Research roundup: Substance use disorder

This issue’s roundup presents recent research and practical implications related to substance use disorder (SUD)

By Practice Research and Policy staff

Oct. 11, 2012—Substance use disorder (SUD) describes the condition in which an individual either abuses a substance by using it in larger than prescribed, unsupervised or unregulated quantities, or has a dependence on a substance, characterized by having a compulsive need to use the substance in order to feel normal. SUD presents alone or with a variety of other disorders, and recent research has improved our understanding of why it may co-occur with different disorders, whether there are causal relationships, and how secondary SUD can be prevented.

Some of the recent research, along with practical implications, is outlined in this issue.

Swendsen, J., Conway, K. P., Degenhardt, L., Glantz, M., Jin, R., Merikangas, K. R.,... &  Kessler, R. (2010). Mental disorders as risk factors for substance use, abuse and  dependence: Results from the 10-year follow-up of the National Comorbidity Survey. Addiction, 105, 1117-1128.  


The comorbidity of substance use disorder (SUD) and mental disorders is known, but understanding which primary mental disorders are linked to nicotine, alcohol, and illicit drug use, abuse, or dependence is not. After the National Comorbidity Survey (NCS) of 1990-1992 in the United States, researchers recruited the 15-24 year old participants to be re-interviewed 10 years later in what they deemed the NCS-2; 5001 subjects participated in the 2001 and 2003 interviews.

Using NCS data as baseline, the researchers were able to analyze participants’ changes in substance use over the 10-year period: 10.4 percent had a first onset of nicotine dependence, 1.1 percent had a first onset of alcohol dependence with abuse, and 0.9 percent had a first onset of drug dependence with abuse.

Some specific baseline conditions tended to precede the development of SUD, with certain disorders and substances being more strongly correlated than others. And, a number of interesting patterns were found between disorders and the categories of use, abuse and dependence. Mental disorders in general were found to be risk factors for secondary SUD, but specifically anxiety disorders were associated with the onset of nicotine use, alcohol dependence with abuse and drug dependence with abuse.

Disruptive behavior disorders were associated with nicotine dependence and illicit drug dependence with abuse, and the likelihood of alcohol dependence with abuse was increased by baseline nicotine dependence, intermittent explosive disorder (IED) and oppositional defiant disorder (ODD). While changes in category of substance use varied with mental disorder and severity of the disorder, the risk of substance use onset increased with number of mental disorders.

Additionally, mood disorders were associated with the development of nicotine dependence, while anxiety was associated with non-dependent tobacco use. Disruptive behavior disorders, additional SUD and the presence of three or more mental disorders existing at the time of the initial survey increased the risk of transition from regular alcohol use to abuse. Dysthymia, anxiety disorders, IED and ODD were identified as risk factors for alcohol dependence among those who were alcohol abusers at baseline.

Major depression or an anxiety disorder other than generalized anxiety disorder, post-traumatic stress disorder or agoraphobia at baseline were the strongest predictors of initial illicit drug use. Disruptive behavior disorders, additional SUD, bipolar disorder (but not major depressive disorder) and comorbidity of disorders were all associated with the transition from drug use to abuse. And, bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) were associated with the shift from illicit drug abuse to dependence.

The treatment of any mental disorder is estimated to prevent 43.4 percent of transitions from alcohol abuse to dependence; 22.2 percent of nicotine dependence cases; 28.5 percent of daily tobacco use cases; 71.9 percent of cases of illicit drug dependence; 61.5 percent of cases of illicit drug abuse; and 34.2 percent of cases of initial drug use.

Researchers also looked at the relationship patterns between primary SUD and secondary mental disorders, but as expected found weaker associations.

Practical Implications

Because SUD and mental disorders often co-occur, it has been speculated that the etiology is similar, but the associations between specific mental disorders and substance type/use suggest that shared factors rather than one attributable factor account for the different associations. Since initial diagnosis of a mental disorder appears to increase the likelihood of subsequent substance use disorder, whereas primary SUD has a weaker association with later mental disorder, there may be more of a causal direction from mental disorder to SUD. If that is the case, early treatment or prevention of mental disorders may greatly reduce transitions from substance use to abuse or dependence and decrease the risk of secondary SUD.

Grattan, A., Sullivan, M., Saunders, K., Campbell, C., & Von Korff, M. (2012). Depression and  prescription opioid misuse among chronic opioid therapy recipients with no history of   substance abuse. Annals of Family Medicine, 10(4), 304-311.


Chronic opioid therapy (COT) is becoming more common in the treatment of non-cancer chronic pain patients, and the misuse and accidental overdose of opioids is rapidly increasing. To measure opioid use and better understand the relationship between its misuse and depression, researchers conducted telephone interviews with 1,334 COT patients for non-cancer pain who did not have a past SUD.

Patients were assessed for current depression (history of past depression was not assessed) and asked questions pertaining to the three focal areas of the study: self-medication for symptoms other than pain (stress, sleep), non-adherence (autonomously increasing dosage) and aberrant behavior (sharing opioids with others).

Regarding self-medication for symptoms other than pain, 51.8 percent of severely depressed participants misused their opioid medication compared to 36.9 percent of non-depressed participants. A majority of severely depressed participants (57.7 percent) did not adhere to the prescribed dosage compared to 27.3 percent of non-depressed participants. And for aberrant behavior, 24.5 percent of severely depressed participants shared their opioid medication compared to 15.5 percent of non-depressed participants, however just 12.3 percent of mildly depressed participants exhibited aberrant opioid use leading researchers to suspect that depression does not have a cohesive impact on aberrant use of the medication. More severe depression consistently indicated a stronger association between using opioid medication for stress or sleep and using more than the prescribed dosage.

Possible reasons the researchers offered for this growing trend of SUD with opioids following COT include the notion that depressed patients experience their pain as more severe, and therefore use more medication, and historically opioids have been used to treat melancholia and mania, so depressed patients may experience mood regulation with the medicine leading them to use it in cases of emotional as well as physical pain.

Practical Implications

Opioids are particularly addictive, in part because their effects can reduce mental or emotional pain as well as physical pain. Participants were not assessed for past depression, but knowing the participants’ history could shed light on whether past depression is a higher risk factor for misuse of opioids, or conversely if the onset of depression is more highly associated with the misuse of the prescription. Discussing the known pattern of SUD with patients prior to beginning an opioid regimen could quell the high risk of misuse, and maintaining awareness regarding the patient’s use would allow for early treatment at the first signs of misuse. 

Lee, S., Humphreys, K., Flory, K., Liu, R., & Glass, K. (2011). Prospective association of  childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and  abuse/dependence: A meta-analytic review. Clinical Psychology Review, 31, 328-341.  


In a meta-analysis reviewing the use and abuse/dependence of nicotine, alcohol, marijuana, cocaine, and illicit drugs in the adolescent years of individuals diagnosed with attention-deficit/hyperactivity disorder (ADHD), findings suggest that the disorder is a strong predictor of the use of a variety of substances. While many studies have indicated ADHD as being a risk factor for SUD, this meta-analysis examines how often ADHD and each of the above substances co-occur.

The 27 studies used in the analysis indicate a positive correlation between diagnosis of ADHD in childhood and substance abuse or dependence: individuals diagnosed with ADHD in childhood were almost three times as likely to have nicotine dependence, and twice as likely to ever use nicotine than people without ADHD; 1.5 times as likely to have a marijuana dependence, and three times as likely to have ever used marijuana; twice as likely to develop cocaine abuse or dependence (no data presented regarding cocaine use alone); 2.5 times as likely to develop a general illicit substance dependence (insignificant data regarding illicit substance use alone); and seven times as likely to abuse alcohol, although no findings indicated that they are more likely to have ever used alcohol than individuals not diagnosed with ADHD.

The researchers tested for methodological and demographic moderators, but were unable to discover any affecting the results of the meta-analysis, which means that the risks of SUD among those with ADHD generalizes across a wide array of demographic characteristics, but it should be noted that ADHD itself is more commonly diagnosed in Caucasian males.

Practical Implications

This meta-analysis did not differentiate between ADHD subtypes, whether or not participants received treatment and which treatment approaches, if any, were used, so it is important to consider the effect prescribed amphetamine salts may have on different individuals and their subsequent substance use behavior.

It is also important to recognize that while ADHD is more commonly diagnosed in Caucasian males, this does not necessarily mean that ADHD occurs more frequently in this demographic. It is possible that other factors of this demographic, and especially stereotype, cultural expectations or access to mental health service and evaluation may lead to the more frequent diagnoses. Nonetheless, understanding the potential risks of adolescent SUD among those diagnosed with ADHD in childhood can act to initiate preventative measures to reduce these risks.

Wu, P., Goodwin, R., Fuller, C., Liu, X., Corner, J., Cohen, P., & Hoven, C. (2011). The  relationship between anxiety disorders and substance use among adolescents in the  community: Specificity and gender differences. J Youth Adolesc., 39(2), 177-188.


In a study examining the relationships between anxiety disorders and the use and abuse of different substances, 781 teenagers and a parent/guardian for each were interviewed to gather information regarding the adolescent’s psychopathology and substance use activity. The main foci of the study were threefold: the relationships among substance use behaviors and specific anxiety disorders, gender differences related to the comorbidity of an anxiety disorder and substance use or abuse and gender differences related to anxiety disorders comorbid with disruptive disorders and substance use.

While the occurrence of anxiety and depression is more common among girls, when comparing participants with one or more anxiety disorders, smoking and drug use was found in both genders. Anxiety was significantly associated with heavy drinking among girls, but not boys. And, for both genders, the relationship between anxiety and illicit drug use was stronger when depression was also present.

Among the boys, social phobia was significantly associated with smoking, and obsessive compulsive disorder (OCD) was significantly associated with illicit drug use, but unlike girls, there were no significant findings associating alcohol use to anxiety.

The significant findings among the girls indicated that separation anxiety and OCD were positively associated with smoking and social phobia was negatively associated with smoking. OCD, separation anxiety and agoraphobia were all positively associated with illicit drug use. When depression was controlled for girls with social phobia were significantly less likely to use illicit drugs than boys, or girls with other anxiety disorders. OCD and agoraphobia were found to be positively associated to heavy drinking among girls, and the association was stronger when multiple anxiety disorders or co-occurring depression was present.

These findings regarding social phobia are speculated to be the result of socially-anxious teens avoiding certain social situations where substance use may start, such as parties, and do not necessarily indicate a negative association between the disorder and substance behaviors. Similar studies of adults have found social phobia to in fact be positively associated with illicit drug use.

Practical Implications

When treating adolescents for anxiety, it may be worthwhile to consider the differences between the genders regarding the substance use patterns seen in the different disorders. Treatment of the anxiety itself may counter many of the risk factors, but close monitoring of the patient and disclosure regarding these particular patterns may also reduce the development of SUD, especially if the substance use started as a form of self-medication due to lack of treatment or infrequent treatment.

Welch, K. A., McIntosh, A. M., Job, D. E., Whalley, H. C., Moorhead, T. W., Hall, J.,... &  Johnstone, E. C. (2011). The impact of substance use on brain structure in people at high  risk of developing schizophrenia. Schizophrenia Bulletin, 37(5), 1066- 1076.


Reduced prefrontal volume and ventricular enlargement are common features among individuals with SUD as well as individuals with schizophrenia, and these abnormalities are greater in individuals with comorbid diagnoses. In a study of 147 16-25 year-olds who were genetically predisposed to schizophrenia but still clinically well, and a control group of 36, researchers studied brain abnormalities related to substance use, and whether the use of particular substances increased the risk of onset of schizophrenia.

Through self-reports, face-to-face interviews, and MRI scanning, researchers found a number of significant associations: alcohol consumption and regular cannabis use was positively correlated to the structural volume of the left and right lateral ventricles and the third ventricle, and alcohol consumption and isolated cannabis use was negatively correlated to the volume of the prefrontal lobes. These results were not found among the control group.

Follow-up assessments were performed every 18 months for five years, and the number of high-risk subjects in this study with alcohol dependence who later developed schizophrenia was larger than those high-risk subjects with all other levels of alcohol exposure combined. Similarly, those with frequent cannabis use were more likely to develop schizophrenia than those with isolated or no cannabis use.

The structural brain images of the high-risk participants who used substances were comparable to what has previously been reported in studies of older adults with SUD. The effect of experimental substance use on the brains of this high-risk population is not seen in healthy controls, and looks similar to what decades of substance misuse or dependence does to a healthy brain. This led the researchers to believe that certain brain differences found among individuals at high-risk for schizophrenia may predispose them to substance misuse, and substances having much more extreme and rapid effects on their brain structures than on healthy brains, but that the interaction between the substance use and the genetic predisposition is likely necessary to result in these extreme abnormalities.

Practical Implications

People genetically predisposed to schizophrenia who use psychoactive substances lose significantly more gray matter in their brains than healthy individuals, and the structural abnormalities associated with the brain tissue loss increases the chance of onset of schizophrenia. The developing adolescent brains of this population are remarkably vulnerable to the effects of a variety of drugs, which is particularly worrisome because experimentation with drugs at this age is not uncommon.

So, while the healthy adolescent may try cannabis or alcohol without necessarily causing permanent structural brain changes, this same type of experimentation seems to result in distinct brain changes and greatly elevates the risk of future psychosis among adolescents at high-risk of developing schizophrenia. Conveyance of this information to genetically-predisposed families may prevent youth from ever reaching a psychotic break, especially if they can understand that their brains may be more sensitive than those of their peers to the drugs’ effects and therefore refrain from such usage.