A variety of neuropathological findings has been described in illicit drug abusers. The majority of these alterations result from the consequences of hypoxia-ischemia and from cerebrovascular diseases. Within the last few years, widespread morphological alterations of the cellular elements of the brain have been detected. These changes consist of neuronal loss, a numerical reduction of astrocytes, widespread axonal damage with concomitant microglial activation and reactive and degenerative changes of the cerebral microvessels. Based on various studies there is also concern that drug abusers develop neurodegeneration or Parkinsonism as they age. However, whether or to what extent neurodegeneration occurs in human drug abusers remains to be established. In the present paper a brief overview on the neuropathological changes in drug abuse is presented for the forensic pathologist/toxi-cologist with reference to the most pertinent literature.
BüttnerA., WeisS.Forensic Pathology Reviews. Vol. 1. Totowa (NJ): Humana Press; c2004. Chapter 4, Central nervous system alterations in drug abuse; p. 79–136.
2.
KarchS.B.Karch's Pathology of Drug Abuse.4th ed.Boca Raton: CRC Press; 2008. 736 p.
3.
QuinnD.I., WodakA., DayR.O.Pharmacokinetic and pharmacodynamic principles of illicit drug use and treatment of illicit drug users.Clin Pharmacokinet.1997 Nov; 33(5): 344–400.
4.
CoffinP.O., GaleaS., AhernJ.Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-1998.Addiction.2003 Jun; 98(6): 739–47.
5.
BüttnerA.The neuropathology of drug abuse.Neuropathol Appl Neurobiol.2011 Feb; 37(2): 118–34.
6.
AnthonyI.C., ArangoJ.C., StephensB.The effects of illicit drugs on the HIV infected brain.Front Biosci.2008 Jan 1; 13: 1294–307.
7.
BackmundM., ReimerJ., MeyerK.Hepatitis C virus infection and injection drug users: prevention, risk factors, and treatment.Clin Infect Dis.2005 Apr 15; 40 Suppl 5: S330–5.
8.
KoobG.F., VolkowN.D.Neurocircuitry of addiction.Neuropsychopharmacology.2010 Jan; 35(1): 217–38.
9.
BrustJ.C.M.Neurological Aspects of Substance Abuse.2nd ed.Philadelphia: Elsevier. Butterworth-Heinemann Ltd; 2004. 477 p.
10.
KaufmanM.J.Brain Imaging in Substance Abuse: Research, Clinical, and Forensic Applications.1 ed.Totowa (NJ): Humana Press; 2001. 448 p.
BüttnerA., WeisS.Neuropathological alterations in drug abusers: the involvement of neurons, glial, and vascular systems.Forensic Sci Med Pathol.2006 Jun; 2(2): 115–26.
13.
AdelmanL.S., AronsonS.M.The neuropathologic complications of narcotic drug addiction.Bull N Y Acad Med.1969 Feb; 45(2): 225–34.
14.
BellJ.E., ArangoJ.C., RobertsonR.HIV and drug misuse in the Edinburgh cohort.J Acquir Immune Defic Syndr.2002 Oct 1; 31 Suppl 2: S35–42.
15.
GosztonyiG., SchmidtV., NickelR.Neuropathologic analysis of postmortal brain samples of HIV-sero positive and -seronegative i.v. drug addicts.Forensic Sci Int.1993 Nov; 62(1-2): 101–5.
16.
Makrigeorgi-ButeraM., HagelC., LaasR.Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts.Clin Neuropathol.1996 Nov-Dec; 15(6): 324–9.
17.
OehmichenM., MeißnerC., ReiterA., BirkholzM.Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse.Acta Neuropathol.1996; 91(6): 642–6.
18.
AshtonC.H.Pharmacology and effects of cannabis: a brief review.Br J Psychiatry.2001 Feb; 178: 101–6.
19.
IversenL.Cannabis and the brain.Brain.2003 Jun; 126(Pt 6): 1252–70.
20.
NahasG.G.The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking.Hum Psychopharmacol.2001 Apr; 16(3): 247–255.
21.
AmeriA.The effects of cannabinoids on the brain.Prog Neurobiol.1999 Jul; 58(4): 315–48.
22.
HowlettA.C., BarthF., BonnerT.I.International Union of Pharmacology. XXVII. Classification of cannabinoid receptors.Pharmacol Rev.2002 Jun; 54(2): 161–202.
23.
GlassM., DragunowM., FaullR.L.Cannabinoid recep-tors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal neonatal and adult human brain.Neuroscience.1997 Mar; 77(2): 299–318.
HerkenhamM.Cannabinoid receptor localization in brain: relationship to motor and reward systems.Ann N YAcad Sci.1992 Jun 28; 654: 19–32.
26.
ThanviB.R., TreadwellS.D.Cannabis and stroke: is there a link?Postgrad Med J.2009 Feb; 85(1000): 80–3.
27.
BrustJ.C.M.Handbook of Clinical Neurology, Vol. 65, Revised Series 21: Intoxications of the Nervous System, Part II. Amsterdam: Elsevier; 1995. Chapter 16, Opiate addiction and toxicity. p. 356–61
PearsonJ., RichterR.W.Addiction to opiates: neurologic aspects. In: VinkensP.J., BruynG.W., editors. Hand book of Clinical Neurology, Vol. 37: Intoxications of the Nervous System, Part II. Amsterdam: North-Holland Publishing Company; 1979. p. 365–400
AndersenS.N., SkullerudK.Hypoxic/ischaemic brain damage, especially pallidal lesions, in heroin addicts.Forensic Sci Int.1999 May 31; 102(1): 51–9.
32.
ConnorM.D., LammieG.A., BellJ.E.Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV autopsy cohort.Stroke.2000 Sep; 31(9): 2117–26.
33.
BrustJ.C.M., RichterR.W.Stroke associated with addiction to heroin.J Neurol Neurosurg Psychiatry.1976 Feb; 39(2): 194–9.
34.
KrinskyC.S., ReichardR.R.Chasing the Dragon: A review of toxic leukoencephalopathy.Acad Forensic Pathol.2012 Mar; 2(1): 67–73.
35.
WoltersE.C., van WijngaardenG.K., StamF.C.Leucoencephalopathy after inhalating “heroin” pyroly-sate.Lancet.1982 Dec 4; 2(8310): 1233–7.
36.
GerostamoulosJ., BurkeM.P., DrummerO.H.Involve-ment of codeine in drug-related deaths.Am J Forensic Med Pathol.1996 Dec; 17(4): 327–35.
BrustJ.C.M.Clinical, radiological, and pathological aspects of cerebrovascular disease associated with drug abuse.Stroke.1993 Dec; 24(12 Suppl): I129–33.
39.
KellyM.A., GorelickP.B., MirzaD.The role of drugs in the etiology of stroke.Clin Neuropharmacol.1992 Aug; 15(4): 249–75.
40.
SloanM.A., KittnerS.J., RigamontiD., PriceT.R.Occurrence of stroke associated with use/abuse of drugs.Neurology.1991 Sep; 41(9): 1358–64.
41.
MCEVOYA.W., KITCHENN.D., THOMASD.G.Intracerebral haemorrhage and drug abuse in young adults.Br J Neurosurg.2000 Oct; 14(5): 449–54.
42.
KakuD.A., LowensteinD.H.Emergence of recreational drug abuse as a major risk factor for stroke in young adults.Ann Intern Med.1990 Dec 1; 113(11): 821–7.
43.
LevineS.R., BrustJ.C., FutrellN.A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride-a review.Neurology.1991 Aug; 41(8): 1173–7.
44.
DavisG.G., SwalwellC.I.The incidence of acute cocaine or methamphetamine intoxication in deaths due to ruptured cerebral (berry) aneurysms.J Forensic Sci.1996 Jul; 41(4): 626–8.
45.
KonzenJ.P., LevineS.R., GarciaJ.H.Vasospasm and thrombus formation as possible mechanism of stroke related to alkaloidal cocaine.Stroke.1995 Jun; 26(6): 1114–8.
46.
QureshiA.I., AkbarM.S., CzanderE.Crack cocaine use and stroke in young patients.Neurology.1997 Feb; 48(2): 341–5.
47.
RajabR., StearnsE., BaithunS.Autopsy pathology of cocaine users from the Eastern district of London: a retrospective cohort study.J Clin Pathol.2008 Jul; 61(7): 848–50.
48.
TreadwellS.D., RobinsonT.G.Cocaine use and stroke.Postgrad Med J.2007 Jun; 83(980): 389–94.
49.
KaufmanM.J., LevinJ.M., RossM.H.Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography.JAMA.1998 Feb 4; 279(5): 376–80.
KugelmassA.D., OdaA., MonahanK.Activation of human platelets by cocaine.Circulation.1993 Sep; 88(3): 876–83.
52.
NolteK.B., BrassL.M., FletterickC.F.Intracranial hemorrhage associated with cocaine abuse: a prospective autopsy study.Neurology.1996 May; 46(5): 1291–6.
53.
VannemreddyP., CalditoG., WillisB., NandaA.Influence of cocaine on ruptured intracranial aneurysms: a case control study of poor prognostic indicators.J Neurosurg.2008 Mar; 108(3): 470–6.
54.
Martin-SchildS., AlbrightK.C., HalleviH.Intracerebral hemorrhage in cocaine users.Stroke.2010 Apr; 41(4): 680–4.
55.
OyesikuN.M., ColohanA.R., BarrowD.L., ReisnerA.Cocaine-induced aneurysmal rupture: an emergent negative factor in the natural history of intracranial aneurysms?Neurosurgery.1993 Apr; 32(4): 518–25.
56.
Díez-TejedorE., FrankA., GutiérrezM., Barreiro P Encephalopathy and biopsy-proven cerebrovascular inflammatory changes in a cocaine abuser.Eur J Neurol.1998 Jan; 5(1): 103–7.
57.
KarchS.B., StephensB.G., HoC.H.Methamphetaminerelated deaths in San Francisco: demographic, patho-logic, and toxicologic profiles.J Forensic Sci.1999 Mar; 44(2): 359–68.
58.
LoganB.K., FlignerC.L., HaddixT.Cause and manner of death in fatalities involving methamphetamine.J Forensic Sci.1998 Jan; 43(1): 28–34.
59.
ZhuB.L., OritaniS., ShimotougeK.Methamphet-amine-related fatalities in forensic autopsy during 5 years in the southern half of Osaka city and surrounding areas.Forensic Sei Int.2000 Sep 11; 113(1-3): 443–7.
60.
BrustJ.C.Vasculitis owing to substance abuse.Neurol Clin.1997 Nov; 15(4): 945–57.
61.
KalantH.The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs.CMAJ.2001 Oct 2; 165(7): 917–28.
62.
ChristophersenA.S.Amphetamine designer drugs-an overview and epidemiology.Toxieol Lett.2000 Mar 15; 112-113: 127–31.
63.
GillJ.R., HayesJ.A., deSouzaI.S.Ecstasy (MDMA) deaths in New York City: a case series and review of the literature.J Forensie Sci.2002 Jan; 47(1): 121–6.
64.
HenryJ.A., JeffreysK.J., DawlingS.Toxicity and deaths from3, 4-methylenedioxymethamphetamine(“ecstasy”).Laneet.1992 Aug 15; 340(8816): 384–7.
65.
MilroyC.M., ClarkJ.C., ForrestA.R.Pathology of deaths associated with “ecstasy” and “eve” misuse.J Clin Pathol.1996 Feb; 49(2): 149–53.
66.
MilroyC.M.“Ecstasy” associated deaths: what is a fatal concentration? Analysis of a case series.Forensie Sci Med Pathol.2011 Sep; 7(3): 248–52.
HarriesD.P., De SilvaR.“Ecstasy” and intracerebral haemorrhage.Seott Med J.1992 Oct; 37(5): 150–2.
70.
HughesJ.C., McCabeM., EvansR.J.Intracranial haemorrhage associated with ingestion of “ecstasy”.Arch Emerg Med.1993 Dec; 10(4): 372–4.
71.
ManchandaS., ConnollyM.J.Cerebral infarction in association with ecstasy abuse.Postgrad Med J.1993 Nov; 69(817): 874–5.
72.
BüttnerA., RohrmoserK., MallG.Widespread axonal damage in the brain of drug abusers as evidenced by accumulation of ß-amyloid precursor protein (ß-APP): an immunohistochemical investigation.Addietion.2006 Sep; 101(9): 1339–46.
73.
AnthonyI.C., RamageS.N., CarnieF.W.Does drug abuse alter microglial phenotype and cell turnover in the context of advancing HIV infection?Neuropathol Appl Neurobiol.2005 Jun; 31(3): 325–38.
74.
TomlinsonG.S., SimmondsP., BusuttilA.Upregulation of microglia in drug users with and without pre-symptomatic HIV infection.Neuropathol Appl Neurobiol.1999 Oct; 25(5): 369–79.
75.
BüttnerA., KroehlingC., MallG.Alterations of the vascular basal lamina in the cerebral cortex in drug abuse: a combined morphometric and immunohisto chemical investigation.Drug Alcohol Depend.2005Jul; 79(1): 63–70.
76.
BellJ.E., ArangoJ.C., AnthonyI.C.Neurobiology of multiple insults: HIV-1-associated brain disorders in those who use illicit drugs.J Neuroimmune Pharmacol.2006 Jun; 1(2): 182–91.
77.
RamageS.N., AnthonyI.C., CarnieF.W.Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers.Neuropathol Appl Neurobiol.2005 Aug; 31(4): 439–48.
78.
AnthonyI.C., NorrbyK.E., DingwallT.Predisposition to accelerated Alzheimer-related changes in the brains of human immunodeficiency virus negative opiate abusers.Brain.2010 Dec; 133(Pt 12): 3685–98.
79.
MashD.C., OuyangQ., PabloJ.Cocaine users have an overexpression of α-synuclein in dopamine neurons.JNeurosci.2003 Apr 1; 23(7): 2564–71.
80.
DavidsonC., GowA.J., LeeT.H., EllinwoodE.H.Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment.Brain Res Brain Res Rev.2001 Aug; 36(1): 1–22.
81.
GuilarteT.R.Is methamphetamine abuse a risk factor in parkinsonism?Neurotoxicology.2001 Dec; 22(6): 725–31.
82.
ThrashB., ThiruchelvanK., AhujaM.Meth amphetamine-induced neurotoxicity: the road to Parkinson's disease.Pharmacol Rep.2009 Nov-Dec; 61(6): 966–77.
83.
RicaurteG.A., McCannU.D., SzaboZ., ScheffelU.Toxicodynamics and long-term toxicity of the rec-reational drug, 3, 4-methylenedioxymethamphetamine (MDMA, “ecstasy”).Toxicol Lett.2000 Mar 15; 112113: 143–6.
84.
CurranH.V.Is MDMA (“ecstasy”) neurotoxic in humans? An overview of evidence and of methodological problems in research.Neuropsychobiology.2000; 42(1): 34–41.
85.
LylesJ., CadetJ.L.Methylenedioxymethamphetamine (MDMA, ecstasy) neurotoxicity: cellular and molecular mechanisms.Brain Res Brain Res Rev.2003 May; 42(2): 155–68.
86.
Gouzoulis-MayfrankE., DaumannJ.Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?Addiction.2006 Mar; 101(3): 348–61.
87.
KishS.J.How strong is the evidence that brain serotonin neurons are damaged in human users of ecstasy?Pharmacol Biochem Behav.2002 Apr; 71(4): 845–55.
