Posted by pinksharkmark (18.104.22.168) on June 24, 2001 at 02:35:25:
Lately I've been doing a lot of research on chemical structures based on the "indole ring" and trying to puzzle out why sumatriptan (Imitrex, Imigran) or ergot compounds (ergotamine, cafergot, sansert) only work temporarily, while hallucinogens such as LSD or psilocybin work for several months to a year.
What is immediately apparent is that both sumatriptan and psilocybin are VERY closely related. Psilocybin is basically phosporated DMT (di-methyl triptamine), while Imitrex is basically sulphonated DMT.
-- anthropological side note --
DMT is a hallucinogenic alkaloid used ritually by many South American tribes. It occurs naturally in the bark and roots of a vine native to the Amazon basin. They brew up a tea of this vine with harmaline (a potent MAO inhibitor) and drink it in order to see mystic visions and receive guidance from the animal spirits, especially the jaguar and the python. The brew is called Ayahuasca. So far I haven't come across any references regarding the use of ayahuasca to treat headaches, but my guess is that it would work quite well.
-- side note finished --
Just as sumatriptan and psilocybin are chemical "kissing cousins", LSD and Sansert (methysergide) are also very closely related. Both are derived from ergotamine.
Given this close chemical link between sumatriptan and psilocybin/psilocin, (and ergot compounds and LSD) it is likely that the two classes of drugs will interact in some way, which is why I advocate abstinence from any of the ergot compounds and triptans before taking LSD or psilocybin.
Despite their closely related chemical structure, there is a major difference between the effect of the ergot compounds and the triptans (sumatriptan, zolmitriptan, naratriptan and all) and the effect of the hallucinogens. The ergots/triptans will keep you painfree only while they are in your bloodstream. The hallucinogens, too, will keep you painfree while they are in your bloodstream. BUT a hallucinogen will also keep you painfree for MONTHS after every last trace of it has vanished from your body. The only logical explanation for this result is that the hallucinogens act as a catalyst for some subtle alteration in brain chemistry that is semi-permanent. In other words, it is not the hallucinogen per se that stops the cycle, but rather the ALTERATION it has made to your synaptic vesicles or your 5HT-2A receptor sites or your hypothalamus or whatever.
Envision a coiled spring in a cylinder with a hinged lid over it. The lid has a latch on it. Bump the latch hard enough and the lid opens, releasing the spring. If you push the spring back down into its cylinder, flip the lid shut and place a heavy ball of ice directly top of it (leaving the latch open), the spring is confined. Once the ice melts, the spring pops out again, since the lid is still unlatched.
But, if you push the spring back into its cylinder, close the lid and reset the latch the spring will be confined until the next time the latch is bumped hard enough to open.
Ergot/triptan is like the ball of ice. It confines the cluster headache (spring) temporarily, but it doesn't correct the basic problem -- the open latch. A hallucinogen, on the other hand, closes the open lid AND resets the latch. The spring (cluster) is confined until the latch gets bumped again.
In normal people, no matter how hard you bump the latch, it won't open. Clusterheads have a faulty latch. In the case of a chronic, the latch will never close on its own. In the case of an episodic, the latch closes on its own for long periods of time, then opens for a while, sort of like a time lock in a bank vault.
The 64 million dollar question is:
If the hallucinogens and the ergot/triptans are so similar in chemical structure, WHY do the former close the latch but the latter simply sit on the lid for a while, leaving the latch open?
The only logical explanation I can come up with is that the same quirk in the structure of a hallucinogen that creates its profound mental impact (in high enough doses) also gives it the ability to "close the latch". In other words, if a hallucinogen weren't "hallucinogenic", it wouldn't work.
The best-known example of trying to "de-hallucinogenize" a hallucinogen is methysergide (Sansert), which was deliberately created by Sandoz hoping it would be as effective against migraines as LSD was known to be, but without any hallucinogenic side effects. Methysergide is basically LSD with the "pizazz" removed. The problem is, this new, crippled LSD not only doesn't let you see visions, it is also significantly less effective at stopping cluster cycles. In essence, Sandoz "threw out the baby with the bathwater".
Given the close similarity between sumatriptan (sulphonated DMT) and psilocybin (phosporated DMT), I wonder if the researchers at Glaxo were trying to do the same thing as their Sandoz colleagues? Were they deliberately trying to create a non-hallucinogenic version of psilocybin? Unfortunately, they achieved the same result: their psilocybin with the "pizazz" removed doesn't stop cluster cycles.
Unlike Q (an ex-chronic clusterhead who has been painfree for months now thanks to LSD), I DON'T think that it is the altered mental state ("hallucinations", if you must) per se that stops the cluster cycle, since so many have reported complete success with doses that just barely yield a noticeable "buzz". These people were FAR from the mental state that LSD and psilocybin are notorious for, yet their "latches" have been closed nonetheless.
No, I believe that it is more of a "catalytic" effect. The hallucinogen TRIGGERS a series of events in the body's own brain chemistry that achieves two separate results: altered perception AND a normalization of the faulty serotonin-regulating mechanism that causes clusters. Once the hallucinogen dissipates, perception returns to normal, and the serotonin-regulating mechanism STAYS normal.
Of course, since we clusterheads are defective, the serotonin-regulating mechanism drifts out of whack again after several months or a year or so, and the process must be repeated.
Damn. I really miss GaryG. I bet he would have some useful input to this theorizing of mine. Anyone else have any thoughts on this? Miguel? Ueli? BobP? Is there a neuropharmacologist in the house?
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