Tuesday, 27.10.2020

Peter R. Martin: Historical Vocabulary of Addiction

 

Craving

 

        According to the current electronic version of Oxford English Dictionary (OED), craving is the noun of the action crave, which is derived from the Old English crafian with traces in Old Germanic and akin to the Old Norse, Swedish, Danish forms meaning “to demand, require, exact.” These initial meanings of the word crave date to c1000 and are now mostly obsolete.  It is the transferred meaning of crave that is the most appropriate with respect to addiction: “Urgent desire; longing, yearning.”  This transferred meaning of crave first appeared in the English language in about 1400-50 (Skeat 1878): “Ȝe couett & craue castels & rewmes.” It subsequently took on a more recognizable form with respect to its current meaning in addiction (Heresbach and Googe 1577): “Who so ploweth his Olyue Garden, craueth fruite.”  As suggested in the work of the English novelist and historian Sir Walter Besant (1836-1901), the meaning continued to evolve and became more compatible with current notions (1890): “The thing…that feeds the disease and that the disease constantly craves.”  In these later quotations, one senses the origins of the modern conceptualization of craving into a dichotomy of “liking and wanting” an object (Berridge and Robinson 2016).  Likewise, the noun craving followed the same evolution as crave (L’Estrange 1692): “A Regular Vicissitude, and Succession of Cravings and Satiety.” Eventually, the noun came to be used in parallel fashion to the verb (Besant 1890): “A man liable to attacks of craving for strong drink.”

        Craving for psychoactive agents is different from hunger for food, but sufficiently overlapping that the notion of “drug hunger” is intuitively understood and hunger has been a neurobiologically useful construct for understanding craving and vice versa (Kassel and Shiffman 1992).  The definition of hunger in OED is instructive: “The uneasy or painful sensation caused by want of food; craving appetite.”  Intuited parallels between hunger for food and craving for alcohol have provided the impetus for ongoing research using our understanding of the neurobiology of food intake to explore alcohol use disorder (Marfaing-Jallat, Larue and Le Magnen 1970):  “Contrary to the classically observed over-responsiveness toward oro-sensory aversive stimuli of hyperphagic hypothalamic rats, a majority of rats in these various experimental conditions increased their intake of the ethanol solution.”  This notion, reminiscent of the primary thesis that alcohol consumption has nutrient value and thus, is related to the fundamental drive of hunger (Richter 1953), has been extended to elucidation of the mechanistic underpinnings of drug/alcohol use disorders and their pharmacologic treatments (Thiele, Navarro, Sparta et al. 2003; Farokhnia, Grodin, Lee et al. 2018).

        In a similar vein, thirst has a long historical association with addiction, especially drinking alcoholic beverages, but also other drugs of abuse (Mello 1975; Ramsden 2015), as intimated by its OED definition: “The uneasy or painful sensation caused by want of drink; also, the physical condition resulting from this want.”  The use of excessive water drinking (Falk 1961) to train laboratory animals to self-administer solutions of alcohol or other psychoactive agents that they might otherwise avoid, has been employed to study the behavioral and neurochemical underpinnings of addiction.  Whether craving for drugs of abuse and thirst are coterminous in the brain is far from certain.  For example, in a functional magnetic resonance imaging (fMRI) study of thirsty heroin addicts (Xiao, Lee, Zhang et al. 2006), when brain responses triggered by neutral and drug-related pictures were compared, increased brain activations in frontal, occipital and cerebellar regions were demonstrated for the drug condition.  By contrast, water-related pictures compared to neutral cues did not increase brain activation in any of those regions, but triggered activity in the anterior cingulate. The researchers concluded: “Our results show an important role of prefrontal cortex in heroin craving and suggest that heroin craving may involve different neural substrates than do desire from basic physiological drives”.   It also seems sensible to convolve craving for drugs of abuse with the neurobiological urge to fulfil drives required for survival of the species, e.g., sexual activity and exploration, much as just discussed for hunger and thirst (Martin, Weinberg and Bealer 2007).  However, on careful examination, while descriptors of hunger, thirst and drives are semantically analogous to craving for drugs of abuse, they are not identical in terms of the underpinning neural pathways, although some elements may overlap.   The emergence of primacy of self-administration of a highly rewarding drug of abuse (e.g., cocaine) compared to fulfilling natural drives as hunger is a well-documented characteristic of the “hijacked brain” in addiction (Leshner 1997), suggesting that the precise brain mechanisms that subserve these states (addictions vs. natural drives) may not be entirely superimposable.  

        Craving as understood in addiction, characterized by intense interest in a free-choice situation, associated approach behaviors and self-administration (Stolerman 1992), is not restricted to psychoactive agents with abuse liability (Richter, Holt and Barelare 1937).  While these behaviors are considered distinct from hunger or thirst, they nevertheless, are manifested as “excessive appetite or craving for special food stuffs….”  Curt Paul Richter (1894-1988), an American psychobiologist and geneticist, studied appetitive behaviors in experimental animals by depriving them of substances essential to survival, demonstrating pre-programmed, genetic-based forms of behavior (Schulkin, Rozin and Stellar 1994).  He recognized that cravings for foods “have their origin in deficiencies…or by altered metabolism” but craving for vitamin B1 is powerful in rats regardless of whether they are deficient in this essential nutrient.  Richter, Holt and Barelare (1937) concluded: “It is of general biological interest that such powerful craving should be associated with a food stuff of the great nutritive importance of vitamin B1.”  Of particular and intersecting interest, vitamin B1 was demonstrated to play a significant role in self-administration of alcohol, an unusual psychoactive agent in that it possesses both abuse liability and role as a foodstuff (Mardones, Segovia and Onfray 1946).

        Craving is inexorably intertwined with addiction which denotes “out-of-control and self-destructive behavior” involving self-administration of a psychoactive agent to which the individual is drawn at many levels, currently dichotomized as “wanting and liking” (Anselme and Robinson 2016; Martin 2016).  In this context, the term is also readily applicable to addictive disorders not involving self-administration of drugs, the so-called behavioral addictions, such as gambling, problematic hypersexuality, etc.  Craving is unquestionably related to the phenomenology of withdrawal from every drug of abuse (Martin 2019), such that the characteristic withdrawal syndromes can include intense craving for the specific drug to which the individual is addicted; accordingly, more often than not, the craving is acted upon and the active addiction continues. This does not mean that craving ceases once withdrawal has abated. Craving represents a significant component of learning-related and enduring brain changes that occur with repeated use of psychoactive substances with abuse liability.  These cravings are triggered even after acute withdrawal has abated by relevant memories, experiences, affective states, and situations previously associated with drug use which, using modern neuroimaging tools, can be identified to have left traces within brain circuits (Grant, London, Newlin et al. 1996; Childress, Mozley, McElgin et al. 1999).  All the same, it is uncertain whether an “urgent desire; longing, yearning” to use a drug that has been discontinued for extended periods is intended to relieve the distress associated with protracted withdrawal phenomena, and hence, is a form of self-medication (Martin 2019). In fact, the experience of craving experienced and acted on much beyond when the acute withdrawal state has subsided is what makes addiction a life-long condition as intimated by Wikler (1961): “physicians, lawmakers  and  the  general  public  every-where  are concerned  above  all  with  one  aspect  of  the  problem, namely, the persistent tendency to repeated relapse after successful withdrawal  of  the  drug  in  question.”  Investigations of recovery from addiction consequently have focused on mechanistic understanding of craving.  Craving seems to be best evaluated in the context of learning and memory and these brain functions are tightly bound to the underlying processes which can be understood and perhaps, even modified, in terms of conditioning (Martin 2019; Wolpe 1964).   

 

References:

Anselme P, Robinson MJF. “Wanting,” “liking,” and their relation to consciousness. J Exp Psychol Anim Learn Cogn. 2016; 42(2):123-40.

Berridge KC, Robinson TE. Liking, wanting, and the incentive-sensitization theory of addiction. Am Psychol. 2016; 71(8):670-9.

Besant W. The demoniac,. N.Y.: U.S. Book Co.; 1890.

Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP. Limbic activation suring cue-induced cocaine craving. Am J Psychiatry. 1999; 156(1):11-8.

Falk JL. Production of Polydipsia in Normal Rats by an Intermittent Food Schedule. Science. 1961; 133(3447):195.

Farokhnia M, Grodin EN, Lee MR, Oot EN, Blackburn AN, Stangl BL, Schwandt ML, Farinelli LA, Momenan R, Ramchandani VA, Leggio L. Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Mol Psychiatry. 2018; 23(10):2029-38.

Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A. Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci U S A. 1996; 93(21):12040-5.

Heresbach C, Googe B. Foure Bookes of Husbandry, collected by M.C. Heresbachius ... Conteyning the whole arte and trade of Husbandry, with the antiquitie and commendation thereof. Newely Englished, and increased, by B. Googe, Esquire. B.L. R. Watkins: London; 1577.

Kassel JD, Shiffman S. What can hunger teach us about drug craving? A comparative analysis of the two constructs. Urges Cravings. 1992; 14(3):141-67.

Leshner AI. Addiction is a brain disease, and it matters. Science. 1997; 278(5335):45.

L’Estrange R. Fables of AEsop, and other eminent mythologists with morals and reflexions. London: London: Printed for R. Sare, T. Sawbridge, B. Took, M. Gillyflower, A. & J. Churchil, and J. Hindmarsh, 1692.

Mardones J, Segovia N, Onfray E. Relationship between the dose of factor N and the alcohol intake of rats under self-selection conditions. Arch Biochem. 1946; 9:401-6.

Marfaing-Jallat P, Larue C, Le Magnen J. Alcohol intake in hypothalamic hyperphagic rats. Physiol Behav. 1970; 5(3):345-51.

Martin PR. Addiction. Peter R. Martin: Historical Vocabulary of Addiction. inhn.org.ebooks. November 24, 2016.

Martin PR. Self-medication. Peter R. Martin: Historical Vocabulary of Addiction. inhn.org.ebooks. November 14, 2019.

Martin PR. Conditioning. Peter R. Martin: Historical Vocabulary of Addiction. inhn.org.ebooks. December 26, 2019.

Martin PR. Withdrawal. Peter R. Martin: Historical Vocabulary of Addiction. inhn.org.ebooks. May 30, 2019.

Martin PR, Weinberg BA, Bealer BK. Healing Addiction: An Integrated Pharmacopsychosocial Approach to Treatment. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2007.

Mello N. Schedule-induced polydipsia and oral intake of drugs. Pharmacol Rev. 1975; 27(4):489-98.

Ramsden E. Making animals alcoholic: shifting laboratory models of addiction. J Hist Behav Sci. 2015; 51(2):164-94.

Richter CP. Alcohol, beer and wine as foods. Q J Stud Alcohol. 1953; 14(4):525-39.

Richter CP, Holt LE, Barelare B. Vitamin B1 craving in rats. Science. 1937; 86(2233):354.

Schulkin J, Rozin P, Stellar E. Curt P. Richter - February 20, 1894-December 21, 1988. Biogr Mem Natl Acad Sci. 1994; 65:311-20.  

Skeat WW. Alexander and Dindimus, or, The letters of Alexander to Dindimus, King of the Brahmans, with the replies of Dindimus. London: Published for the Early English Text Society, by N. Trübner & Co; 1878.

Stolerman I. Drugs of abuse: behavioural principles, methods and terms. Trends Pharmacol Sci. 1992; 13:170-6.

Thiele TE, Navarro M, Sparta DR, Fee JR, Knapp DJ, Cubero I. Alcoholism and obesity: overlapping neuropeptide pathways? Neuropeptides. 2003; 37(6):321-37.

Wikler A. On the nature of addiction and habituation. Br J Addict Alcohol Other Drugs. 1961; 57(2):73-9.

Wolpe J. Conditioned inhibition of craving in drug addiction: A pilot experiment. Behav Res Ther. 1964; 2(2):285-8.

Xiao Z, Lee T, Zhang JX, Wu Q, Wu R, Weng X, Hu X. Thirsty heroin addicts show different fMRI activations when exposed to water-related and drug-related cues. Drug Alcohol Depend. 2006; 83(2):157-62.     

 

August 27, 2020