Ehab Jundi
Section 106
Dr. Sergio Cortes
January 29th, 2013
Ritalin
Ritalin, methylphenidate, is a psychostimulant substance that is used to treat ADHD (attention-deficit
hyperactivity disorder) in both children and adults. ADHD is the most commonly diagnosed psychiatric
disorder of childhood and adolescence which effects approximately 7.8% of children from ages four to
seventeen in the United States of America (Gill). Ritalin is the most commonly prescribed medication
for ADHD. Individuals who suffer from ADHD have lower levels of dopamine, a chemical
neurotransmitter responsible in regulating a person’s behavior. Ritalin increases dopamine, which is
essential for various cognitive functions such as focus and attention. The increase of dopamine also
allows people to be less impulsive and more reliant on rationalizing decisions based on reason rather
emotion. Ritalin is similar to cocaine – as both substances are stimulants. Unlike cocaine, Ritalin is not
addictive in most cases when prescribed, as Ritalin is not directly injected into the bloodstream, but
rather taken in a pill form – allowing it to reach the brain at a much slower rate than cocaine. Due to it's
similarity to cocaine, the following paper will focus primarily on addictions and after effects linked to
Ritalin.
Since its introduction in the 1960s, methylphenidate has been one of the most regularly prescribed
remedy for ADHD. Ritalin takes on the job of a dopamine transporter in order to raise the abundance of
dopamine outside of the cells, primarily in the mesocorticolimbic and mesostriatal systems, by
blocking the re-uptake of dopamine (Gill). Similar to cocaine and methamphetamine, there is evidence
that methylphenidate results in a substantial amount of neuroadaptations within the dopamine system
(Gill). While there have been little studies that have analyzed the long term effects pursuing the use of
methylphenidate in children, there have been studies on young primates, such as mice, which focused
on the changes in dopamine transmitter and receptors functionality function after one year of
methylphenidate treatment.
There is reason to believe that there are links to an increased risk in substance abuse for children that
are on Ritalin and various other prescribed stimulants in their adolescence (Biederman). The current
findings concerning a link to substance abuse has been very slim. While there has not been evidence
that suggests that stimulants lead to future substance abuse, there have been studies that link an
increased danger for future tobacco and cocaine usage in adults that have been treated since their
childhood.
Amongst addiction, another area of question regarding methylphenidate is growth suppression. There
has been some circumstantial evidence that shows that a chunk of students treated with
methylphenidate experience reduced growth curves in both height and weight, while the other portion
has no reported effects on their growth (Safer). There has been a study conducted monitoring the
growth and development of juvenile monkeys that are being medicated with methylphenidate. The
study has monitored the growth patterns of the monkeys with a control group that is representative of
their normal growth curves (Lambert).
The question of addiction has been heavily explored and pursued mainly by using rodents as the
subjects of research. There are studies that reported that methylphenidate treated animals have an
increased susceptibility to the satisfying effects of cocaine (Brandon), while on the other hand, some
studies have observed lesser rates of cocaine self-administration (Gill). Another study has shown that
there is less sensitivity to cocaine in individuals following treatment with Ritalin (Andersen). Since
there have been a substantial amount of ambiguous and conflicting results, it gives reason to further
delve into the research behind this topic.
Since studies involving rodents can only be stretched out so far, I will primarily focus on a study that
uses juvenile primates to observe the effects of habitual methylphenidate treatment. These juvenile
primates are excellent models for developmental research since their childhood and adolescence are
fairly long, making room for more observation, and follow very similar maturation patterns as humans
do. These nonhuman primates also have a very close homology to mankind In addition, nonhuman
primates have close homology to anthropoids in terms of neuroanatomy and neurochemistry of the
dopamine system. These primates also closely fit the elaborate social and cognitive behaviors that are
typical of humans. (Weerts).
The following study monitors sixteen young male rhesus monkeys and were studied in two groups of 8,
separated by age. One group's mean age was 40.5 months while the other was 38.0 months; each
groups were further split into two more groups – drug and vehicle treatments (Gill). These groups were
chosen to be as similar as possible in regards to their body weight and age. These monkeys were fed
with adjustments in respect to each monkeys' body weight. All of the monkeys were said to be in the
transition stage between juvenility and adolescence. After the feeding stage was complete, the rhesus
monkeys were administered either the drug or a vehicle through a syringe. The amount of dosage for
each monkey was initially calculated based on the monkeys blood serum level and then fixed to each
individuals target serum level (Gill). The procedures of administration and monitoring proceeded daily
for a year.
After the first phase of testing was complete, the monkeys were individually housed and maintained
visual and auditory contact with each other. The monkeys were weighed and fed daily and were
prepared for surgery for the second phase of testing. Each monkey underwent surgery with a chronic
indwelling venous catheter which was placed in the femoral vein (Gill). The structure had two photooptic switches, a food receptacle, and three stimulus lights that were positioned above each switch.
The monkeys then were trained to response under a fixed ratio schedule of reinforcement. The
monkeys were trained for approximately 60 minutes with a food pellet delivery schedule (Gill). After
the schedule was established, saline was substituted for food pellets until there appeared to be no trends
in response. The food-maintained responding was re-established and cocaine was substituted for food
pellets. The food-maintained responding was returned for at least three instances until the next cocaine
dose was administered.
The concluding results for the serum concentrations were that there was no relationship between the
serum levels or the dosage and any changes in growth or dopamine markers (Gill.)
There was no significant significant change in the crown-to-rump length, and body mass index, or
growth (Gill). Animals in both control and methylphenidate treated groups showed relatively normal
gains in these three areas over the length of the study; no differences were visible in the two groups
(Gill).
The effects on the brain regions from drug treatment were inconclusive and found no significant
changes. The following image depicts a scan of the control and methylphenidate treated groups. There
is no visible or significant difference in the dopamine 2 or dopamine 3 receptors in the primates' brain
(Gill)
As far as the cocaine and methylphenidate portion of the experiment goes, there was little difference or
any visible relationship between the two groups. Cocaine intake followed a monotonic function of
dosage in the rhesus monkeys and did not differ from the methylphenidate and control group monkeys.
Works Cited Page
Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon Jr WA (2002). Altered
responsiveness to cocaine in rats exposed to methylphenidate during development. Nat
Neurosci 5: 13–14.
Brandon CL, Marinelli M, Baker LK, White FJ (2001). Enhanced reactivity and vulnerability to
cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25:
651–661.
Gill, Kathryn. "Chronic Treatment with Extended Release Methylphenidate Does Not Alter Dopamine
Systems or Increase Vulnerability for Cocaine Self-Administration: A Study in Nonhuman
Primates." Neuropsychopharmacology . 37. (2012): 2555-2565. Web. 29 Jan. 2013.
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Lambert NM, Hartsough CS (1998). Prospective study of tobacco smoking and substance dependencies
among samples of ADHD and non-ADHD participants. J Learn Disabil 31: 533–544.
Safer D, Allen R, Barr E (1972). Depression of growth in hyperactive children on stimulant drugs. N
Engl J Med 287: 217–220.
Weerts EM, Fantegrossi WE, Goodwin AK (2007). The value of nonhuman primates in drug abuse
research. Exp Clin Psychopharmacol 15: 309–327.