Monday, 17.05.2021

Peter R. Martin: Historical Vocabulary of Addiction




        According to the current electronic version of the Oxford English Dictionary (OED), the noun cannabis is a borrowing from the Latin word for hemp, originally from ancient Greek κάνναβις.  The noun cannabis is defined in OED as: “A herbaceous flowering plant, Cannabis sativa (family Cannabaceae), having serrated digitate leaves, fibrous stems, and glandular hairs, native to central Asia and widely cultivated for its fibre (hemp) and for use as a recreational drug.”  Of note, “Cannabis has three subspecies, C. sativa indica, C. sativa ruderalis, and C. sativa sativa, which are sometimes treated as separate species.” The noun hemp is from Old English hęnep, hænep and related forms of old European languages.  The noun hemp is defined in OED as: “An annual herbaceous plant, Cannabis sativa, of the N.O. [natural order of plants], Urticaceæ, a native of Western and central Asia, cultivated for its valuable fibre.”  The noun marijuana is the typically used word in the vernacular for cannabis.  The word is a borrowing from Mexican Spanish, mariguana, marihuana, of uncertain origin.      

        The first use of the word cannabis in the English language is from the translation of The Travels of Monsieur de Thevenot into the Levant… by Jean de Thévenot (1633-1667), a French traveller in the East and also a linguist, natural scientist and botanist (1687): “We found by the way, many plants called Agnus Castus, or Canabis [Fr. Canabis]; for they grow three foot high, and have the leaves divided by fives, like a hand.”  As to be expected, the word hemp appears in the English language in approximately 1000, well before cannabis (Wright and Wülcker 1884): “Cannabum, hænep.”  On the other hand, marijuana was first used in English in the 1874 book, The native races of the Pacific states of North America, by Hubert Howe Bancroft (1832-1918), an American historian and ethnologist: “The bride's parents then send round to the houses of their friends a bunch of mariguana, a narcotic herb, which signifies that all are to meet together at the bride's father's on the next night.”

        The definition of cannabis that is relevant to the field of addiction is: “a dried preparation of the flowering tops or other parts of the cannabis plant, or a resin extracted from it, smoked or consumed, especially as a recreational drug, for the feelings of relaxation and euphoria it induces.” This meaning was first used in the English language in an article in the Public Advertiser, a London newspaper in the 18th century (Anonymous 1793): “Plumbum, 'tis true, when taken inwardly, has in general been found to be fatal to those Creatures; but Cannabis has a much better Effect.”  An example of popular usage of the word is from Kathryn Marie Lette (1958-), an Australian-British bestselling author (1989):  “I mean, he couldn't have smoked it all on his own. Anyone who could consume that amount of cannabis would be a total social-reject, a bong-brain addict, wouldn't he?”  The relevant definition of marijuana is: “(A preparation of) the plant, used as an intoxicating and hallucinogenic drug; especially a crude preparation of the dried leaves, flowering tops, and stem of the plant in a form for smoking.”  It is noted in the OED that: “The currency of the word increased greatly in the United States in the 1930s in the context of the debate over the use of the drug, the term being preferred as a more exotic alternative to the familiar words hemp and cannabis.”  An example of a variant of the word is in John Steinbeck’s 1935 novel Tortilla Flat, “His eyes were as wide and pained as the eyes of one who smokes marihuana.” Steinbeck (1902-1968) was an American author who won the 1962 Nobel Prize in Literature.

        Cannabis has likely been used in folk healing and for socio-religious purposes prior to recorded history.  There is archeological evidence of use of cannabis as a mind-altering drug in Eurasia and Africa (Abel 1982).  The earliest written reference to the drug dates to the 15th century BCE in the Chinese pharmacopeia, the Rh-Ya (Cohen 1977).  Herodotus (c. 484- c. 425 BCE), the ancient Greek historian referred to the central Eurasian Scythians, nomadic Eurasians of Iranian origin, taking cannabis steam baths in his Histories (1970): “The Scythians, as I said, take some of this hemp-seed [presumably, flowers], and, creeping under the felt coverings, throw it upon the red-hot stones; immediately it smokes, and gives out such a vapour as no Greek vapour-bath can exceed; the Scyths, delighted, shout for joy.”  There is additional historical evidence in India, Vietnam, Cambodia and the Middle East of cannabis use in various forms as folk medicine, ritual potion, condiment and for its intoxicating effects.  Cannabis seems to have been imported to the Americas by the Spaniards for its fiber, but then was used for its psychoactive properties. 

        It was not until the 19th century that interest in cannabis spread to the European medical community and its “newly-discovered” role in therapeutics were endorsed in the medical journals of the era as a significant addition to the existing materia medicaThe British and Foreign Medical Review published an editorial about the observations of William Brooke O'Shaughnessy (1809-1889), an Irish physician, then Professor of Chemistry in the Medical College, Calcutta, whose research in India led to introduction of Cannabis sativa to Western medicine (Anonymous 1840):  

        “This pamphlet contains a detail of facts of a very important kind, which, we doubt not, will cause a great sensation among the members of the profession throughout the world…It will appear clearly from what we shall state that Dr. O'Shaughnessy has the merit of having added to our materia medica a drug of great and unequivocal powers, and, probably, a remedy of marked efficacy in diseases hitherto the most unmanageable. For the sake of accuracy, in a matter of so much consequence, we shall avail ourselves, as much as possible, of the author's own words…”

        Dr. O’Shaughnessy begins as follows:

        “The narcotic effects of hemp are popularly known in the south of Africa, South America, Turkey, Egypt, Asia Minor, India, and the adjacent territories of the Malays, Burmese, and Siamese. In all these countries hemp is used in various forms, by the dissipated and depraved, as the ready agent of a pleasing intoxication. In the popular medicine of these nations we find it extensively employed for a multitude of affections. But in western Europe its use either as a stimulant or as a remedy is equally unknown… Much difference of opinion exists on the question, whether the hemp so abundant in Europe, even in high northern latitudes, is identical in specific characters with the hemp of Asia Minor and India. The extraordinary symptoms produced by the latter depend on a resinous secretion with which it abounds, and which seems totally absent in the European kind. The closest physical resemblance or even identity exists between both plants; difference of climate seems to me more than sufficient to account for the absence of the resinous secretion and consequent want of narcotic power in that indigenous in colder countries…”

        Dr. O’Shaughnessy proceeded to review the chemical properties, popular uses, and the results of his own experiments in laboratory animals.  He then described how the resinous extract is prepared into a tincture appropriate for administration to patients and the doses employed in various treatment applications.  For Rheumatism, he describes “alleviation of pain in most, remarkable increase of appetite in all, unequivocal aphrodisia, and great mental cheerfulness. In no one case did these effects proceed to delirium, nor was there any tendency to quarrelling. The disposition developed was uniform in all, and in none was headach or sickness of stomach a sequel of the excitement.”

        John Clendinning (1798-1848), an English physician recognized as first prescribing cannabis for migraine headaches, was very familiar with O’Shaughnessy’s findings and thoughtfully examined the effects of cannabis compared to opium, then the most common medicine in the pharmacopeia (1843):

        “The objects I have had in view in the trials of the hemp... [and the] cases in which I have experienced beneficial effects from the new remedy… are these:

1. To determine as nearly as I could, the question, whether the hemp narcotic be in reality possessed of medicinal properties sufficiently energetic and uniform to entitle the drug to admission into our pharmacopoeia; and,

2. To determine how far the extract could be used with advantage as a substitute for opium in various important diseases, acute and chronic.

        “In answer to the former question, I have no hesitation in affirming that in my hands its exhibition has usually, and with remarkably few substantial exceptions, been followed by manifest effects as a soporific or hypnotic in conciliating sleep; as an anodyne in lulling irritation; as an antispasmodic in checking cough and cramp; and as a nervine stimulant in removing languor and anxiety, and raising the pulse and spirits; and that these effects have been observed in both acute and chronic affections, in young and old, male and female.

        “In reply to the latter question, I should say that these useful, and in several cases most salutary effects have been obtained without any important drawback or deduction on account of indirect or incidental inconveniences… The only class of cases in which I have found the hemp not to act as a competent substitute for opium, is in the intestinal fluxes, such as the diarrhaeas… In such cases, opium is the great controlling remedy of the narcotic class, and admits of no deputy…”

        Due to the effects of cannabis as “soporific or hypnotic in conciliating sleep” (Clendinning 1843) it was only a matter of time before this agent was administered to psychiatric patients as described by Sir Thomas Smith Clouston (1840-1915), a Scottish psychiatrist (1870):

        “…with the view of obtaining more accuracy as to the immediate and remote effects of bromide of potassium and its combinations, as compared with opium, on maniacal excitement...I had amongst other things been giving both bromide of potassium and tincture of cannabis Indica to procure sleep in this case, which was one of melancholia, with great excitement and hallucinations, and by way of experiment I gave the patient a combination of the two. I found the effects to be so very wonderful in this case that I employed the bromide alone, and in conjunction with Indian hemp very largely thereafter in similar cases.” 

        It is with nostalgia that one views this work, as by the next century, cannabis was found mostly to be ineffective as an antidepressant (Pond 1948) and recognized as a cause, not a treatment for psychosis (Hollister 1964).  All the same, cannabis remained an agent of wonderment and experimentation with palpable effects on consciousness as described by Edward Wheeler Scripture (1893): “The statement is generally made that the extract of Cannabis Indica…causes time and space greatly lengthened in consciousness.  Wishing to know what is meant by these statements I obtained the prescription…”

        Further understanding of the role of cannabis in pharmacotherapy required identification of the active principle of Cannabis indica resin (Work, Bergel and Todd 1939), an arduous task due to the very many compounds with diverse pharmacological actions found in this plant.  Decades of chemistry research culminated in the synthesis of dl-cannabidiol (CBD) and dl-delta-3,4-tetrahydrocannabinol (THC), “the psychotomimetically active constituents” of marijuana (Mechoulam and Gaoni 1965), and eventually the stereochemical requirements of the major psychoactive constituent, THC (Mechoulam and Gaoni 1967).  Of note, THC and CBD seem to have dissimilar actions; the major difference seems to be the lesser psychotomimetic action, and hence, abuse liability, of CBD (Babalonis, Hane, Malcolm et al. 2017).  Identification of receptors in the brain that specifically bind these agents and synthesis of specific cannabinoid receptor agonists and antagonists ensued (Devane, Dysarz, Johnson et al. 1988).  Arachidonylethanolamide, or anandamide, an arachidonic acid derivative in porcine brain, was then identified as an endogenous ligand of the cannabinoid receptors, termed an endocannabinoid (Devane, Hanus, Breuer et al. 1992).  The endocannabinoid system is in striking analogy to endogenous opioids (Barinaga 1992).  These discoveries led to elucidation of the complexity of the cannabis plant and widened therapeutic horizons (Hollister 1986; Iversen 1993). Whether cannabis has a role in medicine, so-called “medical marijuana,” continues to be examined and debated (National Academies of Sciences, Engineering, and Medicine 2017).  Evidence for beneficial effects of cannabis exist but the multitude of compounds in the plant make such research pharmaceutically daunting.  An exciting research direction has been the potential beneficial role of CBD over THC in treatment of psychiatric disorders (Hindley, Beck, Borgan et al. 2020).

        The potential for self-harm from the use of cannabis, especially addiction, had been a source of greater concern in the U.S. than any possibility of its use for healing. This was the rationale for passing of the U.S. Marihuana Tax Act in 1937, prohibiting the production, importation, possession, use and dispersal of cannabis, rendering cannabis an illicit drug, despite widespread recreational use.  By the 20th century, toxicity of cannabis became a subject of investigation (Forney 1971) superseding its potential in therapeutics.  How to view cannabis use has remained a conundrum in the U.S. and throughout the world.  The range of viewpoints on marijuana are exemplified by the film Reefer Madness.  This morality tale, filming of which was financed by a church group, was intended to teach parents about the dangers of cannabis use.  Ultimately, the film became an unintentional satire among advocates of decriminalization of the drug (Peary 1982).  The counterpoint in the debate is disimpassioned examination of cannabis use by a committee of experts, which pronounced the drug as near harmless compared to alcohol or nicotine, which are legalized (LeDain 1970; Nutt, King, Saulsbury et al. 2007).

        The controversy pertaining to the safety of cannabis as a recreational drug continues unresolved.  It is well documented that cannabis is a drug of abuse and cannabis use disorder is highly prevalent, particularly in those with other psychiatric and drug use disorders (Martin, Weinberg and Bealer 2007; Schiff, Zweig, Benbenishty and Hasin 2007; Mitchell, Bhatia and Zebardast 2020).  Chronic use of cannabis may be correlated with psychological withdrawal symptoms, such as irritability or insomnia, but cannabis withdrawal symptoms are typically mild and are not life-threatening (Fraser 1949; Bahji, Stephenson, Tyo et al. 2020).  Due to the high lipid solubility of THC and very slow elimination from the brain, the withdrawal syndrome was mostly theoretical, until it could be demonstrated to be precipitated by cannabinoid receptor antagonists (Budney and Hughes 2006).  Chronic use of cannabis is associated with medical (Page, Allen, Kloner et al. 2020) and behavioral (Andreae 2018) toxicity.  However, the sale and use of cannabis in various formulations has become legalized in many jurisdictions in the U.S. and around the world with mixed results (Abuhasira, Shbiro and Landschaft 2018; Smart and Pacula 2019; McBain, Wong, Breslau et al. 2020).  Only time will tell what the effects on human health and societal consequences will be if cannabis becomes as negligibly regulated as alcohol and tobacco.



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January 28, 2021