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hallucinogens and depression

Steven J. Mcclue sjm at mole.bio.cam.ac.uk
Mon Nov 14 04:24:00 EST 1994

In article <3a0aj9$3fj at newsbf01.news.aol.com>, dsprouse at aol.com (DSprouse) wrote:

> In article <eortega-110994224508 at tstiefel.extern.ucsd.edu>,
> eortega at sdcc13.ucsd.edu () writes:
>      According to my psychobiology textbook (copyright 1992), LSD binds to
> the serotonin type 2 receptor and produces an agonistic (stimulating as
> opposed to blocking) effect on this receptor.  A dose of LSD will
> temporarily reduce the number of these receptors for a couple of days
> after administration (thus the rapid tolerance build-up, and the need to
> essentially double the dose of LSD in order to achieve comparable effects
> if taken the day after the first dose).  However, this reduction in 5ht
> (serotonin) receptors is temporary and these receptors come back after a
> few days.  There is no evidence, according to my psychopharmacology
> textbook (1993) of any link between LSD use and depression. 

I missed the beginning of this thread, but you are correct in that LSD binds to the 5-HT2 receptor, where it is a *partial* agonist ( that is, it stimulates the receptor to a lesser extent than serotonin). It could be that it is this partial agonist effect that is important, since a number of other hallucinogens with little or no structural similarity to LSD also act as partial agonists at the 5-HT2 receptor.
 As for the use of LSD as an antidepressant, I seem to recall that psychotherapists thought, when it was first being used, that LSD's ability to "unblock" psychological trauma might help in the treatment of patients whose depression was due to some such trauma.

sjm at mole.bio.cam.ac.uk

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