New Clinical Information Regarding the Treatment of Individuals for Cocaine and Methamphetamine Dependence

1. New Clinical Information Regarding the Treatment of Individuals for Cocaine and Methamphetamine Dependence Richard A. Rawson, Ph.D Professor Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles www.uclaisap.org rrawson@mednet.ucla.edu Supported by: National Institute on Drug Abuse (NIDA) Pacific Southwest Technology Transfer Center (SAMHSA) International Network of Treatment and Rehabilitation Resource Centres (UNODC)

2. Stimulants COCAINE CRACK METHAMPHETAMINE

3. Stimulants Description: A group of synthetic and plant-derived drugs that increase alertness and arousal by stimulating the central nervous system. Medical Uses: Short-term treatment of obesity, narcolepsy, and hyperactivity in children Method of Use: Intravenous, intranasal, oral, smoking

4. Types of Stimulant Drugs Cocaine Products • Cocaine Powder (Generally sniffed, injected, smoked on foil) • “Crack” (smoked) • Major areas of use: South America; USA (predominantly major urban centers, disproportionately impacts African American community); Increasing in Europe.

5. Types of Stimulant Drugs Amphetamine Type Stimulants (ATS) • Amphetamine “Speed” • Dexamphetamine “Ice” • Methylphenidate “Crank” • Methamphetamine “Yaba” “Shabu”

6. Methamphetamine vs. Cocaine • Cocaine half-life: 1-2 hours • Methamphetamine half-life: 8-12 hours • Cocaine paranoia: 4 -8 hours following drug cessation • Methamphetamine paranoia: 7-14 days • Methamphetamine psychosis - May require medication/hospitalization and may not be reversible • Neurotoxicity: Appears to be more profound with amphetamine-like substances

7. According to surveys and estimates by WHO and UNODC, methamphetamine is the most widely used illicit drug in the world except for cannabis. World wide it is estimated there are over 26 million regular users of amphetamine/methamphetamine, as compared to approximately 16 million heroin users and 14 million cocaine users Scope of the Methamphetamine Problem Worldwide

8. Acute Stimulant Effects Psychological • Increased energy • Increased clarity • Increased competence • Feelings of sexuality • Increased sociability • Improved mood • Powerful rush of euphoria - freebase and intravenous only

9. Acute Stimulant Effects Physical • Increased heart rate • Increased pupil size • Increased body temperature • Increased respiration • Constriction of small blood vessels • Decreased appetite • Decreased need for sleep • Numbness of nasal mucosa - intranasal only

10. Chronic Stimulant Effects Physical • Weight loss/anorexia • Sleep deprivation • Respiratory system disease • Cardiovascular disease • Headaches • Severe Dental disease • Needle marks and abscesses - intravenous only • Seizures

11. Cocaine Hydrochloride • Crystalline white powder • Snorted in “lines” of 10-35 mg each • Adulterated w cheap local anesthetics, stimulants, and inert white powders • Yields moderate to high blood levels • Gradual onset of effects at 15-20 min with peak at 30-60 min

12. Cocaine Hydrochloride:Intravenous Administration • Soluble in water • Peak blood levels achieved instantaneously • Rapid onset, brief duration, intense “crash” • Rapid develop. of compulsive use pattern • “Speedball” when mixed with heroin to cushion the “crash”

13. Cocaine Freebase“Crack” • Extracted from cocaine HCL using ether, ammonia, or sodium bicarbonate • Extraction does not remove impurities • Pharmacodynamics almost identical to intravenous use • Avoids many medical hazards of I.V. use

14. Cocaine: Mechanism of CNS Action • Stimulates dopamine secretion in dopaminergic pathways in brain • Prevents dopamine reuptake at synapse • Acute effect- dopamine flooding • Chronic effect- dopamine depletion • Dopamine agonists/replacements have not proved therapeutically useful in addicts

15. Cocaine: Acute Effects • Euphoric mood • Increased energy, alertness • Increased sexuality • Paranoia • Increased heart rate, blood pressure

16. Cocaine: Chronic Effects • Lethargy, fatigue • Reduced attention span • Sexual dysfunction • Depression, irritability, anhedonia • Paranoid psychosis

17. Cocaine: Toxic Reactions • Cardiac arrhythmias, fibrillation • Hyperthermia- > 106 degrees F • Convulsions, loss of consciousness • Respiratory & cardiac arrest • Abruptio placentae (miscarriage) • Fatal reactions rare, but unpredictable

18. Cocaine “Crash” • Rebound dysphoria • Agitation, restlessness • Intensifies w dosage & chronicity of use • Cravings & drug-seeking behavior • Abuse of alcohol & other drugs • Suicidal ideation, behavior • Often followed by prolonged sleep

19. Cocaine: Clinical Considerations • No clearcut physical withdrawal syndrome • Pharmacotherapies: See Vocci notes • Serious medical consequences are uncommon • Psychiatric consequences are extremely common: • Depression, anhedonia, labile moods, irritability, paranoia, suicidal ideation • Usually remit within several days/weeks of abstinence & without pharmacotherapy • Persisting symptoms beyond 6 to 8 weeks may warrant psychiatric evaluation & possible pharmacotherapy

20. Speed • It is methamphetamine powder ranging in color from white, yellow, orange, pink, or brown • Color variations are due to differences in chemicals used to produce it and the expertise of the cooker • Other names: Shabu, Crystal, Crystal Meth, Crank, Tina, Yaba

21. Ice • High purity methamphetamine crystals or coarse powder ranging from translucent to white, sometimes with a green, blue, or pink tinge

30. Their Brains have been Re-Wired by Drug Use Because…

31. Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 ml/gm METH Abuser (1 month detox) Normal Control METH Abuser (24 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

32. 33 year old man, high on methamphetamine admitted to emergency room complaining of severe headache in Portland Oregon. • X-ray revealed 12, 2 inch nails (6 on each side) in his head, administered with aq nail gun. • The man at first claimed it was an accident, but he later admitted that it was a suicide attempt. The nails were removed, and the man survived without any serious permanent damage. • He was eventually transferred to psychiatric care; he stayed for almost one month under court order but then left against doctors’ orders MSNBC-TV

33. Brain Serotonin Transporter Density and Aggression in Abstinent Methamphetamine Abusers** Sekine, Y, Ouchi, Y, Takei, N, et al. Brain Serotonin Transporter Density and Aggression in Abstinent Methamphetamine Abusers. Arch Gen Psychiatry. 2006;63:90-100.

34. Cardiac Disorders and MA Use • Coronary Syndromes • Arrhythmia • Cardiomyopathy • Hypertension • Valvular Disease

35. Neurologic Disorders and MA Use • Headache • Seizure • Cerebrovascular • Ischemic stroke • Cerebral hemorrhage • Cerebral vasculitis • Cerebral edema

36. Respiratory Disorders and MA Use • Pulmonary edema • Bronchitis • Pulmonary hypertension • COPD

39. METH Use Leads to Severe Tooth Decay “METH Mouth” Source: The New York Times, June 11, 2005.

40. MethamphetaminePsychiatric Consequences • Paranoid reactions • Permanent memory loss • Depressive reactions • Hallucinations • Psychotic reactions • Panic disorders • Rapid addiction

41. MA Psychosis Inpatients from 4 Countries

42. MA Psychosis • 69 physically healthy, incarcerated Japanese females with hx MA use • 22 (31.8%) no psychosis • 47 (68.2%) psychosis • 19 resolved (mean=276.2±222.8 days) • 8 persistent (mean=17.6±10.5 months) • 20 flashbackers (mean=215.4±208.2 days to initial resolution) • 11 single flashback • 9 Recurrent flashbacksYui et al., 2001 • Polymorphism in DAT Gene associated with MA psychosis in Japanese Ujike et al., 2003

43. Treatment

44. Is Treatment for Methamphetamine Effective? • A pervasive rumor has surfaced in many geographic areas with elevated MA problems: • MA users are virtually untreatable with negligible recovery rates. • Rates from 5% to less than 1% have been quoted in newspaper articles and reported in conferences.

45. Meth. Treatment Statistics During the 2002-2003 fiscal year: • 35,947 individuals were admitted to treatment in California under the Substance Abuse and Crime Prevention Act funding. • Of this group, 53% reported MA as their primary drug problem

46. Statistics Analysis of: • Drop out rates • Retention in treatment rates • Re-incarceration rates • Other measures of outcome All these measures indicate that MA users respond in an equivalent manner as individuals admitted for other drug abuse problems. • Analysis of data from 3 other large data sets and 3 clinical trials data sets suggest treatment response (using psychosocial treatments) of MA and cocaine users is indistinguishable.

47. Additional Information on Population

48. Mean Days of Primary Drug Use in Last 30 Days

49. Why the “MA Treatment Does Not Work” Perceptions? • Many of the geographic regions impacted by MA do not have extensive treatment systems for severe drug dependence. • Medical and psychiatric aspects of MA dependence exceeds program capabilities. • High rate of use by women, their treatment needs and the needs of their children can be daunting. • Although some traditional elements may be appropriate, many staff report feeling unprepared to address many of the clinical challenges presented by these patients

50. Bupropion: An Efficacious Pharmacotherapy? • Newton et al., (2005): • Bupropion reduces craving and reinforcing effects of meth • Elkashef (recently completed): • Bupropion reduces meth use in an outpatient trial, with particularly strong effect with less severe users.