Psychopharmacology = w0w! These carbon rings get ya stoned! Imitrex migraine med made from Magic Mushrooms? Trippy!

Over the weekend I got a pretty rough (and intensely visual) migraine while I was finishing the Politics in Minnesota legislator profiles. I called up a friend of mine who has an interest in biochemistry, asking if they have figured out what the heck a migraine actually is. I certainly attribute this migraine to too much coffee and cigarettes, since when I moderate these substances I don't get the damn things. I rarely have cigs except when things are stressful.

Anyhow this led me to take a look at biochemical websites, and - gasp - the structures of illegal drugs. My friend told me that since migraines are somehow related to serotonin, the prescription migraine medication Imitrex (sumatriptan) is actually a somewhat altered psychedelic mushroom variant.

I went to go check this out. This Canadian website had a ton of useful biochem info for Imitrex (and everything else), including receptors, gene sequences and various genetic racial differences in affected alleles.

Indeed we can see that big Pharma wanted to use the weirder serotonin receptors activated by hallucinogens like mushrooms: Imitrex is the first image. The second two are the major components of magic mushrooms via Erowid, and finally serotonin:

Indeed, my very basic chemistry knowledge indicates that everything except the red sprong is the same between mushrooms and Imitrex. Actually i think the N-S-02 structure isn't even that different from psilocybin. (wikipedia notes that Imitrex can give you heart attacks because its main purpose is vasoconstriction of dilated arteries)

While it is certainly not well-understood why mushrooms generate hallucinations, it's believed they activate certain odd serotonin receptors - perhaps the same ones that thrash around when I get a migraine. The visual effects of a migraine - the "halos" of shimmering incongruence that made it impossible for me to read the computer screen for a full 36 hours - are perhaps not that different than the wobbly weird look of intense mushroom trips.

Only LSD has been isolated as an agonist for the 5-HT6 serotonin receptor, according to the Wiki. I found that LSD itself (lysergic acid diethylamide-25) was actually created by Dr. Hofmann and Sandoz while they were making variants of ergot to treat migraines:

In 1918, Arthur Stoll isolated ergotamine, which was introduced by Sandoz (now Novartis) under the trade name Gynergen in 1921 and marketed as a safer and more reliable form of the medieval midwife's nostrum. Controlled trials in the 1930s showed it to be effective in relieving migraine headache.

Also during the 1930s, two U.S. chemists succeeded in identifying the common nucleus of the ergot drugs, which they named lysergic acid. With this information, it became feasible to synthesize the ergot compounds, a project undertaken by Albert Hofmann in Stoll's laboratory at Sandoz, among others (2). In 1935, Sandoz chemists succeeded in synthesizing ergonovine, which was developed as methylergonovine (Methergine) and widely used to control postpartum hemorrhage. Further efforts to isolate the various alkaloids occurring naturally in ergot led to the development of a preparation of ergoloid mesylates (Hydergine) for treating dementia. In 1943, Hofmann synthesized dihydroergotamine (DHE), marketed for the treatment of blood pressure and later shown to be highly effective for migraine.

Migraine drugs

In the course of Hofmann's trial-and-error synthesis of lysergic acid derivatives, the 25th compound, lysergic acid diethylamide (LSD-25), failed to show any therapeutic promise in early testing on animals. In 1943, five years after it was first synthesized and tested, Hofmann decided to synthesize LSD-25 again for further testing. While completing the synthesis, he was overcome by strange sensations, which later developed into mild euphoria accompanied by pleasant visual hallucinations.

Surmising that he had somehow absorbed or ingested some of his newly synthesized compound, Hofmann proceeded to test the substance on himself by taking what he believed to be a minuscule dose--0.25 mg--and was rapidly plunged into what can only be described as a very bad trip. Like the natural ergot from which it was derived, LSD proved to be too potent, risky, and unpredictable to have a medical application.

In the course of exploring the ergot family, Sandoz chemists went on to discover yet another important antimigraine drug, methysergide (Sansert). Used for daily preventive therapy rather than abortive treatment of migraine, methysergide is a serotonin antagonist, whereas ergotamine is a serotonin agonist. Interestingly, "unworldly feelings" or hallucinations are among methysergide's possible side effects (3).

Likewise, it is interesting to survey and compare the chemical structures of amphetamine, methamphetamine and MDMA (ecstasy), morphine, heroin, ketamine, and all the other favorites. I thought it was kind of funny that esoteric drugs like salvia divinorum's active parts actually look really weird. So let's survey a few.

Salvia's parts:

We're drawing all this material from the valuable yet rebellious Erowid psychoactive chemistry index. There's even a nifty side-by-side comparison engine. For example, check out amphetamine VS methamphetamine, reflecting on that extra polyatomic ion's effect:

And here's MDMA - ecstasy - which essentially has a speed half (on the right) glued to a hallucinogen half.

DXM and Ketamine: dextromethorphan hydrobromide, a cough suppressant that provokes nasty hallucinations at high levels, and burns holes in your brain called Olney's Lesions. Ketamine is a more powerful (and apparently related) disassociative and anasthetic:

Nicotine: (S)-3-(1-Methyl-2-pyrrolidinyl)pyridin, industrial toxin/stimulant beloved by global capitalism.

LSD: 9,10-Didehydro-N,N-diethyl-6-methylergoline-8ß-carboxamide / D-lysergic acid diethylamide

Caffeine and alcohol

THC: Tetrahydrocannabinols / Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol, which of course have many strange and therapeutic neurotransmitter effects that medical researchers aren't allowed to determine (thanks, schedule One):

Let's get into Opiates: (Please!) It's interesting that heroin was invented to let the painkiller part of the molecule slip through the lipid barrier. Lipids - ie fat membranes - slow down non-lipid-soluble drugs. First is codeine, then heroin.



Absinthe - Thujone - the green dragon:

Cocaine:

I don't write this to celebrate these substances, as of course many of them have destroyed many lives. Namely alcohol and tobacco, mostly. But we don't usually think about the chemistry of drugs, and even though it's hard to visualize, these materials really do work on the atomic level. It's funny how some carbon rings are more political than others, and of course it's funny that cutting-edge pharmacological research basically just recuts mushrooms to treat migraines.

Now that's what I call weird science. Somewhere, Dr. Hofmann is laughing. (late addition: Hofmann's research on Mexican and South American traditional magic drugs)