Stimulants and HIV: What Clinicians Need to Know

1. Stimulants and HIV:What Clinicians Need to Know Thomas Freese, Ph.D. tefreese@ix.netcom.com Pacific Southwest Addiction Technology Transfer Center UCLA Integrated Substance Abuse Programs Steve Shoptaw, Ph.D. sshoptaw@mednet.ucla.edu Pacific AIDS Education and Training Center UCLA Center for Health Promotion and Disease Prevention

2. AIDS Education and Training Centers’ National Resources Warmline: (800) 933 - 3413 PEPline: (888) 448 – 4911 (888) HIV– 4911 Perinatal Hotline: (888)-448-8765 www.aids-etc.org

3. Educational ObjectivesAt the end of this presentation, participants will be able to: • Review the epidemiology, neurobiology and medical consequences of stimulant use. • Understand the links between the HIV and substance abuse epidemics. • Review the evidence for behavioral interventions that reduce substance-related risk behaviors.

4. Overview • Epidemiological concepts • Local versus national • Neurobiology and medical consequences • What do stimulants do? • Linkages between HIV risk and drug use • Specific drug used matters • Sexual behaviors increase drug-related risks • Interventions to reduce risk • Conclusions

5. SPEED Methamphetamine powder: white, yellow, orange, pink, or brown Color variations due to different chemicals used and expertise of the cook ICE High purity methamphetamine crystals or coarse powder: translucent to white, sometimes with a green, blue, or pink tinge The Methamphetamine Family

6. KEY POINTS • Common street names for Methamphetamine: amphetamine, crystal, ice, speed, tina • Cheap, readily available, has long half life • Has functional attributes (helps you work more), social attributes (better party) sexual attributes (longer and more intense), emotional attributes (brightens mood, sharpens attention) • Powdered: Snorted, smoked, injected, “booty bumped” (inserted anally), eaten • Crystal (ice): Smoked

7. Behavioral Risks:Injection Drug UsersMen Who Have Sex with Men

8. KEY POINTS • Epidemiology of drug use and HIV are linked. • National epidemiology reports of HIV and stimulant use may distort the local picture.

9. U.S. Adult Male AIDS Cases by Risk Behavior by Year CDC, 2004 L.A. County Adult Male AIDS Cases by Risk Behavior by Year L.A. County HIV Epi Pgm, 2004

10. KEY POINTS • The slide contrasts the national AIDS cases for males with the LA County AIDS cases by risk behavior between 1990-2001. • The vast majority of AIDS cases in LA County remain MSM. Not so for national prevalence.

11. U.S. Adult Female AIDS Cases by Risk Behavior by Year CDC, 2004 L.A. County Adult Female AIDS Cases by Risk Behavior by Year L.A. County HIV Epi Pgm, 2004

12. KEY POINTS • AIDS prevalence nationally and in Los Angeles County by behavior for women between 1990-2001 also show differences. • In Los Angeles County, heterosexual women show the increasing rates of prevalence. Not so on the national level

13. Geography and IDUs • West of the Mississippi River, prevalence rates remain much lower than in the East • No differences in risk behaviors • May be attributes of the heroin itself can be protective HIV Prevalence in IDU 1994-1996 2.3% 21.5% Garfein et al., 2004

14. KEY POINTS • Geographical differences area also observed in injection drug users (IDUs) with very low HIV prevalence rates in the west and moderate to high rates in the east. • There are no geographic differences in risk behaviors for IDUs. • Attributes of heroin itself may lower risk of transmission. Mexican tar (primary western US) heroin is hard to dissolve requiring a higher temperature to make it injectable than china white (primary east). The increased heat inactivates some of the HIV virus.

15. CDC, 2005

16. KEY POINTS • Across the US the only behavioral risk group showing continued increases in new HIV cases is MSM. • These increase are likely linked to drug use and the drugs involved are likely to be stimulants.

17. Exposure Risks by Geography, 2002 CDC, WONDER, 2004

18. KEY POINTS • Even within the same state geography counts • Reviewing selected cities AIDS prevalence rates by behavioral risk groups show that metropolitan areas in CA are similar; cities in the central valley have prevalence rates more similar to New York City. • It is important to know your local prevalence rates when considering prevention or treatment approaches. • Prevalence rates can be obtained online from http://wonder.cdc.gov.

19. CRACK COCAINE AND HIV

20. Crack Cocaine and HIV Infection • HIVNET: 4,892 persons at high-risk for HIV infection enrolled in cohort between 1995-1997 • Cohort incidence: 1.3 infections per 100 persons per year (ppy) • MSM incidence: 2.0 per 100 ppy • Definitely interested in vaccine: 2.0 per 100 ppy • Female crack cocaine users: 1.6 per 100 ppy Seague et al., 2001

21. KEY POINTS • Crack cocaine use increases HIV incidence, particularly among females. • Incidence among crack cocaine using females is lower than among MSM, but significantly higher than general high-risk groups • Infection with HIV and other STIs in crack using females significantly associates with greater numbers of sexual partners and inconsistent condom use (Wilson et al., 1998)

22. Crack Cocaine and HIV Risks • HIV risk behaviors in 637 crack, powder cocaine and heroin users in central Harlem: • Injectors (OR = 2.5) • Engaged in fraud/cons (OR = 2.6) • Separated/divorced/widowed (OR = 2.2) • Multiple sex partners (OR = 1.7) • Females (OR = 1.7) Davis et al., 2006

23. KEY POINTS • In minority crack and heroin users in Harlem, several factors associated with being HIV positive (23.9% of the sample was HIV infected). • Links between being infected clearly had more to do with behaviors associated with drug use than any type of interaction between drug use and being HIV infected. • African American females were significantly more likely to be HIV infected.

24. Methamphetamine Addiction The brains of people addicted to Methamphetamine are different than those of non-addicts

25. KEY POINTS • Using methamphetamine changes the way the brain functions. • This is obvious from the ways in which people behave, but with advances in technology, we are now able to understand exactly how this is true

27. KEY POINTS • While methamphetamine operates in many areas of the brain, one key area of impact is the reward center of the brain (nucleus acumbens). • This area is responsible feeling good what a person encounters pleasing things.

29. KEY POINTS • Neurons operate like a one-way street. Information come in along projections called dendrites. • Impulse passes through the cell body (called the soma) and goes out to neighboring neurons along projections called the axon. • At the end of the axon is the terminal button, here the impulse either dies or is passes to the next neuron.

30. dopamine reservoir synapse

31. KEY POINTS • This slide is a cartoon of the terminal button. Inside the terminal are reservoirs that hold neurotransmitters. The neurotransmitter primarily operative in this area of the brain is dopamine. • At the end of the terminal is a space, called a synapse. On the other side of the space is the dendrite of the next neuron. • On the surface of this is are receptors that are specifically designed for each neurotransmitter.

33. KEY POINTS • When a neuron is stimulated, the reservoirs travel to the edge of the synapse and release their dopamine into the synapse. • The dopamine travels across the synapse and binds to the receptor on the other side. If enough neurons get stimulated, the next neuron fires and the signal continues. • The dopamine is then taken out of the synapse by the dopamine transporters. These are like little vacuums that suck up the dopamine and deposit it back into the reservoir where it can be used again.

34. Methamphetamine or cocaine

35. KEY POINTS • Methamphetamine and cocaine do not operate directly on the receptor (like opioids do). • Instead, they block the re-uptake system (transporters), causing dopamine to build up in the synapse and the receptors to get over stimulated. This results in the euphoric rush. • Meth has also been shown to travel inside the cell and results in the destruction of the terminal button. Cocaine appears to only operate in the synaptic space and may therefore be less neurotoxic.

36. Natural Rewards Elevate Dopamine Levels FOOD SEX 200 200 NAc shell 150 150 DA Concentration (% Baseline) 100 100 15 % of Basal DA Output 10 Empty Copulation Frequency 50 Box Feeding 5 0 0 Scr Scr Scr Scr 0 60 120 180 Bas Female 1 Present Female 2 Present Mounts Time (min) Sample Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips

37. KEY POINTS • Dopamine is important in everything that feels good. • If you feed a hungry rat, you see a spike in dopamine • If you allow a rat to mate, you see an even bigger spike in dopamine

38. Effects of Drugs on Dopamine Release COCAINE 1500 1000 500 0 METHAMPHETAMINE Accumbens 400 Accumbens DA 300 DOPAC HVA % of Basal Release % Basal Release 200 100 0 0 1 2 3hr Time After Methamphetamine Time After Cocaine 250 ETHANOL NICOTINE 250 Accumbens Dose (g/kg ip) 200 Accumbens 200 0.25 Caudate 0.5 150 % of Basal Release 1 % of Basal Release 2.5 150 100 0 1 2 3 hr 100 0 0 0 1 2 3 4hr Time After Ethanol Time After Nicotine Source: Shoblock and Sullivan; Di Chiara and Imperato

39. KEY POINTS • The same is true with drugs of abuse. • With cocaine you see you get an intense spike of dopamine after administration. • Alcohol works on many systems in the brain, but it too attributes some of it effect to dopamine in this area of the brain. • Nicotine works similarly • Amphetamine produces and extremely greater effect.

40. PET Scan of Long-Term Meth Brain Damage

41. KEY POINTS • Study of monkey brains. In this slide the closer to red, the more brain activity. • Monkeys never exposed to meth had their brains scanned showing normal activity (egg shape areas in the center) • Researchers gave the monkeys high doses of methamphetamine for 10 days, waited a month and rescanned. • Worse at 6 months • Better at one year, but still different from baseline. • Not different from baseline at 2 years. • Take-home message—recovery takes a long time.

42. 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.

43. KEY POINTS • The question always comes up, does it work the same for humans? The answer is that we think it might. • First scan, normal control matched demographically to a meth user. • Second scan show meth user one month post detox • Last scan shows meth user 24 months post detox. Functioning much closer to control.

44. Control > MA 4 3 2 1 0

45. KEY POINTS • Scan from Dr. London’s lab at UCLA showing the prefrontal cortex (executive decision making). • This scan shows comparison of normal meth user to a normal control. This area of the brain is significantly less active. • Translation, decision making is not working so well.

46. 5 4 3 2 1 0 MA > Control

47. KEY POINTS • This scan is a comparative look at the amydgala (emotions). This area is hyperactive in meth users. • Indicating more emotional activation.

48. Cognitive Impairment in Individuals Currently Using Methamphetamine Sara Simon, Ph.D. VA MDRU Matrix Institute on Addictions LAARC

49. KEY POINTS • Dr. Simon wanted to see what cognitive impact these brain changes may have. • She conducted studies looking at memory in meth users

50. Longitudinal Memory Performance number correct test