# Presentation: 571367

## Substance Abuse in the Elderly – An Overview

**Timothy P. Condon, Ph.D.**
**Deputy Director,**
**National Institute on Drug Abuse **
**National Institutes of Health**
**Department of Health and Human Services**

- Drug Abuse in the 21st Century - What Problems Lie Ahead for the Baby Boomers?
- Bethesda, Maryland
- Thursday, September 16, 2004

## What do we know?

## Past Year Illicit Drug Use, by Age: 2002

**Past Year Illicit Drug Use, by Age: 2002**

- Source: 2002 National Survey on Drug Use & Health (SAMHSA)

## What do we anticipate seeing from the aging baby boomer generation?

## What is a Baby Boomer?

## What is a Baby Boomer?

**Those born between (and including) 1946 and 1964 (40-58 yrs old)**
**Currently represent 29% of the U.S. population**

## Changing Demographics: More Elderly

- Source: A Profile of Older Americans: 2003, Administration on Aging, HHS

**Changing Demographics: More Elderly**

## Estimated Cost of the Consequences of Substance Abuse Among Mature Women in 1998 - $22.3 Billion*

- Inpatient Hospital Charges ($10.1 Billion)
- Medicare - $8.5 Billion
- Medicaid - $338 Million
- Private insurers/individuals - $1.3 Billion

- Nursing Home Expenses ($12.2 Billion)
- Medicare - $1.4 Billion
- Medicaid - $5.8 Billion
- Private insurers/individuals - $5 Billion

**Only 2%**
**was spent to treat the substance abuse problem itself.**

- *Does not include outpatient hospital visits, physician office visits and home health care.

*Source: CASA, Under the Rug: Substance Abuse and The Mature Woman, June 1998.*

**Notes:**
Estimate may be low because study relied on physician diagnoses and substance abuse is often under-diagnosed in this population.
The remaining 98% was spent on treating the consequences of substance abuse such as cancer, heart disease and hip fractures.
Projected to cost $100 Billion in 20 years.

## What are the cultural/societal factors that may impact differences in drug use and abuse in this generation as compared to the previous generation?

## Birth cohorts that experience high rates of illicit drug use in youth or young adulthood have subsequently shown higher rates of use as they age, relative to other cohorts.

- Source: The NHSDA Report, Substance Use Among Older Adults; Nov 2001

## What are some of the behavioral and sociological factors?

## Americans are Living Longer

- *Projected

- Sources: US Census Bureau and Centers for Disease Control and Prevention

## Sex, Drugs & Rock ‘N Roll

**Sex, Drugs & Rock ‘N Roll**

## Disposable Income

## Fewer Family Responsibilities

## Americans Are Living Better?

**Americans Are Living Better?**

## Mid-Life Crises – Distress Over Getting Older

- “50 is the new 30”
- Physical impairments
- Losses
- Kids leaving house
- Decreased physical prowess
- Retirement

## “Quick Fix” Society

- More Treatment Options Available
- Increased Availability of Medications
- Less Stigma Associated
- Advertising

## Just a Click Away - Drug Advertising is Ubiquitous

- Source: IMS Health and Competitive Media Reporting, Inc

**Just a Click Away - Drug Advertising is Ubiquitous**

## 30% of Americans talked to their doctor about medicine they saw advertised.Of these, 44% received the prescription drug they asked about 

- Source: Kaiser Family Foundation *Understanding the Effects of Direct-to-Consumer Prescription Drug Advertising, *November 2001

## As Prescriptions Increase Emergency Room Visits For Non-Medical Abuse Have Also Increased

- Number of Prescriptions (in 1000s)

**0**

**10000**

**20000**

**30000**

**40000**

**50000**

**60000**

**70000**

**80000**

**1994**

**1995**

**1996**

**1997**

**1998**

**1999**

**2000**

**2001**

- Source: SAMHSA, DAWN, 2002

**Hydrocodone**

**Oxycodone**

## 	   Availability on the Internet Delivered in the Privacy of your Home

**	****   ****Availability on the Internet *****Delivered in the Privacy of your Home***

**“****Some reasons why you should consider using this pharmacy”**
**No prescription required!**

## Are There Biological Factors to Consider?

## How Does the Brain Change with Age?

## Brain Changes Across the Lifespan

- Sowell et al, Nature Neuroscience v 6,3 p 309, 2003

**Notes:**
Figure 6: Volume graphs.Magnetic resonance imaging of 176 normal individuals ranging in age from 7 to 87 years. Scatterplots of the nonlinear effects of age on total brain white matter, total brain gray matter and total brain CSF volume. Volume in milliliters is shown on the y-axis.

## How Does Aging Affect the Pathways Associated with Substance Abuse?

## Dopamine Pathways

**Dopamine Pathways**

_**Functions**_
**reward (motivation)**
**pleasure,euphoria**
**motor function**
**  ****(fine  tuning)**
**compulsion**
**perseveration**

**Serotonin Pathways**

_**Functions**_
**mood**
**memory**
**  ****processing**
**sleep**
**cognition**

**nucleus**
**accumbens**

**hippocampus**

**striatum**

**frontal**
**cortex**

**substantia**
**nigra/VTA**

**raphe**

## Age-related reductions in D2 receptor binding in striatum

***Source: Volkow, N.D. et al., Brookhaven****** ******National Laboratory.***

**24 years**

**44 years**

**86 years**

**Notes:**
Source: Modified from Volkow, N.D. et al. American Journal of Psychiatry, 155, pp. 345-349, March, 1998, images but not graph included in original paper.
Aging is associated with a loss of DA D2 receptors in the human brain
Estimates for DA D2 losses obtained from PET range between 4-8% per decade of life
The consequences of the loss of DA D2 receptors in the human brain are not known.
Reductions are associated with changes in motor and cognitive functions, though clinically asymptomatic.
There is a parallel loss of DAT and DA D2-R with age

## Age-related decline in dopamine transporter binding

**24 years**

**44 years**

**86 years**

***Source: Volkow, N.D. et al., Brookhaven National Laboratory.***

**Notes:**
Source: Modified from Volkow, N.D. et al. Annals of Neurology, 44, pp. 143-147, 1998, images but not graph included in original paper.
Aging is associated with a loss of dopamine transporters in the human brain
Estimates for DAT losses obtained from PET range between 6-8% per decade of life 
The consequences of the loss of dopamine transporters in the human brain are not known.	
There is a parallel loss of DAT and DA D2-R with age
Cell loss cannot account for the decrease in DAT binding because the rate of decline in DAT binding is faster than the reported rate of cell loss.

## Age-related Decreases in Serotonin Transporter Binding

*Source: Yamamoto M.. et al., Life Sciences, 71, pp. 751-757, July, 2002.*

**Notes:**
PET scans using 5-HTT ligand [11C](+)McN5652 of 28 healthy male volunteers aged between 20 and 79 years. 
The ligand used in this study was [11C](+)McN5652 – the same ligand used by Ricaurte’s group (Ricaurte was not a co-author on this study) with the same caveats about specificity.

## Will age-related changes in brain function affect susceptibility to reward or sensitivity to illicit substances?

## Age-related declines in cannabinoid receptor function in mice are linked to age-related declines in alcohol preference 

- Source: Wang, Lei et al. (2003) Proc. Natl. Acad. Sci. USA 100, 1393-1398

**Notes:**
Cannabinoid agonist stimulated G-protein Binding is used as an indicator of cannabinoid signaling. 
No changes in anandamide, 2-AG or CB1 levels were detected with age in cerebellum, limbic forebrain, amygdala or hypothalamus .
When old mice were given anandamide, they increased their EtOH intake.

Fig. 3.   Cannabinoid agonist-stimulated [35S]GTP[ S] binding is selectively reduced in the limbic forebrain of old compared with young CB1+/+ mice. [35S]GTP[ S] binding was measured in membrane preparations from cerebellum, hypothalamus, amygdala, and limbic forebrain from 13 old (open columns) and 16 young (hatched columns) CB1+/+ mice as described in Materials and Methods. Columns and bars represent means ± SE of the difference in GTP[ S] binding measured in the absence and presence of 100 nM HU-210. 

## How does aging affect susceptibility to the toxic effects of drugs of abuse?

## Age-related increases in methamphetamine-induced toxicity

- Modified from Miller et al., Annals of the New York Academy of Sciences 914 (1) 194, 2000

**Age-related increases in methamphetamine-induced toxicity**

**Notes:**
Age as a Susceptibility Factor in the Striatal Dopaminergic Neurotoxicity Observed in the Mouse following Substituted Amphetamine Exposure -- MILLER et al. 914 (1) 194 -- Annals of the New York Academy of Sciences
FIGURE 5. d-METH significantly (p < 0.05) increases striatal GFAP (glial fibrillary acidic protein) levels. All mice received an injection s.c. every 2 h beginning at 10 am for a total of four injections, but the dosage varied by age. Mice aged 1, 2, 5, and 12 months received 10 mg/kg. An additional group of mice aged 12 months received 5 mg/kg as did mice aged 23 months. Note that mice aged one month exhibited a minimal GFAP response to a dosage of 10 mg/kg, whereas mice 2 months of age exhibited a pronounced increase as did 23-month-old mice receiving 5.0 mg/kg. Also note that control mice exhibit an age-related increase in striatal GFAP levels as we have previously noted. 26,27 Data are presented as the mean ± SEM with an n = 5-6 mice per group with the exception of the group of 12-month-old mice given 10.0 mg/kg d-METH. Data are presented from the three survivors. *Significantly different (p < .05) from SAL. 

## How does early exposure to drugs of  abuse affect the aging process? What are the potential consequences?

## Prolonged Drug Use Changes

**the Brain In Fundamental**
**and Long-Lasting Ways**

***Science Has Generated A Lot of***
***Evidence Showing That... ***

## Dopamine D2 Receptors are Lower in Addiction

**DA D2 Receptor Availability**

**control**

**addicted**

**DA**

**DA**

**DA**

**DA**

**DA**** **

**DA**** **

**DA**

**Reward Circuits**

**DA**** **

**DA**** **

**DA**** **

**DA**** **

**DA**** **

**Reward Circuits**

**DA**

**DA**

**DA**

**DA**

**DA**** **

**DA**

***Drug Abuser***

***Non-Drug Abuser***

## Increased white matter lesions in cocaine dependent subjects with age

***Source: Bartzokis, G. et al., American Journal of Neuroradiology, 20, pp. 1628-1635, October, 1999.***

**Notes:**
The incidence of hyperintense brain lesions observed on T2-weighted MR images of 62 male "crack" (smoked) cocaine–dependent participants ranging in age from 25 to 66 years were compared with 116 normal male control participants ranging in age from 25 to 80 years. 
Percent of participants with severe lesions in the cerebral white matter versus age. Cocaine-dependent participants have a significantly increased incidence of severe cerebral white matter lesions compared with normal control participants. The lines are derived from logistic regression analysis. The raw data from each group were divided into age quartiles and are displayed at the median age of the quartile. The sample sizes of the age quartiles (in order of ascending age) were 10, 22, 14, and 16 for the cocaine group and 28, 29, 28, and 31 for the normal group. Severe lesions graded as grade 3 based on a 0 to 3 severity scale.

## Rats Exposed to Nicotine in AdolescenceSelf-Administer More Nicotine Than Rats First Exposed as Adults 

*Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2*

**Notes:**
Female rats first exposed to nicotine as adolescents self-administered nicotine more often and in higher total doses per session than rats first exposed as adults.

## Rats First Exposed to Nicotine in Adolescence Show Greater Sensitization to Cocaine Than Rats First Exposed as Adults 

*Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2*

- *Activity level after cocaine administration was measured by counting the number of times in 10 minutes each rat crossed light beams projected in a grid across its cage.

**Notes:**
Rats exposed to nicotine in adolescence and then exposed to cocaine were more sensitive to cocaine's locomotor stimulating effects than rats first exposed to nicotine as adults. Nicotine-induced presensitization to cocaine was greatest in young male rats. 

## What might be the effect in the elderly?

**Consumption becomes compulsive, despite negative**
**social  and health consequences**

**If in youth, drug addiction can cause serious medical complications...**

**What might be the effect in the elderly?**

## Elderly persons use prescription medications approximately three times as frequently as the general population

- Source: Patterson, et al. Psychiatric Times, April 1999.

## What are the consequences of drug interactions (e.g. between prescription drugs and illicit drugs)?

## How does aging affect drug disposition/metabolism?  

- Pharmacokinetics change with aging
- Reduction in renal drug elimination resulting in increased drug serum levels and the potential for adverse drug reactions.
- Volume of drug distribution decreases resulting in higher plasma concentrations.
- Pharmacodynamic effects with aging
- Neurotransmitter receptor properties may change with age.
- Reduction in homeostatic mechanisms resulting in more time required to regain steady-state following drug therapy

## What is the relationship between drug abuse and co-morbid conditions in the elderly?

- Psychiatric disorders
- Neurological disorders
- Cardiovascular disease
- Cancer

- Kidney Disease
- Liver disease
- Musculoskeletal disorders
- HIV

## Some relevant issues in developing prevention, detection/diagnosis, and treatment programs for the elderly

- Age-related brain changes
- Changes in drug sensitivity
- Use of different drugs
- Side effects more severe/more of an issue
- Different access to the drugs
- Different settings (i.e. nursing homes)
- Age-specific screening instruments needed
- Stigma
- Need better education re. prescription drugs
- Data systems to track prescription use

## PHARMACOLOGICAL THERAPIES with a Strong Base of Scientific Evidence – NOT TESTED ON ELDERLY

**METHADONE**
**NALTREXONE**
**BUPROPION **
**NICOTINE REPLACEMENT THERAPY **
**BUPRENORPHINE**

## Future Research

- Research on animal models
- Expanding longitudinal epidemiological studies to examine drug abuse in the elderly
- Behavioral and sociological studies in aging populations and substance abuse.
- Developing age-specific prevention programs, screening tools, and treatments
- Brain imaging over life course

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