Methamphetamine: How it Influences the Brain and Behavior of Users Richard A. Rawson, Ph.D Adjunct Associate 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)

Methamphetamine Methamphetamine is a powerful central nervous system stimulant that strongly activates multiple systems in the brain. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of methamphetamine are greater.

Methamphetamine: Speed 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

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

The Eastward Spread of Methamphetamine

Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1992 (per 100,000 aged 12 and over) 35 - 58 12 - 35 < 12 No data > 58

Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1997 (per 100,000 aged 12 and over) 35 - 58 12 - 35 < 12 No data > 58 < 12

Primary Amphetamine/Methamphetamine Admission Rates by State: 2002 Admissions per 100,000 population aged 12 and over 3-27 28 - 54 55 or more 200 or more 150 or more 100 or more

Figure 1. Methamphetamine/Amphetamine Treatment Admission Rate per 100,000 Population Aged 12 or Older: 1992-2002 Source: 2002 SAMHSA Treatment Episode Data Set (TEDS).

IHS-Wide RPMS PCC Outpatient Encounters for Amphetamine Related Visit by Calendar Year

Meth Epidemic; less drama, more long term risk/danger Cocaine/Crack epidemic hit fast (in NYC 1986-87, as well as other major east coast cities); overnight emergency, tremendous media attention. Big federal response (Reagan and Bush I). High visibility deaths, stigmatization as a ghetto drug. Dramatic decreases in indicators by early 1990s, except in inner cites of east coast. Crack epidemic: Rapid onset; Rapid decrease Meth epidemic: Slow west to east spread. No decrease in western cities. Use becomes endemic?

Methamphetamine: A Growing Menace in Rural America In 1998, rural areas nationwide reported 949 methamphetamine labs. Last year, 9,385 were reported. This year, 4,589 rural labs had been reported as of July 26. Source: El Paso Intelligence Center (EPIC), U.S. DEA

Anhydrous Ammonia Tank Tips Officers to Possible Meth Lab 5/4/04 Omaha, Neb. – A large anhydrous ammonia tank helped Sarpy County Sheriff’s deputies bust a suspected methamphetamine lab Tuesday. By large, they mean 9,600 gallons…The owners had run a hose from the tank inside the house. “This was a semi trailer parked in a residential neighborhood. Nobody called.” SOURCE: TheOmahaChannel.com

Methamphetamine Acute Physical Effects Increases -Decreases Heart rate Appetite Blood pressure Sleep Pupil size Reaction time Respiration Sensory acuity Energy

Methamphetamine Acute Psychological Effects Increases Confidence Alertness Mood Sex drive Energy Talkativeness Decreases Boredom Loneliness Timidity

Methamphetamine Chronic Physical Effects - Tremor - Sweating - Weakness - Burned lips; sore nose - Dry mouth - Oily skin/complexion - Weight loss - Headaches - Cough - Dental Problems - Sinus infection - Anorexia

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

Meth Use in Hawaii 2005 (mid-May) - 38 deaths 2004 - 68 deaths As of the middle of May, not even halfway through the year, the city medical examiner's office already recorded 38 deaths connected to crystal methamphetamine. So, we're well on the way to exceeding last year's total of 68. Deaths: 2005 (mid-May) - 38 deaths 2004 - 68 deaths 2003 - 56 deaths 2002 - 62 deaths 2001 - 54 deaths 2000 - 34 deaths

Methamphetamine Chronic Psychological Effects - Confusion - Irritability - Concentration - Paranoia - Hallucinations - Panic reactions - Fatigue - Depression - Memory loss - Anger - Insomnia - Psychosis

Methamphetamine Psychiatric Consequences Paranoid reactions Permanent memory loss Depressive reactions Hallucinations Psychotic reactions Panic disorders Rapid addiction

What It Does to Their Brains A Major Reason People Take a Drug is they Like What It Does to Their Brains

Natural Rewards Elevate Dopamine Levels 50 100 150 200 60 120 180 Time (min) % of Basal DA Output NAc shell Empty Box Feeding Source: Di Chiara et al. FOOD 100 150 200 DA Concentration (% Baseline) Mounts Intromissions Ejaculations 15 5 10 Copulation Frequency Sample Number 1 2 3 4 6 7 8 9 11 12 13 14 16 17 Scr Bas Female 1 Present Female 2 Present Source: Fiorino and Phillips SEX

Effects of Drugs on Dopamine Release Time After Methamphetamine % Basal Release METHAMPHETAMINE 1 2 3hr 1500 1000 500 Accumbens 100 200 300 400 Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 100 150 200 250 1 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE 100 150 200 250 1 2 3 4hr Time After Ethanol % of Basal Release 0.25 0.5 2.5 Accumbens Dose (g/kg ip) ETHANOL Source: Shoblock and Sullivan; Di Chiara and Imperato

Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways

Decreased dopamine transporter binding in METH users resembles that in Parkinson’s Disease patients %ID/cc If DAT is decreased in young METH users (almost to that observed in Parkinson’s Disease), and DAT decreases with age, may we see an increase in the number of Parkinsonian patients over time? Control Methamphetamine PD Source: McCann U.D.. et al.,Journal of Neuroscience, 18, pp. 8417-8422, October 15, 1998. .

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

Methamphetamine: Neurochemical Mechanisms Methamphetamine enters the brain and is removed from the synapse by dopamine transporters

Methamphetamine: Neurochemical Mechanisms Enters dopamine vesicles Vesicles deplete themselves of dopamine

Methamphetamine: Neurochemical Mechanisms Free-floating DA produces “free radicals” (neurotoxins), so it is forced out of the neuron. The synapse is flooded with dopamine, producing a profound sense of pleasure.

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

Control > MA 4 3 2 1

MA > Control 5 4 2 1 3

Is Treatment for Methamphetamine Effective? A major demand that competes for scarce community resources are for the treatment needs of those who have become addicted to methamphetamine (MA).

Meth Treatment Effectiveness? 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. **The resulting conclusion is that spending money on treating MA users is futile and wasteful, BUT no data exists that supports these statistics**

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

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.

Urinalysis Results Results of Ua Tests at Discharge, 6 months and 12 Months post admission ** Matrix Group TAU Group D/C: 66% MA-free 65% MA-free 6 Ms: 69% MA-free 67% MA-free 12 Ms: 59% MA-free 55% MA-free **Over 80% follow up rate in both groups at all points

Clinical Challenges of MA Users Poor treatment engagement rates High drop out rates Severe paranoia High relapse rates Ongoing episodes of psychosis Severe craving Protracted dysphoria Anhedonia

Steps to Address Treatment Needs of MA Users Psychiatric/Professional Mental Health Staffing Add Treatment Programming for Women Exposed to Violence and Their Kids Training, Training, Training

Medications Currently, there are no medications that can quickly and safely reverse life threatening MA overdose. There are no medications that can reliably reduce paranoia and psychotic symptoms, that contribute to episodes of dangerous and violent behavior associated with MA use.

Special treatment consideration should be made for the following groups of individuals: Female MA users (higher rates of depression; very high rates of previous and present sexual and physical abuse; responsibilities for children). Injection MA users (very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis). MA users who take MA daily or in very high doses. Homeless, chronically mentally ill and/or individuals with high levels of psychiatric symptoms at admission. Individuals under the age of 21. Gay men (at very high risk for HIV and hepatitis).