Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Background to An Oral History of the First Fifty Years
Addiction (Volume Six): 4b. Contributions of interviewees
(Bulletin 58)
Of the remaining 11 interviewees in Volume Six, six (Blaine, Jaffe, Jasinsky, Kleber, Kreek and Wayner) were involved in the development of treatment for addiction (Ban 2011; Kleber 2011).
In 1966, Mary Jeanne Kreek co-authored one of the two papers by Dole and Nyswander on methadone in opioid dependence that launched substitution therapy with methadone (Dole and Nyswander 1965; Dole, Nyswander and Kreek 1966). In the late 1960s she described the role of µ and К opioid receptors in normal physiology, responsiveness to stress and in specific addictive diseases (Kreek 1969). In the 1990s, the focus of Kreek’s research shifted to genes associated with addiction (Kreek, Nielsen and LaForge 2004).
Donald R. Jasinsky was among the first to study the effects of naltrexone, a full antagonist, and of buprenorphine, a partial antagonist of µ and competitive antagonist of К opioid receptors, in the treatment of opioid dependence (Jasinsky, Fudala and Johnson 1989; Jasinsky, Pavnick and Griffith 1978; Martin, Jasinsky and Mansky 1973). A close collaborator of W.R Martin, one of the leaders of the Lexington group, Jasinsky coauthored the paper with Martin in which the concept of “protracted abstinence” was introduced (Martin and Jasinsky 1969).
Jerome H. Jaffe was one of the first in 1970 to report on the effects of levoacetylmethadol (LAAM), a long-acting orally available opioid, in the treatment of chronic heroin users and compared its effect with methadone (Jaffe, Schuster, Smith and Blachly 1970; Jaffe and Senay 1971). In the late 1970s Jaffe’s interest turned to smoking as an addictive disorder (Jaffe and Kranzler 1979).
Findings with LAAM in the treatment of addiction received further substantiation by Jack D. Blaine in the late 1970s (Blaine, Renault, Levine and Whysner 1978). Blaine was a member of David Janowsky’s team which studied the effects of cannabis on simulated flying ability (Janowsky, Meacham, Blaine, Schoor and Bozzetti 1976).
In the late 1970s, Herbert D. Kleber, in collaboration with Gold and Redmond, discovered that administration of clonidine, an α–adrenergic agonist, could ameliorate opiate withdrawal symptoms (Gold, Redmond and Kleber 1978). Ten years later, in the mid-1980s, he demonstrated that co-administration of clonidine and naltrexone significantly shortens the opioid withdrawal syndrome without substantially increasing patient discomfort (Kleber, Topazian and Gaspari 1987). Kleber was one of the first to show that dronabinol, a synthetic levoisomer of tetrahydrocannabinol, could mitigate the symptoms of marijuana withdrawal (Levin and Kleber 2008).
In the mid-1990s Matthew J. Wayner demonstrated the effect of alcohol on lateral hypothalamic dentate granules and suggested a possible relationship between this effect and alcohol-induced memory changes. Wayner also showed that losartan, an angiotensin II inhibitor, improved performance in ethanol-intoxicated rats (Tracy and Wayner 1997; Wayner and Phenix 1993).
Three interviewees (Charalampous, Klee and Schoolar) were involved with psychomimetics in their research. In the late 1950s Gerald D. Klee studied the effects LSD-25 on mental performance and on time sense (Aronson, Silverstein and Klee 1959). In the early 1960s, he reported on the effect of the substance on ego functions (Klee 1963). Klee was among the first in 1960 to explore the effects of 5-hydroxytryptophan on schizophrenia and to question the relationship between the action of LSD on serotonin and the mental effects of the substance (Klee, Bertino, Callaway and Weintraub 1960; Klee, Bertino, Gudineau and Aronson 1960).
The first autoradiogaphic study with LSD was carried out in the late 1960s by Joseph Schoolar in collaboration with Idenpään Heikkilä. By tracking the substance in mice, they found high concentrations in the brain, adrenals, hypophysis, kidney, liver and lung and demonstrated that LSD passes the placental barrier (Idenpään-Heikkilä and Schoolar 1969).
Kanellos D. Charalampous was first, in the mid-1960s, to demonstrate the metabolic fate of mescaline in man (Charalampous, Walker and Kinross-Wright 1966). He was also first, in the mid-1970s, to show the effects of acute ethanol administration on brain cyclic nucleotides and of chronic morphine administration on cerebellar cAMP levels (Charalampous and Askew 1977a, b).
Finally, two interviewees (Noble and Schuckit) contributed to genetic research in addiction. In the 1990s Marc Schuckit demonstrated an increased risk for alcoholism among sons of alcoholics (Schuckit 2000, 2009; Schuckit and Smith 1997). He identified patterns of drinking in the offspring and showed a different level of response to alcohol in the offspring of heavy drinkers (Kreikebaum, Hinnga and Allen 2008; Schuckit, Smith, Danko et al. 2007).
In 1993 Ernest P. Noble and his team reported on an allelic association of the D2 dopamine receptor gene (DDR2) with cocaine dependence (Noble, Bloom, Khals et al. 1993). Subsequently, he found similar associations between DDR2 and other substances and hypothesized that DDR2 is a “reward gene” (Noble 2003; Noble, St. Jeor, Ritchie et al. 1994).
Interviewees included in Volume Six entered the field at different stages in the development of the neuropsychopharmacology of addiction. Hence, the transcripts cover 50 years of history during which norepinephrine was replaced by dopamine as the molecular substrate of reinforcement; opiate receptors were identified in the brain; the site of brain structures involved with addiction was extended from the limbic lobe to the frontal cortex; and behavioral methodologies in the study of addiction were supplemented with brain imaging and molecular genetic techniques (Ban 2011).
Herbert D. Kleber, the editor of this volume, has been one of the leaders of addiction psychiatry in the past decades. In his Introduction and Dramatis Personae he provides an overview of developments in the field and biographic information on the interviewees with a précis of their contributions.
References:
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Charalampous KD, Askew WE. Effects of acute ethanol administration on brain cyclic nucleotides. Res Comm Psychol Psychiatr Behav 1977a; 2: 287-96.
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February 21, 2019