1. Drug dependence and substance abuse
Prof elham aljammas
april2017

3. Addiction is a Developmental Disease: It Starts Early
67%
26%
First Marijuana Use, (Percent of Initiates)
5.5%
Addiction is a developmental disease that usually begins in adolescence. For example, 67 percent of those who try marijuana for the first time are between the ages of 12 and 17. Prevention efforts are therefore of primary importance—to stop drug abuse before it ever starts.
1.5%
<12
12-17
18-25
>25

4. Basic Science Tells Us that Adolescents’ Brains Are Still Developing…
Research shows that brain development continues throughout adolescence and into early adulthood.

5. MRI Scans of Healthy Children and Teens Over Time
Magnetic Resonance Imaging (MRI) Scans allow us to map the maturation of the brain. This slide illustrates brain development through early adulthood, with blue indicating the mature state. The prefrontal cortex (white circles), which governs judgment and decision-making functions, is the last part of the brain to develop. This may help explain why teens are prone to risk-taking, are particularly vulnerable to drug abuse, and why exposure to drugs at this critical time may affect propensity for future addiction.
Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101,
Copyright ©2004 by the National Academy of Sciences

6. Adults Rely More on the Frontal Cortex
When Reading Emotion…
Adults Rely More on the Frontal Cortex
While Teens Rely More on the Amygdala
Adolescents’ brains are “wired” differently than adults. Because the prefrontal cortex is one of the last areas of the brain to mature during development, adolescents tend to use other areas – in this case emotional areas – of the brain in making decisions. For example, brain activity, seen with functional MRI, shows that when judging emotion represented on a face, a teenager’s amygdala (right) is activated, reflecting more of a gut reaction than a reasoned one, while the adult’s (left) brain is activated in an area of the prefrontal cortex involved more in reasoning and reflection.
Source: Deborah Yurgelon-Todd

7. Do Adolescents React Differently than Adults to Substances of Abuse?
Given the different physiology of adolescents’ brains, do they react differently to substances of abuse? Research findings point to “yes.”

8. Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults
Animal studies show a differential response to drugs of abuse in early-exposed “adolescents.” For example, 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. Corresponding and persistent changes in the brain were also found in those animals that were exposed early to nicotine.
Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2

9. Do We Need Fundamentally Different Strategies At
Different Stages of Adolescence?
Thus, NIDA is supporting research to learn more about how to best prevent drug abuse and treat drug addiction in adolescents. One important area is understanding adolescent decision-making, including the social and biological factors that influence the decision to use drugs.

10. Americans’ Views of the Seriousness of Health Problems (Top 10 of 36 Problems)
65%
68%
69%
71%
73%
74%
75%
78%
82%
Stress
Alcohol abuse
Smoking
Child abuse
Violence
HIV/AIDS
Heart disease
Drunk driving
Cancer
Drug abuse
% saying “very serious problem”
Harvard School of Public Health/Robert Wood Johnson Foundation/ICR, August 2000
Drug abuse
Cancer
Drunk driving
Heart disease
HIV/AIDS
Violence
Child abuse
Smoking
Alcohol abuse
Stress

11. Definitions Drug Use Drug Abuse Drug Dependence
Taking a psychoactive substance for non-medical purposes, out of curiosity
Drug Abuse
Drug use that leads to problems (e.g. loss of effectiveness in society; behavioral psychopathology, criminal acts)
Drug Dependence
A maladaptive pattern of drug use leading to clinically-significant impairment or distress, associated with difficulty in controlling drug-taking behavior, withdrawal, and tolerance
The state of needing a drug to function within ‘normal limits’

12. Nature of Addiction - a continuum of use?
Loss of control 
However, addiction is more than mere drug use…

13. DSM-IV Criteria for Substance Dependence
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12 month period:
Tolerance
Withdrawal
Substance taken in larger amounts or over a longer period than intended
Persistent desire or unsuccessful efforts to cut down or control substance use
Great deal of time spent in activities necessary to obtain substance, use substance (e.g., chain smoking), or recover from effects
Important social, occupational, or recreational activities given up or reduced because of substance use
Substance use continued despite knowledge of persistent or recurrent physical or psychological problem likely to have been caused or exacerbated by substance

14. Addiction Involves Multiple Factors
Research has also taught us that addiction is a complex disease, influenced by a multitude of highly entangled factors. No single factor determines whether someone will or will not become addicted to drugs.

15. Addiction Medical DRUGS Social Economic Neurotoxicity AIDS, Cancer
Mental illness
The effects of drug abuse are wide ranging and affect people of all ages. Besides addiction, drug abuse is linked to a variety of health problems, including HIV/AIDS, cancer, heart disease, and many more. It is also linked to homelessness, crime, and violence. Thus, addiction is costly to both individuals and society.
Health care
Productivity
Accidents
Homelessness
Crime
Violence

16. Physical vs. Psychological Dependence
Physical Dependence
Withdrawal symptoms in the absence of the drug
Tolerance to its effects with repeated use
Psychological Dependence
“a relatively extreme, pathological state in which obtaining, taking, and recovering from a drug represents a loss of behavioral control over drug taking which occurs at the expense of most other activities and despite adverse consequences” (Altman et al)
“a situation where drug procurement and administration appear to govern the organism’s behavior, and where the drug seems to dominate the organism’s motivational hierarchy” (Bozarth)

17. Physical Dependence or Withdrawal Model (Negative Reinforcement)
Some drugs produce physical dependence and withdrawal symptoms upon cessation of drug-taking.
Withdrawal symptoms are produced by the body in order to compensate for the unusual effects of the drug.
Withdrawal symptoms are generally the opposite of the effect produced by the drug.
Addicts continue to use drugs in order to avoid withdrawal.
Over time, drugs no longer have the same rewarding effects - they merely allow the person to feel “normal.”

18. Positive Incentive (Hedonic) Models (Positive Reinforcement)
Drugs produce pleasure - a “high.”
Some drugs provide indirect positive incentive - they disinhibit behavior that is normally suppressed (e.g., alcohol and social skills).
Most drugs of abuse stimulate the brain’s reward circuits.
All known drugs of abuse stimulate release of DA/opioids in the nucleus accumbens
Animals will work to micro-inject drugs of abuse and electrically stimulate the same parts of the brain
Normal rewards (food, drink, sex) also stimulate DA release

19. Drug Dependence Among Ever-Users
Tobacco
Heroin
Cocaine
Alcohol
Stimulants
Marihuana 10 20 30 40
% Dependent

20. Why do Mental Illnesses and Substance Abuse Co-occur?
Self-medication hypothesis
substance abuse begins as a means to alleviate symptoms of mental illness
Causal effects of substance abuse
Substance abuse may increase vulnerability to mental illness
Common or correlated causes
the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap
Why? Reasons that mental illnesses and substance abuse tend to co-occur include the propensity of people to self-medicate to relieve mental distress or illness, the heightened vulnerability to mental illness brought on by drug abuse, and the overlap of risk factors for both conditions. Understanding the various contributions of these factors to peoples’ vulnerability to drug abuse will help us develop more effective prevention and treatment interventions.

21. Why Do People Take Drugs in The First Place?
To Feel Good
To have novel:
feelings
sensations
experiences
AND
to share them
To Feel Better
To lessen:
anxiety
worries
fears
depression
hopelessness
Why would anyone abuse drugs? Research has shown that people generally take drugs to either feel good (i.e., sensation seekers or anyone wanting to experiment with feeling high or different) or to feel better (i.e., self-medicators or individuals who take drugs in an attempt to cope with difficult problems or situations, including stress, trauma, and symptoms of mental disorders).
Images: courtesy of Vivian Felsen

22. Why Can’t Addicts Just Quit?
Drive
Saliency
Memory
Control
Non-Addicted Brain NO GO
Addicted Brain
Addiction changes brain circuitry, making it hard to “apply the brakes” to detrimental behaviors. In the non-addicted brain, control mechanisms constantly assess the value of stimuli and the appropriateness of the planned response, applying inhibitory control as needed. In the addicted brain, this control circuit becomes impaired through drug abuse, losing much of its inhibitory power over the circuits that drive response to stimuli deemed salient.
Because Addiction Changes Brain Circuits
Source: Adapted from Volkow et al., Neuropharmacology, 2004.

23. We Need to Treat the Whole Person! In Social Context
Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry
We Need to Treat the
Whole Person!
Pharmacological
(medications)
Behavioral Therapies
Addiction requires treatment that addresses its complexity. Substance abuse treatment should address the whole person and can include medications, behavioral therapies, and ancillary support services.
Medical and Social Services
In Social Context

24. But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma
But medications alone are not enough. Drug addiction, like other chronic, relapsing diseases requires long-term treatment of its varied consequences. The goal of treatment is to help people get to a point where they can manage their long-term recovery, including drug abstinence.
McLellan et al., JAMA, 2000.

25. We Need to Keep Our Eye on
In Treating Addiction…
We Need to Keep Our Eye on
the Real Target
Abstinence
Addiction treatment aims to help people achieve abstinence and become full participants in society. Ancillary support services, in addition to behavioral and pharmacological treatments, help to connect people to needed social, medical, and employment services, to get their lives back on track.
Functionality in
Family, Work
and Community

26. 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
Drug Abuse and HIV/AIDS are intertwined epidemics in ways that go beyond the sharing of drug injection equipment. While injection drug users are still at great risk, anyone under the influence of drugs or alcohol is also at heightened risk of contracting or transmitting HIV. Drug abuse can also contribute to a more serious HIV disease progression, possibly through direct effects or interactions with HIV on the immune system, and also by adversely impacting adherence to HIV treatment.

27. Dopamine Pathways Serotonin Pathways Functions mood memory processing
nucleus
accumbens
hippocampus
striatum
frontal
cortex
substantia
nigra/VTA
raphe
Functions
reward (motivation)
pleasure,euphoria
motor function
(fine tuning)
compulsion
perserveration
decision making
Serotonin Pathways
Functions
mood
memory
processing
sleep
cognition

28. Drug Disorder Cocaine and Methamphetamine Schizophrenia, paranoia,
anhedonia, compulsive
behavior
Stimulants
Anxiety, panic attacks,
mania and sleep disorders
LSD, Ecstasy & psychedelics
Delusions and hallucinations
Alcohol, sedatives, sleepaids
& narcotics
Depression and mood
disturbances
PCP & Ketamine
Antisocial behavior

29. Targets of Medication Methadone, LAAM and Buprenorphine
Activate opioid receptors
Naloxone
Block opioid receptors
Nicotine gum/patch
Activate nicotinic receptors