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Intoxication: Street Drugs

  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 417 Downloads

Abstract

The use of street drugs like cannabis, opiates, cocaine, amphetamine, and methamphetamine are serious medical and economic problems in the Western countries.

Clinical signs due to drug toxicity include cardiovascular complications (infarction, subarachnoidal hemorrhage), psychiatric symptoms, neurologic symptoms (resulting from cerebral ischemia and cerebrovascular diseases), sudden paraparesis, or paraplegia of the thoracolumbar region leading to death in some cases due to transverse myelitis/myelopathy, and motor disorders.

Subtle changes in cerebral blood flow (CBF), glucose metabolism, and receptor densities or metabolite profiles are seen by in vivo imaging techniques.

Fatalities in opioid abusers are a major public health issue worldwide. Significant risk factors include loss of tolerance after a period of abstinence and concomitant use of alcohol and other CNS depressants. Systemic disease, e.g., pulmonary and hepatic disease as well as HIV-infection, may increase susceptibility to a fatal overdose. Bilateral, symmetrical ischemic lesions/necrosis of the globus pallidus can be found in 5–10% of heroin addicts. No morphological evidence of cellular injury in rapid death after heroin injection. In hypoxic-ischemic leukoencephalopathy, loss of neurons in the hippocampal formation and/or Purkinje cell layer are evident as well as enhanced expression of glial fibrillary acidic protein by astrocytes and/or a proliferation of microglia. Hypoxia secondary to respiratory depression affects the cerebral white matter. Spongiform leukoencephalopathy (non-specific toxic demyelination), almost exclusively seen after inhalation of pre-heated heroin (“chasing the dragon,” “Chinese blowing”), shows diffuse spongiosis of the white matter with loss of oligodendrocytes, reduction of axons, and astrogliosis while the gray matter is usually unremarkable. A lipophilic toxin related to contaminants in conjunction with cerebral hypoxia is considered to be the cause, but a definite toxin has not yet been identified. All opiate effects are mediated via μ- and δ-opioid receptors. In addition, second messenger signaling systems seem to play a crucial role.

Cocaine abuse represents the third most common addiction disorder next to alcohol and cannabis. Intracerebral and subarachnoidal hemorrhages or ischemic infarctions can be found in every brain region. Most of the CNS effects of cocaine are mediated through alterations of the neurotransmitters dopamine (DA), norepinephrine (NE), serotonin (5-HT), acetylcholine (ACh), and γ-aminobutyric acid (GABA). Cocaine blocks the presynaptic reuptake of neurotransmitters resulting in their accumulation in the synaptic cleft, thus producing a sustained action on the receptor system followed by neurotransmitter depletion.

Cannabis abuse is the most common illicit drug in use today. ∆9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has a high abuse potential and leads to psychological dependency. Infarcts may be found in cannabis abusers. THC and other cannabinoids exert their effects by the interaction with cannabinoid-receptors (CB1 and CB2). Both receptors are coupled through G-proteins to signal transduction mechanisms. Chronic exposure to THC fails to irreversibly alter brain cannabinoid receptors. At the cellular level, abnormalities in the expression of transcription factors, NO formation, and alterations in the brain dopaminergic system have been reported.

Amphetamine and methamphetamine abuse have significantly risen worldwide over the past years. Amphetamines are the second-most common cause (after cocaine) of ischemic stroke, hemorrhagic stroke occurring largely in persons younger than 45 years, subarachnoidal hemorrhages, and intracerebral hemorrhages. Amphetamine and methamphetamine are a subclass of psychostimulants which bind to the dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters. The neurotoxic effects of amphetamine and methamphetamine lead in the dopaminergic system to a desensitization of DA receptor function, marked reduction of DA levels, alterations in the serotonergic system, and methamphetamine-induced loss of dopaminergic cell bodies in the substantia nigra. The pathophysiology of cerebrovascular complications includes a sudden elevation in blood pressure, cerebral vasculitis, and induction of inflammatory genes in human brain endothelial cells. A vasoconstrictive effect of both substances may also lead to the development of ischemic stroke.

The abuse of designer drugs, i.e., amphetamine, methamphetamine, and amphetamine derivatives such as 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) is an important medical issue. Common substances include in abbreviated form DOM, DOB, MDA, MDEA, MDE (“Eve”), MDMA (“Ecstasy,” “Adam,” “XTC”), 4-MTA (“Flatliners”), and PMA. Acute and long-term neurotoxic effects include impaired cognitive performance and increased incidence of neuropsychiatric disorders. The cause of death may be due to cardiovascular collapse, hyponatremia, hepatic failure, rhabdomyolysis, and acute renal failure. Central nervous system complications include ischemic stroke, hemorrhagic cerebral infarction of unknown etiology, intracranial hemorrhage, subarachnoidal hemorrhage, sinus vein thrombosis, hypersensitivity vasculitis, and leukoencephalopathy. MDMA acts mainly on the serotonergic system of the peripheral and central nervous system (CNS). It has sympathomimetic properties and modulates psychomotor and neuroendocrine functions. Mechanisms of MDMA-induced neurotoxicity include formation of toxic MDMA metabolites, generation of free radicals, disturbances in neurotransmitter systems, nitric oxide system, and hyperthermia.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

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