Title:  A tale of two stimulants. (Ritalin and cocaine) 
(adapted from the Archives of General Psychiatry, June 1995)
                                                                        

The stimulant drugs methylphenidate (Ritalin) and cocaine are similar in many 
ways. Both inhibit the reuptake (reabsorption) of the neurotransmitter dopamine 
(DA) at the same receptor sites in the same regions of the brain. Yet 
methylphenidate is considered acceptable as a treatment for children with 
attention deficit disorder. A new experiment suggests that the two drugs differ in 
apparent abuse potential because of differences in the rate at which they are 
cleared from the brain. Eight men were given intravenous injections of 
methylphenidate and asked how they felt at intervals for an hour and a half. PET 
(positron emission tomography) scans were used to observe the patterns of 
absorption, distribution, and outflow of the drug in the brain. The results were 
compared with data on cocaine from earlier experiments.

Methylphenidate and cocaine were concentrated in the same region, the corpus 
striatum. Both entered the brain at the same rate and reached a peak level in 
about the same time - four to ten minutes for methylphenidate and two to eight 
minutes for cocaine. The feeling of pleasure after taking methylphenidate was 
greatest five minutes after injection and subsided almost completely in a half hour 
to 40 minutes. The pattern for cocaine was similar. But methylphenidate 
maintained its peak concentration for 15 to 20 minutes and cocaine for only two 
to four minutes. Methylphenidate also remained in the brain much longer; 50% 
of the cocaine was gone within 20 minutes, 50% of the methylphenidate in 90 
minutes.

The authors conclude that methylphenidate and cocaine give pleasure chiefly 
while the concentration of DA in the corpus striatum is increasing. Once it levels 
off, the brain begins to adapt, and the drug loses its pleasurable effect. But 
cocaine clears out so quickly that there is no time for this adaptation, and the 
brain is ready to respond to another injection is less than a half hour. 
Methylphenidate, in contrast, remains in the brain for hours, blocking any 
further sensation of pleasure from a new dose. The authors note that the effects 
of cocaine in animals become less intense when  brain levels are kept constant by 
intravenous infusion. They also point out that when cocaine is taken orally it 
clears from the brain almost as slowly as methylphenidate. That might be one 
reason why the coca leaves chewed by South American Indians are so much less 
harmful than injected or smoked (crack) cocaine.