Ronald Ehrman

Conditioning factors in drug abuse: can they explain compulsion?

There is a good deal of clinical evidence suggesting that compulsion to resume drug taking is an important part of the addiction syndrome. The symptoms comprising motivation to resume drug use, namely craving and compulsion, have been studied experimentally in human subjects. While much work remains to be done, there is evidence showing that these symptoms are influenced by learning. The research has been guided by animal studies demonstrating that drug effects can be conditioned. Much attention has been directed toward demonstrating the existence of drug conditioning in human addicts and exploring the neurological structures that may underlie such learned responses. We do not yet know the relative importance of learning in the overall phenomenon of relapse, and treatments based on conditioning principles are still under investigation.

Conditioned responses to cocaine-related stimuli in cocaine abuse patients

Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine-related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.

Integrating systematic cue exposure with standard treatment in recovering drug dependent patients

Repeated drug administration readily produces classically conditioned responses in animal and human experimental studies. The majority of patients applying for treatment of drug dependence show both autonomic and subjective responses when exposed to drug-related stimuli. These responses are presumed to have been conditioned during a period of active drug use, persist after traditional treatment for drug dependence, and may constitute one of several factors which predispose to relapse. Preliminary data are presented from a novel treatment approach which is designed to test whether drug-conditioned responses can be reduced or extinguished by systematic exposure to drug-related cues and whether such extinction improves the overall results of treatment.

Comparing levels of cocaine cue reactivity in male and female outpatients

Thirty-eight female and 26 male cocaine-dependent outpatients were exposed to cocaine cues in a laboratory setting. Stimuli consisted of an audiotape of patients discussing cocaine use, a videotape of simulated cocaine preparation and use, and the handling of cocaine paraphernalia. Overall, the stimuli produced significant decreases in skin temperature and skin resistance, and significant increases in heart rate, self-reported drug states (high, craving, and withdrawal), and self-reported negative moods. Females were more likely to report increased craving in response to the cues than males, but there were no other gender differences in any of the responses. Levels of reactivity in females were comparable to the results of previous studies with all male samples. These results support the use of a constant set of cues in future treatment studies employing gender-balanced patient samples.

Prelude to passion: limbic activation by "unseen" drug and sexual cues.

Background The human brain responds to recognizable signals for sex and for rewarding drugs of abuse by activation of limbic reward circuitry. Does the brain respond in similar way to such reward signals even when they are “unseen”, i.e., presented in a way that prevents their conscious recognition? Can the brain response to “unseen” reward cues predict the future affective response to recognizable versions of such cues, revealing a link between affective/motivational processes inside and outside awareness? Methodology/Principal Findings We exploited the fast temporal resolution of event-related functional magnetic resonance imaging (fMRI) to test the brain response to “unseen” (backward-masked) cocaine, sexual, aversive and neutral cues of 33 milliseconds duration in male cocaine patients (n = 22). Two days after scanning, the affective valence for visible versions of each cue type was determined using an affective bias (priming) task. We demonstrate, for the first time, limbic brain activation by “unseen” drug and sexual cues of only 33 msec duration. Importantly, increased activity in an large interconnected ventral pallidum/amygdala cluster to the “unseen” cocaine cues strongly predicted future positive affect to visible versions of the same cues in subsequent off-magnet testing, pointing both to the functional significance of the rapid brain response, and to shared brain substrates for appetitive motivation within and outside awareness. Conclusions/Significance These findings represent the first evidence that brain reward circuitry responds to drug and sexual cues presented outside awareness. The results underscore the sensitivity of the brain to “unseen” reward signals and may represent the brains primordial signature for desire. The limbic brain response to reward cues outside awareness may represent a potential vulnerability in disorders (e.g., the addictions) for whom poorly-controlled appetitive motivation is a central feature.

Comparing attentional bias to smoking cues in current smokers, former smokers, and non-smokers using a dot-probe task

Much evidence documents that individuals with emotional and drug-use disorders demonstrate biased attention toward stimuli associated with their disorder. This bias appears to diminish following successful treatment. Two studies examined whether current cigarette smokers show biased attention toward smoking-related images compared with non-smokers (Studies 1 and 2) and whether this bias is less pronounced in former smokers (Study 2). Attentional bias toward cigarette-related photographs was examined using the dot-probe task. Pairs of images (one smoking-related) appeared side by side for 500 ms on a computer screen prior to the presentation of a probe (an asterisk) replacing one of the photographs. Subjects struck a key as quickly as possible to indicate the probe location. Attentional bias was defined as faster reaction times when the probe replaced the smoking-related image. In both studies, current smokers displayed significantly greater attentional bias toward cigarette stimuli than did non-smokers. Former smokers in Study 2 displayed an intermediate level of bias, but did not differ significantly in bias score from either of the other groups. These results support further use of the dot-probe task as a measure of attentional bias in non-abstinent smokers and in individuals undergoing smoking cessation treatment.

Can induced moods trigger drug-related responses in opiate abuse patients? ☆

This study investigated the ability of four hypnotically induced mood states (euphoria, depression, anxiety, and anger) to trigger craving and other drug-related conditioned responses in detoxified opiate abuse patients. Hypnotically induced depression produced significant increases in drug craving for opiates. Depression also tended to increase global self-ratings of opiate withdrawal. Other trends included increases in self-rated craving by induced anxiety and increases in withdrawal symptoms by induced anger. These results suggest that negative mood states, perhaps in the context of repeated attempts at self-medication, may become conditioned stimuli capable of triggering craving and other drug-related conditioned responses. The ability of depression to produce reliable effects in this particular patient group may reflect the high lifetime prevalence of depression diagnoses for this sample. The implications of these findings for therapeutic strategies are discussed.

Reliability and validity of 6-month timeline reports of cocaine and heroin use in a methadone population.

Fifty-nine persons addicted to heroin and maintained by methadone reported on daily heroin and cocaine use during 2 timeline calendar interviews administered 6 weeks apart. Retrospective reports covering 6 months were compared with urine samples taken weekly during the interval. Test-retest correlations were high and timeline estimates of drug use frequency were significantly correlated with the frequency of drug-positive urine results. Thus, timeline reports of drug-use frequency appeared both reliable and valid. Individual participants either over- or under-reported by an average of about 15%, and they did not identify instances of drug use with greater than chance accuracy when particular episodes of drug use occurred. These results support the use of timeline reports to make group comparisons of long-term drug use, but suggest that timeline data should not be used to identify specific drug-use episodes. Work with other drug-use population is necessary to extend these conclusions.

The Role of Attentional Bias in Substance Abuse

There has been much recent interest in the idea that drug users show biased attention toward drug-related events. Because drug stimuli produce conditioned responses that may motivate drug taking, biased attention toward these cues may play an important role in drug use and relapse following treatment. The performance of drug users on the Stroop task and visual dot-probe task has been interpreted as demonstrating attentional bias toward drug cues specific to an individuals drug use history. However, studies often fail to include necessary control groups or comparison stimuli, thereby making it difficult to definitively conclude that reported results reflect a specific attentional response to personally relevant drug events. Although promising, these initial studies need to be followed up with better controlled demonstrations of attentional bias and with studies linking bias levels to other measures of drug taking.

Relationships among physiological and self-report responses produced by cocaine-related cues☆

In response to cocaine cues, 150 subjects with a history of cocaine abuse showed decreases in skin temperature and skin resistance and increases in heart rate and reported craving, high, and withdrawal responses. These responses were consistent across four years of data collection. Craving reports were not consistently associated with either high or withdrawal responses, and many subjects endorsed increases in both high and withdrawal states. Correlations revealed no pattern of association among physiological variables and responding did not differ between subjects who did and those who did not report increases in each of the drug states. Finally, physiological variables did not predict reported drug states in discriminant analyses. Cocaine cue reactivity cannot be easily related to a unitary state of high, withdrawal, or craving. It is suggested that future studies focus more on the prediction and measurement of treatment outcome than on the form of cue responses.