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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse

May, 1997

Research Findings

Clinical and Services Research

Very Long-Term Users of Marijuana in the United States: A Pilot Study

In a feasibility study to examine long-term use of marijuana and associated consequences, Pope and his colleagues at McLean Hospital/Harvard recruited a sample of 37 Americans, aged 30-74, who had smoked marijuana on at least 5,000 separate occasions. These subjects belonged to a wide range of ethnic groups, educational backgrounds, occupations, and annual income and did not display any obvious features which distinguished them from the population as a whole. They typically began smoking in the early 1960s or early 1970s, and then continued to smoke heavily into middle adulthood because they felt that marijuana relieved unpleasant feeling states such as anxiety or depression. According to the authors, individuals of this type are recruitable but have not been previously examined; and additional studies of older, long-term marijuana users are needed (Gruber, A., Pope, H.G., and Oliva, P. Substance Use and Misuse. 32(3), pp. 251-266, 1997). In addition, Pope and his team reviewed the literature and found a series of 5 cases where marijuana was used because it produced a direct antidepressant effect in those who had mood disorder. According to the authors, if it is true, these observations argue that many patients may use marijuana to "self-treat" depressive symptoms. Do Patients Use Marijuana as an Antidepressant? Gruber, A., Pope, H., and Brown, M. Depression, 4, pp. 77-80, 1996.

Marijuana and Mortality

Sidney and his colleagues at Kaiser Permanente in Oakland, California reviewed medical charts of approximately 67,000 patients enrolled in the HMO and found that the current use of marijuana was not associated with increased mortality in non-AIDS men or women. However, the current use of marijuana was associated with increased risk of AIDS mortality in men (RR of 1.90 [95% CI of 1.33, 2.73)]. Sidney, S., Beck, J., Takawa, I.S., Quesenberry, C.P., and Friedman, G.D. Am. J. Pub Health, April 1997. A study is underway to examine if the living AIDS patients use or have used marijuana for medical purposes.

Drug Use History and Criminal Behavior Among 133 Incarcerated Men

To investigate the relationship between crime and substance abuse, Pope and his team at Harvard/McLean Hospital evaluated consecutively 133 male prisoners using the DSM-III-R criteria for substance abuse. They also assessed whether there was a relationship between the nature of substance dependence and the type of crime committed, whether sexual, violent, or non-violent. About 95% of the prisoners were dependent on one or more substances of abuse; 58% were acutely intoxicated with one or more substances at the time of committing the index crime and an additional 6% were withdrawing from a substance at the time of crime. However, there was no significant correlation between the type of substance abused or the number of individuals intoxicated and the type of crime committed. Kouri, E., Pope, H., Powell, K., Campbell, C., Oliva, P., and Katz, D. American Journal of Drug and Alcohol Abuse, In press.

Psychiatric Effects of Exogenous Anabolic/Androgenic Steroids

In an excellent book chapter, the authors have reviewed the current literature on the psychiatric effects of anabolic steroids. The use of large doses of anabolic steroids (up to 1,000 mg/wk) is associated with manic episodes, accompanied by psychotic symptoms, while depressive symptoms are associated with withdrawal from steroid dependence, both of which require clinical intervention. Further, violence toward others and "reverse anorexia nervosa" are also associated with steroid dependence. In the latter syndrome, the individuals perceive themselves to be small and weak, even when they are in fact large and muscular. This syndrome appears to represent a subtype of body dysmorphic disorder. Authors point out that most findings are based on data collected in men and thus additional studies are needed to examine the adverse consequences of steroid use in women. Pope, H.G. Jr, and Katz, D.L. In Wolkowitz, O.M., and Rothschild, A.J. (eds.) Psychoneuroendocrinology for the Clinician, In press.

Genetic Basis Indicated for Abuse of Marijuana

Michael Lyons, Ming Tsuang and colleagues have determined that positive or negative feelings following the smoking of marijuana are, in part, genetically determined. These data were obtained from interviews of monozygotic (n = 352 pairs) and dizygotic (n = 255 pairs) twins from the Vietnam Era Twin Registry. Responses to the questionnaires were statistically combined into two factors of "positive" and "negative" feelings. Using twin pair scores on these factors, the most parsimonious model explaining the variance included only the genetic component (heritability, h3 = 26.6% ("negative" factor), 28.6% ("positive" factor)) and the unique environmental component (common environment, c2 = 73.4% ("negative" factor 1), 71.2% ("positive" factor 2)). Shared environment did not contribute to the variance as also evidenced by correlations between factor scores that were more than double for the monozygotic twins compared to the dizygotic. These new models show that while unique environment -- influences such as friends, acquaintances, and communities that each twin might experience separately -- plays the major role, there is a strong biological component that determines whether an individual will feel pleasure or lack of pleasure upon trying marijuana that, in turn, has a significant influence on continued use. In fact, further data from the study show that more positive feelings after smoking marijuana predicted higher amounts of use and longer lasting smoking histories; negative feelings predicted lower amounts and shorter histories. Lyons, M.L., Toomey, R., Meyer, J.M., Green, A.I., Eisen, S.A., Goldberg, J., True, W.R., & Tsuang, M.T. How Do Genes Influence Marijuana Use? The Role of Subjective Effects. Addiction, 92 (4), 1997.

Neurochemical Alterations in Cocaine Abuse

Robert B. Innis and colleagues of the Yale University Medical School have developed neurochemical brain imaging probes that measure pre-, post-, and intra-synaptic aspects of dopaminergic transmission in the human brain using SPECT (single photon emission computed tomography). Research studies with acutely abstinent cocaine addicts are on-going to determine if numbers of DA transporters are elevated. Such an elevation would be predicted to cause diminished dopaminergic synaptic function, since an elevated number of transporters would rapidly deplete dopamine from the synapse. Also, transmitter activity alteration could be partly responsible for the addictive properties of cocaine including craving. Laruelle, M., Abi-Dargham, A., van Dyck, C. H., Rosenblatt, W., Zea-Ponce, Y, Zoghbi, S.S., Baldwin, R.M., Charney, D.S., Hoffer, P.B., Kung, H. F., & Innis, R.B. SPECT Imaging of Striatal Dopamine Release after Amphetamine Challenge. Journal of Nuclear Medicine, 36, 1996.

Abnormal Cerebral Metabolite Levels Following Drug Abuse

Perry F. Renshaw and colleagues at the Harvard Medical School have demonstrated that polydrug abusers have abnormal cerebral metabolite levels suggestive of both membrane dysfunction and cerebral bioenergetic disturbances. Differing profiles of metabolite disturbance were found for primarily cocaine dependent and primarily heroin-dependent subjects. In addition, a positive correlation was found for metabolite levels and number of weeks a heroin-dependent subject was in methadone maintenance therapy. This finding implies that successful substance abuse treatment may lead to improvements in cerebral metabolite levels and could be used to detect changes indicative of treatment response. Kaufman, M.J., Pollack, M.H., Rose, S., Kukes, T.J., Mendelson, J.H., Cohen, B.M., and Renshaw, P.F. Abnormal Cerebral Metabolism in Polydrug Abuse: Detection with Phosphorus Magnetic Resonance Spectroscopy, to be presented at the Annual Meeting of the American Psychological Association, Chicago, Illinois, August, 1997.

Therapeutic Communities in American Prisons

This chapter focuses on the application of Therapeutic Communities (TC) in prison settings including a discussion of the history of the TC model and its demonstrated effectiveness. It also discusses several of the major challenges to implementing this model in the current environment and possible new directions for working with prisoners with co-occurring substance abuse and mental health disorders. Wexler, H. Therapeutic Communities in American Prisons. In F. Cullen, L. Jones, and R.Woodward (Eds.), Therapeutic Communities for Offenders, New York: John Wiley & Sons, 1997.

Motivation and Readiness for Treatment

DeLeon and his colleagues examined the effect of motivation and readiness for treatment across different groups of drug abuses (primary cocaine, primary crack cocaine, primary alcohol, primary marijuana, and primary heroin). These investigators found few primary drug differences in the rates of retention, the overall levels of motivation and readiness, or in the persistence of the Circumstance, Motivation, Readiness, and Suitability (CMRS) for Treatment Scales. They conclude that their findings are consistent with other clinical and research findings that emphasize the importance of dynamic rather than fixed variables as determinants of treatment retention. In essence, substance abusers who are not sufficiently motivated to change, or who do not appear ready to use treatment to deal with their drug problem, are at higher risk for early dropout. DeLeon, G., Melnick, G., and Kressel, D. Motivation and Readiness for Therapeutic Community Treatment Among Cocaine and Other Drug Abusers, Am. J. Drug and Alcohol Abuse, 23(2), pp. 169-189, 1997.

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