The Pepsi Challenge with controlled substances.
[Today’s post comes to us from Neurological Correlates, a blog devoted to the neuroscience of dysfunctional behavior. It was written by Swivelchair, who refers to himself as “an anonymous biopharma worker." It’s an excellent blog, one of the few that focuses on the biological basis of addiction.]
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Things go better with meth, as compared to cocaine, if you’re dopamine transporter challenged, anyway.
By Swivelchair
Methamphetamine is taken up more quickly, and lasts longer than cocaine. (Fowler et al, Abstract below).
And here’s something from Microgram Bulletin, October 2008, Published by the Drug Enforcement Administration Office of Forensic Sciences Washington, D.C. 20537: The DEA South Central Laboratory (Dallas, Texas) recently received a submission of approximately 4972 fake “kidney beans” (total net mass 3,210 grams), all containing a fine tan powder, suspected heroin. The “beans” were actually small plastic packets that had been painted to resemble kidney beans... Analysis of the powder... confirmed 90.3% heroin hydrochloride.
The perhaps undeniable point: probably the self-selecting population of people who are first drawn to drugs, and then become irretrievably addicted, are those who lack sufficient dopamine transport to feel fulfilled (or other insufficiency, depending on the choice of drug). They are, in essence, self-medicating, rather than using drugs for recreational use. I mean, you don’t load up kidney beans for recreational drug users.
I’m reminded of a friends’ younger brother, from a locally well-known family, whose arrest was reported as bringing in “the largest amount” of cocaine in those parts. His remark: He was a wholesaler, and the newspaper quoted street (”retail”) values, so the report inflated his inventory value. This was purely about money for him — he made far more money selling coke than any job he was qualified to do (which was, well, probably none, unless being a bon vivant and sparkling raconteur with insufficient money to fund a high rent party lifestyle qualifies as a profession, which it may). If the US were to decriminalize drug use, and fund a program to make an agonist which was not addictive (a la the whole methadone thing), probably we could solve much of the crime problem in the Western Hemisphere.
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“Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.” Fowler JS, Volkow ND, Logan J, et. al. Medical Department, Brookhaven National Laboratory, Upton, NY 11973
Abstract from Neuroimage. 2008 Dec; 43(4):756-63.
“Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum.
Methamphetamine’s uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine’s brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. “Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine’s fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.”
Related Links
PET studies of d-methamphetamine pharmacokinetics in primates: comparison with l-methamphetamine and ( –)-cocaine. [J Nucl Med. 2007] PMID:17873134
Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles. [Neuropsychopharmacology. 2008] PMID:17625500
Graphics Credit: methamphetaminetx.com
addiction 
drugs 
dopamine
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