Page 589 - Basic _ Clinical Pharmacology ( PDFDrive )

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Drugs of Abuse

Christian Lüscher, MD

C ASE STUD Y

A 15-year-old high school student is brought to the emergency When questioned by the intern, he reports that space-
department after his parents found him in his room staring at cookies were served at the party. He also says that smoking
the ceiling and visibly frightened. Earlier that evening, he marijuana has become a habit (three to four joints a week)
attended a party but was depressed because his girlfriend just but denies consumption of alcohol and other drugs.
broke up with him. Jerry is failing this year at school and has How do you explain the state he was found in? What is
stopped playing soccer. His parents are also worried about a the difference between hashish and marijuana? What may
change in his behavior over the last few months. He has lost be the link to his poor performance at school? Are all drug
interest in school, at times seems depressed, and tells his par- users necessarily using several drugs?
ents that his pocket money is not sufficient.

Drugs are abused (used in ways that are not medically approved) of drug abuse—it can also occur with many classes of non-
because they cause strong feelings of euphoria or alter percep- psychoactive drugs, eg, sympathomimetic vasoconstrictors and
tion. However, repetitive exposure induces widespread adaptive bronchodilators, and organic nitrate vasodilators. Addiction, on
changes in the brain. As a consequence, drug use may become the other hand, consists of compulsive, relapsing drug use despite
compulsive—the hallmark of addiction. negative consequences, at times triggered by cravings that occur in
response to contextual cues (see Box: Animal Models in Addiction
■ BASIC NEUROBIOLOGY OF Research). Although dependence invariably occurs with chronic
exposure, only a small percentage of subjects develop a habit, lose
DRUG ABUSE control, and become addicted. For example, very few patients who
receive opioids as analgesics desire the drug after withdrawal. And
DEPENDENCE VERSUS ADDICTION only one person out of six becomes addicted within 10 years of
first use of cocaine. Conversely, relapse is very common in addicts
There is a conceptual and mechanistic separation of “dependence” after a successful withdrawal when, by definition, they are no
and “addiction.” The older term “physical dependence” is now longer dependent.
denoted as dependence, whereas “psychological dependence” is
more simply called addiction.
Every addictive drug causes its own characteristic spectrum of ADDICTIVE DRUGS INCREASE THE
acute effects, but all have in common the characteristic that they LEVEL OF DOPAMINE: REINFORCEMENT
induce strong feelings of euphoria and reward. With repetitive
exposure, addictive drugs induce adaptive changes such as toler- To understand the long-term changes induced by drugs of abuse,
ance (ie, escalation of dose to maintain effect). Once the abused their initial molecular and cellular targets must be identified. A
drug is no longer available, signs of withdrawal become apparent. combination of approaches in animals and humans, including
A combination of such signs, referred to as the withdrawal syn- functional imaging, has revealed the mesolimbic dopamine system
drome, defines dependence. Dependence is not always a correlate as the prime target of addictive drugs. This system originates in

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