"We are dealing with not only a problem of the abuse and diversion of these substances, but we are dealing with toxic compounds," Volkow said. "Opioid analgesics can produce death from overdose."
From 2001 to 2002, drug abuse-related emergency department (ED) visits involving narcotic analgesics increased 20% (from 90,232 to 108,320 visits), with hydrocodone and oxycodone being the narcotic analgesics most frequently mentioned (Drug Abuse Warning Network, 2004). Looking at motives underlying drug abuse-related ED visits involving narcotic analgesics, dependence headed the list (47%; 50,623 visits), followed by suicide (22%; 24,308 visits), psychic effects (15%; 16,153 visits), other motives (2%; 1,790 visits) and unknown motive (14%; 15,446 visits).
Common Characteristic
The reason that alcohol; cocaine; marijuana; heroin or prescription medications such as opioid analgesics, benzodiazepines or stimulants can produce addiction is that all of them have a common characteristic. They increase the concentration of dopamine, Volkow pointed out in her lecture. Methylphenidate (Ritalin, Concerta, Metadate), for example, increases the synaptic concentration of dopamine by blocking the dopamine transporters.
Volkow was among the first researchers to use positron emission tomography (PET) to investigate the nature of acute brain changes in dopamine activity induced by drugs of abuse as well as long-term brain changes in dopamine activity and the functional consequences of these changes in drug-addicted subjects (Volkow et al., 2004a, 2004b).
Such studies, she explained, have corroborated the role of dopamine in the rewarding effects of drugs of abuse in humans and also its involvement in motivation. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events (e.g., food, sex, social interaction). In addition, imaging studies have documented a role of dopamine in motivation, which appears to be encoded by fast as well as smooth dopamine increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells (Volkow et al., 2004b).
In a recent article, Volkow et al. (2004b) explained that dopamine function is markedly disrupted in drug-addicted individuals. There are decreases in dopamine release and in dopamine D2 receptors in the striatum. This hypodopaminergic state may lead to deregulation of reward, motivation and inhibitory control circuits.
"So what happens when that individual who is addicted is exposed to a natural reinforcer such as food or sex? Well, the amount of dopamine to start with is significantly reduced, and then the receptors are also lower. Therefore, the probability of an interaction of dopamine with a receptor is significantly decreased, and the likelihood of a person who is addicted to perceive a natural reinforcer as pleasant is going to be dramatically affected … They won't be motivated for basic, natural reinforcers," she said in the lecture.
