Methamphetamine: Chemistry, Effects, and Risks

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

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

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

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

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

7. Effects of Drugs on Dopamine striatum frontal cortex hippocampus substantia nigra/VTA nucleus accumbens Mounts Intromissions Ejaculations Dopamine Pathways Principal “Pleasure” System of the Brain COCAINE AMPHETAMINE Accumbens 1100 Accumbens 400 1000 900 DA 800 DA 300 700 600 % of Basal Release 500 200 % of Basal Release 400 300 100 200 100 0 0 0 1 2 3 4 5 hr 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine Source: Di Chiara and Imperato Natural Rewards Elevate Dopamine FOOD SEX 200 200 NAc shell 150 150 100 100 15 % of Basal DA Output 10 Empty DA Concentration (% Baseline) 50 Copulation Frequency Box Feeding 5 0 0 Scr Scr Scr Scr 0 60 120 180 Bas Female 1 Present Female 2 Present 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Time (min) Sample Number Di Chiara et al. Fiorino and Phillips

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

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. 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. 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. 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. 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.

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. 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. 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 Short-Term Effects of Methamphetamine Source: Judith Cohen, Ph.D., Presentation to NASADAD, June 2005

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 ALWAYS REVERSE WITH ABSTINENCE

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

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

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

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. 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. 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. 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. 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. 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. 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 Who to test?

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. 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. 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 Newborn signs of meth exposure

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

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

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