Neuroscience 6e Web Topic 6.2 - Addiction

Drug addiction is a chronic, relapsing disease with obvious medical, social, and political consequences. Addiction (also called substance dependence) is a persistent disorder of brain function in which compulsive drug use occurs despite serious negative consequences for the afflicted individual. The diagnostic manual of the American Psychiatric Association defines addiction in terms of both physical dependence and psychological dependence (in which an individual continues the drug-taking behavior despite obviously maladaptive consequences).

The range of substances that can generate this sort of dependence is wide; the primary agents of abuse at present are opioids, cocaine, amphetamines, marijuana, alcohol, and nicotine. Addiction to more “socially acceptable” agents such as alcohol and nicotine are sometimes regarded as less problematic, but in fact involve medical and behavioral consequences that are at least as great as for drugs of abuse that are considered more dangerous. Importantly, the phenomenon of addiction is not limited to human behavior, but is demonstrable in laboratory animals. Primates, rodents, and other species will self-administer most of these same agents if they are provided with the opportunity to do so.

In addition to a compulsion to take the agent of abuse, a major feature of addiction for many drugs is a constellation of negative physiological and emotional features, loosely referred to as withdrawal syndrome, that occur when the drug is not taken. The signs and symptoms of withdrawal are different for each agent of abuse but in general are characterized by effects opposite those of the positive experience induced by the drug itself. Consider, as an example, cocaine; in 2014, approximately 1 million Americans were dependent on this drug. The positive effects of the drug smoked or inhaled as a powder in the form of the alkaloidal free base are a “high” that is nearly immediate but generally lasts only a few minutes, typically leading to a desire for additional drug in as little as 10 minutes to half an hour. The “high” is described as a feeling of well-being, self-confidence, and satisfaction. Conversely, when the drug is not available, frequent users experience depression, sleepiness, fatigue, drug-craving, and a general sense of malaise.

Another aspect of addiction to cocaine or other agents is tolerance, defined as a reduction in the response to the drug upon repeated administration. Tolerance occurs as a consequence of persistent use of several drugs but is particularly significant in drug addiction, since it progressively increases the dose needed to experience the desired effects.

Although it is fair to say that the neurobiology of addiction is incompletely understood, for cocaine and many other agents of abuse the addictive effects involve activation of dopamine receptors in critical brain regions involved in motivation and emotional reinforcement (see Chapter 31 of the textbook). The most important of these areas is the midbrain dopamine system, especially its projections from the ventral tegmental area to the nucleus acumbens. Agents such as cocaine appear to act by raising dopamine levels in these areas, making this transmitter more available to receptors by interfering with reuptake of synaptically released dopamine by the dopamine transporter. The reinforcement and motivation of drug-taking behaviors are thought to be related to the projections to the nucleus acumbens.

The most common opioid drug of abuse is heroin. Heroin is a derivative of the opium poppy and is not legally available for clinical purposes in the United States. It is estimated that more than 4 million people in the United States alone are heroin users. The positive feelings produced by heroin, generally described as the “rush,” are often compared to the feeling of sexual orgasm and begin in less than a minute after intravenous injection. There is then a feeling of general well-being (referred to as “on the nod”) that lasts about an hour. The symptoms of withdrawal can be intense; these are restlessness, irritability, nausea, muscle pain, depression, sleeplessness, and a sense of anxiety and malaise. The reinforcing aspects of the drug entail the same dopaminergic circuitry in the ventral tegmental area and nucleus acumbens as does cocaine, although additional areas are certainly involved, particularly the sites of opioid receptors described in Chapter 10 of the textbook.

Interestingly, addiction to heroin or any other agent is not an inevitable consequence of drug use, but depends critically on the environment. For instance, returning veterans who were heroin addicts during the Vietnam War typically lost their addiction upon returning to the United States. Likewise, patients given other opioids (e.g., morphine) for painful conditions rarely become addicts.

The treatment of any form of addiction is difficult and must be tailored to the circumstances of the individual. In addition to treating acute problems of withdrawal and detoxification patterns of behavior must be changed, which may take months or years. Addiction is thus a chronic disease state that requires continual monitoring during the lifetime of susceptible individuals.

References

American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV). Washington, D.C.

Hyman, S. E. and R. C. Malenka (2001) Addiction and the brain: The neurobiology of compulsion and its persistence. Nature Rev. Neurosci. 2: 695–703.

Kauer, J. S. and R. C. Malenka (2007) Synaptic plasticity and addiction. Nat. Rev. Neurosci. 8: 844–858.

Laakso, A., A. R. Mohn, R. R. Gainetdinov and M. G. Caron (2002) Experimental genetic approaches to addiction. Neuron 36: 213–228.

Madras, B. K. and 5 others (2006) Cell Biology of Addiction. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

O’Brien, C. P. (2006) Goodman and Gilman’s The Pharmaceutical Basis of Therapeutics, 11th Edition. New York: McGraw-Hill, Chapter 23, pp. 607–627.

Schultz, W. (2010) Dopamine signals for reward value and risk: Basic and recent data. Behav. Brain Funct. 6: 24.