Re: MAPS: Plasma MDMA Levels Nonlinear with Dose

["Nicholas V. Cozzi, Ph.D." <nvcozzi@xxxxxxxxxxxxxxxx>]

At 11:12 AM 5/7/99 -0400, you wrote:

>in divided doses.  This being the case, often one can acheive the same
>subjective effects by using the same amount of drug or maybe a little more
>in divided doses rather than all at once, thus keeping peak plasma levels
>down, and keeping concentrations in areas where the drug may be toxic
>from reaching too-high levels.

The time of peak plasma concentration must not be confused with the time of
peak effect.  Effects often lag behind plasma concentrations, sometimes
because the tissue concentration at the site of action has not yet reached
its peak and sometimes because a response may have latency.  One example is
fluoxetine, which takes from 10 days to 6 weeks before its psychoactive
effect is seen.  Sometimes effects precede peak plasma concentrations
because reflex or compensatory processes exist which limit the drug effects
before the concentration becomes maximal.

Divided doses do not reduce the concentration level required to produce
subjective effects.  However, as Cyrus pointed out, one may avoid an
"overshoot" into a concentration range that might be toxic.



Nicholas V. Cozzi, Ph.D.
Department of Pharmacology
East Carolina University School of Medicine
Greenville, NC  27858

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