Some Research on Stimulant Medication and DNA
The Center for Science in the Public Interest warned years ago that Ritalin appeared to cause cancer. See their letters on this subject.
Much in the news lately is a study expected to be published in the journal Cancer Letters, in which Texas researchers found that after only three months, every one of a dozen children treated with Ritalin had a three-fold increase in chromosome abnormalities associated with increased risks of cancer. Marvin Legator, PhD, Professor, Division of
Environmental Toxicology, University of Texas, is the primary investigator.
See some of the articles describing the study and comments by the researchers.
Other research, listed in reverse date order:
|Lott 2005||Dopamine transporter gene associated with diminished subjective response to amphetamine.|
|Brandon 2003 ||Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum.|
|Andersen 2002||Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nature Neuroscience, 2002 Jan;5(1):13-4|
Altered responsiveness to cocaine in rats exposed to methylphenidate during development.
Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr.
Department of Psychiatry, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA. firstname.lastname@example.org
Evidence in laboratory animals indicates that exposure to stimulants produces sensitization to their rewarding effects, a process that in humans would be expected to increase the risk of substance abuse. However, therapeutic administration of stimulants such as methylphenidate (MPH) in children with attention deficit hyperactivity disorder reportedly reduces the risk of substance abuse. Here we show in rats that exposure to MPH during pre-adolescence causes behavioral and neurobiological adaptations that endure into adulthood, and that are consistent with increased sensitivity to the aversive effects of cocaine.
Note: This study is an attempt to show that use of Ritalin in childhood decreases the possibility of drug abuse later on. However, any biological change in response to drugs like cocaine may be cause for concern in our opinion.
Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum.
Brandon CL, Steiner H.
Eur J Neurosci. 2003 Sep;18(6):1584-92.
Department of Cellular and Molecular Pharmacology, Finch University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Methylphenidate is a psychostimulant which inhibits the dopamine transporter and produces dopamine overflow in the striatum, similar to the effects of cocaine. Excessive dopamine action is often associated with changes in gene expression in dopamine-receptive neurons. Little is known about methylphenidate's effects on gene regulation. We investigated whether a methylphenidate treatment regimen known to produce behavioural changes would alter gene expression in the striatum. . . Acute methylphenidate treatment (0-10 mg/kg, i.p.) produced a dose-dependent increase in the expression of c-fos and zif 268 ["immediate-early" genes]. These effects were most pronounced in the dorsal striatum at middle to caudal striatal levels, and were found for doses as low as 2 mg/kg. Repeated treatment with methylphenidate (10 mg/kg/day, 7 days) increased the expression of dynorphin [a neuropeptide], which was highly correlated with the acute immediate-early gene response across different striatal regions. Moreover, after repeated methylphenidate treatment, cocaine-induced expression of c-fos and zif 268, as well as of substance P [another neuropeptide], was significantly attenuated throughout the striatum. These effects of repeated methylphenidate treatment mirror those produced by repeated treatment with cocaine or other psychostimulants and are considered to reflect drug-induced neuroadaptations. Thus, our findings demonstrate that acute and repeated methylphenidate treatment can produce molecular alterations similar to other psychostimulants.
Dopamine transporter gene associated with diminished subjective response to amphetamine.
Lott DC, Kim SJ, Cook EH Jr, de Wit H.
Department of Psychiatry, The University of Chicago, Chicago, IL 60637, USA.
Individual variability in responses to stimulant drugs may influence risk of stimulant abuse and treatment response. . . . The dopamine transporter is an important site of amphetamine action. Therefore, the dopamine transporter gene (DAT1) is a logical candidate gene to study. Using a drug challenge approach, we tested for association between DAT1 genotype and subjective responses to amphetamine in healthy adults. Volunteers participated in a double-blind, crossover design, randomly receiving placebo, 10 mg, and 20 mg oral D-amphetamine, and completed self-report measures on subjective effects including anxiety and euphoria. Subjects were genotyped for the DAT1 3'-untranslated region VNTR polymorphism and divided into groups based on genotype: homozygous for nine repeats (9/9, N=8), heterozygous (9/10, N=36) and homozygous for 10 repeats (10/10, N=52). . . In 9/10 and 10/10 subjects, amphetamine produced its expected effects of increased Euphoria, Anxiety, and Feel Drug . .. However, in 9/9 subjects, the effects of amphetamine were indistinguishable from placebo, suggesting that the 9/9 genotype has diminished subjective response to acute amphetamine. Interestingly, recent findings also implicate the 9/9 genotype in decreased therapeutic response to the stimulant methylphenidate in ADHD children. The current findings have important implications for understanding the genetic determinants of variability in stimulant response and risk of abuse.