1. 1 The American Indian/Alaska Native National Resource Center for Substance Abuse and Mental Health Services Dale Walker, MD Patricia Silk Walker, PhD Michelle Singer May 10, 2007 Sacramento, California What is Methamphetamine and what are its effects?

2. 2 Overview The issues Chemistry Pharmacology: how the body handles the drug Pharmacology: mechanisms The desired effects: why people like it The problems: why people hate it Methamphetamine vs other drugs Pregnancy: mother and child

3. 3 Views of the Most Important Problems Facing Teenagers Today Harvard School of Public Health/Robert Wood Johnson Foundation/ICR, July 2000

4. 4 National Drug Intelligence Center National Drug Threat Assessment 2005 - February 2005

5. 5 A Major Reason People Take a Drug is they Like What It Does to Their Brains A Major Reason People Take a Drug is they Like What It Does to Their Brains The first use is usually voluntary

6. Why do people take drugs? To feel good To have novel: Feelings Sensations Experiences AND To share them To feel better To lessen: Anxiety Worries Fears Depression Hopelessness Withdrawal

7. 7 nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA Dopamine Pathways Principal “Pleasure” System of the Brain Dopamine Pathways Principal “Pleasure” System of the Brain 0 50 100 150 200 0 60120180 Time (min) % of Basal DA Output NAc shell Empty BoxFeeding Di Chiara et al. FOOD 100 150 200 DA Concentration (% Baseline) Mounts Intromissions Ejaculations 15 0 5 10 Copulation Frequency Sample Number 12345678 91011121314151617 Scr BasFemale 1 Present Scr Female 2 Present Scr Fiorino and Phillips SEX Natural Rewards Elevate Dopamine 0 0 100 200 300 400 0 0 1 1 2 2 3 3 4 4 5 hr Time After Cocaine % of Basal Release DA Accumbens COCAINE 0 0 100 200 300 400 500 600 700 800 900 1000 1100 0 0 1 1 2 2 3 3 4 4 5 hr Time After Amphetamine % of Basal Release DA Accumbens AMPHETAMINE Source: Di Chiara and Imperato Effects of Drugs on Dopamine

8. 8 Forms of Methamphetamine Methamphetamine Powder Beige/yellowy/off-white powder Base / Paste Methamphetamine ‘Oily’, ‘gunky’, ‘gluggy’ gel, moist, waxy Crystalline Methamphetamine White/clear crystals/rocks; ‘crushed glass’ / ‘rock salt’

9. 9 Chemistry 1: Methamphetamine does not occur in nature. It is like two chemicals found in the body: Adrenaline, released in “fight or flight” Dopamine which controls both reward and movement in the brain

10. 10 Chemistry 2: Methamphetamine is very close to Amphetamine (“speed”) in structure

11. 11 Chemistry 3: Compounds from plants that are chemically similar are ephedrine and mescaline Methamphetamine is easy to make from materials that are hard to control; pseudoephedrine, iodine, and red phosphorus from matchbooks Waste by-products from the synthesis are toxic and environmentally harmful

12. 12 Methamphetamine Absorption Fat soluble, so easily and rapidly absorbed. Gets into the brain faster than amphetamine Onset: oral - about 30-60 minutes Snorted - 2-5 minutes injected or smoked – almost instantaneous

13. 13 Methamphetamine Elimination Elimination half life about 12 hours Effects can last 24 hours 55% broken down by the liver remainder excreted as methamphetamine or amphetamine Drug and metabolites detectable 2-4 days Urine or saliva can be used for testing Impurity profiling for medico-legal purposes. There are about 245 possible impurities!

14. 14 The most important action… Meth enters the nerve ending, and causes the transmitter to be released. It displaces the transmitter from the storage site. This means that even if the nerve in the reward pathway has not been stimulated, the transmitter will be released and “reward” experienced.

15. 15 Methamphetamine has several mechanisms: It directly releases dopamine and norepinepherine from the nerve endings in the brain (and also outside the brain) It inhibits the transporter leading to increased material in the synapse (like cocaine) It both CAUSES nerves to fire and AMPLIFIES existing nerve activity.

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17. 17 Desired Effects Energy, less fatigue, wakefulness – enhanced performance May promote impulsive decision making Feelings of joy, power, success, high self- esteem Enhanced sexual desire and interest Later in the addiction process the user may have very little interest in sex.

18. 18 Undesired Effects Delusional, risky, paranoid, violent Itching, welts on the skin Nausea, vomiting, diarrhea Uncontrolled body movements “The crash” Increased blood pressure, heart rate, body temperature. Risk of stroke, seizures Japan – most deaths from meth toxicity USA – most deaths from homicide/suicide

19. 19 Short-Term Effects of Methamphetamine PSYCHOLOGICAL Confidence Alertness Mood Sex drive Energy Talkativeness Boredom Loneliness Timidity PHYSICAL Heart rate Respiration Blood pressure Pupil size Sensory acuity Energy Appetite Sleep Reaction time Source: Judith Cohen, Ph.D., Presentation to NASADAD, June 2005

20. 20 Long-term Problems Disturbed sleep Social isolation and withdrawal Lifestyle-related “accident” Amphetamine psychosis Violent and/or paranoid behavior Irritability, nervousness, distractibility, difficulty focusing and remembering Extreme depression, suicidal ideation NOT ALL OF THESE REVERSE WITH ABSTINENCE

21. 21 Methamphetamine Chronic Physical Effects Tremor Weakness Dry mouth Weight loss Cough Sinus infection Sweating Burned lips; sore nose Oily skin/complexion Headaches Diarrhea Anorexia

22. 22 Methamphetamine Chronic Psychological Effects Confusion Concentration Hallucinations Fatigue Memory loss Insomnia Irritability Paranoia Panic reactions Depression Anger Psychosis

23. 23 Methamphetamine Psychiatric Consequences Paranoid reactions Permanent memory loss Depressive reactions Hallucinations Psychotic reactions Panic disorders Rapid addiction

24. 24 What about brain damage? This is often stated as a consequence of methamphetamine use. Usually recovers. There is convincing evidence in humans and animals, both by imaging and behavioral studies, that brain damage occurs

25. 25 What about behavioral consequences? Attention, verbal learning, memory, decision making are all impaired during early abstinence After 8 months abstinence, still slow on some tasks Headaches and depression may not improve, and there may be ongoing cognitive impairment.

26. 26 Flashbacks ( recurrence of methamphetamine psychosis ) do occur Associated with frightening/stressful experience during use. Mild stress then triggers flashbacks Longer exposure to the situation makes flashbacks more frequent

27. 27 Methamphetamine Users Compared to Other Drug Users Use daily More likely to be Caucasian, male, gay/bi, HIV positive, practice unsafe use (sharing needles etc.), have a psychiatric diagnosis, be on psychiatric meds Develop addiction more rapidly Seek treatment earlier Use more marijuana and/or less alcohol (but use alcohol or sedatives for sleep) Have more serious medical and psychiatric conditions

28. 28 Prenatal Exposure to Methamphetamine Methamphetamine easily crosses the placenta The fetal brain is very sensitive to any level of methamphetamine Metabolism of methamphetamine in the fetus is not the same as in adults We must have a high index of suspicion to adequately test moms and infants exposed to methamphetamine

29. 29 In pregnancy… Very little data. Growth restriction occurs with full-term infants, (constriction of the umbilical artery?) 4% have a recognizable withdrawal syndrome. Evidence of cognitive deficit in children born to mothers who use meth Weak evidence for physical defects in children whose mothers used meth.

30. 30 Who to test? Maternal red flags –History of drug use during pregnancy –Premature birth –Late, sporadic, or no prenatal care –Numerous skin lesions –Extremely poor dentition –Very rapid labor/delivery Infant red flags –Maternal history of drug use –Maternal refusal for drug screen –Excessive irritability –Excessive jitteriness –Very poor feeding, not responding to intervention –Physical features suggestive of alcohol/drug use

31. 31 Maternal Effects of Methamphetamine During Pregnancy Increased maternal blood pressure Increased maternal heart rate Increased risk of premature birth Constricts blood flow in the placenta, thereby impacting oxygen flow to the fetus

32. 32 Effects of Methamphetamine on the Developing fetus/infant Poor fetal growth—small for gestational age Elevated fetal blood pressure (stroke) Birth defects (6 times the normal rate) –Cleft palate/lip –Heart disease –Kidney disease –Intestines born outside the body –Premature birth Placental hemorrhage

33. 33 Newborn signs of meth exposure Withdrawal –Jittery –Poor feeding –Poor wake /sleep cycle –Irritable –High pitched cry –Tremors –Hypertonia These symptoms may last as long as 6 weeks, in contrast to withdrawal from other drugs which may only last the first week of life

34. 34 Biology/Genes Environment DRUG Addiction ADDICTION INVOLVES MULTIPLE FACTORS Brain Mechanisms

35. 35 And One of the Most Powerful Triggers for Relapse In Recovering Addicts Research Tells Us That STRESS Can Be A Major Factor In the Initiation of Drug Use…

36. 36 Contact us at 503-494-3703 E-mail Dale Walker, MD onesky@ohsu.edu Or visit our website: www.oneskycenter.org