Saturday, June 2, 2012

       In their article "Applying Extinction Research and Theory to Cue-Exposure Addiction Treatments," Conklin and Tiffany discuss the effectiveness of the cue-exposure extinction treatments currently in use for disorders such as substance abuse and other addictions, and suggest directions for improvement, based on new research performed with animals.
Conklin and Tiffany (2002) begin by stating that it has been known for a while now that cue exposure is an effective means of treatmeant for individuals addicted to drugs (Hammersley, 1992).  As evidence for this, they present the fact that "... drug-use and relapse are often strongly cue and context-specific" (Conkin and Tiffany, 2002, p. 155). This theory is compatible with commentary offered by Domjan (2009), in which he states that "It has been known for a long time that the administration of a drug constitutes a conditioning trial which cues related to drug administration are paired with the pharmacological effects of the drug," (Domjan, 2009, p. 115). It is also consistent with evidence obtained from a study by Siegel (2000), in which he found that an initial self-administration of a smaller amount of a drug (which, among drug addicts, is commonly followed-up by the self-administration of a larger amount of the same drug, leading to the initial, smaller amount of the drug becoming a conditioned stimulus predicting an impending administration of a larger amount of the same drug). When these lines of evidence are taken together, it becomes clear that, if the power of contextual cues related to drug self-administrations to elicit cravings could somehow be extinguished, individuals formerly addicted to drugs might have an easier time remaining abstinent from addictive substances. The present study by Conklin and Tiffany (2002) explores how this might be accomplished.

       Conklin and Tiffany (2002) go on to describe how the process of cue-exposure treatment for drug addiction currently proceeds. According to them, it involves repeated exposure to contextual stimuli associated with drug use, with the crucial change that, unlike in the addict's previous episodes of drug self-administration, in these instances, presentations of such cues would not be reinforced with the administration of the drugs themselves. The hope is that, eventually, such repeated exposure to the cues and the unexpected absence of the drug itself will lead to extinction of the drug cravings normally triggered by drug cues.
       Evidence that drug-related cues do indeed trigger drug-related cravings in the manner described by Conklin and Tiffany (2002) has been obtained from a study performed by Ehrman, Robbins, Childress, and O'Brien (1992). That study involved two groups of men: one group who had a history of using cocaine (but not heroin), and a control group of men who had no history of using either cocaine or heroin. The study involved exposing the participants to several conditions, including that of exposing them to cues related to cocaine, through such means as having them listen to audiotapes and watch videos of other individuals involved in cocaine-related actions, as well as having them pretent to use cocaine by acting out the motions involved in doing so. The participants were then exposed to another test condition in which they performed the same actions and were exposed to the same cues, although this time as related to the use of heroin (a drug to which they had never been addicted, and, thus, one to which they should show a greatly attenuated reaction, in comparison with their reaction to cocaine). Finally, the participants were exposed, in the same manner, to a set of control stimuli unrelated to the use of any drug. The results of the study showed that only the participants with a history of cocaine use showed a strong increase in heart-rate as well as a high degree of self-reported cravings for cocaine and symptoms of cocaine withdrawal. The fact that these symptoms were not evident among the same participants when they were exposed to the other two sets of stimuli (those related to heroin, which they did not have a history of using, and those related to neutral, non-drug-related control stimuli), indicates that drug-related cues trigger strong drug cravings for a drug to which those cues are related, and that this occurs only among individuals with a previous history of having used that particular drug. This serves as one line of evidence justifying Conklin and Tiffany's (2002) emphasis of extinguishing drug cravings among drug addicts by extinguishing the power of drug-related cues to elicit drug-related cravings.

       Conklin and Tiffany (2002) present the rationale for the use of cue-exposure treatments for drug addiction as being rooted in a classical conditioning model, in which "the drug is the unconditioned stimulus (US) and the drug effects are the unconditioned responses (UR). The conditions under which the drug is used become conditioned stimuli (CS) that evoke conditioned responses (CR) that moderate or mediate drug seeking and drug consumption," (Conklin and Tiffany, 2002, p. 156). Such a conceptualization is consistent with the above-cited studies by Siegel (2000) and Ehrman et al. (1992).
 Interestingly, research by O'Brien, Childress, McLellan, and Ehrman (1990) has also found that the procedures designed to extinguish the potential of drug-related stimuli to elicit drug-related cravings can indeed be successful in humans; in that study, thirty participants who had formerly been dependent on cocaine but had now been abstinent for some time were initially exposed to two conditions: one in which they were exposed to cues related to the self-administration of cocaine, and another condition in which they were exposed to neutral stimuli. The results of these baseline measures indicated that the participants showed a heightened sensitivity and responsiveness to cues related to the self-administration of cocaine, as compared to the neutral stimuli. In response to exposure to cues related to cocaine self-administration, the participants experienced heightened physiological arousal, along with increases in self-reported symptoms of cocaine cravings, cocaine-related "highs," and withdrawal symptoms. Significantly, these reactions were not present during their exposure to the neutral control stimuli. During the treatment phase of the experiment, the participants were exposed to a cue-exposure addiction treatment in which they were repeatedly exposed to cues related to the self-administration of cocaine, without actually being exposed to the drug itself. Such treatment was performed for a total of fifteen one-hour sessions. Crucially, the participants reported a complete extinction cocaine-related cravings by the end of the fifteenth session of cue-exposure treatment, indicating that the cue-exposure treatment had been successful in eliminating the capacity of the cocaine-related stimuli to stimulate drug-related cravings in these participants! Furthermore, the experiences of "highs" and cocaine-related "withdrawal symptoms" which the participants had initially reported were eliminated by the end of the sixth week of treatment- a fact serving as further evidence of the efficacy of this treatment. Furthermore, the results of that study indicated that participants in the experimental group (the ones who received this cue-exposure treatment) showed a greater ability to maintain the results obtained over the course of treatment than did the participants in the control group, who had been exposed to standard treatment for cocaine addiction alone (i.e.,without the addition of the cue-exposure treatment), (O'Brien et al., 1990). These results indicate that the cue-exposure treatment therapy discussed by Conlin and Tiffany (2002) is indeed promising.

Interestingly, Conklin and Tiffany (2002) also note that the methods by which researchers have orchestrated cue-exposure therapy for drug addiction have largely been consistent across different types of addictive substances. In their words, "Typically, addicts are exposed to personally-relevant drug cues either in vivo (i.e., handling drug paraphernalia) or imaginal (i.e., imagining being in a situation typical of past drug use)," (Conklin and Tiffany, 2002).
       Given this, it might be interesting to conduct an investigation in regards to which of these two methods of exposure is more effective. For instance, if the objective, physical exposure to drug-related cues turns out to be more effective, then cue-exposure treatment should, in the future, focus mainly on this method of exposure; if, by contrast, the imaginal treatment turns out to be equally or perhaps even more effective, then this might be an indication that the roots of drug addiction are more cognitive in nature, and that cue-exposure treatment should include more cognitive and perhaps even more motivational components in the future.

In their review of past studies of cue-exposure treatment for drug addiction, Conklin and Tiffany include fifteen studies involving a variety of addictive substances, including "opiates (N= 6), nicoteine (N= 5), alcohol (N= 5) and cocaine (N=1), " (Conklin and Tiffany, 2002, p. 157). They also note that one study included in their review involved both participants addicted to cocaine and participants addicted to opiates. In regards to their selection criteria, Conklin and Tiffany (2002), "... any treatment involving exposing addicts to cues associated with past drug use in an attempt to extinguish learned responding to those cues," (Conklin and Tiffany, 2002, p. 156), although they did not include "... studies [that] involved exposure to drug cues for the purpose of replacing a learned response with an alternative response (e.g., covert sensitization)," (Conklin and Tiffany, 2002, p. 157). Furthermore, they note that while approximately half of the studies were conducted with individuals maintaining abstience from the addictive substances during the course of the study, many of the studies involved participants who were still involved in ingesting the drug of abuse during the course of the study (the specific reasons for this varied widely across studies). The most prevalent mode of presentation of drug cues over the course of the studies was "in vivo," (Conklin and Tiffany, 2002, p. 157), a mode of presentation which was used in fifteen of the eighteen studies. Conklin and Tiffany (2002) operationally defined this mode of drug cue presentation as "... including handling one's own or simulated drug paraphernalia and drug itself, ingestion of actual drug (e.g. priming doses of alchol) or simulated drug (e.g. injecting saline), preparing drugs for use (e.g. lighting a cigarette, 'cooking up' and 'tying off'), and outside exposure in an environment associated with past drug use," (Conklin and Tiffany, 2002, p. 157). Other modes of presentation (which were often presented in combination with that mode), included the presentation of photographic cues (i.e., pictures of addicts actively engaged in abusing drugs), video cues (i.e., videos of addicts onvolved in obtaining or ingesting drugs), audio cues (i.e., those involving recordings of individuals discussing their drug-taking experiences), as well as imaginal cues (which involved asking participants to visualize a drug-taking experience). While the number of cue-exposure sessions in the studies reviewed by Conklin and Tiffany (2002) varied, as did the length of the treatment sessions and the number of cues a participant was exposed to over the course of any single session, the studies were consistent in that they used one of three possible methods to determine the length of time for which participants in a study were exposed to any partilcular drug-related cue. Specifically, the three possible methods for determining how long a participant was to be exposed to a particular drug-related cue included "(1) a specific amount of time was predetermined... (2) a specific acttion was required and when it was completed exposure to that cue ended... and (3) the treatment was terminated when the participant's self-reported craving/ urge level dropped to half the peak intensity experienced during exposure to the target cue," (Conklin and Tiffany, 2002, p. 157). Furthermore, "Treatment sessions either occurred for a set number of days... or were distributed across a specific number of days," (Conklin and Tiffany, 2002, p. 157).

Conklin and Tiffany (2002) evaluated the effectiveness of the cue-exposure treatments among the studies they reviewed by "...applying meta-analytical techniques to the abstinence or drug-use reduction results from each treatment outcome study," (Conklin and Tiffany, 2002, p. 157). All of the studies included in their meta-analysis met the following two selection criteria: "(1) the study included a control or comparison treatment group and (2) a post-treatment follow-up, during which abstinence or drug use was measured, was reported for each group," (Conklin and Tiffany, 2002, p. 159). Conklin and Tiffany (2002) then used "DSTAT, a computer program for meta-analytical reviews of research literature," (Conklin and Tiffany, 2002, p. 159), to compute the effect sizes for each of the studies represented in their review. As Conklin and Tiffany (2002) went on to explain, "Effect sizes showing greater abstinence or less drug use for the cue-exposure treatment group were assigned a positive value, while negative values denoted less abstinence or greater drug use for the cue-exposure group," (Conklin and Tiffany, 2002, p. 159). These effect sizes were then corrected for bias and tested for homogeneity. Results indicated that "The overall effect-size of cue-exposure treatment (d= 0.0868; 95% confidence interval - 0.11 ± 0.28) was not significant. The Q statistic reached significance (Q(9)= 16.078; p= 0.0413), indicating that effect sizes were not consistent across studies," (Conklin and Tiffany, 2002, p. 159).

In light of these results indicating that cue-exposure treatment for preventing relapse among drug addicts is, at the present time, less than efficacious, Conklin and Tiffany (2002) go on to present suggestions for its improvement. They justify such efforts with their commentary that "... there is a pervasive belief that if the optimal parameters for cue-exposure could be discovered (e.g. the right cues are chosen, the best number of sessions are conducted, it is combined with the right psychotherapy) addiction treatment might have a new 'gold standard' for treatment efficacy," (Conklin and Tiffany, 2002, p. 159), and they present recently-obtained results from animal studies involving extinction of learned behavior as an indication of the best means to go about doing so.

Conklin and Tiffany (2002) go on to descrbe how, originally, extinction was viewed as a weakening or undoing of a CS-US association first learned during acquisition. This is the way extinction had been conceptualized by, for instance, by Rescorla and Wagner (1972), as cited in Conklin and Tiffany (2002). Conklin and Tiffany (2002) go on to explain that, currently, extinction is viewed not as an unlearning of a previously-conditioned association, but rather with the idea that, "...during extinction, CS-US learning remains intact, but new associations develop to the original CS," (Conklin and Tiffany, 2002, p. 159). As Conklin and Tiffany (2002) go on to explain, "From this perspective, the effectiveness of extinction, and similarly the efficacy of cue exposure, is determined by the probability that exposure to an extinguished drug cue post treatment will evoke behavior learned during extinction (i.e., abstinence) rather than that learned during original conditioning (i.e., drug use), (Conklin and Tiffany 2002, p. 159).
This thesis is in line with Domjan's (2009) commentary that, rather than being simply the unlearning of an originally-acquired association, extinction involves the learning of a new "inhibitory S-R association," (Domjan, 2009, p. 300). According to Domjan, the inhibitory nature of this newly-formed association arises from the "frustrative effects of the unexpected absense of reward," (Domjan, 2009, p. 300).
An example of how extinction conditions [which, as Domjan (2009) explains, can involve either a lack of presentation of a US after the presentation of the CS normally predicting that US, or a failure to reward an instrumnetal response with the reward that is normally contingent upon the organism making that response] can result in frustration, and, ultimately, in the inhibition of behavior is presented in a study performed by (Neuringer, Kornell, and Olufs, 2001). That study involved two groups of rats, divided into an experimental and control group. During the acquisition phase, all of the rats were rewarded for each series of three responses they made using the levers and other equipment provided. However, the rats in the experimental group were reinforced only if they varied the order of the three responses they made, whereas the rats in the yoked control group were rewarded for making three responses, regardless of the specific order in which they made them. After the rats had developed a well-established pattern of responding, the second phase of the experiment began. In this phase, all of the rats were shifted to extinction conditions, in which they were not reinforced with food no matter what pattern of lever-presses they employed. The results indicated the expected difference in terms of variability between the two groups (i.e., the rats who were rewarded for varying their responses did so much more than did rats that were not reinforced for doing so). However, what is really interesting about the results of this study by Neuringer et al. (2001) is that the shift to extinction conditions resulted in a significantly reduced rate or responding for both subjects (evidence for the formation of an inhibitory assocation following the introduction of extnction conditions!) as well as an increase in the variability of responses made by both groups of subjects (Neuringer et al., 2001). Furthermore, as Domjan (2009) notes in his commentary on this study, the fact that these were the only effects is evidence that extinction "... did not alter the basic structure of the behavior," (Domjan, 2009, p. 302)- a fact which is in itself further evidence that extinction doesn't involve the unlearning of a previously acquired behavior, since, had that been the case, the effects of the introduction of extinction conditions would have been much more drastic!

Furthermore, Conklin and Tiffany (2002) identify several factors which pose challenges for research attempting to translate results from extinction studies involving animals into results applicable to human participants attempting to overcome their drug dependence. These include "... the renewal effect, spontaneous recovery, reinstatement, and failure to extinguish the most salient conditioned cues," (Conklin and Tiffany, 2002, p. 159).
Conklin and Tiffany (2002) begin their discussion of such challenges by describing the renewal effect by citing the fact that the context in which extinction was conducted can play a major role in determining the extent to which animals will maintain the same failure to respond they learned during extinction training when faced with a new context. To this ends, Conklin and Tiffany (2002) operationally define "contexts" as being the environmental locations in which drug-taking takes place,and the presence of cues which normally immediately precede a drug self-administration. As they go on to explain, contexts can play a crucial role in the expression of the learned behaviors involved in drug addiction; for instance, if a the behavior of repeated drug self-administration is acquired in one context and extinguished in another, a switch to a different context following extinction can often lead to a re-emergence of the previously-acquired drug-taking behavior! (Bouton and Ricker, 1994). Unfortunately, renewal often occurs when former drug addicts return to their original home location following the completion of their drug treatment, resulting in relapse (Conklin and Tiffany, 2002).
        Conklin and Tiffany (2002) go on to explain the mechanisms that might be responsible for the appearance of this effect. Apparently, "... following extinction, the CS has acquired two meanings: one associated with the original conditioning and one associated with extinction. The context in which the cue is presented determines which of these two meanings will be expressed," (Conklin and Tiffany, 2002, p. 160). This explanation underscores the fact that extinction involves the learning of another, inhibitory assocation, on top of the association that has originally been learned during acquisition! It also presents a significant challenge for researchers attempting to extinguish renewal effects among previous drug addicts.
       One means of decreasing the detrimental effects of renewal upon abstinence from drugs has been to attempt to extinguish a problem behavior in the same context as the one in which it was originally learned. While this does indeed result in decreased renewal effects, unfortunately, the decreased rate of renewal effects which results is often specific to the context in which the acquisition and subsequent extinction took place, and does not generalize to other contexts. A study by Bouton and Ricker (1994) involving rats confirmed this effect. In that study, Bouton and Ricker (1994) found that rats who had acquired a particular pattern of conditioned responding in one context and then had that pattern of responding extinguished in that same context, they did indeed fail to demonstrate renewal effects in that context. However, when, following this, these same rats were tested in different context, they readily showed renewal effects. Furthermore, Bouton and Ricker(1994) found this to be true in both experiments involving conditioned suppression and experiments involving appetitive conditioning. Bouton and Ricker(1994) also found these results to hold true when both contexts were equally familiar and equally associated with reward (or equally associated with both reward and lack thereof). As Bouton and Ricker (1994) went on to explain, and both Conklin and Tiffany (2002) and Domjan (2009) also commented, these results indicate that the effects of acquisition generalize more easily than do the effects of extinction, because the effects of extinction are more context-dependent. This presents bad news for therapies aimed at the extinction of conditioned behaviors.
       Luckily, however, there is a more effective means of preventing the renewal effect from occurring; a study by Gunther (1998), for instance, found that the effects of comparator stimuli could be dependent on context in the same way as could regular Pavlovian associations. As Conklin and Tiffany (2002) argue, this is one among several lines of evidence that when extinction is trained in several contexts, its effects generalize more readily than when it is trained in a single context (in other words, when extinction training is conducted in several contexts, the renewal effect is less likely to occur than when extinction training is conducted in only one context).
       As Conklin and Tiffany (2002) mention, this presents several interesting new questions, including one in regards to how many different contexts extinction should optimally be trained in, and whether the additive effects of conditioning extinction in different contexts ultimately plateau, and even whether the optimum number of contexts in which extinction should ideally be trained might vary between drugs.
       Interestingly, another study also conducted by Bouton and Brooks (2003) found that pairing a cue with the context in which extinction is conducted and then having that cue serve as a reminder of the extinction context can significantly reduce renewal effects. This finding led Bouton and Brooks (2003) to conclude that renewal effects often appear due to a failure upon the part of the subject to remember the context of extinction when they returned the context of acquisition  (i.e.,when they returned to the outside world after completing treatment at an inpatient facility for instance). This is consistent with Conklin and Tiffany's (2002) explanation (described above) of how, over the course of both acquisition and later extinction conditioning, the CSs associated with drug use (i.e., the needles used in heroin injections) acquire the capacity to elicit memories of both acquisition and extinction - and how, all too often, they stimulate memories of acquisition (as opposed to extinction) when former addicts return home following inpatient treatment.
Conklin and Tiffany (2002) go on to suggest several means of enhancing the effectiveness of such a cue, including those of having the reminder cue be novel and paired only with extinction (to avoid having it become associated with multiple processes, in the same manner that contextual cues, for instance, come to be associated with both acquisition and extinction), and, to the same ends, having it only be used in situations in which the former addict really needs a reminder of the extinction context (again, in oder to avoid a situation in which the reminder cue comes to be associated with too many different stimuli, resulting in its becoming less effective). Domjan (2009) presents several possible examples of such cues, including a calling card with the phone number of the patient's therapist, whom the patient is instructed to call if they feel that they are in danger of relapsing (in this situation, the calling card, unbenknownst to the patient, also serves the secondary function of calling forth memories of the extinction context!)

Conklin and Tiffany (2002) also discuss another phenomenon which can wreak havoc on results obtained during extinction training- namely, the phenomenon on spontaneous recovery, which, as they mention, can occur if a conditioned stimulus is presented after some time has been allowed to pass since the completion of extinction training.As Conklin and Tiffany (2002) explain, the crucial factor in spontaneous recovery is the passage of time between the end of extinction training and the time at which a subject is re-exposed to a conditioned stimulus.
Thus, Conklin and Tiffany (2002) argue that the effects of extinction can also be optimized via the manipulation of both the time intervals between sessions during which a participant is exposed to a cue to which extinction is being conditioned and the time intervals between the exposures to a particular cue within a particular session. To this ends, Conklin and Tiffany (2002) criticized many animal studies for conducting extinction via the presentation of multiple different types of cues within a single session, with each cue being presented only briefly, arguing that such brief presentations of each cue prevent any one cue from being extinguished completely. Instead, they argue that extinction should proceed with one cue at a time, with the target cue being presented multiple times within a single experimental session.
      Additionally, the results of a research conducted by Rescorla (2004) which involved  several experiments, including a classical conditioning procedure to train appetitive conditioning in rats, a separate experiment involving conditioning of instrumental responding in rats, and a sign-tracking experiment with pigeons found that the magnitude of spontaneous recovery is greater when shorter intervals of time are allowed between the intial acquisition training and later testing. These results stand in contrast to results obtained by a study performed by Myers, Ressler, and Davis (2006), on fear extinction. In that study, Myers et al. (2006) examined the effects of the spacing between acquisition trials and extinction trials on the extinction of fear. Myers et al. (2006) took as the basis for their study the understanding the acquisition of conditioned fear causes changes in the brain at the level of synaptic connections which can be "unlearned" (where "unlearned" is operationalized as the changes no longer remaining visible) a short time after the fear learning takes place, but not following the passage of a longer amount of time. Given these premises, they hypothesized that perhaps newly-acquired fears can be successfully extinguished (i.e., with the effects of spontaenous recovery, renewal, and reinstatement not taking hold) if extinction conditioning is performed shortly after the acquisition of a fear, but not if a longer period of time is allowed to pass. Their results (obtained from a behavioral experiment conducted with rats) were consistent with this hypothesis, showing that, in cases where extinction conditioning was conducted 24-72 hours after the original acquisition of fear, the subjects showed the expected patterns of renewal, spontaenous recovery, and reinstatement effects (all of which are challenges to successful extinction). By contrast, Myers et al. (2006) also found that, among the rats with whom extinction was conducted only between 10 and 60 minutes following initial acquisition, these effects were far less likely to occur. On the basis of these findings, Myers et al. (2006) concluded that, in order to increase the effectiveness of extinction procedures to optimum levels, it might be useful to conduct extinction procedures as soon as possible following acquisition. While the fact that these studies came out with such contradictory results might seem strange at first, Domjan (2009) effectively resolves this contradiction by explaining that the designs of the two studies were very different, with the study by Myers et al. (2006) being a within-subjects investigating fear conditioning, and the research by Rescorla (2004), by contrast, utilizing a between-subjects design to explore various types of appetitive conditioning.

In terms of translating results from animal studies such as those by Myers et al. (2006) and Rescorla (2004) into successful extinction treatment for people recovering from drug addictions, Conklin and Tiffany (2002) reccomend extinguishing one cue stimulus at a time, and allowing for the passage of sufficient amount of time for spontaneous recovery to occur, with the idea being that, once it occurs, extinction treatment would then be conducted once again, with the process repeating up until such a time as when responding to that particular cue is extinguished entirely. Furthermore, they recommend that after responding to a particular cue has been entirely extinguished further extinction training to that cue should still be conducted, following the passage of a significant amount of time. Finally, Conklin and Tiffany (2002) argue that the specific patterns according to which extinction training should ideally be conducted likely vary across subjects, and should be determined according to each individual's pattern of responding. They ackowledge, however, that until the specific mechanisms underlying extinction training are better understood, it will be difficult to put these recommendations into practice.

Conklin and Tiffany (2002) continue their discussion  cue-exposure addiction treatments by turning their attention to the phenomenon of reinstatement, which is another threat to the long-terms maintenance of extinction. Specifically, they define reinstatement as "... a phenomenon whereby responding to an extinguished CS re-emerges as a consequence of post-extinction exposures to a US," (Conklin and Tiffany, 2002, p. 162). They go on to explain that "After a Condtioned Stimulus has been extinguished, responding can be reinstated by presenting the Unconditioned Stimulus alone in the conditioning context. When the extinguished Conditioned Stimulus is subsequently presented alone in that context, conditioned responding can then occur as it did prior to extinction," (Conklin and Tiffany, 2002, p. 162).
In a study performed by Carroll and Comer (1996) for instance, a drug was administered to a group of animals. After a while, administrations of the drug were replaced with those of a vehicle (i.e., a CS for the drug) by itself. Over time, this resulted in the extinction of responding. Following this, the researchers administered various interoceptive and exteroceptive stimuli to the animals, in order to see if they would result in the animals making the same sort of responses as they did to the reinforcing effects of the drug itself. The study especially focused on the use of interoceptive stimuli, such as priming injections of the drug that had been previously used in the same study, as well as other drugs. The results of the study indicated that priming injections of a drug, especially a drug of the same class as the drug to which conditioned responding had previously developed during acquisition, (and later been extinguished during extinction), did indeed result in the the reinstatement of the animals' previous response. Interestingly, Carroll and Comer (1996) also noted that the magnitude of the reinforcement effects was directly proportional to the magnitude of the interoceptive stimuli administered, and that other factors- namely, restricted food intake and stress- also increased the magnitude of the reinstatement effects, at least studies of animals that had been previously addicted to cocaine. The results of this study are interesting both in that they offer another line of evidence [in addition to that offered by the study conducted by O'Brien et al. (1990) that exposing addicts to even a small amount of the drug to which they were previously addicted to can trigger relapse- and in that they suggest that other environmental factors, in addition to exposure to drug-related cues and contextual stimuli, can trigger relapse. Furthermore, the fact that, as Carroll and Comer (1996) mention, relapse can also be triggered by stress and inadequate nutrition seems to imply that perhaps individuals newly exiting rehabilitation facilities should be provided with a gradual reintroduction to their previous living environment and responsibilities, so as to preclude the possibility of the stress of the transition causing them to relapse.
       In regards to the possibility of reinstatement effects triggering relapse following extinction of drug-taking behaviors among newly-recovering addicts, Conklin and Tiffany (2002) mention that "Although it may not be common for addicts to experience non-contingent re-exposure to illegal drugs, it is common for addicts in recovery to be exposed to drugs such as painkillers or cough medicines that may contain narcotics or alcohol," (Conklin and Tiffany, 2002, p. 162). These incidental exposures, combined with possible lapses in the addicts' own willpower and the breaches in abstinence that may result in the reinstatement of conditioned responding to drug cues. As a result of this and other possibilities for relapse following the extinction of drug self-admnistration behaviors, Conklin and Tiffany (2002) suggest, based on research conducted with animals, that one of the most effective means of enhancing the robustness of extinction treatments, in terms of preventing relapse, may be to combine them with other forms of psychotherapy.


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