blacks with a lifetime diagnosis of cocaine dependence report lower rates of remission than their White counterparts. Psychosocial factors that commonly affect Black populations, including discrimination and lower levels of social capital, have been recognized as established barriers to dependence remission and triggers to use or relapse [41
]. Furthermore, an array of genetic factors appear to increase the vulnerability to develop cocaine dependence among Blacks [42
Men were less likely than women to remit from dependence on all the substances assessed. Women tend to experience worse physical, mental, and social consequences of substance use than males [43
], which may lead to an increased motivation to stop using drugs and help explain women’s higher rates of remission. Feelings of guilt and concerns regarding the effects of using substances during pregnancy and child-rearing can lead to decrease drug use among women [44
]. Gender differences in the neural response to cue-induced craving and stress [45
], as well as in the activity of the lateral and medial regions of the orbitofrontal cortex (OFC), which modulates impulsivity and decision making [46
] can also help explain the different course of cocaine dependence among males and females.
Substance use comorbidity and PD predicted remission across most substances assessed. Individuals with a diagnosis of a PD had a lower probability of remission from alcohol or cannabis dependence. Converging evidence supports the commonalities between PD and SUDs [47
]. For instance, there are high rates of comorbidity between PD with high impulsivity traits (e.g., borderline PD) and SUD. Individuals with PD with high levels of stress reactivity, neuroticism and anxiety sensitivity can engage use substances to relieve their feelings. Novelty-seeking, reward-seeking, extraversion and gregariousness can also motivate drug use experimentation and sustained drug intake [47
]. Associations between polymorphisms at candidate genes and personality dimensions correlated with the liability to SUD have also been documented [48
]. A temporal relation in this association has been noted, with PD anteceding the onset of SUD [47
]. The chronic course of PD [49
] may increase the risk for relapse and interfere with psychological and social factors that help motivate remission [47
]. The lack of association between previous diagnosis of mood and anxiety disorders and dependence remission observed in this study has been documented before [50
Dependence on one substance tended to decrease the probability of remission from dependence on another substance. Chronic substance users may have difficulty overcoming the effect of drug-associated environmental cues and associative learning related to their drug-seeking behavior [51
]. Vulnerability to relapse and drug use maintenance have been also associated with the development of molecular adaptations resulting from chronic drug use, including the elevation of the GluR1 glutamate receptor subunit in the ventral tegmental area, alterations in the content and function of proteins such as the tyrosine hydroxylase, dopamine transporters, RGS9-2, and D2
autoreceptors and the D1
-receptor- mediated stimulation of ΔFosB, a transcriptional regulator that modulates the synthesis of certain AMPA glutamate receptor subunits and cell-signaling enzymes [53
]. The existence of shared molecular pathways as well as the potential of certain drugs of abuse to induce cross-tolerance and cross-sensitization to one another can also contribute to the lower probability of remission among individuals with dependence on other drugs [55
]. Genetic studies also suggest a significant overlap across substances in the genetic liability to dependence. For example, nicotine and alcohol dependence may share over 60% of their genetic vulnerabilities and alleles of several genes have been associated with alcohol, nicotine and polysubstance dependence [56
]. The existence of comorbid SUDs poses a therapeutic challenge for clinicians, given the mixed evidence supporting sequential treatment over simultaneous treatment [57
]. The findings of this study also emphasize the need to understand common mechanisms underlying the rewarding effects of drugs and the sequential neuropharmacological neuroadaptations once an addiction has developed.[54
This study has the limitations common to most large-scale mental health surveys. First, self-report of substance use and psychiatric disorders are prone to social desirability bias leading to underreport of substance use and SUD and overreport of remission. Second, diagnoses of SUD, individual SUD criteria endorsement, or age of remission reported may be subject to recall bias (the longer the time interval between the event and assessment, the higher the probability of incorrect recalls) and to cognitive impairment resulting from the use of drugs. Third, institutionalized individuals or those who experienced fatal or severe consequences due to their SUD may have not been sampled, leading to overestimation of the cumulative probability of remission. Fourth, lack of a uniform operational definition of dependence remission across population-based studies limits our ability to compare our results with estimates from previous reports [3
]. Fifth, lack of information on the number and duration of dependence remission episodes experienced over the individual’s lifetime limits our understanding of the role of these factors on dependence remission and relapse. Sixth, factors that may help explain the racial-ethnic differences, such as socio-economic status could not be included in the models as a time-dependent covariate since the NESARC, as most large scale surveys, does not include information on changes in income over time.
Despite these limitations, the current study expands the knowledge gained from previous investigations. The results of this study indicate that the majority of individuals with nicotine, alcohol, cannabis and cocaine dependence achieve remission at some point in their lives, although the probability and time to remission vary by drug and racial/ethnic group. Although there are no common predictors of remission across all four substances, several of these predictors were shared by at least two substances, suggesting that the processes of remission overlap, but are not identical. The lower rates of remission among individuals with comorbid PD or dependence on other drugs identified in this study highlight the need to recognize biological and social mechanisms that interfere with recovery from substance dependence, strengthen preventive efforts, particularly among vulnerable population subgroups, and provide coordinated psychiatric and substance abuse interventions.