ADHD and Substance Abuse

Jay Giedd, MD


June 03, 2003


Parents are bombarded with conflicting information about attention-deficit/hyperactivity disorder (ADHD) and its treatment. Increased use of stimulant medications has sparked debates about whether more people are being appropriately recognized and treated or whether people are being overmedicated. A particularly powerful issue in these debates is the relationship between ADHD and substance abuse. Three questions often arise in discussions of this issue: (1) Are people with ADHD more like to develop substance abuse?; (2) Does using stimulant medication to treat ADHD lead to substance abuse?; and (3) Are the stimulant medicines themselves addictive?

The first of these questions, "Are people with ADHD more like to develop substance abuse?", is the least controversial and is answered in the affirmative by a plethora of epidemiologic data indicating that the diagnoses of ADHD and substance abuse occur together more frequently than expected by chance alone. Comorbidity of ADHD with bipolar or conduct disorder has a greater than additive effect on the risk of developing substance abuse. Furthermore, those with ADHD are at greater risk for earlier onset substance abuse, and even a family history of ADHD is a risk factor for developing substance abuse.[1]

The second question, "Does using stimulant medication to treat ADHD lead to substance abuse?", was recently addressed in a meta-analysis of 6 ADHD studies that contained adolescence or adulthood substance abuse outcome data on people who were diagnosed with ADHD as children.[2] The pooled odds ratio comparing substance abuse outcome in the combined sample of 674 medicated subjects vs 360 unmedicated subjects was 1.9, meaning untreated ADHD subjects were about twice as likely as ADHD subjects treated with stimulant medications to develop substance abuse.

One of the studies was conducted by pre-eminent ADHD researcher Russell A. Barkley, PhD, whose team followed 147 clinic-referred children with ADHD for approximately 13 years.[3] Parent and patient interviews were conducted at age 15 years and again in adulthood (19-25 years). Drug use/abuse details (alcohol, cocaine, amphetamines, all stimulants, marijuana, narcotics, sedatives, "others") and symptoms of ADHD and conduct disorder and were obtained and correlated with stimulant treatment in childhood and high school. Although there was no significant correlation between duration of stimulant treatment in childhood or high school and frequency of use of any drug in adulthood, the frequency of cocaine use in adulthood was higher among treated vs nontreated groups (treated in childhood, P = .059; treated in high school, P = .043). However, when covaried for the severity of ADHD and conduct disorder symptoms, the results no longer held, indicating that an interpretation that the stimulant medication use led to the cocaine use would be confounded by the phenomenon of those with the most severe illness receiving the most treatment and also having the poorest outcome.

Another of the studies was conducted by Joseph Biederman and colleagues[4] at Harvard, who examined subjects at baseline and then again 5 years later (mean age at follow up was 16 years). At follow up, substance abuse was found in 14 of the 19 unmedicated ADHD subjects (75%), 14 of the 56 medicated ADHD subjects (25%), and 25 of the 137 age-matched subjects in the control group (18%).

An interesting finding emerging from the meta-analysis was that stimulant treatment was far more likely to reduce substance abuse during adolescence (5.8-fold) than in adulthood (1.4-fold). Although the finding may be somewhat accounted for by adolescents not being fully through the age of substance abuse risk, it may, in fact, reflect a particular vulnerability of the adolescent brain to substance abuse.

The third question, "Are the stimulant medicines themselves addictive?", is being explored elegantly by the neuroimaging work of Nora Volkow. Research shows that the faster the rate of uptake, the greater the potential -- methylphenidate takes an hour to raise dopamine levels whereas cocaine takes seconds. One of the effects of stimulants is to block dopamine transporters, which are located on the presynaptic neurons and serve to remove the dopamine from the synaptic cleft. Using positron emission tomography, Dr. Volkow compared the potency of methylphenidate vs cocaine in blocking these transporters. To her surprise, methylphenidate was more potent than cocaine in blocking dopamine. A dosage of 0.5 mg/kg, a typical amount prescribed for children, blocked 70% of dopamine transporters.[5] This was widely misinterpreted in the general media with headlines such as "top researcher shows Ritalin no different than cocaine," even though Dr. Volkow was careful to stress in the same article that a key element of the addiction process is the speed at which dopamine levels are increased. Oral methylphenidate takes about an hour to raise dopamine levels in the brain. Inhaled cocaine takes seconds. Although differences in rate of uptake and clearance from the brain may seem subtle to the casual observer of neuroscience, it is hard to overstate the resulting profound differences in physiologic and psychological effects. The faster the rate of uptake, the greater the abuse potential.

One of the main advantages to the new generation of longer acting stimulants, such as Concerta, is that the methylphenidate is embedded in a thick paste that precludes IV use or snorting.[6,7] The medicine has little "street value" and is not often found in the possession of people arrested for drug use or distribution. Also, once-a-day medicines administered in the morning before school are much less likely than medicines administered at school to be given away or sold to other students.

The increased risk of substance abuse in untreated ADHD subjects has profound implications for parents, teens, and society. Stimulants are the most studied class of medicines in child psychiatry. Although all medicines have side effects and should be used judiciously, more than 1000 studies have demonstrated stimulants to be safe and effective in the vast majority of properly diagnosed patients receiving them. Perhaps more than any other medicines, stimulants seem to suffer from unfounded "bad press" -- most likely related to the public's blurring of the distinctions between them and drugs of abuse. Given the large number of people and their families potentially affected, efforts to help the public understand these distinctions would be very well spent.


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