by Charlotte Gutfreund
K.J., a young heroin user died from an overdose of heroin. He had been hospitalized numerous times for his continued drug abuse, so had had his blood morphine levels (heroin is broken down to morphine once in the bloodstream) recorded numerous times. Interestingly, his blood morphine levels were no higher than they ordinarily were, yet this particular heroin injection proved fatal (Gerevich, Bacskai, Farkas, & Danics., 2005). So what was it that made this high tragically different than his previous ones?
K.J. had not been using heroin as steadily recently, due to his frequent hospital visits, but studies have shown that, although tolerance to heroin definitely increases over continued usage, periods of abstinence do not then, re-lower tolerance (Druid, et. al., 2007), so that could not have been the cause of his different reaction this time. The only thing that was different about the last time he injected himself with heroin was that he was doing so in a different location than he normally did (Gerevich, et. al., 2005).
Surprisingly, this is actually in agreement with a phenomenon shown in other studies. In 1985, Siegel and his colleagues gave two groups of rats continued morphine injections of progressively higher dosage. Each time the injection was given in the same location. The highest location was then given again, and half of the rats were in a new location for this last dose. The rats in the new location repeatedly showed a significantly higher mortality rate, even though they were getting the same exact dose as the other group and the same dose as they had been injected with (and survived) previously. This is because, as a conditioned response to the stimuli present during previous drug use, the body learns to “expect” the drug coming when in the presence of these stimuli, and physiologically prepares itself to “tolerate” the drug (Siegel, et. al., 1985). Tolerance for a drug is caused when long-term use of the drug alters the function of neurons in the brain. For example, with long-term use of opiates, brain neurons begin to require higher and higher levels of the opiate in order to function properly. When frequently exposed to a drug, the brain will alter itself to compensate for the effects of the drug, thereby creating a “tolerance”. An increased tolerance means that the person must use a higher level of the drug to get the same effect, and so their tolerance continually increases (Somers, 2006).
The stimuli present during repeated drug use can elicit very distinct neural reactions in other ways too. Deroche-Gamonet, et. al. allowed to rats to self-administer themselves with cocaine by nose-poking in a certain hole. One group of mice was given a particular cue light every time they were injected with cocaine, the other group was shown no light, and both the groups showed generally similar cocaine-usage patterns. Then, the light stopped being shown to both groups for a prolonged period of time and both groups’ cocaine craving (based on the frequency with which they nose-poked for it) stabilized. But, when reintroduced to the cue-light, the cue-light group’s cocaine use increased drastically, even though the light originally did not seem to affect their use (Deroche-Gamonet, et. al., 2002). This indicates how a stimulus conditioned to be associated with drug use can spark a craving for the drug later on because of learned conditioning.
Originally neutral stimuli can having varied effects when they are associated with repeated drug use. But, although these stimuli can seem completely inconsequential, they can mean the difference between life and death, as with K.J., or the difference between sobriety and relapse.
Deroche-Gamonet, V., Piat, F., Le Moal, M., & Piazza, P. V. (2002). Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration. European Journal of Neuroscience, 15(8), 1363-1370.
Druid, H., Strandberg, J. J., Alkass, K., Nyström, I., Kugelberg, F. C., & Kronstrand, R. (2007). Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis. Forensic Science International, 168(2-3), 223-226.
Gerevich, J., Bacskai, E., Farkas, L., & Danics, Z. (2005). A case report: Pavlovian conditioning as a risk factor of heroin ‘overdose’ death. Harm Reduction Journal, 2(1), 11.
Siegel, S., Hinson, R. E., Krank, M. D., & McCully, J. (1982). Heroin “Overdose” death: Contribution of drug-associated environmental cues. Science, 216(4544), 436-437.
Somers, T. (2006). Opiate Addiction. Retrieved from The Society for Neuroscience: http://www.sfn.org/skins/main/pdf/brss/BRSS_opiateAddiction.pdf.