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ADHD and Comorbid Substance Use Disorder

ADHD and Comorbid Substance Use Disorder

Epidemiological studies show that, 4% to 5% of the general population have severe ADHD.1 Of this number, half have a comorbid substance use disorder, such as cigarette smoking.2 As it stands, few physicians feel comfortable diagnosing and managing ADHD in adults, and even fewer would contemplate treating an adult with ADHD who has an addiction.3,4 The aim of this article is to help physicians understand and man-age this challenging combination of comorbidities.

ADHD diagnosis

Establishing the number and severity of symptoms on the basis of a validated checklist is necessary but not sufficient. To establish a diagnosis, an open-ended question such as “What makes you think you might have ADHD?” elicits a clear history of lifelong impairment in multiple domains of the patient’s life. The primary domains are academic, social, and vocational, but one should also inquire about career advancement, parenting, health, intimate relationships, substance abuse, and legal concerns. A good second question might be, “What did it say in the comments section of you report cards?”

ADHD and addictionAssuming that doing well in elementary or high school rules out ADHD is one common pitfall. A vigilant parent can compensate so well for a child’s ADHD that the disorder does not manifest clinically until college, when the unstructured environment, lack of parental prompting, and the critical need for time management brings the dysfunction to the fore. Another pitfall is the assumption that the lack of hyperactivity precludes ADHD. This is how many young women with ADHD are missed. ADHD is just as likely in a child that quietly doodles and stares off into space as it is in the disruptive child who will not sit still and climbs on the furniture. Assuming that the lack of typical ADHD symptoms rules out the diagnosis is also a common pitfall. Patients can be focused and attentive while doing things they like or when under pressure, but yet be totally disorganized, scattered, chronically late, impatient, and always on the go.

In essence, the diagnosis of ADHD is not made on the basis of traits the patient does not have; the diagnosis of ADHD requires at least 6 symptoms of distractibility/executive dysfunction or hyperactivity/impulsivity, but not both. Finally, because younger patients may be somewhat in denial and adult patients may have difficulty in remembering the past, the most reliable diagnosis of ADHD is made with longitudinal information, that is, corroborated by a parent, older sibling, or partner.

Where neurobiology and diagnosis intersect

Each of the brain’s numerous circuits has a primary neurotransmitter that turns it on and secondary neurotransmitters that fine-tune the circuit. While ADHD and addiction are distinct disorders, the diagnosis can be difficult because they often share the under-function of one or more of the dopaminergic circuits.5

Rather than struggling with ADHD as an atheoretical grab bag of symptoms, a more cohesive conceptualization of ADHD is to deconstruct it neurobiologically into 4 symptom clusters. Each of these is hypothesized to derive from the underfunction of a different dopaminergic circuit, which loops from one part of the cortex, through the striatum and thalamus, and then back to the cortex.

• Poor selective attention: difficulty in focusing, listening, reading; difficulty in sticking to task, thoughts always wandering, losing and forgetting things; underfunction of the dorsal anterior cingulate cortex– lower striatum-thalamus loop.

• Poor sustained attention: difficulty in organizing, planning, problem solving, managing time; lack of foresight to potential consequences; lack of hindsight; inability to learn from mistakes; difficulty in choosing between com-peting priorities; underfunction of the dorso-lateral-prefrontal cortex–upper striatum-thalamus loop.

• Poor motor control: fidgeting, being physically restless, difficulty in sitting for prolonged meals, meetings, movies; underfunction of the prefrontal motor cortex–lateral striatum-thalamus loop.

• Poor impulse control: acting before thinking, talking before thinking, interrupting, intruding, being impatient; underfunction of the orbitofrontal cortex–lower striatum-thalamus loop.



  • ADHD and addiction are distinct disorders, but they both have dysregulation of one or more of the dopaminergic circuits. ADHD is associated with earlier onset of substance use, more severe addiction, and more difficulty in maintaining abstinence.
  • Various genetic, environmental, and drug-induced insults combine to create an area of disrupted dopamine neurotransmission, which is associated with diminished perception of reward, worsened cognition, and impaired behavioral inhibition.

Tuning the dopamine circuits

Dopaminergic circuits are tuned by noradrenaline, acetylcholine, glutamate, serotonin, and γ-aminobutyric acid (GABA). While dopamine isolates the signal to which one should pay attention, noradrenaline amplifies the volume of the signal.5 Acetylcholine, acting through nicotinic receptors, also increases the strength of the dopamine signal. Acetylcholine receptor (nAChR) genes are associated with the age of initiation of substance abuse and early subjective responses to alcohol and nicotine.6

Serotonin (5-HT) can either increase or decrease dopamine neurotransmission depending on which receptors it is working through. 5-HT2A receptors have a stimulating effect on dopamine neuronal activity in the ventral tegmental area. 5-HT2C receptors have an inhibitory effect on dopamine neurotransmission.7 Glutamate is an excitatory neurotransmitter that interacts with the N-methyl-D-aspartate receptor to overcome background inhibition and elicit neuronal activity. Glutamatergic projections stimulate mesocorticolimbic dopaminergic neurons—a process thought to be associated with the euphoria of drug seeking. This process has been shown to correlate with “drug liking” and psychological dependence.8

GABA is an inhibitory neurotransmitter. It opens a channel in the membrane through which negatively charged chloride ions can enter the cell. This influx makes the cell less likely to be excited by incoming stimuli. Inhibition is important for keeping the excitation in check and resetting the circuit.5 GABA-ergic projections decrease dopaminergic transmission and are associated with decreased drug liking and decreased craving.9

Addiction and reward circuitry

Humans have evolved an unconscious awareness of the need to pay attention to certain important events. These include threats, competition, sex needs, socialization, and sustenance. Salient events trigger dopamine neurotransmission, which stimulates parts of the brain that allow us to increase vigilance; inhibit unnecessary movement; and focus, filter, take in, process, and store information. They also stimulate the experience of reward.

Experiencing a natural high from normal stimuli (eg, hugging your children, listening to music, mountain biking) is the marker of a healthy reward circuit. Reward circuit underfunction has been described in the literature and named, “reward deficiency syndrome.”10 People with reward deficiency do not experience pleasure from normal stimuli. There is no one particular personality type in people with reward deficiency. Some will live in quiet desperation; others will compensate with stimulus-seeking behaviors that offer more intense but natural highs. Stimulus seeking can manifest quite broadly by any behavior that consistently increases thrill, risk, opposition, drama, and/or chaos. Others will use substances. It is worth emphasizing that reward deficiency syndrome increases the likelihood of “using” to cope. It does not equate with addiction. Addiction requires the added criteria of being unable to control the reward seeking, despite evidence of harm.


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