What does the self-reported 'high' from stimulants in a patient with attention deficit hyperactivity disorder (ADHD) correlate with, in terms of neurochemistry?

Self-Reported "High" from Stimulants in ADHD Correlates with Rate of Drug Delivery to the Brain

The self-reported "high" or euphoria from stimulant medications in ADHD patients primarily correlates with the rate of drug delivery to the brain (option D), not with plasma drug levels or changes in intracellular or extracellular dopamine alone. 1

Neurochemical Basis of Stimulant Effects

Mechanism of Action

Stimulant medications like methylphenidate (MPH) work by:

• Binding to dopamine transporters in the striatum
• Increasing synaptic dopamine and norepinephrine
• Enhancing executive control processes in the prefrontal cortex 1

Rate of Delivery vs. Drug Concentration

The critical factor determining whether a stimulant produces euphoria is not simply the presence of the drug or even its concentration, but rather how quickly it reaches the brain:

• When given orally, methylphenidate occupies a high proportion of dopamine transporter sites in the striatum but is not associated with euphoria 1
• The same drug administered intravenously (rapid delivery) produces euphoria despite similar overall dopamine transporter occupancy 1
• This phenomenon explains why college students might grind up immediate-release stimulant tablets to snort them, seeking a faster rate of delivery to produce euphoria 1

Clinical Implications for Drug-Seeking Behavior

Formulation Considerations

• Immediate-release formulations have a steeper absorption curve ("ramp effect"), potentially increasing abuse potential 1
• Extended-release formulations produce a gradual ascending increase in medication concentration without the sharp peaks that contribute to euphoria 1
• The bolus effect from rapid absorption was previously thought necessary for ADHD symptom reduction, but newer studies show that gradual concentration increases can be equally effective for treating ADHD symptoms 1

Identifying Potential Misuse

When evaluating a college student for possible drug-seeking behavior, consider:

1. Request for immediate-release formulations specifically
2. Reports of "losing" medication frequently
3. Resistance to extended-release formulations
4. Knowledge about specific stimulant brands that have higher abuse potential

Prescribing Considerations

Reducing Abuse Potential

For patients where there is concern about drug-seeking:

• Prescribe extended-release formulations that provide gradual drug delivery
• Consider non-stimulant alternatives like atomoxetine, which has no documented abuse potential 2
• Implement regular monitoring with random drug screens
• Use prescription monitoring programs to identify multiple prescribers

Monitoring Treatment

• Regular follow-up to assess both therapeutic response and potential misuse
• Education about proper use and legal consequences of diversion
• Written treatment agreements specifying expectations regarding medication use

Common Pitfalls in Assessment

1. Assuming that plasma drug levels correlate with euphoria (they don't)
2. Believing that all ADHD medications have equal abuse potential
3. Failing to distinguish between therapeutic effects and euphoria
4. Overlooking that the same medication can have different effects based on route of administration

By understanding that the euphoric "high" from stimulants correlates with the rate of drug delivery to the brain rather than simply drug levels or dopamine changes, clinicians can make more informed decisions about medication selection and formulation to minimize abuse potential while effectively treating ADHD symptoms.