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NIDA. (2016, August 25). Slow-Release Amphetamine Medication Benefits Patients With Comorbid Cocaine Addiction and ADHD. Retrieved from

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August 25, 2016
By Eric Sarlin, M.Ed., M.A., NIDA Notes Contributing Writer

In this clinical trial:

  • Treatment with an extended-release stimulant medication plus cognitive behavioral therapy (CBT) was associated with reductions in cocaine use and in attention-deficit/hyperactivity disorder (ADHD) symptoms in patients with both disorders.
  • Some patients required dosage adjustments to alleviate adverse effects, but no serious adverse effects were linked to the treatment.
  • Researchers observed no signs of misuse or diversion of the stimulant medication.
A schematic showing the chemical formulation of amphetamines

Formulations of mixed amphetamine salts (e.g., Adderall) are widely used and effective for treating ADHD. Two of their pharmacological actions suggest that they might also be used to help people with cocaine use disorder (CUD) abstain from using the drug. First, the amphetamines compete with cocaine for access to receptors for neurotransmitters, which might prevent cocaine from triggering the massive dopamine release that makes users feel high. And, they stimulate the brain’s reward system, which might reduce drug craving.

Dr. Frances R. Levin and Dr. John Grabowski and researchers from the New York State Psychiatric Institute (NYSPI), Columbia University, and the University of Minnesota (UM) hypothesized that mixed amphetamine salts would alleviate ADHD and CUD in patients with both disorders. They tested the idea with 126 adults, 18 to 60 years old, who had come to NYSPI and UM seeking treatment for CUD and also were diagnosed with ADHD.

The patients received an extended-release formulation of mixed amphetamine salts, in starting doses of 80 milligrams per day or 60 milligrams per day, or a placebo. All patients also were scheduled for weekly CBT sessions that addressed their CUD and ADHD. Each week, each patient reported his or her past-week cocaine use and gave up to three urine samples for testing for cocaine metabolites. Clinicians rated their ADHD symptoms with several different rating instruments weekly, biweekly, or monthly.

See text description below Figure. Amphetamine-Based Medication Reduces Cocaine Use in Patients With Both ADHD and CUD Patients receiving 80 milligrams of slow-release mixed amphetamines were less likely to produce cocaine-positive urine samples during the 13-week study than patients receiving 60 milligrams a day, who were less likely than patients receiving placebo.
Text Description of graphic

The figure shows a line graph of the proportion of study participants using cocaine during a 13-week study period. The vertical (y-) axis shows the proportion of participants using cocaine in percent, and the horizontal (x-) axis shows the week of the study (in 1-week intervals). Cocaine use among participants receiving placebo fell from more than 90 percent on week 2 to about 75 percent by week 5, after which it rose to between 80 and 90 percent for the remainder of the 13-week study period. Cocaine use among participants receiving 60 milligrams of amphetamines per day fell from about 87 percent on week 2 to about 60 percent by week 7, after which it rose to between 60 and 70 percent for the remainder of the 13-week study period. Cocaine use among participants receiving 80 milligrams of amphetamines per day fell from about 86 percent on week 2 to about 60 percent by week 3, held steady between 50 percent and 60 percent for 12 weeks, and fell to below 50 percent at the end of the study (i.e., week 13).

The patients in the 80-milligrams-per-day group produced the lowest percentage of cocaine-positive urine samples throughout the 13-week study, followed by the 60-milligrams-per-day group, and the placebo group (see Figure). The percentages of patients who were completely abstinent from cocaine during the final 3 weeks of the study were 30.2 in the 80-milligrams-per-day group, 17.5 of those receiving 60 milligrams per day, and 7.0 percent of those receiving placebo.

The 60-milligrams-per-day dosage of mixed amphetamine salts was most effective for reducing ADHD symptoms. Three-quarters (75.0 percent) of the patients receiving this dose experienced at least a 30 percent easing of the severity of their ADHD symptoms over the course of the study. Well over one-half (58.1 percent) of patients who received 80 milligrams per day of amphetamine salts reported a similar reduction in their symptoms. By contrast, only 39.5 percent of patients who received a placebo gained this much relief.

Patients in all three groups completed a mean of 8.9 out of 12 CBT sessions with no statistical differences across groups: 9.1 sessions for those receiving 80 milligrams per day; 9.5 sessions for those receiving 60 milligrams per day and 8.1 sessions for those receiving placebo. The researchers therefore could not determine whether patients benefited from the pharmacotherapy alone or from its administration along with CBT. Further research will be needed to resolve an important question: Will reducing cocaine use improve ADHD symptoms, or vice versa?

Dr. Levin notes that the medication dosages used in the study were higher than those typically used to treat ADHD. She says that clinical experience and previous study results suggest that users of cocaine may require robust dosages of amphetamines, owing to cocaine-induced dysregulation of brain dopamine levels.

No patient in the study had a severe adverse effect. However, about one-third of the patients in each group receiving amphetamine salts required dosage reductions because of increased blood pressure and heart rate, insomnia, anxiety, or other problems. Ultimately, the mean dosage in the group that initially received 80 milligrams per day was 70.8 milligrams per day, and that in the group that originally received 60 milligrams per day was 53.3 milligrams per day.

The researchers monitored the patients’ compliance with their medical regimens through self-reports and urine testing for amphetamine metabolites. Although they can’t guarantee that all patients took their medications as prescribed, they observed no signs of amphetamine misuse or diversion. Dr. Levin notes that the extended-release formulations of mixed amphetamine salts used in the study have less abuse liability than shorter-acting amphetamines. Moreover, some research indicates that users of cocaine do not experience amphetamines as highly reinforcing.

An estimated 10 percent to 24 percent of adults who seek treatment for substance use disorders (SUDs) also have ADHD. Accordingly, Dr. Levin and colleagues stress that it is important to screen patients with SUDs for ADHD and to develop effective interventions for people who have both disorders. Although several medications are available for treating ADHD, no medication has yet been proved effective for CUD. Dr. Levin’s and her colleagues’ trial may advance the field a step closer to meeting this important need.

This study was supported by NIH grants DA023651, DA023652, DA029647, and DA022412.


Levin, F.R.; Mariani, J.J.; Specker, S., et al., Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/hyperactivity disorder and cocaine use disorder: A randomized clinical trial. JAMA Psychiatry (72)6: 593-602, 2015. Full text