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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