# Presentation: 547338

## METHAMPHETAMINE

**Nora D. Volkow, M.D.**
**Director**
**National Institute on Drug Abuse**

**METHAMPHETAMINE**
**& HIV/AIDS**

***What Do We Know About the Link?***

## Drug Use Has Played a Prominent 

**Role in the HIV/AIDS Epidemic**
**In Several Ways**

***Disease Transmission***
**    ****IV Drug Use**
**    ****Drug User Disinhibition Leading to **
**    ****High Risk Sexual Behaviors    **
***Progression  of Disease***

## Changing Nature of the HIV Epidemic

**Changing Nature of the HIV Epidemic**

## Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users

**Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users**

**HIV Prevalence**

- 13%

- CI 12-15%

- 12%

- CI 9-16%

**Drug Treatment Program**

**(n=2121 2001-2004)**

**Respondent-Driven Sampling **

**(n=448 2004)**

- 15%

- CI 11-19%

- 17%

- CI 12-21%

***Source: Des Jarlais et al AIDS, 21: 231-235, 2007.***

## IV Methylphenidate Enhanced Sexual Desire

- Placebo

- Intravenous Methylphenidate

- Sexual Desire
- (0-10)

- P < 0.001

**IV Methylphenidate Enhanced Sexual Desire**
**In Both Controls and Cocaine Abusers**

***Source: Volkow, N.D. et al., AJP 164(1): 157-160, 2007.***

## In Adults, Emotional Self Regulation Is Normally

**In Adults, Emotional Self Regulation Is Normally**
**Implemented By A Neural Circuit Comprising**
**Various *****Prefrontal Regions*****...& *****Subcortical                                               Limbic Structures***

## Effects of Alcohol Intoxication on Brain Glucose Metabolism (Marker of Brain Function)

***Alcohol decreases activity of areas involved with control and increases activity of areas involved with emotional reactivity***

**Effects of Alcohol Intoxication on Brain Glucose Metabolism (Marker of Brain Function)**

## Drug Use Has Played a Prominent 

**Role in the HIV/AIDS Epidemic**
**In Several Ways**

***Disease Transmission***
**    ****IV Drug Use**
**    ****Drug User Disinhibition Leading to **
**    ****High Risk Sexual Behaviors    **
***Progression  of Disease***

## Acceleration of HIV Degeneration of 

**Acceleration of HIV Degeneration of **
**Dopamine Cells With Cocaine**

**Notes:**
  Generalized cerebral atrophy most prominent in the frontal and temporal regions as well as basal ganglia atrophy with its shrinkage of the head of the caudate is noted.
  Diffuse periventricular white matter high signal intensity lesions are seen on a T2 weighted image.

## Methamphetamine Impacts the Spread and Course of HIV/AIDS:

**Increases risky sexual behavior, especially among men who have sex with men (MSM)**
**Reduces medication adherence to HAART **
**Increases replication of FIV in brain cells (the feline equivalent of HIV) **
**Meth dependence increases the risk of HIV-related cognitive problems**

## Past Year Methamphetamine Use among Persons Aged 12+, by Age:  2002-2006 

**Percent Using in Past Year**

**Age in Years**

**+**** Difference between this estimate and the 2006 estimate is statistically significant at the .05 level.**

**Note: Estimates are based on new 2006 questions. 2002-2005 estimates are adjusted for comparability.**

**0.7**

**2.0**

**0.5**

**0.7**

**0.7**

**1.9**

**0.5**

**0.8**

**0.7**

**1.9**

**0.6**

**1.8**

**0.5**

**1.7**

**0.6**

**1.0**

**+**

**0.7**

**0.7**

**0.7**

**0.8**

**0**

**1**

**2**

**3**

**12 or Older**

**12 to 17**

**18 to 25**

**26 or Older**

**2002**

**2003**

**2004**

**2005**

**2006**

## Methamphetamine Treatment Admissions

***2005 SAMHSA Treatment Episode Data Set***

**0**

**20000**

**40000**

**60000**

**80000**

**100000**

**120000**

**140000**

**160000**

**Number of Admissions**

**1995**

**1996**

**1997**

**1998**

**1999**

**2000**

**2001**

**2002**

**2003**

**2004**

**2005**

## Concerns with Methamphetamine

**    ****drug self administration  **
**  ****Highly addictive**
**  ****Intoxication associated with **
**    ****behaviors that increase risks for**
**    ****infection with HIV and HCV**
**  ****Can be easily manufactured by**
**    ****small clandestine laboratories**

**Concerns with Methamphetamine**

## Brain Dopamine System

**DA**

**DA**

**DA**

**DA**

**DA**** **

**DA**** **

**DA**

**signal**

**Dopamine Cell**

**DA Transporters**

**DA Receptors**

**Metabolism**

**Brain Dopamine System**

## Dopamine Transporters in 

**Dopamine Transporters in **
**Methamphetamine Abusers****  **

***p < 0.0002***

**Normal Control**

**Methamphetamine Abuser**

**Time Gait**

**(seconds)**

**Dopamine Transporter**

**(Bmax/Kd) **

**Delayed Recall**

**(words remembered)**

**Dopamine Transporter**

**Bmax/Kd **

**Motor Activity**

**Memory**

**Loss is associated with**
**slowing of motor reactions**

**Loss is associated with**
**memory impairment**

## Brain Glucose Metabolism in METH Abusers  

**Brain Glucose Metabolism in METH Abusers  **

**BNL, UCLA, SUNY**

**Metabolic Rate**

**(micromol/100 gr/min)**

**Controls**

**METH**

**Whole Brain**

**p < 0.05**

## METH abusers < controls

***Late Detoxification***

***METH abusers < controls***

- (FWHM = 16mm, pixel threshold = 0.001)

## HIV Seroconversion at 18 MonthsBy Receipt of Treatment

**HIV Seroconversion at 18 Months****By Receipt of Treatment**

**0**

**5**

**10**

**15**

**20**

**25**

**Rate of Seroconversion (%)**

**Treatment Status**

**No treatment**

**Partial treatment**

**Continuous treatment**

**Source: Metzger, D. S., Woody, G. E., McLellan, A. T., O’Brien, C. P., Druley, P., Navaline, H., De Philipps, D., Stolley, P., & Abrutyn, E. (1993). Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. Journal of Acquired Immune Deficiency Syndromes, 6, 1049-1056.**

**The Most Effective HIV/AIDS Prevention**
**Strategy is *****Drug Abuse Treatment***

## Treatments for Methamphetamine

**Treatments for Methamphetamine**

**  ****Cognitive Behavioral Therapies**
**  ****Contingency Management**
**  ****MATRIX Model**
**  ****New Medications **
**    ****(treatment and overdose)****    are being developed**

## Efficacy of the Matrix Model

*Source: Rawson et al. (2004) Addiction 99:708-17.*

**Mean number of days of MA use**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**Baseline**

**Discharge**

**6-month Follow-up**

## Bupropion Reduces Meth Abuse In Low to Moderate Abusers

**Bupropion Reduces Meth Abuse ****In Low to Moderate Abusers**

***Elkashef et al. 2007, Neuropsychopharm Epub***

- Placebo + Treatment as Usual

- Placebo + Treatment as Usual

**Notes:**
A recently completed Phase II clinical trial with bupropion has shown it to be significantly effective in reducing meth abuse in low/moderate users. A follow-up trial is planned. 

## Opportunities to Develop Targeted Strategies

**Scientific Research is Providing **
***Opportunities to Develop Targeted Strategies***
**for Preventing HIV/AIDS**

## HIV Screening as Cost-Effective as Screening for Colon Cancer and Other Conditions

**HIV Screening as Cost-Effective as Screening for Colon Cancer and Other Conditions**

***Paltiel, et al. and Sanders et al., NEJM 352(6), 2005.***

***How can this apply to at-risk populations such as CJ?***

## 1,000,000 people in USA are infected with HIV
40,000 new cases each year
250,000 – 300,000 of persons with HIV are unaware they are infected
1⁄4 of persons who test HIV+ fail to return to receive results
CDC now recommends offering routine HIV testing to persons at risk for HIV

**1,000,000 people in USA are infected with HIV**
**40,000 new cases each year**
**250,000 – 300,000 of persons with HIV are unaware they are infected**
**1⁄4 of persons who test HIV+ fail to return to receive results**
**CDC now recommends offering routine HIV testing to persons at risk for HIV**

**Integrating HIV Rapid Testing and Counseling **
**into Drug Treatment**

**FDA approved **
**blood from a finger stick or oral fluid **
**20 minutes**
**$12-15/kit**
**can be done by counselors**

**HIV Rapid Test**

## Smoking Prevention Programs Have Proven to Be

**An Effective Strategy in Combating Cancer **

## DRUG USE--------HIV/AIDS

**PREVENTION is Also Key to**
***Breaking the Cycle *****of **

**DRUG USE--------HIV/AIDS**

**NIDA’s Goal Is to Use the SCIENCE to **
**PREVENT Drug Abuse and HIV/AIDS **

## Brain Metabolism in METH Abusers with Abstinence

**Control**

**METH Abuser (3 m Detox)**

**METH Abuser (13 m Detox)**

***Thalamus***

- Ratio

***Striatum***

*+12±9%, p *_*<*_* 0.015       +2.7±6.7%, p = 0.34 *

## Dopamine D2 Receptors are  Lower in Addiction

**DA D2 Receptor Availability**

**control**

**addicted**

**Cocaine**

**Alcohol**

***Drug Abuser***

***Non-Drug Abuser***

**Heroin**

**Meth**

**Dopamine D2 Receptors are  Lower in Addiction**

## Chronic Drug Use Disrupts Inhibitory Control

**Correlations Between D2 Receptors in Striatum and**
** ****Brain Glucose Metabolism**

**Chronic Drug Use Disrupts Inhibitory Control**

## ?

**the Focus of Many Scientific Studies **

***PubMed Citations***
**Alcohol + HIV =  2885**
**Opiates + HIV = 1181 **
**Cocaine + HIV = 1137**
**THC (or Marijuana) + HIV = 390**
**Methamphetamine + HIV = 154 **

**Although Many Laboratory Studies Have Shown**
**That Drug Abuse May Exacerbate **
**HIV Progression....Epidemiological Studies**
**Have Shown Mixed Results**

**?**

## Effects of METH Detoxification on DAT 

**Effects of METH Detoxification on DAT **

**DA Transporters**

**(Bmax/Kd)**

***Caudate***

***p < 0.003***

***Putamen***

***p < 0.05***

## METH abusers > controls

***Late Detoxification***

***METH abusers > controls***

- (FWHM = 16mm, pixel threshold = 0.001)

- 3.0

- 4.0

- 5.0

## What are the Mechanisms Underlyingthe Relationship Between 

***Drug Use and HIV/AIDS?***

**  ****Acute Drug Effects**** – Drug Intoxication and **
**    ****Decision Making   **

**  ****Chronic Drug Effects**** – Disruption of Inhibitory**
**    ****Control**

**  ****Interaction**** of Drugs and HIV**

## Bupropion Reduces Methamphetamine-Induced Highand Cue-Induced Craving

**Bupropion Reduces Methamphetamine-Induced High****and Cue-Induced Craving**

***Newton TF et al. 2006, Neuropsychopharm 31:1537-44.***

**Notes:**
mBupropion, marketed as Welbutrin®, offers promise as an anti-addiction medication for several illicit drugs. Recent study findings reveal that bupropion reduced acute meth-induced subjective effects as well as cue-induced cravings.