Wednesday, 28.10.2020

Peter R. Martin: Historical Vocabulary of Addiction



        According to the current electronic version of Oxford English Dictionary (OED), intoxication is the noun of the action intoxicate, which is the participial stem of the medieval Latin verb intoxicāre.  Specifically, intoxicate is a merging of the prefix in- with toxicāre, meaning to smear with poison; in Latin, poison is toxicum, derived from the Greek τοξικόν.  Understandably, intoxicate was initially defined as “to poison” but more recently has come to mean: “To stupefy, render unconscious or delirious, to madden or deprive of the ordinary use of the senses or reason, with a drug or alcoholic liquor; to inebriate, make drunk” or “To stupefy or excite as with a drug or alcoholic liquor; to render unsteady or delirious in mind or feelings; to excite or exhilarate beyond self-control.”  This historical progression of meanings encapsulates a paradox that persists to this day, whether the intoxication process per se should be understood as toxic, harmful, and akin to self-poisoning, or rather, as rewarding, a positive experience, likely to be repeated, and thereby represents the underpinnings of addiction, which may eventually be complicated by organ pathology (Martin 2016).  In the former view, it is the drug that poisons and is the culprit, whereas in the later it is the out-of-control use of an agent (that in itself may not be harmful) which eventually overwhelms the behavioral repertoire.

        A version of the word intoxicate was first used in the English language (despite the French title of the book) in 1530  by John Palsgrave (c. 1485-1554), a priest and tutor in the royal court of Henry VIII of England, in his L'esclarcissement de la langue francoyse (2003): “I intoxycat, I poyson with venyme.” This quotation refers to a meaning of intoxicate, the act of poisoning, now considered obsolete usage according to OED, even though medical science has repeatedly demonstrated that repeated administration of most drugs of abuse is associated with toxicity independent of psychoactive effects (Abbott 1896).  The use of intoxicate that more closely corresponds with the current meaning was expressed (1885) by the Elizabethan geographer Richard Hakluyt (c. 1552-1616): “It..goeth downe very pleasantly, intoxicating weake braines.” The word intoxication seems to have acquired the meaning it now has in the field of addiction by the second half of the 17th century, suggested by a quotation from Sir Thomas Browne (1605- 1682), the English polymath and physician (1672): “The prevalent intoxication is from the spirits of drink dispersed into the veynes and arteries.”  Historically, the term intoxication was most commonly used with respect to overindulgence in alcohol.  However, the word reflects a generic phenomenon, the subjective and objective effects on the nervous system and other organs of the body of self-administration of any psychoactive agent.  These consist of a wide range of consequences on physical and mental functioning governed by the characteristic pharmacological actions of the particular agent in the individual within their psychosocial context, often including altered mood, sensorium, consciousness and reaction to the environment and impaired insight and judgement (Mitford, L’Estrange and Harness 1870): “He [Coleridge] had for some time relinquished his English mode of intoxication by brandy and water for the Turkish fashion of intoxication of opium.”  Recognition of intoxication as a temporary state of compromised mental and bodily functions necessitated formal consideration of the term in social mores and the legal system.  For example, Jeremy Bentham (1748-1832), the English philosopher, jurist and social reformer and founder of modern utilitarianism viewed the state of intoxication as non-contributory in adjudication of criminal activity (1789): “The English law does not admit intoxication as a ground of excuse.”  On the other hand, in ancient Greece, not being of sound mind due to intoxication was considered a crime per se (Plato and Jowett 1875): “In Sparta…anyone found in a state of intoxication is severely punished.”

        The fundamental determinants of the state of intoxication are based on the pharmacological actions of the agent, the dose and time course of self-administration, as well as previous experience with the drug (Martin et al. 1995).  We have known, probably even before the time of Seneca (c. 4 BC-AD 65), the Roman Stoic philosopher, statesman and dramatist, that “every vice is loosened and comes forth” upon intoxication with alcohol (Motto and Clark 1990).  Also, that “When wine’s fierce power has taken effect on a man, and its heat has disseminated and spread into his veins, his limbs grow heavy, the wobbling man’s legs are impeded, his tongue falters, his mind is soused, his eyes swim: shouting gasping, quarreling ensue.”  More recently Benjamin Rush (1746 – 1813), a physician and signer of the United States Declaration of Independence described alcohol intoxication as “unusual garrulity…unusual silence…a disposition to quarrel…uncommon good humor and an insipid simpering or laugh…disclosure of their own or other people’s secrets…a rude disposition to tell those persons in company whom they know, their faults…certain extravagant acts which indicate a temporary fit of madness.” 

        The now well recognized clinical characteristics of intoxication with alcohol or other central nervous system depressants include anxiolysis, disinhibition, somnolence, impaired attention and memory, slurred speech, incoordination, unsteady gait and nystagmus, possibly progressing to stupor or coma (Martin, Lovinger and Breese  1995); when memory is disproportionately affected, the so-called blackout has its own entry (Martin 2020).  Understanding that this complement of findings constitutes a clinical syndrome that might be quantified not simply described, dates to more recent times. The beginnings of this approach is exemplified by the work of Ogston (1833), who based his classificatory system of “advanced stages of intoxication…chiefly derived from the notes of cases treated at the Police Office of this city (Edinburgh) for some years back, and the histories having been drawn up either on the spot, or very soon after they were observed, their accuracy may be relied on.” The “Phenomena of the more Advanced Stages of Intoxication” included examination of the pupils, pulse, sensorium, extremities, face and breathing and “two or three natural groups have been formed, of which, while the members are found to differ considerably from each other, yet the cases in each, when considered as a separate class, present a corresponding degree of mutual resemblance. Thus, if we take the cases which agree in having a contracted pupil, they coincide as much, it will be seen, as regards the state of the circulation, respiration, and animal temperature, as they differ in these respects from the remainder. The cases with dilated pupil have fewer symptoms in common, but their disagreement will be considerably lessened if this class be subdivided into two sets, the one with dilated pupil and imperceptible pulse, and the other with a like condition of the eye, but with less prostration of the circulation. In the remarks which follow, this arrangement, though liable to some objections, will be adopted.”   

        The next advance in understanding intoxication parallels the emergence of pharmacology as a new scientific discipline in the mid-19th century, with the founding at the University of Dorpat in Estonia of the first pharmacological institute by Rudolf Buchheim (1820-1879), whose student Oswald Schmiedeberg (1838-1921) was generally recognized as the founder of modern pharmacology.  From the pharmacologic perspective, it became apparent that the clinical observations regarding intoxication could be related to the dose of the agent that was self-administered.    Furthermore, with advances in chemical analysis it was clear that estimates of how much of the agent was consumed and the level of resulting impairment could be predicted from measurement of concentrations of the inciting agent in body fluids (Carter 1927).  A challenge when elucidating dose-response relationships of a drug of abuse is specificity of the intoxication syndrome with respect to changes of brain functioning due to various other causes (Engel, Webb and Ferris 1945).  Additionally, when the patient has self-administered more than one drug of abuse simultaneously, the dose-response relationship may be disturbed.

        As mentioned above, the syndrome of intoxication is determined by the pharmacological actions of the self-administered agent (Martin, Lovinger and Breese 1995).  For example, intoxication with stimulants is characterised by mental stimulation (euphoria, hypervigilance, anxiety, tension, anger, impaired judgement), psychomotor agitation (stereotyped behaviors, dyskinesias, dystonias), energy (decreased need for sleep), anorexia, autonomic arousal (tachycardia, hypertension, pupillary dilation, perspiration, chills), cardiac arrythmias, respiratory depression, confusion and seizures.  Intoxication with opioids is quite different but with some overlapping features: activation or “rush” and sedation/apathy or “nod”; euphoria or dysphoria, facial flushing or warmth; impaired judgment, attention or memory; analgesia, constipation, pupillary constriction and drowsiness; respiratory depression, areflexia, hypotension, tachycardia; and in the most severe cases, apnea, cyanosis and coma.  It can probably be predicted that these different classes of drugs which have distinctly different pharmacological effects can be combined by either the physician to therapeutically modify intoxication (Hargrove and Ford 1952) or by patients to augment or modify their experience of intoxication (Jasinski and Preston 1986).  Moreover, it is apparent that physicians who see patients who have been experimenting with combinations of drugs of abuse, may have considerable difficulty distinguishing the cause of intoxication based on the characteristics of the manifested clinical presentation alone and might require the assistance of toxicology laboratory for clarification (Martin, Lovinger and Breese 1995).

        It is also challenging for many physicians to distinguish intoxication from withdrawal as these manifestations are closely related in most clinical situations.  Whereas the clinical findings of intoxication are an expression of the specific pharmacological actions of the drug of abuse, withdrawal is typically the opposite progression of events enhanced by the accompanying stress response (Martin 2020).  It is meaningful to dichotomize these phenomena only if one recognizes that they represent stages of a longitudinal process, namely the interaction between an individual and a self-administered psychoactive agent — intoxication always progresses to a withdrawal syndrome, which for central nervous system depressants can be as minor as a hangover to as severe as delirium, the severity being a function of dose and duration of exposure of the drug of abuse and previous experience with the drug.  The likelihood of confusing intoxication and withdrawal is illustrated in the following characterisation of intoxication as a “brain fever” (Armstrong 1813):

        “There is an interesting disorder of the brain, the effect of intoxication, and which deserves infinitely more attention from the faculty in general than, as far as I know, it has hitherto received… This disease, which I shall continue to designate brain-fever, is preceded by restlessness, defective recollection, paleness of the face, and slight tremors of the limbs; by anxiety, and irregularity of thought. At first the patient's slumbers are short, and interrupted by frightful dreams; but he soon becomes watchful, and passes days and nights without sleep; he dislikes to be alone, and if his friends have him in private, he is clamorous till they return, or goes about the house in search of them. His appetite is considerably diminished, and he frequently loaths the very sight of animal food. He is more especially sick at the stomach towards the morning; he often vomits his breakfast; and the slightest exercise, or agitation of mind, produces perspiration. As the complaint advances, the skin becomes hot and dry, the tongue parched, and the pulse weak and rapid. The surface of the body, however, soon grows cooler, and is covered with sweat, and the tongue puts on a cleaner appearance; but the irregularity of mind increases; the patient imagines that his friends are all conspiring against him, or that they have suffered some great misfortune, in which he is himself deeply implicated: — at other times he supposes that his chamber is haunted by spectres, and furiously calls for assistance to drive them away; or supposes that he is in a prison, and that his friends have all deserted him; sometimes, however, he is in high spirits, laughing and talking by turns incessantly.  Occasionally, too, he converses with the medical attendant about his ordinary business, with apparent precision; tells him that he has been continually engaged, and walked or rode to several places in the neighbourhood, since he last saw him, when, in reality, he had never left his own room: — at  the next visit he mistakes the physician for some other person, and loads him with abuse.  If any one happen to contradict him, he most pertinaciously adheres to his opinion, and becomes highly indignant.  If he be soothingly dealt with, he will sometimes answer questions readily and distinctly; but if many interrogations be put to him in succession, he grows confused, and relapses into delirium.

        “The symptoms already described continue more or less urgent for four, five or six, and seldom longer than 10 days. If the patient falls into a sound and tranquil sleep he generally wakens refreshed and collected, and from that time recovers rapidly: but short disturbed slumbers, accompanied with subsultus tendinum, from which the patient starts with affright, and then falls into a low muttering delirium, are amongst the most dangerous indications.  I have seen one case accompanied by convulsions from the very beginning of the disease; but they were speedily subdued by a large dose of aether, and the patient recovered very well.” 

        It is apparent to the modern reader that this comprehensive clinical description is of the phenomena associated with intoxication and that it incorporates the entirety of the longitudinal course from intoxication to withdrawal from alcohol.  This description would certainly be more confusing in modern times when the challenge becomes unpacking intoxication and withdrawal in patients who may have been intoxicated with more than one drug of abuse simultaneously, say alcohol, methamphetamine and opioids; for example, as mentioned above, intoxication with methamphetamines shares characteristics of alcohol withdrawal.



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July 9,  2020