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Informing America’s Policy on Illegal Drugs: What We Don’t Know Keeps Hurting Us
lasting changes in brain functioning that continue after the last dose of the drug (Leshner, 1997; O’Brien, 1995).2 While all illegal drugs affect brain systems, they do so in different ways and thus have different behavioral effects. Table 2.1 displays nine general classes of drugs by functional or behavioral activity. In terms of behavioral responses, alcohol and marijuana are sedating, whereas cocaine and amphetamines are powerful stimulants. Opiates such as heroin have multiple effects, including stimulation, relaxation, and analgesic actions. Nicotine stimulates and relaxes different systems. All of these are associated with the development of dependence, and all can lead some users to report craving, obsession-like thinking about drug use, and compulsion to use drugs, even when the degree of stimulation or sedation is minimal.
Other drug-related conditions and processes also come into play, including the purity and efficacy of one drug relative to another. Similarly, the route of administration appears to influence the addictive properties. Drugs that are smoked or injected reach the brain more rapidly than those that are ingested; these routes of administration are associated with more rapid onset and produce more powerful effects. The importance of purity and mode of administration can be demonstrated in considering the coca plant. Crack cocaine is far more addictive than chewed coca leaves, although both come from the same source. Crack cocaine is smoked, thereby producing volatized pure drug in the lungs’ surface area. This process is far more fast-acting and addictive than occurs when powder cocaine absorbed via the nasal passage (Institute of Medicine, 1997).3
The potency and form of administration may also play important roles in the initiation and intensification process. Smoking and injecting drugs cause discomforts that may discourage use and intensification. In contrast, ingesting drugs in either liquid or tablet form is not likely to cause similar physical discomfort.
There is a recent line of neuroscience research on the mechanisms that govern sensitization and tolerance, including research on postsynaptic signaling mechanisms. Through this research, it has been possible to discover pathways by which exposure to cocaine and other drugs can provoke neural and behavioral plasticity. It appears that the plasticity occurs in response to a cocaine-associated alteration in the expression of genes within the nucleus of the neuron postsynaptically. This cocaine-modulation of gene expression is linked to development of sensitivity to the drugs, possibly contributing to the drug dependence process (e.g., Kelz et al., 1999).
It would be unethical to expose cocaine-naïve human subjects to crack cocaine and to powder cocaine in order to determine which form of cocaine is more “addictive,” but the presently available evidence suggests most rapid and pronounced development of cocaine dependence symptoms when crack cocaine is smoked or when powder cocaine HCl is injected intravenously (e.g., see Gossop et al., 1994; Hastukami and Fischman, 1996).