Posted by lars1 on January 2, 2005, at 1:36:19
In reply to Re: True Amphetamines Prohibited!, posted by ed_uk on January 1, 2005, at 17:03:33
> Hi everyone!
>
> Thanks for your responses :-)
>
> Don't forget that Ritalin does have a high abuse potential.... all those people grinding up their pills and snorting them to get a cocaine-like high!I've read about this happening. Apparently snorting it puts it into the bloodstream very rapidly and produces a "rush" that is quite different from what happens when you take it orally. From what I gather, it's not particularly addictive so long as you take it as directed (i.e., in the prescribed dose, by the prescribed route). Kids with ADD don't seem all that enthusiastic about taking it.
> I imagine that quite a few people sell their prescriptions.
>I am of two minds about this. On the one hand, it shows that an illicit demand does exist. On the other hand, it shows that people who regularly use the drug are still quite willing to part with it, which is hardly consistent with a dangerously addictive drug. It's hard to imagine the same thing happening if, say, a heroin addict somehow got hold of a prescription for heroin.
> Although high doses of amphetamines may be neurotoxic, I'm not sure whether this is a problem with much smaller therapeutic doses.
>
> Regards,
> Ed.I'm not sure either. Unfortunately, most of the research in this area seems to be sponsored by NIDA (the National Institute on Drug Abuse, an agency of the US Government) as part of the "war on drugs," with the goal of "proving" that drugs are dangerous, not showing how much of them you can safely take. Therefore, there are many studies showing that high doses of amphetamines are damaging, but very few that would shed light on the threshold dose for this damage to occur. One interesting study in rats(1) found that doses of about 16mg/kg/day of either amphetamine (AMPH) or methamphetamine (METH), administered via continuous infusion over a period of 3 days, caused significant dopaminergic damage, while METH administered at the same rate for 1.5 days did not. Neither did METH administered at 8mg/kg/day for 6 days. (The experimenters also tried the latter two schedules for AMPH, but for some reason did not report their results.) These doses are expressed as mg of the base, not of the salt the way Adderall and Dexedrine are dispensed. To convert, you would need to multiply by about 1.6. Also, keep in mind that rats metabolize AMPH about 10 times faster than humans, so the drug concentration in their blood will reach only a tenth of what it would be for the same (mg/kg) dose in humans. After applying both of these correction factors, the study would seem to suggest that for a 60kg (132 lb) human, 80mg/day of Dexedrine or Adderall would be safe, while 160mg/day would not. According to the Adderall prescribing info, the maximum recommended dose is 30mg/day, so it appears that if you stay under that, you will be safe. However, human-animal equivalents are only approximations, and the margin of safety is not as big as you might like. Also, humans tend to take amphetamines in discrete doses, not by continuous infusion like the rats did, and it's not clear if that would make a difference. Finally, in the rat study, the high dose of amphetamine had to be administered for 3 days before damage occurred. It's possible that damage would eventually occur at lower doses, and the study just didn't run long enough for that to happen.
One other thing that concerns me is that in humans, some of the beneficial effects of amphetamines (increased energy and motivation) seem to decline over time. Potentially, this could be a reflection of neurological damage, i.e., the drugs are burning out the same neural systems that they are stimulating. However, this tolerance could equally well be just a result of a (reversible) down-regulation of dopamine receptors.
The above may sound rather negative about amphetamines, but the general medical consensus still seems to be that amphetamines are safe when used in the recommended doses. Many people with ADD take them for years without noticeable problems. And FWIW, I do take them myself. I would be interested in any comments anyone else might have about amphetamine safety.
With best regards,
Lars(1) Brain Res. 1984 Jun 15;303(2):359-64.
Further evidence that amphetamines produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers.Ricaurte GA, Seiden LS, Schuster CR.
Methamphetamine and amphetamine were continuously administered to rats for 3 days by means of subcutaneously implanted osmotic minipumps. The total daily dose of each drug was approximately 4 mg/day. Dopamine, norepinephrine and serotonin determinations two weeks later indicated that both amphetamines produced a selective striatal dopamine depletion. Anatomical studies indicated that this depletion was associated with striatal nerve fiber degeneration. To determine whether this fiber degeneration induced by amphetamines was dopaminergic, the long-lasting dopamine depletion produced by methamphetamine was antagonized with alpha-methyl-para-tyrosine. This prevented the appearance of nerve fiber degeneration after methamphetamine. These findings suggest that amphetamines produce a long-term striatal dopamine depletion by destroying striatal dopamine nerve fibers.
[Some of the interesting results of this study are only mentioned in the full article. I have an electronic copy which I'd be happy to send to anybody who'd care to babblemail me. BTW, this study has the same lead author as a notorious study on MDMA (Ecstasy) neurotoxicity from 2002, which eventually had to be retracted. -L]
poster:lars1
thread:436140
URL: http://www.dr-bob.org/babble/20041228/msgs/436668.html