SEROTONIN AND ITS AGONISTS (ahem)

Sometimes I wish I’d taken organic chemistry back there somewhere.  I wish that for about three minutes.  Then I get busy to try to figure out this stuff without tinkertoy diagrams of what’s connected to what.  The main interacting three I have trouble figuring out are serotonin, dopamine and epinephrine/norepinephrine.  The figure above means nothing to me so far.   I don't think it's a VENN diagram.  I do know that the three are monoamines.  Thus:  "Monoamines are any of a class of compounds derived from ammonia by replacement of one or more hydrogen atoms with organic groups." "Organic chemistry involves the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms."  This is why smart alec college students taking organic chemistry refer to their parents as "carbon units."

I’ll use the rest of this post on serotonin and put the other two off to the future.  I’ll cherry pick some characteristics, but they are much complicated by the context, because what an increase or decrease “does” depends on what all the other molecules are doing and how much of them is present.  At animal control we knew that an out-of-control horse that had to be darted with tranquilizer would react one way before it was really full of adrenaline, and the opposite way if it had been thoroughly terrified and driven.  Making the judgment on the state of a horse is no easier than making the same judgement about a street person on the rampage.  The consequences can be fatal.  So sometimes "control" means just "give it time and space to calm down."  (Tell the cops.)

Serotonin is one of the molecules that make the synapses between neurons work. 

Serotonin is chemically derived from tryptophan and is primarily found in the guts, platelets (the little blood cell entities that control clotting) and and the brains and spines of animals, including humans. It is popularly thought to be a contributor to feelings of well-being and happiness. 

Approximately 90% of the human body’s total serotonin is located in the epithelial (skin)-derived cells that line the GI tract, where the molecule regulates intestinal movements.   If it detects toxins and sometimes other dangers, it empties the gut fast.  These interact with -- but do not have the same origin as -- the enteric nerve cell network embedded in the gut walls that connects to the autonomic nervous pathways. These include the regulation of mood, appetite, and sleep.  Infant stuff: eat, sleep, cry, babble, the foundation of everything else.

It is claimed that serotonin has some kind of interaction with the social order -- that it keeps subordinates from running away while encourages flight in isolates and alphas.  Alpha male macaque monkeys have twice the level of serotonin in the brain than that found in subordinate males and females. Dominance and high levels of cerebro-serotonon levels seem to go hand in hand.  But not in dominant females.  No one knows  why.  

The vagus nerve (a big part of the enteric autonomic nerve system) sends information directly from the gut to the brain, but if it is cut, the guts go on working.  No one knows what this means, but it seems like a good thing.

Molecular action in the brain (and in the rest of the body) is a matter of emitting and receiving.  The number and willingness of receivers has as much to do with what happens as does the amount and timing of the emissions.  For instance, this ominous sentence:  “In humans, levels of 5-HT_1A receptor activation in the brain show negative correlation with aggression, and a mutation in the gene that codes for the 5-HT_2A receptor may double the risk of suicide for those with that genotype.”  In ordinary English, I take this to mean that if one kind of serotonin receivers are taking in the hormone, the person will calm down, but if another kind of receptor is mutated (no indication whether that would mean taking in more or less) then the withdrawal will become aggression turned against the self or even the ultimate withdrawal of suicide, depending upon how you interpret the act and its circumstantial causes.  Suicide can be lashing out as well as simple departure. 

psilocybin mushrooms

“The psychedelic drugs psilocin/psilocybin, DMT, mescaline, phencyclidine and LSD are agonists, primarily at 5HT_2A/2C receptors. . . .  ⁽Agonist: A substance that acts like another substance and therefore stimulates an action. Agonist is the opposite of antagonist.  Antagonists and agonists are key players in the chemistry of the human body and in pharmacology.”)  So the psychedelic molecules are not primary substances, but intensify the main hormones by the action of “agonists” or allies at the receptors. 

“The empathogen-entactogen MDMA releases serotonin from synaptic vesicles of neurons.”  Once again, this is the ground of controversy.  The effect of the popular drug seems to be peace, harmony, sympathy and a kind of hypnotic susceptibility to suggestion.  But some object that patients will resist anything called an “empathogen” because they won’t connect it to “empathy” but rather to “pathology.”  Maybe since the effect is sort of beatific, they would accept the term “entheogen,” meaning a drug that connects one to God.  What’s in a name?  Opinion.

And then there’s the idea that maybe the therapist should be the one to take a bit of this in order to better to respond to his or her clients, remaining calm though horrific narratives.  But what if the alpha therapist taking serotonin releasers loses his place in the pecking order and flees the room?  Should all therapists be female (esp. if they are macque monkeys) so they will not be susceptible to this effect?  What if the effect on the client is to over-empower him or her?  Therapists are not exactly safe in there alone with someone unstable.  Some of them have an alarm buzzer that rings to bring help, like the ones at the bank teller wickets in case of a holdup.

All this stuff (meaning molecules) is interactive, partly produced by the body and affected by emotion (yes, even “empathic” emotion from someone else’s experience) as well as present in such unsuspected “health food” sources as St. John’s Wort and ginseng.  It’s not impossible for interactions to trigger “serotonin overload” which includes all the basic generalized stress symptoms like confusion, agitation or restlessness, dilated pupils, headache, changes in blood pressure and/or temperature, nausea and/or vomiting, diarrhea, rapid heart rate, tremor, loss of muscle coordination or twitching muscles, shivering and goose bumps, heavy sweating.  In short, it would be tough to tell whether the victim were suffering from alcohol poisoning, electric shock or Ebola unless there were clues in the situation. 

The Borgias

My better judgment being undermined due to a shortage of streaming BBC Masterpiece Theatre series, I’ve been watching “The Borgias.”   Since the terms of drama are protagonist and antagonist, It could be called “the story of Pope Serotonin,” all about pecking order, kings as "agonists", the Vatican as an enteric nerve/mucous membrane digester of strategy, and whether it would be better to survive through retreat or by empathogens that really ARE pathological.  All those toxic chemicals sneaking around in food and drink!  The essentials of Communion reverting to carnivory and agony!  The longing for MDMA becoming mammary, for the women are not so much the victims of serotonin pecking order and are often soothers.

A Borg, surely a Puritan

This is all pretty imaginary, which is a precursor of science, but not science until it’s tested and the causal links are found.  Whether it is sparing us from Borgians or Borgs is a different question.  But image is an agonist for inspiration.