CPDD 72nd Annual Meeting • Scottsdale, Arizona - The College on ...

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ABUSE DETERRENT ADJUSTED MEASUREMENT MODEL:
ADJUSTING FOR LOCAL PRESCRIPTION OPIOID
AVAILABILITY AND LOCAL USE OF HEROIN.
Ryan A Black, S H Budman, T A Cassidy, S F Butler; Inflexxion, Inc.,
Newton, MA
Aims: Recently, pharmaceutical companies have developed abuse deterrent formulations
in an effort to address the problem of prescription opioid abuse in the
US. <strong>The</strong> ADAMM methodology was created to determine the impact of such
formulations on actual levels of abuse. <strong>The</strong> two-part statistical model adjusts levels
of abuse of various prescription opioids by local availability of each prescription
opioid (“exposure covariate”). Since the extent to which heroin is locally
available has been shown to impact local abuse rates of prescription opioids,
addition of a second covariate that provides an indication of local use of heroin
is examined. We estimated the relative levels of abuse of several prescription opioids,
adjusted for both covariates, and examined the effect local use of heroin has
on abusing each prescription opioid.
Methods: Data were analyzed from 3904 patients in substance abuse treatment
representing 208 3-digit client home ZIP codes from 2008 ASI-MV data. A negative
binomial single hurdle model estimated (1) the odds of abusing OxyContin
relative to comparators (any hydrocodone, Duragesic, Kadian, and Dilaudid) at
least once in the past 30 days and (2) the rate (# of days/past 30 days) of continued
abuse for those reporting any abuse.
Results: Results revealed expected patterns of prescription opioid abuse levels as
well as effects of prescription opioid availability and local heroin use on abuse of
each opioid product. Local availability was defined as the number of dispensed
morphine equivalent milligrams divided by the population in each 3-digit ZIP
code, and local heroin use was the number of self-identified heroin users in each
3-digit ZIP code divided by the number of clients in the same ZIP code who
completed the ASI-MV. Inclusion of local use of heroin as a covariate may help
to “even the playing field” when estimating levels of abuse across prescription
opioids.
Conclusions: This model continues to show promise as way of evaluating an
ADF’s public health impact.
Financial Support: Inflexxion, Inc.
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DAT BLOCKER/SERT SUBSTRATES: COMPOUNDS WITH
HYBRID TRANSPORTER ACTIVITY.
Bruce Blough 1 , A Landavazo 1 , J S Partilla 2 , F I Carroll 1 , R B Rothman 2 ; 1 RTI
International, Research Triangle Park, NC, 2 Clinical Psychopharmacology, IRP,
NIDA, Baltimore, MD
Aims: <strong>The</strong> aim was to assess very small molecules as neurotransmitter releasers
and/or uptake inhibitors at the biogenic amine transporters.
Methods: Standard transporter release and uptake inhibition assays were used to
assess these candidates.
Results: It was found that some small compounds are able to block one (or more)
transporter, while acting as a substrate of another, releasing whatever is stored in
those neurons. For example, 2-(N-cyclopropylamino)-4’-chloro-3’methylpropiophenone
(PAL-820) was found to inhibit DAT with an IC50 of 592 nM while
inducing serotonin release with an EC50 of 181 nM. PAL-820 also inhibited
NET with an IC50 of 3583 nM. A series of analogs will be presented.
Conclusions: It has long been assumed that if a non-selective compound is a
neurotransmitter releaser (substrate) or transport inhibitor at one transporter
such as DAT, it does so at the other biogenic amine transporters. This assumption
has been reinforced by years of study of large molecules as transport blockers,
and a lack of recognition that small molecule releasers such as amphetamines
are actually substrates of these transporters. This assumption has been found to
be incorrect. Compounds with hybrid activity exist. This hybrid activity is
unique compared to releasers like amphetamine, which acts as a substrate of multiple
transporters (DAT and NET) or venlafaxine, which acts as a blocker of multiple
transporters (SERT and NET). Such hybrids represent a novel therapeutic
class of compounds.
Financial Support: This work was supported by funding from NIDA
(DA12970).
<strong>CPDD</strong> <strong>72nd</strong> <strong>Annual</strong> <strong>Meeting</strong> <strong>•</strong> <strong>Scottsdale</strong>, <strong>Arizona</strong>
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SEX DIFFERENCES IN THE INFLUENCE OF NEGLECT ON
TOTAL INTRACRANIAL WHITE MATTER IN HIGH-RISK
ADOLESCENTS.
Rebecca Blanton, L Mayes, M Potenza, R Sinha; Yale University, New Haven, CT
Aims: Few studies have examined sex differences in brain morphology in adolescents
at-risk for substance abuse. This study examined sex differences in at-risk
adolescents in brain morphometric measures of the amygdala nucleus, total
intracranial (IC) volumes of grey and white matter and measures of trauma.
Relationships between brain morphometric variables and childhood trauma
questionnaire (CTQ) responses were also examined.
Methods: At-risk adolescents (26 males; 16 females; ages 14-17 years) from a
longitudinal cohort of children followed since birth and well characterized on
prenatal cocaine exposure (PCE) and other psychosocial variables participated in
a single magnetic resonance imaging (MRI) session. Total intracranial volumes of
grey and white matter were automatically computed using BrainSuite software
after removal of extracerebral tissue and correcting for possible radio frequency
inhomogeneities. <strong>The</strong> left and right amygdala were traced in the coronal viewing
plane using Multitracer software by one rater blind to gender and other variables.
Results: After co-varying for PCE, an overall main effect of sex was found
between left (F(1,37=14.26, p=.001) and right amygdala volumes
(F(1,37)=5.45, p=.025). However, these effects did not hold after adjusting for
total IC volume. After adjusting for PCE, males but not females showed significant
correlations between IC white matter volume and CTQ score (r=-.58,
p=.004), emotional neglect (r=-.54, p=.008), physical neglect (r=-.57, p=.004),
and denial (r=.48, p=.021), resulting in significant differences in the independent
correlations of IC white matter volume and measures of trauma between male
and females.
Conclusions: <strong>The</strong>se preliminary results suggest significant sex differences in the
relationship between IC white matter volume during adolescence and measures
of childhood trauma. Further studies using diffusion tensor imaging may be of
benefit in elucidating the specific fiber pathways that may be affected in males
relative to female children at-risk for substance use disorders.
Financial Support: (Supported by P50-DA016556).
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PERCEPTIONS OF METHAMPHETAMINE/ DRUG USE
AMONG AGENCY PERSONNEL IN SOUTHWEST NATIVE
AMERICAN COMMUNITIES.
M P Bogenschutz 1 , Alyssa A Forcehimes 1 , J M Houck 1 , A Mondragon 1 , M P
Davis 1 , A Reid 1 , K Foley 2 ; 1 CASAA, University of New Mexico, Albuquerque,
NM, 2 Na’nizhoozhi Center Incorporated, Gallup, NM
Aims: In 2003, the Indian Health Service reported that methamphetamine use
among Native Americans was three times higher than that of the general population.
However, little is known about the use and prevalence of methamphetamine
and other drug use in Native American populations within New Mexico.
Telephone surveys were conducted with providers, counselors and law enforcement
personnel to assess their perceptions of drug use throughout New Mexico
and the Four-Corners area. Here we present preliminary findings of this ongoing
study.
Methods: Treatment providers (n=15), school administrators (n=15), police officers
and correctional facility officials (n=7) in Native American Communities in
the Southwest were asked to participate in a phone survey regarding their perceptions
of Native American methamphetamine and other drug use. <strong>The</strong> 15minute
structured questionnaire contained questions that were both quantitative
and qualitative in nature.
Results: Most respondents (67.5%) identified alcohol as the number one problem
substance in their communities, followed by marijuana (17.5%), heroin
(5.0%), and methamphetamine (5.0%). Most participants (86.8%) reported that
methamphetamine was a mild or moderate problem in their communities; 13.2%
said that it was a severe problem. <strong>The</strong> number of meth users encountered per
month ranged widely between participants, with a mean of 13.5(sd 20.6) and
median of 3.0. <strong>The</strong> degree to which participants saw methamphetamine as a problem,
and the number of methamphetamine users they saw per month, were not
significantly correlated with the rank assigned to methamphetamine as a problem
substance (Spearman ρ = -.143, p = .450; ρ = -.304, p = .068, respectively).
Conclusions: Methamphetamine was perceived as less of a problem than other
substances by most survey respondents. <strong>The</strong> findings of this survey shed light on
the geographic distribution of methamphetamine problems in Indian Country,
and will help to focus future efforts in prevention and treatment research.
Financial Support: NIDA CTN