Substance Abuse in WV - West Virginia State Medical Association

Marshall University Joan C. Edwards School of Medicine | NEWSMarshall Research Sheds Light on Meth AddictionIn West Virginia, teensrank near the top nationally inmethamphetamine use, meth labincidents outnumber those of allstates in the northeast combined-- and Marshall research hasidentified three mechanisms thathelp account for the drug’s virulentlyaddictive and neurotoxic profile.With work that has garnered agrant from the National Institute forDrug Abuse (DA-254452), invitedpresentations at the national level,and several awards, MD/PhDstudent Melinda Asbury uses anin vitro model to identify how theblast of dopamine released by methabuse leads to the death of braincells in the nucleus accumbens,where neurodegeneration is knownto have a causative role in theearly development of addiction.“Methamphetamine is aparticularly devastating drug,” shesaid. “Its abuse has been shownto cause localized brain damageequivalent to that seen in patientswith early dementia and greater thanthat seen in those with schizophrenia.”She noted that the brain damage, inturn, makes it more difficult for methabusers to come clean – by reducingimpulse control, for example.In an abstract presented atthe Neuroscience 2009 meeting,Asbury presented her findings thatthree mechanisms of dopaminerelateddamage can be targeted toprevent the associated apoptosisin an in vitro system that closelyresembles meth abusers.• Restoring antioxidant capacity.Untreated neural cells begandying within 24 hours of beingexposed to amounts of dopamineequivalent to those released inmeth abuse. Cells pretreatedwith an antioxidant, however,survived exposure to up to50 micromolars of dopamine(the normal range in vivo is1-10). Asbury said the findingsraise the interesting possibilitythat nutritional interventioncould be one avenue involvedin treating addiction.• Blocking receptor activation thatproduces apoptosis. Exposureto a D1 agonist caused morecells to die, and to die morequickly. However, using a D1antagonist and blocking a relatedsignal eliminated dopaminerelatedapoptosis. While researchelsewhere has found D1 agoniststo encourage abstinence andprevent relapse in an animalmodel, Asbury said the Marshallresearch suggests that braindamage may be occurring despitethe desirable change in behavior.• Inhibiting the action of theDNA transcription factoractivator protein 1 (AP-1). Usinga dominant negative to knockout all AP-1 in the cells similarlyprevented dopamine-relatedapoptosis. This finding, Asburysaid, has great implicationsfor research into potentialgene therapy for addiction.Asbury said she hopes the findingswill enable the development ofnew therapeutic approaches that,when given as a pre-treatment,will minimize further neurologicaldamage to those struggling withthe disease of meth addiction.Dysfunctional Family Red Flag for Drugs in Pregnant PatientsElsewhere in this issue, Stitelyet al discuss their study showingthat nearly one in five infants bornin West Virginia has a significantdrug or alcohol exposure.Dr. David Chaffin, thecorresponding author and director ofMarshall’s Division of Maternal FetalMedicine, has seen “an enormousexplosion” of drug-addicted mothers.“Managing these patients bringshome all the more that substanceabuse is a social problem evenmore than a medical problem,”he said. The most consistentcommonality among the patients,he said, is a dysfunctional family,with drug problems sometimesspanning four generations.Physicians who see indicatorsthat a patient has such a settingmight want to explore the possibilityof substance abuse more fully, hesaid: often there are no visible cluessuggesting patients are addicted.“The most important thing ingetting patients off the drug habit oronto an alternative is to get them outof that dysfunctional milieu,” he said.Based on interviews with hispatients, he said the percentage ofaddicts who started as recreationalusers appears smaller than thosewho became hooked during medicaltreatment involving narcotics.He described one patient whosejourney started with a prescriptionfor a narcotic painkiller with threerefills: “By the end of that timeshe was hooked, and she’s beenhooked ever since,” he said.SUBSTANCE ABUSE IN WV | Vol. 1061