New research sheds light on why individuals taking therapeutic doses of methylphenidate rarely abuse it or become addicted, even though it is a stimulant with properties similar to those of cocaine and amphetamines. Ritalin, an oral form of methylphenidate, is the drug prescribed most frequently for children, adolescents, and adults diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).
Findings reported in the October 1, 1998, issue of the American Journal of Psychiatry confirm that oral doses of methylphenidate do not reach peak concentrations in the brain until 60 minutes after ingestion, compared to 5 minutes for cocaine or 9 minutes for methylphenidate taken intravenously. The fact that Ritalin taken orally is drawn so slowly into the brain is a likely reason why patients do not experience a high from this means of use. In general, if brain concentrations of a substance peak quickly, the potential for abuse and addiction increases, as an individual experiences the drug more dramatically and, thus, is more likely to try to repeat the experience more frequently.
"This research is important for a number of reasons", said Dr. Alan I. Leshner, director of the National Institute on Drug Abuse (NIDA), National Institutes of Health, which contributed funding for the research. "First, it helps clarify why Ritalin rarely leads to abuse and addiction when taken properly as a treatment for ADHD. Second, it helps explain why non-ADHD individuals might abuse methylphenidate or become addicted to it when they take the drug intravenously or when they crush and inhale the pills. It is extremely important to clarify that different methods of taking a medication can alter its medicinal effects and can make it more or less dangerous in ways totally unrelated to its clinical indications."
Ritalin is not a new medication - for about 30 years it has been prescribed, increasingly, to treat ADHD. Estimates indicate that about 5 to 10 percent of the general population have the disorder. Exactly how methylphenidate works to calm ADHD individuals is not completely understood, but the drug has long been thought to block reuptake of dopamine in the brain. The current research, conducted by Dr. Nora Volkow and colleagues at the Department of Energy's Brookhaven National Laboratory and the State University of New York at Stony Brook, is the first to measure the drug's actual effectiveness in blocking the molecular gatekeepers to dopamine uptake, known as dopamine transporters (DATs). Since DATs are target sites for the action of cocaine and other stimulating drugs of abuse as well, the researchers also evaluated methylphenidate for its abuse potential.
Using positron emission tomography (PET) scanning, which enables researchers to measure levels of DAT blockage in the brain, the Brookhaven researchers studied the effects of oral methylphenidate in seven healthy young adults who did not have ADHD. These individuals also were asked to rate the subjective effects of methylphenidate by verbally rating their feelings of "drug effects", "restlessness", or being "high". Calibrated for subject weight, a range of oral doses was tested that included doses commonly used therapeutically.
The researchers found that, taken orally at the levels currently prescribed for ADHD (0.25 mg/kg to 1.0 mg/kg), methylphenidate is very effective at blocking DATs and is likely to occupy more than 50 percent of them in the brain. It is believed that this level of occupancy may be necessary for therapeutic efficacy.
The oral doses of methylphenidate, however, did not produce a "high" in all but one of the subjects in this study, in contrast with cocaine which, in previous Brookhaven research, was shown to produce a "high" when the drug reached a level blocking 60 percent of the DATs. The researchers believe the explanation for the lack of experienced "high" has to do with the amount of time it takes orally administered methylphenidate to reach peak concentration in the brain. In a parallel PET study using a baboon, the scientists found that it took a full 60 minutes for peak concentrations to be reached after oral administration of methylphenidate.
Importantly, previous research has shown that the more quickly a drug works, the greater the perceived "high". Hence, the route of administration may make a difference in the kind of "high" produced by methylphenidate. "When the drug is abused", Dr. Volkow notes, "it tends to be snorted or used intravenously. That causes brain concentrations to rise and spike very rapidly, and this likely accounts for the 'high' the abuser experiences".
On November 16-18, 1998, the National Institutes of Health will sponsor a Consensus Development Conference on the Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder. Primary sponsors of the meeting are NIDA, the National Institute of Mental Health, and the NIH Office of Medical Applications of Research.