On page 1218 of Kandel, Schwartz, and Jessell's canonical Principles of Neural Science (4th ed), a diagram describing the "Action of antidepressant and other drugs at seratonergic and noradrenergic synapses" contains the following annotation for the post-synaptic 5-HT receptor: (Antidepressant) "stimulation of 5-HT receptors as partial agonist (lysergic acid diethylamide)." And in the caption: "Lysergic acid diethylamide (LSD) acts as a partial agonist at postsynaptic serotonergic receptors in the central nervous system. A number of specific compounds are now candidates to act as receptor-blocking agents at various serotonergic synapses."
Jesus Christ! My understanding is that most psychedelic substances are agonists of the 5-HT2a receptor. In fact, I think I've read some papers which used 5-HT2a stimulation (in the rat aorta of all places) as a test of hallucinogenic activity. But I've never thought of these substances as anti-depressants, despite their common activity in the serotonin system. Of course, antidepressants (all of which increase the availability of serotonin in the synapse, at least initially) take weeks to have clinical effects despite their immediate impact on the serotonin system (well, at least SSRI's and the tricyclics have immediate effects), so it's unlikely that a substance that is washed from the body in a matter of hours would have an effect on depression due to its serotonergic activity.
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2 comments:
it's a not so well known folk tale in the psychedelic community that low dose, in the LSD 10-40 gamma range ( 10-40 mcg.) has a anti-depression effect...of course opiates have an even better anti-D effect too. Well known in the Oxycontin user base! Apparently, since people not in pain like Oxycodone so much. Since they're not in pain what site is the opiate working on?
It was my fondest wish that dropping acid would alleviate my depression. Interestingly, before I took sertraline in sufficient doses, or during withdrawal, I experienced vertigo and acid-like flashbacks. But modafinil in the short-term works the best as off-label depression medication.
Not all anti-depressants increase serotonin levels directly, as you know, some affect the other members of the happy trifecta, dopamine and norepinephrine. And they are all crutches for the weak who don't enjoy a bout of suicidal ideation every now and then.
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