ADHD, substance use disorders and stimulant treatment: understanding the relationships

Adults with attention‐deficit/hyperactivity disorder (ADHD) are at increased risk for substance use disorders, with rates 2‐3 times higher than the general population. Several questions about this association immediately come to mind. What might be the basis for this increased risk? Are specific drugs of abuse associated with ADHD? Is there an association with past or current stimulant use? And how concerned should we be about stimulant misuse and/or abuse, which is increasingly prevalent ¹ ?

Substance abuse often begins in adolescence, and its onset is earlier in individuals with ADHD. Risk is particularly elevated when there is comorbidity, most specifically with conduct disorder. But increased risk for substance use disorders is not solely accounted for by comorbidity. ADHD, conduct disorders and substance use disorders all share high levels of impulsivity and sensation seeking. They also share genetic variants. Moreover, all three disorders are characterized by a hypodopaminergic state and associated low reward responsiveness.

Drugs of abuse produce an increase in dopaminergic neurotransmission. Psychostimulants have been a mainstay of ADHD treatment, and their beneficial effects are also attributed to enhanced dopaminergic activity. Several studies in animal models have found that early exposure to stimulants may produce sensitization to later exposure ² . Hence, the question of whether stimulant treatment increases risk of substance use disorders has been raised.

A relatively large literature has examined this question. The most recent meta‐analysis found no increased or decreased risk ³ . Longitudinal data from the Multimodal Treatment Study of ADHD also did not find increased risk; stimulant use went down dramatically during adolescence, as substance use was increasing ⁴ . Most compelling are data from Swedish registries, which indicate a marked decrease in substance abuse in association with stimulant treatment ⁵ . Longer duration of treatment was associated with lower rates of substance abuse. Thus, while it is possible that for selected individuals stimulant treatment could contribute to substance abuse, available data indicate that this is rare if it occurs. More likely is that a variety of biopsychosocial risk factors, such as impulsivity, reward sensitivity, and associated comorbid conditions (such as conduct, mood and personality disorders) contribute to risk of substance abuse, particularly in the context of psychosocial stressors.

Consistent with the above, several studies have shown beneficial effects of ADHD treatment on rates of substance abuse. Early stimulant treatment is associated with lower cannabis use in adolescents. Methylphenidate treatment is associated with decreased smoking risk and greater abstinence from nicotine. Atomoxetine treatment produced a greater reduction of heavy drinking in recently abstinent adults with ADHD. Moreover, high‐dose treatment with long‐acting racemic amphetamine resulted in lower drug use in individuals with cocaine use disorder ⁶ . While these findings are encouraging, positive effects of treatment are best measured by reduction in use rather than abstinence, which remains elusive.

More concerning are the high rates of misuse, diversion and abuse of prescription stimulants. Before delving into this subject, some definitions are in order ⁷ . Misuse is intentional therapeutic use of a substance in an inappropriate way. Abuse is the intentional non‐therapeutic use of a drug to achieve a desirable psychological or physiological effect. Of note, misuse is much more common than abuse. Non‐medical use is the use of a drug without a prescription or in a way other than prescribed, which includes both misuse and abuse. Finally, diversion is giving or selling the drug to another person.

Stimulant non‐medical use is a particular problem among late adolescents and young adults – the 18‐25 year old group is most vulnerable – and is particularly problematic in communal social settings. This phenomenon has been amply reported among US college students, but the problem has also been documented in other countries. Rates of misuse are highest with immediate release stimulant formulations, which have the fastest onset of effect and are the easiest to obtain. In the US, amphetamines are the most frequently misused stimulants ¹ . Whether this is because they are more abusable or simply more available remains unknown.

The most common motivation for stimulant non‐medical use is to improve academic performance ¹ , ⁷ . Other motivations include self‐medication of suspected ADHD, which is indeed more prevalent in stimulant misusers than non‐misusing controls, weight reduction, and increasing energy or staying awake. More concerning is the desire for euphoria or to heighten the effects of alcohol. A minority of stimulant non‐medical use is specifically to get “high”. This is sometimes achieved via insufflation or injecting the drug. Non‐oral use is especially concerning, because it is associated with the highest rates of untoward medical consequences.

A variety of environmental and psychological factors are known to contribute to stimulant non‐medical use, including lack of awareness by prescribers, the perception that stimulant misuse is common, and that it is harmless and morally acceptable. Methods to combat stimulant misuse build on knowledge regarding the types of medications most often misused and abused, and the psychosocial factors which either breed or enable this behavior.

Recommendations include using non‐stimulants or long‐acting stimulants ⁸ , restricting the prescription of immediate release stimulants, limiting the number of pills in each dispensation and monitoring use, obtaining toxicology testing when indicated, counseling patients and families about potential medical and legal dangers of misuse and diversion, and conducting educational and preventive intervention programs for prescribers and students – ideally addressing the psychosocial and perceptual risk factors described above.

Taking all of the above into consideration, how should we understand the complex relationships among ADHD, substance use and stimulant medication? And how should abuse of stimulant medication be managed? In many countries, some or all of the prescription stimulants are classified as drugs of abuse, and their use is either forbidden or severely restricted. Seen from one vantage point, this is certainly understandable. Abuse of prescription stimulants is a public health problem and efforts to curtail it are warranted. But, on the other hand, so is ADHD. This is the most prevalent child neuropsychiatric disorder worldwide. It is highly impairing for individuals, families and society. It is associated with numerous behaviors and clinical features that carry high morbidity and mortality. It increases risk for other psychiatric disorders later in life – including substance abuse.

Most importantly, stimulant treatment does not in itself increase risk for substance abuse, and has been shown to be protective at the population level. In addition, stimulant treatment can partially mitigate the severity of substance abuse and can aid in treating selected individuals with the condition. Moreover, the large majority of people do not abuse their stimulant medication, and people who abuse stimulants also abuse other drugs. Indeed, early stimulant misuse likely indicates emerging substance use disorder ⁹ .

In summary, the relationship between ADHD and substance use disorder is complex. The two conditions frequently co‐occur, complicating management. Stimulant treatment does not in itself cause substance use disorders, and can be used to advantage provided certain precautions are taken. Stimulant misuse is more likely to be associated with substance use disorders ¹ . Mitigation strategies include prioritizing non‐stimulant medications, and using long‐acting formulations if stimulant treatment is needed. Monitoring for misuse, offering abuse prevention programs to high‐risk populations, and combining psychosocial treatment with medication are also effective methods for decreasing risk.