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Stimulants

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Stimulants

  1. 1. Cocaine, Stimulants, and MDMA
  2. 2. ASAM’s 2008 Review Course in Addiction Medicine ACCME required disclosure of relevant commercial relationships : Dr. Drexler has nothing to disclose.
  3. 3. Objectives <ul><li>The participant will be able to understand: </li></ul><ul><li>How chemical structure of stimulants influences pharmacology </li></ul><ul><li>Basic neurobiology of stimulant dependence </li></ul><ul><li>How to recognize and manage acute stimulant intoxication and withdrawal </li></ul>
  4. 4. Overview <ul><li>Background </li></ul><ul><li>Stimulant- structure and pharmacology </li></ul><ul><li>Neurobiology of stimulant addiction </li></ul><ul><li>Management of acute intoxication and withdrawal </li></ul><ul><li>Relapse Prevention </li></ul>
  5. 5. Background <ul><li>Stimulants have been used by humans for thousands of years to increase energy. </li></ul><ul><li>Plant-derived stimulants have been refined and new drugs developed to increase potency and duration. </li></ul><ul><li>As potency increases negative effects become apparent. </li></ul>
  6. 6. History of Stimulant Use <ul><li>3000 B.C. – Ma-Huang </li></ul><ul><li>0 A.D. – Coca leaf chewing and coca tea </li></ul><ul><li>1860 – Cocaine isolated </li></ul><ul><li>1887 – Amphetamine synthesized </li></ul><ul><li>1914 – Harrison Narcotic Act </li></ul><ul><ul><ul><li>MDMA </li></ul></ul></ul><ul><li>1919 – Methamphetamine </li></ul><ul><li>1930s – Benzedrine inhaler </li></ul><ul><li>1959 – Benzedrine banned </li></ul><ul><li>1980s – Crack </li></ul>
  7. 7. Epidemiology <ul><li>Cocaine </li></ul><ul><ul><li>2 nd most widely used illicit drug in U.S. </li></ul></ul><ul><ul><li>Most frequent illicit drug in ED visits </li></ul></ul><ul><ul><li>In 2004 (NHSDA and DAWN) </li></ul></ul><ul><ul><ul><li>11.2% lifetime use; 1.5% past year; 0.8% past month </li></ul></ul></ul><ul><ul><ul><li>2.7% lifetime prevalence of dependence </li></ul></ul></ul><ul><ul><ul><li>19% of drug-related ER visits </li></ul></ul></ul><ul><ul><ul><li>39% of drug-related deaths </li></ul></ul></ul>
  8. 8. Cocaine Abuse/Addiction Liability
  9. 9. Epidemiology <ul><li>Synthetic Stimulants </li></ul><ul><ul><li>Non-prescription use peaked at 1.3% in 1985 </li></ul></ul><ul><ul><li>In 2004 (NHSDA) </li></ul></ul><ul><ul><ul><li>6.6% lifetime non-prescription use </li></ul></ul></ul><ul><ul><ul><li>1.7% lifetime prevalence of dependence </li></ul></ul></ul><ul><ul><ul><li>Methamphetamine </li></ul></ul></ul><ul><ul><ul><ul><li>Most commonly used synthetic stimulant </li></ul></ul></ul></ul><ul><ul><ul><ul><li>In 2004, 59% of users had a use disorder </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Up from 27.5 % in 2002. </li></ul></ul></ul></ul></ul>
  10. 10. Methamphetamine Lab Seizures
  11. 11. Trends in Illicit Drug Use
  12. 12. Trends in Methamphetamine Use
  13. 13. Trends in Drug Use Disorders
  14. 14. Club Drugs Epidemiology DAWN, July 2001
  15. 15. Overview <ul><li>Background </li></ul><ul><li>Stimulant- structure and pharmacology </li></ul><ul><li>Neurobiology of stimulant addiction </li></ul><ul><li>Management of acute intoxication and withdrawal </li></ul>
  16. 16. Structure and Pharmacology <ul><li>All stimulant drugs share a common basic phenylalkylamine structure. </li></ul><ul><ul><li>Additions to the phenyl group tend to increase hallucinogenic properties. </li></ul></ul><ul><ul><li>Additions of a methyl group to the nitrogen atom tend to increase the stimulant properties. </li></ul></ul>N OH OH
  17. 18. Stimulant Drugs <ul><li>Plant-derived </li></ul><ul><ul><li>Caffeine </li></ul></ul><ul><ul><li>Cocaine </li></ul></ul><ul><ul><li>Ephedra </li></ul></ul><ul><ul><li>Khat </li></ul></ul><ul><li>Synthetic </li></ul><ul><ul><li>Amphetamine </li></ul></ul><ul><ul><li>Methamphetamine </li></ul></ul><ul><ul><li>Methylphenidate </li></ul></ul><ul><ul><li>Mazindol </li></ul></ul><ul><ul><li>Phenylpropanolamine </li></ul></ul><ul><ul><li>Ephedrine </li></ul></ul><ul><ul><li>Pseudoephedrine </li></ul></ul><ul><ul><li>Phenylephrine </li></ul></ul><ul><ul><li>MDA / MDMA* </li></ul></ul>
  18. 19. Clinical Uses of Stimulants ADHD Narcolepsy II Rits, Vit R Ritalin Methylphenidate ADHD Wt control II Ice, crystal Meth, Speed Adipex Desoxyn Methamphetamine Wt control IV Sanorex Mazindol Local anesthetic II Coke, Crack Flake, Snow Cocaine ADHD, Wt control Narcolepsy II Amp, Dex Bennies Adderal Dexedrine Amphetamine Indications CSA Street name Trade name Drug
  19. 20. Cocaine Chemical Properties <ul><li>Cocaine HCl </li></ul><ul><ul><li>High melting point (195 °C) </li></ul></ul><ul><ul><li>Pyrolysis destroys most of the drug </li></ul></ul><ul><ul><li>Soluble in water (EtOH:H 2 O = 1:8) </li></ul></ul><ul><ul><li>Easily dissolved for injection or absorption across mucous membranes </li></ul></ul><ul><li>Crack or Freebase </li></ul><ul><ul><li>Low melting point (98 °C) </li></ul></ul><ul><ul><li>Easy to smoke </li></ul></ul><ul><ul><li>Insoluble in water (EtOH:H 2 O = 100:1) </li></ul></ul><ul><ul><li>Difficult to dissolve for injection </li></ul></ul>
  20. 21. Stimulant Chemical Properties <ul><li>Most variations on phenylethylamine </li></ul><ul><li>Phenylisopropylamine stimulants have stereoisomers </li></ul><ul><ul><li>D-isomers - 3 – 5 times more CNS activity </li></ul></ul><ul><ul><ul><li>D-methamphetamine – potent stimulant </li></ul></ul></ul><ul><ul><ul><li>L-methamphetamine- OTC decongestant </li></ul></ul></ul>N OH OH
  21. 22. MDMA Properties <ul><li>3,4- Methylenedioxymethamphetamine </li></ul><ul><li>Stimulant, hallucinogenic, empathogenic </li></ul><ul><li>Taken orally as a pill </li></ul><ul><ul><li>50 mg to 250 mg </li></ul></ul><ul><ul><li>“ Stacking” with other drugs (LSD, DM, ephedra) </li></ul></ul><ul><li>Non-linear kinetics </li></ul><ul><ul><li>Saturation of high-affinity enzymes </li></ul></ul><ul><ul><li>Large increase in response to small dose increase </li></ul></ul>
  22. 23. Clinical Uses of Stimulants <ul><li>Prescription cocaine </li></ul><ul><ul><li>Local anesthetic </li></ul></ul><ul><li>Prescription stimulants </li></ul><ul><ul><li>ADHD </li></ul></ul><ul><ul><li>Narcolepsy </li></ul></ul><ul><ul><li>Weight loss </li></ul></ul><ul><ul><li>Bronchdilation </li></ul></ul><ul><ul><li>Depression, pain* </li></ul></ul><ul><li>Parenteral phenylephrine </li></ul><ul><ul><li>Spinal anesthesia </li></ul></ul><ul><ul><li>Antihypotensive </li></ul></ul><ul><ul><li>Terminate SVT </li></ul></ul><ul><li>OTC stimulants </li></ul><ul><ul><li>Decongestion </li></ul></ul><ul><ul><li>Bronchodilation </li></ul></ul><ul><li>None for MDMA </li></ul>
  23. 24. Methamphetamine <ul><li>Brand name: Desoxyn </li></ul><ul><li>ADHD: 20 – 25 mg / day </li></ul><ul><li>Obesity: 15 mg / day </li></ul><ul><li>Binge: 125 mg – 1000 mg/dose </li></ul><ul><li>Toxic doses*: </li></ul><ul><ul><li>4- 6 mg/kg q2h (>3 gm/day) </li></ul></ul><ul><ul><li>37% loss of dopamine </li></ul></ul>*Segal et al: 2003; Neuropsychopharmacology
  24. 25. Pharmacokinetics <ul><li>Smoking and IV </li></ul><ul><ul><li>Reaches brain in 6 – 8 seconds </li></ul></ul><ul><ul><li>Onset of action and peak occur in minutes </li></ul></ul><ul><ul><li>Rapid decline in effect </li></ul></ul><ul><ul><li>Rapid onset of withdrawal symptoms and craving </li></ul></ul><ul><li>Intranasal and oral </li></ul><ul><ul><li>Slower absorption and peak effect (30 – 45 minutes) </li></ul></ul><ul><ul><li>Longer peak effect and gradual decline </li></ul></ul><ul><ul><li>Peak intensity less than smoking or IV </li></ul></ul><ul><ul><li>Alkalinization enhances absorption </li></ul></ul>
  25. 26. Pharmacokinetics Smoked Oral
  26. 27. Metabolism and Elimination <ul><li>Cocaine </li></ul><ul><ul><li>Hydrolysis of ester bonds </li></ul></ul><ul><ul><ul><li>Ecgonine methylester </li></ul></ul></ul><ul><ul><ul><li>Benzoylecgonine </li></ul></ul></ul><ul><ul><li>Cytochrome P450 </li></ul></ul><ul><ul><li>Eliminated in urine </li></ul></ul><ul><ul><ul><li>Benzoylecgonine detectable for ~3 days </li></ul></ul></ul><ul><ul><ul><li>Acidifying  s excretion </li></ul></ul></ul><ul><li>Amphetamines </li></ul><ul><ul><li>To metabolites </li></ul></ul><ul><ul><ul><li>Deamination- inactive </li></ul></ul></ul><ul><ul><ul><li>Oxidation- active </li></ul></ul></ul><ul><ul><ul><li>Parahydroxylation- active </li></ul></ul></ul><ul><ul><li>Eliminated in urine- </li></ul></ul><ul><ul><ul><li>Increased by lower pH </li></ul></ul></ul>
  27. 28. Drug Interactions <ul><li>Other stimulants-  sympathetic activity </li></ul><ul><ul><ul><li>Cardiac arrhythmia </li></ul></ul></ul><ul><ul><ul><li>Hypertension </li></ul></ul></ul><ul><ul><ul><li>Seizure </li></ul></ul></ul><ul><ul><ul><li>Death </li></ul></ul></ul><ul><li>MAOIs- inhibit metabolism of stimulants </li></ul><ul><li>Tricyclics- may block presynaptic uptake </li></ul><ul><li>Cocaine + EtOH = cocaethylene </li></ul><ul><ul><li> cardiac toxicity due to longer half-life </li></ul></ul>
  28. 29. Stimulant Effects <ul><li>Range of effects vary depending on </li></ul><ul><ul><li>Structure </li></ul></ul><ul><ul><li>Dose </li></ul></ul><ul><ul><li>Route of administration </li></ul></ul><ul><ul><li>Duration and intensity of use </li></ul></ul><ul><li>Typical initial doses for desired effects: </li></ul><ul><ul><li>5 to 20 mg of oral amphetamine, methylphenidate </li></ul></ul><ul><ul><li>100 to 200 mg of oral cocaine </li></ul></ul><ul><ul><li>15 to 20 mg of smoked cocaine </li></ul></ul><ul><ul><li>50 to 250 mg of MDMA </li></ul></ul>
  29. 30. Acute Stimulant Effects <ul><li>CNS </li></ul><ul><ul><li>Euphoria (low dose) </li></ul></ul><ul><ul><ul><li> energy, alertness </li></ul></ul></ul><ul><ul><ul><li> sociability </li></ul></ul></ul><ul><ul><ul><li> appetite </li></ul></ul></ul><ul><ul><li>Dysphoria (high dose) </li></ul></ul><ul><ul><ul><li>Anxiety, panic attacks </li></ul></ul></ul><ul><ul><ul><li>Irritability, agitation </li></ul></ul></ul><ul><ul><ul><li>Suspciousness </li></ul></ul></ul><ul><ul><ul><li>Psychosis </li></ul></ul></ul><ul><ul><ul><li>Movement disorders </li></ul></ul></ul><ul><ul><ul><li>Seizures </li></ul></ul></ul><ul><li>Cardiovascular </li></ul><ul><ul><li> HR, BP, vascular resistance, temperature </li></ul></ul><ul><ul><li>Acute myocardial infarction (AMI), ischemia, arrhythmia </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><li>Pulmonary </li></ul><ul><ul><li>Shortness of breath </li></ul></ul><ul><ul><li>Bronchospasm </li></ul></ul><ul><ul><li>Pulmonary edema </li></ul></ul>
  30. 32. Acute Stimulant Effects (cont) <ul><li>Musculoskeletal </li></ul><ul><ul><li>Rhabdomyolysis </li></ul></ul><ul><li>Renal </li></ul><ul><ul><li>Acute renal failure secondary to myoglobinuria </li></ul></ul><ul><li>Endocrine </li></ul><ul><ul><li>Ketoacidosis in diabetics </li></ul></ul><ul><ul><li>Activation of HPA </li></ul></ul><ul><li>Sexual function </li></ul><ul><ul><li>Increased arousal </li></ul></ul><ul><ul><li>Prolonged erections </li></ul></ul><ul><li>Head and neck </li></ul><ul><ul><li>Chronic rhinitis, nasal septal perforation </li></ul></ul><ul><ul><li>Xerostomia </li></ul></ul><ul><ul><li>Bruxism </li></ul></ul><ul><li>Fetal effects </li></ul><ul><ul><li>Most Category C </li></ul></ul>
  31. 33. Mechanisms of Action <ul><li>All stimulants enhance monoamine activity </li></ul><ul><ul><li>Inhibition of presynaptic monoamine transporters </li></ul></ul><ul><ul><ul><li>Dopamine – reward, psychosis </li></ul></ul></ul><ul><ul><ul><li>Norephinephrine – physiological arousal </li></ul></ul></ul><ul><ul><ul><li>Sertonin – mood elevation, psychosis </li></ul></ul></ul><ul><ul><li>OTC stimulants bind to and activate norepinephrine receptors </li></ul></ul>
  32. 34. Mesocorticolimbic Pathway Ventral tegmental area Nucleus accumbens Anterior cingulate Prefrontal cortex
  33. 40. Dopamine (DA) <ul><li>Stimulants acutely enhance dopamine activity </li></ul><ul><ul><li>Cocaine, methylphenidate- transporter blockers </li></ul></ul><ul><ul><li>Amphetamines- false substrates </li></ul></ul><ul><li>Stimulants chronically deplete dopamine </li></ul><ul><li>DA activity key in mediating addictive potential </li></ul><ul><ul><li>Fluctuations in mesolimbic DA parallel cocaine self-administration </li></ul></ul><ul><ul><li>Stimulant potency correlates with potency for binding at DA transporter </li></ul></ul>
  34. 41. Cocaine Microdialysis in Awake Squirrel Monkeys
  35. 42. Norepinephrine (NE) <ul><li>Stimulants acutely block NE transporter </li></ul><ul><ul><li> plasma NE and epinephine </li></ul></ul><ul><ul><li>NE release correlates with subjective and physiological stimulant effects </li></ul></ul><ul><li>Ephedrine related compounds stimulate alpha-adrenergic NE receptors </li></ul>
  36. 43. Serotonin (5-HT) <ul><li>All stimulants acutely enhance 5-HT activity by blocking serotonin transporter </li></ul><ul><ul><li>MDMA  s 5-HT by blocking transporters </li></ul></ul><ul><ul><li>Cocaine acutely  s firing in mesolimbic serotonergic neurons, but  s firing in dorsal raphe nucleus </li></ul></ul><ul><li>Serotonin appears to play a permissive, but not obligatory role in reward </li></ul>
  37. 44. Other Neurotransmitters <ul><li>Endogenous opioid activity </li></ul><ul><ul><li>No direct stimulant effect </li></ul></ul><ul><ul><li>Cocaine indirectly  s </li></ul></ul><ul><li>Mesolimbic glutamate </li></ul><ul><ul><li>Cocaine  s </li></ul></ul><ul><ul><li>Amphetamine  s </li></ul></ul><ul><li>Acetylcholine </li></ul><ul><ul><li>Cocaine  s </li></ul></ul><ul><li>Sodium channel blockade (cocaine only) </li></ul>
  38. 45. Overview <ul><li>Background </li></ul><ul><li>Stimulant- structure and pharmacology </li></ul><ul><li>Neurobiology of stimulant addiction </li></ul><ul><li>Management of acute intoxication and withdrawal </li></ul>
  39. 46. DSM-IV Substance Dependence <ul><li>>/= 3 of the following over a 12-month period: </li></ul><ul><ul><li>Tolerance </li></ul></ul><ul><ul><li>Characteristic withdrawal </li></ul></ul><ul><ul><li>Larger amounts than intended </li></ul></ul><ul><ul><li>Persistent efforts to cut down or control use </li></ul></ul><ul><ul><li>A great deal of time spent getting the substance, taking it, or recovering </li></ul></ul><ul><ul><li>Important activities given up or reduced </li></ul></ul><ul><ul><li>Continued use despite psychological or physical problem caused by or exacerbated by use </li></ul></ul>
  40. 47. Neurobiology of Dependence <ul><li>Sensitization of incentive salience </li></ul><ul><ul><li>Drug </li></ul></ul><ul><ul><li>Conditioned cues </li></ul></ul><ul><li>Impairment of inhibition of urges to use </li></ul><ul><li>Chronic effects of drug </li></ul><ul><ul><li>Signal transduction </li></ul></ul><ul><ul><li>Gene transcription </li></ul></ul>
  41. 48. Mesocorticolimbic Pathway Ventral tegmental area Nucleus accumbens Anterior cingulate Prefrontal cortex
  42. 49. Amygdala – Limbic Connections Nucleus accumbens Amygdala
  43. 50. Prefrontal - Limbic Inhibition Nucleus accumbens Orbitofrontal cortex
  44. 51. Left Right -34 mm -19 mm -9 mm +34 mm +19 mm +9 mm insula anterior cingulate amygdala subcallosal cortex nucleus accumbens area drug use - neutral Cocaine craving-related neural activations: Men
  45. 52. Overview <ul><li>Background </li></ul><ul><li>Stimulant- structure and pharmacology </li></ul><ul><li>Neurobiology of stimulant addiction </li></ul><ul><li>Management of acute intoxication and withdrawal </li></ul>
  46. 53. Initial Evaluation of Stimulant Intoxication <ul><li>Drug history </li></ul><ul><li>Physical examination </li></ul><ul><li>Laboratory examination </li></ul><ul><li>Manage basic life support functions </li></ul><ul><ul><li>T> 102 °F – Cooling blanket </li></ul></ul><ul><ul><li>T> 106 °F – Cool saline hydration, ice water lavage </li></ul></ul><ul><li>Remove drug from GI tract </li></ul><ul><ul><li>Activated charcoal or gastric lavage </li></ul></ul><ul><ul><li>If within one hour of ingestion </li></ul></ul>
  47. 54. Management of Severe Agitation <ul><ul><li>Benzodiazepines- first line </li></ul></ul><ul><ul><ul><li>Protect against CNS and cardiovascular toxicity </li></ul></ul></ul><ul><ul><ul><li>Lorazepam 2 – 4 mg PO or IV q 15 min until sedate </li></ul></ul></ul><ul><ul><ul><li>Repeat every 1 – 3 hours </li></ul></ul></ul><ul><ul><li>Antipsychotics- second line </li></ul></ul><ul><ul><ul><li>May prevent heat dissipation, lower seizure threshold, prolong QTc, increase dyskinesias </li></ul></ul></ul><ul><ul><ul><li>Haloperidol 2 to 10 mg PO, IM or IV q 6 – 24 hours </li></ul></ul></ul><ul><ul><li>Avoid physical restraints </li></ul></ul>
  48. 55. Cardiovascular Effects of Stimulants <ul><li>Myocardial ischemia is common. </li></ul><ul><ul><li>Vasoconstriction </li></ul></ul><ul><ul><li>Increased myocardial workload </li></ul></ul><ul><ul><li>Increased platelet aggregation </li></ul></ul><ul><ul><ul><li>Differential - AMI, aortic dissection, pneumothorax, endocarditis, or pneumonia </li></ul></ul></ul><ul><li>Arrhythmias </li></ul><ul><ul><li>Due to ischemia, catecholamines, or sodium channel blockade </li></ul></ul>
  49. 56. Management of Chest Pain <ul><li>Observe for 12 – 24 hours </li></ul><ul><li>ECG- </li></ul><ul><ul><li>Low sensitivity (36%) </li></ul></ul><ul><ul><li>Low predictive value (18%) </li></ul></ul><ul><li>Cardiac enzymes: </li></ul><ul><ul><li>Serial CPK- MB or troponin </li></ul></ul><ul><li>~ 15% of patients with stimulant-induced chest pain will have AMI. </li></ul>
  50. 57. Management of Arrhythmias <ul><li>Treat underlying conditions </li></ul><ul><ul><li>AMI </li></ul></ul><ul><ul><li>Electrolyte and acid-base abnormalities </li></ul></ul><ul><ul><li>Hypoxia </li></ul></ul><ul><li>Many will resolve without treatment </li></ul><ul><li>Avoid Class I antiarrhythic drugs </li></ul><ul><li>Follow ACLS guidelines </li></ul>
  51. 58. Management of Seizures <ul><li>Benzodiazepines </li></ul><ul><ul><li>Lorazepam 2 to 10 mg IV over 2 minutes </li></ul></ul><ul><ul><li>Diazepam 5 to 10 mg IV over 2 minutes </li></ul></ul><ul><ul><li>Repeat as needed </li></ul></ul><ul><ul><li>Monitor respirations, intubation available </li></ul></ul>
  52. 59. Management of Rhabdomyolysis <ul><li>Diagnosis requires high suspicion </li></ul><ul><ul><li>Muscle swelling and myalgia often absent </li></ul></ul><ul><ul><li>Plasma CK > 5 times normal </li></ul></ul><ul><ul><li>Urinalysis positive for heme without RBCs </li></ul></ul><ul><li>IV hydration – urine output 2 ml/kg/hour </li></ul><ul><li>Urine pH > 5.6 – sodium bicarbonate </li></ul>
  53. 60. Management of Hypertension <ul><li>Benzodiazepines first line </li></ul><ul><ul><li>Lower myocardial oxygen demand </li></ul></ul><ul><ul><li>Lower seizure risk* </li></ul></ul><ul><li>If severe hypertension persists </li></ul><ul><ul><li>Alpha-adrenergic blocker </li></ul></ul><ul><ul><ul><li>Phentolamine 2 to 20 mg IV over 10 min </li></ul></ul></ul><ul><ul><li>No beta-adrenergic blockers </li></ul></ul><ul><ul><ul><li>Unopposed alpha stimulation  s vasoconstriction </li></ul></ul></ul>
  54. 61. DSM-IV Cocaine Withdrawal <ul><ul><li>A. Cessation of (or reduction in) cocaine use that has been heavy and prolonged. </li></ul></ul><ul><ul><li>B. Dysphoric mood and two (or more) : </li></ul></ul><ul><ul><ul><li>Fatigue </li></ul></ul></ul><ul><ul><ul><li>Vivid, unpleasant dreams </li></ul></ul></ul><ul><ul><ul><li>Insomnia or hypersomnia </li></ul></ul></ul><ul><ul><ul><li>Increased appetite </li></ul></ul></ul><ul><ul><ul><li>Psychomotor retardation or agitation </li></ul></ul></ul>
  55. 62. Management of Withdrawal <ul><li>Most symptoms resolve within 2 weeks without treatment </li></ul><ul><li>Hospitalization for suicidality or psychosis </li></ul><ul><li>Pharmacologic treatment not necessary </li></ul>
  56. 63. Relapse Prevention <ul><li>Psychosocial treatment </li></ul><ul><ul><li>Cognitive behavioral therapy (CBT) </li></ul></ul><ul><ul><li>Contingency management (MIEDAR) </li></ul></ul><ul><ul><li>12-step facilitation- ? </li></ul></ul><ul><ul><li>Motivation Enhancement Therapy- ? </li></ul></ul><ul><ul><li>MATRIX model </li></ul></ul><ul><li>Treat comorbidities </li></ul><ul><li>Pharmacotherapy </li></ul><ul><ul><li>No FDA approved medications </li></ul></ul><ul><ul><li>Antidepressants </li></ul></ul><ul><ul><li>Dopaminergic agents </li></ul></ul><ul><ul><li>Disulfiram </li></ul></ul><ul><ul><li>Anticonvulsants (GVG, topiramate) </li></ul></ul>
  57. 65. Disulfiram Patients Have Less Cocaine Use Carroll et al, 2004
  58. 66. Modafinil Decreases Cocaine Use Dackis 2005
  59. 67. Summary <ul><li>Stimulants are common causes of drug-related morbidity and mortality. </li></ul><ul><li>Chemical structure of stimulants relates to the pharmacologic properties. </li></ul><ul><li>Neurobiology of stimulant addiction is related to blockade of monoamine transporters. </li></ul><ul><li>Management of acute intoxication and withdrawal is symptom driven. </li></ul><ul><li>Relapse prevention is based on comprehensive biopsychosocial treatment. </li></ul>

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