OPIOIDS

Opium teaches only one thing, which is that
aside from physical sufffering, there is nothing real

André Malraux
(1901-1976)

Opoids are drugs directly derived from the opium poppy -- papaver somniferum -- and the many synthetic compounds that have been created which emulate the effects of those drugs, as well as the endogenous peptides that interact with the opioid receptor.  Opium is a very ancient drug.   At sufficient doses, there is no amount of suffering that it cannot relieve.  Opium has been prized by the human race for millenia; wars have been fought over it; an incalculable number of people murdered; whole cultures destroyed; countless lives ruined.  In terms of sheer, historical destructive power, it has harmed or destroyed almost as many people as Christianity has. But, as with that religion, the harm it has done must be weighed against the suffering it has dispelled, the lives it has brightened, and the unbearable pain it has spared the human race.   So emotionally charged is the subject that it is not even possible to consider these drugs from anything remotely like a detached scientific perspective without failing utterly to describe what they are. 

In human culture, reason has little impact when opioid drugs are at issue, as can be seen starkly in a single fact:  one particular opioid, diacetylmorphine (diamorphine, Heroin), has been singled out as a sort of Ultimate Metaphysical Evil, even though there is really nothing special about it in pharmacological terms.  It is just another opioid agonist, yet its symbolic and emotional power is enormous.  A discussion of the pharmacology of diacetylmorphine which entirely omitted this fact would be egregiously incomplete.  In the early 21st century, users of heroin are viewed either as wretched or evil.  The very use of the drug is said by the biopsychiatrists to be a disease; their claim is that the "disease model," in which the addict receives "treatment" -- by force, if necessary -- is more "humane" than pushing them through the criminal justice system.  More humane it may be, but it is less honest, because the use of heroin is not a disease and, in any case, the truth of the situation becomes clear when one considers the fact that "treatment" is involuntary.  This and many other issues involving biopsychiatry and the "disease model" of aberrant or unwanted thoughts, feelings, and behaviors is taken up at length in another essay.  For now, let's just note that as long as the argument is framed (in the style of, "Have you stopped beating your wife yet?") as "Drug Use: Disease or Crime?" there is no possibility of even the slightest progress on any of the problems associated with drugs.

In contrast to the story of the benzodiazepines, the story of the opioids does not begin in a laboratory, with chemists and pharmacologists fiddling around with molecules and trying to invent something marketable.  The poppy invented itself and has been more effective in its self-marketing than the most wildly successful human marketing campaign.  Contrary to prevailing beliefs that envision evil "pushers" tempting innocent kids into becoming junkies, in fact, people actively seek out opioids with no prompting whatsoever.  Many know even from childhood that they want to eventually seek out opioids.  Why this should be the case is simply not a scientific question, as it asks after the most personal and existential aspects of human personality.  But a vast amount of scientific knowledge has been accumulated regarding these drugs, and one objective of this essay is to cover that knowedge, replacing mythology with fact wherever possible.  The first essay in this series, which discussed the benzodiazepines, covered a fair amount of basic pharmacology in the process, and I don't want to repeat this information for every drug we consider.  Someday, I may get around to extracting the basics of pharmacology from that article and creating a seperate essay on that subject.  I have mixed feeling about this, though.  Why does someone read about a drug on www.etfrc.com?  Certainly not because he or she wants to be a physician, and thinks the information here will be helpful with a pharmacology test.  People come here for detailed information on commonly used drugs.  In light of that, I'd hate it if the site degenerated into a pharmacology textbook, with chapters on absorbtion, metabolism, elimination and pharmacokinetics that had to be read in order to understand anything else.  That's just the kind of learning that the ETFRC holds in contempt.  So, for now, it's probably best to poke around the benzodiazepine essay if you need to get a basic feel for the science of pharmacology and its various conceptual parts.  And since, underlying the science of any psychotropic drug, there will always be organic chemistry and cellular neurophysiology, brief intoductory essays -- which we call "backwards chaining" essays -- are provided too.  These very short treatments of very complex subjects aren't supposed to substitute for studying a textbook on the subject, but our hope is that they'll provide enough information to prevent the reader from getting stuck in science-babble, philosophy-babble, or whatever other kind of babble is flooding the page at any given moment.  The amount of babble in the world is immense, and the irony of it is that the subject-specific babble, or "jargon," is actually intended to tame the complexity of the subject, by providing a specialized language in which single words or phrases stand in for paragraphs or even essays worth of information.  Of course, one must know that information for the babble to stop sounding like babble.

In taking up the drugs whose original expression was found in the poppy, after studying benzodiazepines, we are moving from wholly synthetic molecules created in a laboratory to molecules synthesized by complex, enzyme-catalyzed reactions occuring in a plant.  A look at the molecules should instill an appropriate humility into us: synthetic drugs, by and large, are very simple molecules when compared to some of the molecular structures nature tosses up.  The latex exudate of the opium poppy contains over twenty alkaloids (naturally occuring drugs containing at least one nitrogen atom).  So, we'll begin by looking at the structure of opium's principal alkaloid, morphine:

Morphine, and morphine shown with its heterocyclic rings distinguished.

In 1806, Sertürner isolated a pure substance from opium, which he called morphine, after Morpheus, the Greek god of dreams.  This compound accounts for the largest amount of alkaloid in the plant by weight.  There are, it turns out, two chemically distinct groups of alkaloids in opium: the phenanthrenes, of which morphine is a representative, and the benzylisoquinolines, of which papaverine is generally taken as the prototype.  The classical activity associated with opioids -- analgesia, anxiolysis, euphoria, and sedation -- are seen exclusively with the phenanthrenes, and indeed the benzylisoquinolines exhibit no affinity for opioid receptors (discussed at greater length below).  Sertürner's discovery made the medical use of the pure alkaloid possible, and morphine has superior analgesic activity and causes less constipation than raw opium.  Offsetting these benefits, of course, was the increased toxicity and propensity to produce dependence that came with the ability to deliver higher concentrations of the pure drug to the nervous system.

Effects of Morphine

The effects of the opioid analgesics are now well-known all over the world, and so they will only be quickly reviewed here.  Morphine has both stimulant and depressant properties at various nervous system structures.  The overall effect of a modest dose (10 to 15 mg given by intramuscular injection in a drug-naive subject) is increased tolerance to pain, sleepiness, changes in mood, and diminished concern with external stimuli.  A debate has long raged as to whether opioid analgesics actually relieve pain, that is, prevent nociceptive (painful) stimuli from becoming conscious, or whether their action is more in the manner of relieving suffering, which is the affective (mood-related) response to pain.  A combination of the two actions seems the most likely explanation for opioid analgesia.  Some pain patients given moderate doses of morphine are still able to describe the locus and intensity of pain, but report that they are no longer troubled by it; while others report that the pain is entirely gone.  The effects of opioids on the spinal cord (spinal analgesia) seem to directly block the transmission of pain sensations, while the effects on brain structures (supraspinal analgesia) seem responsible for the indifference to pain (and        indeed, at sufficient doses, to virtually everything) and the +"rewarding" or "euphoric" actions of the drugs.  It is the supraspinal component which is responsible for nonmedical use and dependence, and this is surely due to the ability of opioid analgesics to quell all forms -- physical and psychological -- of human suffering, to obtund all motivation and desire, e.g., for food, sex, social status, etc., and to induce a state in which no aversive stimuli reach consciousness, and all wants and needs are either satiated or irrelevant.

It must be immediately noted that not all persons experience the effects of morphine in so heavenly a manner.  A rather large percentage of pain-free subjects who are given the drug in a laboratory setting report dysphoria, nausea, vomiting, and an inability to concentrate or to think clearly (referred to as "mental clouding" in the medical literature); most such subjects say that they would not be interested in repeating the experience.  It is often said of heroin, "It's so good, don't even try it once."  But in fact, the percentage of people who find their fist encounter with an opioid a revelation, treasure the experience, and go on to become addicts is quite small.  From this, it is easy to speculate or conjecture about possible genetic and biochemical features underlying the "propensity" for addiction, but it is also important to remember that all such talk is just that: speculation.  There exist no scientific data which could support or falsify such speculations.  Of course, scientific data isn't the only kind of information worth considering.  The number of addicts who say that they never felt "quite right" until their first encounter with an opioid is quite large; so is the number of people who have wholly negative associations with opioids, whose experience of them consisted largely of dysphoria, nausea, and vomiting.  It doesn't hurt to speculate, as long as we remember that we are speculating, and don't start confusing our speculations with facts.  I've always felt that, at the very least, there was something innately different about those who respond to their first encounter with an opioid with astonished bliss.  Such a difference would perforce entail a biochemical difference somewhere, but no one who elaborates this into some kind of theory about "endorphin deficiency" or anything else should be taken seriously.  The available data just doesn't justify such great leaps of attempted logic.

Morphine also, more-or-less consistently, has some less than thrilling effects.  Nausea and vomiting, especially in those new to narcotics, are frequent; constipation is pretty much universal.  Finally, no description of the subjective effects of opioids would be complete without mentioning the phenomenon of nodding, which is treasured by opiophiles but regarded by normal people as troublesome, disorienting, and even frightening.  To nod is to segue from full awareness of the boundary between one's thoughts and one's surroundings into a semi-asleep state in which it is difficult to distinguish one's environment from a dream world entirely unrelated to it.  When conversation with an opiophobe is attempted during a nod, the results can be quite frightening for the opiophobe, for sentences may begin by referring to objects and events which both parties perceive, and then move into statements which have no apparent connection to anything at all.  Fortunately, the person on opioids appears extremely sleepy, or even asleep, when this happens, so he or she doesn't cause the kind of alarm that, say, a schizophrenic speaking identical words might.  In a full nod, the subject simply drifts through the dream world, occasionally coming close to waking consciousness -- perhaps even waking up for a few seconds -- and then resumes nodding again.  The dreams are uniformly blissful, and it is this state which must have inspired Sertürner to name his newly isolated compound after the God of Dreams.  This state is also the Holy Grail of opiophiles.

Copyright © 2002 by The Eaton T. Fores Research Center

A Work In Progress.

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