Substance use and misuse.

SUBSTANCE USE & MISUSE , VOL. , NO. , – http://dx.doi.org/./..

ORIGINAL ARTICLE

Prescription Opioid Craving: Relationship With Pain and Substance Use-Related Characteristics

Lisham Ashrafiouna,b

aDepartment of Psychology, Bowling Green State University, Bowling Green, Ohio, USA; bVISN  Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, Canandaigua, New York, USA

KEYWORDS Craving; prescription opioids; pain; desire; opiates

ABSTRACT Background: Craving is associated with prescription opioid use in opioid-addicted pain patients. Objec- tives: This study evaluated the relationship between craving for prescription opioids and selected pain and substance use characteristics. Method: In this cross-sectional study, patients (N = 106) being treated for opioid dependence were recruited from one of three sites from December 2012 to April 2013. Participants completed the multi-dimensional Desire for Drugs Questionnaire to assess crav- ing, and other questionnaires to assess pain, substance use, and demographic characteristics. Data were analyzed using Pearson product-by-moment correlations, ANOVAs, and multiple linear regres- sions. Results: At the bivariate level, desire-and-intention to use prescription opioids and craving for relief from negative states were positively associated with both pain severity and interference. Lin- ear regression analyses revealed significant positive associations between Desire-and-Intention sub- scale scores and obsessive thoughts and compulsive behaviors associated with prescription opioids and pain severity. Negative Reinforcement subscales scores were positively associated with obsessive thoughts and compulsive behaviors associated with prescription opioids and the outcome expectan- cies of pain reduction, but not pain severity. Conclusions/Importance: This study extended previous research assessing the link between pain and craving by demonstrating that desire-and-intention, but not craving for the negative reinforcing effects are associated with pain severity after considering var- ious substance use characteristics. Additional research is needed to clarify the relationship between pain and aspects of craving while also considering pain-specific covariates. This study highlights that the multi-dimensionality of craving is an important aspect to consider when clinicians and researchers evaluate the relationship between pain and craving.

Prescription opioid misuse has increased dramatically in the past decade (Substance Abuse and Mental Health Ser- vices Administration, 2013a, 2013b). Research has shown that pain is common among patients with substance use disorders (SUDs), and in particular with opioid use dis- orders. For example, Trafton, Oliva, Horst, Minkel, & Humphreys (2004) reported that 52% of patients receiv- ing treatment for opioid addiction reported moderate to severe pain. Among SUD patients, pain has been associ- ated with higher rates of treatment drop-out, nonmedi- cal use of prescription sedatives, illicit substance use, and overdose (Bonar, Ilgen, Walton, & Bohnert, 2014; Britton, Wines, & Conner, 2010; Caldeiro et al., 2008; Larson et al., 2007; Potter, Prather, & Weiss, 2008; Trafton et al., 2004). In addition, Price, Ilgen, and Bohnert (2011) found that increased nonmedical prescription opioid use was associ- ated with greater pain severity.

Clinicians and researchers have hypothesized that craving may contribute to these poorer pain and

CONTACT Lisham Ashrafioun Lisham.Ashrafioun@va.gov VISN  Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center,  Fort Hill Avenue, Canandaigua, NY , USA.

addiction-related clinical outcomes (Martel, Dolman, Edwards, Jamison, & Wasan, 2014; Trafton et al., 2004; Wasan et al., 2009; Wasan et al., 2012).Although the definition of craving has been debated (Skinner & Aubin, 2010; Tiffany & Wray, 2012), researchers have defined craving as an intense subjective desire to use a sub- stance, in this case prescription opioids (see Rosenberg, 2009 for a review). Using various definitions of crav- ing, numerous models of craving have been proposed with many focusing on the negative reinforcing effects of substances (Skinner & Aubin, 2010). These negative reinforcement models generally propose that individuals are motivated to use substances to relieve a variety of negative experiences. For example, Khantzian, Mack, & Schatzberg (1974) proposed that individuals resort to opioid use to self-medicate negative emotions such as anxiety and depression. In the case of the relation- ship between craving and pain, negative reinforcement models of drug addiction might predict that prescription

This article not subject to US copyright law.http://dx.doi.org/10.1080/10826084.2016.1188948mailto:Lisham.Ashrafioun@va.gov

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opioids are reinforcing because they relieve, attenuate, help avoid, or help escape negative thoughts, emotions, and/or experiences related to pain (Garland, Froeliger, Zeidan, Partin, & Howard, 2013; Skinner & Aubin, 2010). For example, Garland et al.’s (2013) model of chronic pain and opioid addiction posits that individuals crave opioids to maintain psychological well-being when experiencing recurrent pain. Specifically, individuals use opioids to relieve pain-related stress and negative emotions. Cues paired with this opioid use (e.g., sight of pills) capture and hold one’s attention and such exposure elicits craving (Garland et al., 2013).

Despite empirical evidence and theoretical support of the relationship between craving and pain, research on their relationship is equivocal. For example, several inves- tigations have found no significant difference in pain lev- els among pain clinic patients as a function of craving (Martel, Dolman, et al., 2014; Wasan et al., 2009; Wasan et al., 2012). These studies are consistent with another investigation that found no relationship between crav- ing and pain severity among university students report- ing prescription opioid use in their lifetime (Ashrafioun & Carels, 2014). On the other hand, some investigators have found a relationship between craving and pain severity. For example, Rosenblum and colleagues (2003) found a significant relationship between craving and pain severity among patients in methadone maintenance and inpatient drug treatment who had chronic pain even after control- ling for withdrawal pain, demographics, number of drugs used, pain as a reason for use, chronic illness, psychiatric diagnosis and distress, and months in drug treatment.

Taken together, the methodological differences in these studies may provide important insights for the disparate findings. For example, there were differences in the setting from which participants were recruited (pain clinics, a university, inpatient drug treatment), the opera- tionalization and measurement of pain (e.g., current pain severity using a visual analog scale, average pain in the past 24 hours, worst pain level over the last 6 months, pain interference scores) and the measurement of craving (visual analog scales for current craving and craving in past 24 hours, multi-dimensional craving measure, craving for opioids vs. for any drug). Other differences might include order of pain and addiction onset and participant interaction with healthcare professionals over the course of their treatment for pain and/or addiction.

The current literature on the relationship between craving and pain could be extended and improved in sev- eral ways. Assessing prescription opioid craving utilizing a multi-dimensional measure of current craving would provide a more nuanced evaluation of craving compared to that of a single-item rating scale. In addition, recruit- ing participants with a range of pain severity scores from

several SUD treatment settings would increase the gen- eralizability of this line of research. Furthermore, it may be useful to examine other substance use-related factors that may contribute to or exacerbate craving for prescrip- tion opioids. Drug use severity and psychiatric sever- ity are two factors that may impact the extent to which one craves prescription opioids (e.g., Cicero, Lynskey, Todorov, Inciardi, & Surratt, 2008; Tiffany & Wray, 2012). In addition, there are theoretical, relationships between increased craving and endorsement of several cognitive- behavioral factors, such as outcome expectancies, and obsessive thinking; however, there is limited empirical investigations assessing these relationships (e.g., Franken, 2003; Ilgen et al., 2011; Marlatt, 1985).

Therefore, this study was designed to evaluate the associations between craving, assessed using a multi- dimensional questionnaire, and pain-related characteris- tics, cognitive-behavioral aspects of substance use, and psychiatric problems. Although this study did not assess specific chronic pain conditions and specific impacts on individuals’ psychosocial functioning, its broad objective was to assess pain intensity and craving in the context of other key substance use and mental health character- istics. Specifically, it was hypothesized that more intense craving would be positively associated with pain sever- ity, expected reduction of pain from prescription opioids, obsessive thoughts and compulsive behaviors related to prescription opioids, and drug use severity. In addition, it was hypothesized that the relationship between prescrip- tion opioid craving and pain severity would persist when controlling for the variance explained by those key sub- stance use characteristics described above.

Method

Participants and procedure

Following approval of the project by the Institutional Review Board, participants were recruited from Decem- ber 2012 to April 2013 at one of three addiction treatment centers: an urban community based outpatient substance abuse and methadone maintenance program that serves mostly those from the inner city of Detroit; (2) a sub- urban community-based behavioral health care agency that has inpatient and outpatient programs serving rural, suburban, and urban populations in northwest Ohio; or (3) an outpatient university-based addiction medicine clinic providing methadone and buprenorphine mainte- nance serving rural, suburban, and urban populations in Western New York. Individuals were eligible if they were between the ages of 18 and 65, were able to read English, were opioid dependent, and preferred prescrip- tion opioids as their primary drug of choice. Clinical staff

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Table . Background characteristics for the overall sample.

Mean (SD) or % of Background characteristics total sample (n = ) Recruitment site area

Toledo metro % Buffalo metro % Detroit metro %

Age (years) . (.) Sex

Male % Female %

Ethnicity Black % White % Other %

Education level No high school diploma or GED % GED % High school diploma % Some college, but did not graduate % Two or four year college degree %

# of days worked in past  . (.) Marital status

Never married % Separated % Divorced % Married % Widowed %

Pain experienced in past  months % Sources of paina

Shoulder % Face/mouth % Hip % Knee/leg % Foot/ankle % Neck % Middle back % Lower back % Abdomen/stomach %

# of pain locationsa . (.) Pain intensity levelb . (.)

Worst pain levela,b . (.) Least pain levela,b . (.) Average pain levela,b . (.) Current pain levelb . (.)

Pain interferencea,c . (.)

a In the past three months. b Based on a rating scale from  (no pain) to  (worst pain imaginable). c Based on rating scale from  (no interference) to  (completely interferes).

provided the researcher with individuals who had been using prescription opioids to further assess eligibility and interest. After providing consent, participants completed a multi-item craving questionnaire and a battery of other questionnaires (described below). To conclude, partici- pants were debriefed and given a card with $20 credit for compensation.

A total of 127 individuals were approached to assess their interest in participation, 12 of whom were not interested or were unavailable. Of the remaining 115 individuals, nine were excluded because they did not meet the eligibility criteria. Tables 1 and 2 display infor- mation regarding demographic, pain, and substance use characteristics on the 106 participants.

Table . Drug use characteristics for sample.

Mean (SD) or % of Drug use characteristics sample (n = ) Past  day drug use

Heroin % Prescription opioids % Sedatives/Hypnotics/Tranquilizers % Cocaine % Cannabis %

Addiction Severity Indexa

Psychiatric status composite . (.) Drug use composite . (.)

# of days in current treatment  to  days %  to  days %  to  days %  days or more %

Opioid maintenance therapy Buprenorphine/Naloxone % Methadone %

Age of st time used opioids . (.) Opioids usedb

Hydrocodone % Oxycodone % Codeine % Morphine % Hydromorphone % Oxymorphone % Fentanyl %

Routes of administration Orally % Intravenously % Nasally % Topically % Inhalation %

Method of procurement Given by friend/family % Stolen from friend/family % Stolen from a stranger % Drug dealer % Prescription from a doctor % Any non-medical procurement %

Last time used prescription opioids  to  days %  to  days %  to  days %  days or more %

OCDS-Rc . (.) PMEQd

Pleasure and social enhancement . (.) Pain . (.) Negative experience reduction . (.)

DDQe

Desire-and-intention . (.) Negative reinforcement . (.)

a Composite scores range from  to . b In past  days of use, not including maintenance treatment drug. c Obsessive Compulsive Drinking Scale-Revised; scores range from  to . d Pain Medication Expectancy Questionnaire; scores range from  to . e Desires for Drug Questionnaire; scores range from  to  for the Desire-and

Intention subscale and  to  on the Negative Reinforcement subscale.

Measures

Desires for Drug Questionnaire (DDQ) The DDQ, which originally written for heroin crav- ing (Franken, Hendriks, & Van Den Brink, 2002), was adapted to assess current craving for prescription opioids.

SUBSTANCE USE & MISUSE 1515

Respondents were asked to indicate their level of agree- ment with each of 13 items using a seven-point Likert Scale, so that higher scores indicated stronger craving. Franken et al. (2002) reported support for the validity and reliability for three subscales: (1) Desire-and-Intention (i.e., the desire and intention to use prescription opi- oids), (2) Negative Reinforcement (i.e., craving for the relief from negative states), and (3) Control (i.e., per- ceived control over use). In the present sample, internal consistency reliabilities were .90 for the Desire-and- Intention subscale, .80 for the Negative Reinforcement subscale, and .54 for the Control subscale. Given the relatively low internal consistency reliability for the Control subscale, only the Desire-and-Intention and Negative Reinforcement subscales were included in the analyses.

Obsessive Compulsive Drinking Scale-Revised (OCDS-R) Morgan, Morgenstern, Blanchard, Labouvie, & Bux (2004) revised the original OCDS (Anton, Moak, & Latham, 1995) that asks about experiences such as the fre- quency of obsessive thoughts of drug use, amount of dis- tress associated with thoughts of drug use, amount of time spent using drugs, drug-related interference in daily activ- ities, and perceived degree of control over drug use over the last week. Higher scores on the OCDS-R suggest more obsessive thoughts and compulsive behaviors associated with prescription opioids. Morgan et al. (2004) provided support for the psychometric properties for the OCDS-R. Internal consistency reliability for the current sample was .90.

Pain Medication Expectancies Questionnaire (PMEQ) The PMEQ is a 38-item measure designed to assess out- come expectancies of prescription opioids (Ilgen et al., 2011). Respondents are asked to rate the likelihood from 1 (“Not at all likely”) to 10 (“Very likely”) that they would use a pain medication for each of the 38 reasons divided into three subscales: (1) pleasure/social enhancement, (2) pain reduction, and (3) negative experience reduction. Higher scores suggest greater endorsement of prescrip- tion opioid use outcome expectancies. Ilgen et al. (2011) found initial psychometric support for these subscales. Internal consistency reliabilities in the current sample were .98 for the pleasure/social enhancement subscale, .92 for the pain subscale, and .97 for the negative experience reduction subscale.

Self-administered Addiction Severity Index (ASI) The drug use and psychiatric severity indices of the ASI were utilized (McLellan, Luborsky, Woody, & O’Brien, 1980). Computational formulas were used to generate

composite scores that range from 0 (no endorsement of any problems) to 1 (maximal endorsement of all prob- lems). Research supports the psychometric properties of the self-administered ASI (McLellan et al., 1980; Rosen, Henson, Finney, & Moos, 2000).

Brief Pain Inventory-Short Form The Brief Pain Inventory was used to assess a partici- pant’s pain severity and interference in daily functioning due to pain (Cleeland & Ryan, 1994). The first two ques- tions asked if respondents had experienced pain other than everyday types of pain (e.g., minor headaches, tooth aches, sprains) over the last three months and, if so, the location of the pain. Pain severity is calculated by aver- aging respondents’ worst, least, and average pain in the last three months, and their current pain each of which based on an 11-point rating scale from 0 (“No Pain”) to 10 (“Worst Pain Imaginable”). Respondents were also asked to rate how much their pain interfered with func- tioning in seven domains from 0 (“Does not interfere”) to 10 (“Completely interferes”). Cleeland (2009) provides support for the psychometric properties of the origi- nal BPI. Internal consistency reliabilities for the present sample were .93 for pain intensity and .89 for pain interference.

Demographics and prescription opioid questionnaire This questionnaire assessed participants’ demographic characteristics (e.g., race/ethnicity, age), and prescription opioid use history (e.g., opioids used, routes of adminis- tration).

Data analysis Frequency counts and means and standard deviations were calculated to summarize features of the sample. Pre- liminary analyses included the testing of bivariate rela- tionships between craving and other measured variables using t-tests, ANOVAs, and Pearson product-by-moment correlations. Primary analyses were tested using linear regression analyses with DDQ-Desire-and-Intention and DDQ-Negative Reinforcement scores as dependent vari- ables and with simultaneous entry of ASI-Drug Use and Psychiatric Indices, OCDS-R, PMEQ, and BPI pain sever- ity scores as the independent variables. Basic statistical assumptions were met and suggestions for decreasing the likelihood of overfitting were taken (Babyak, 2004). Variables entered in the regression models were selected because research has found them to be associated with craving (e.g., Cicero et al., 2008; Franken, 2003; Ilgen et al., 2011; Tiffany & Wray, 2012). Analyses were con- ducted with the entire sample regardless of one’s pain status.

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Results

Relationship between craving and other key variables

Demographics There were no significant associations between the crav- ing subscale scores and gender (tDesire-and-intention(103) = −1.00, p = .32; tNegativeReinforcement(103) = −.52, p = .61), race (tDesire-and-intention(103) = −1.83, p = .07; tNegativeReinforcement(103) = −.14, p = .89), level of education (FDesire-and-intention(3,97) = .99, p = .40; FNegativeReinforcement(3,97) = 1.44, p = .24), marital status (tDesire-and-intention(103) = .06, p = .95;tNegativeReinforcement(103) = .19, p = .85). In addition, there was no significant correlations between craving subscales scores and age (rDesire-and-intention(102) = .09, p = .36; rNegativeReinforcement(102) = −.08, p = .42) or days worked (FDesire-and-intention(102) = −.10, p = .34; rNegativeReinforcement(102) = −.03, p = .75).

Pain To identify whether current craving was associated with several aspects of pain, the associations between Desire- and-Intention scores and Negative Reinforcement scores with four specific pain-related variables were assessed (see Table 3). Scores on the Desire-and-Intention sub- scale were significantly greater among those participants who reported experiencing pain in the last three months (M = 25.5, SD = 13.4) compared to those who did not (M = 18.0, SD = 8.2), t(104) = −2.33, p < .05. Desire- and-intention of using prescription opioids was also sig- nificantly correlated with pain severity, r(104) = .35, p < .001, pain interference, r(102) = .28, p < .01, and num- ber of pain locations, r(104) = .20, p < .001. There was no significant association between pain reported in the past three months and Negative Reinforcement scores, t(104) = −1.35, p > .05 (see Table 3). However, Nega- tive Reinforcement scores were significantly, though not as strongly, associated with both pain severity, r(104) = .20, p < .05, and pain interference, r(102) = .23, p < .05, but not with number of pain locations, r(104) = .16, p > .05.

Prescription opioid use The relationships between craving subscale scores several prescription opioid use characteristics were also evaluated (see Table 3). Those who reported having used prescrip- tion opioids within the past seven days had significantly higher craving scores (M = 31.5, SD = 2.5) than those who reported having last used within in the previous 31 to 90 days (M = 16.4, SD = 2.8) and those who reported having last used more than 90 days previously (M = 17.4,

Table . Bivariate relationships between craving and pain and pre- scription opioid use characteristics.

DDQ-Desire-and- Intentiona

DDQ-Negative Reinforcementa

F-, t-, or r F-, t-, or r Characteristics M (SD) statistic M (SD) statistic

Pain experienced in past  months No . (.) − .∗ . (.) − . Yes . (.) . (.)

# of days since last use  to  days . (.) .∗∗ . (.) .  to  days . (.) . (.)  to  days . (.) . (.)  days or more . (.) . (.)

# of pain locationsb — .∗ — . Pain severity — .∗∗∗ — .∗ Pain interferenceb — .∗∗ — .∗ OCDS-Rc — .∗∗∗ — .∗∗∗ PMEQd

Pleasure/social enhancement

— .∗∗ — .∗∗∗

Pain relief — .∗∗∗ — .∗∗∗ Negative experience reduction

— .∗∗ — .∗∗∗

ASIe

Psychiatric status

— .∗ — .∗

Drug use — .∗ — .

∗∗∗p< .; ∗∗p < .; ∗p < .. a Desires for Drug Questionnaire; scores range from  to  for the Desire-and

Intention subscale and  to  on the Negative Reinforcement subscale. b In the past three months. c Obsessive Compulsive Drinking Scale-Revised. d Pain Medication Expectancy Questionnaire. e Addiction Severity Index

SD = 2.4), F(3,69) = 7.19, p < .001, partial η2 = .24. However, Negative Reinforcement from using prescrip- tion opioids did not differ as a function of the number of days since last use, F(3,69) = 1.03, p > .05, partial η2 = .04.

Furthermore, desire-and-intention to use prescrip- tion opioids was significantly associated with obsessive thoughts and compulsive behaviors related to prescrip- tion opioids, r(103) = .49, p < .001. This dimension of craving was also significantly associated with outcomes expectancies of pleasure and social enhancement, r(103) = .30, p < .005, pain reduction, r(103) = .43, p < .001, and anticipation of relief from negative experiences, r(102) = .28, p < .005. Similarly, craving for relief from neg- ative states was significantly associated with obsessive thoughts and compulsive behaviors related to about pre- scription opioids, r(103) = .44, p < .001. In addition, scores were significantly positively associated with out- comes expectancies of pleasure and social enhancement, r(103) = .43, p < .001,pain reduction, r(103) = .47, p < .001, and anticipation of relief from negative experiences, r(102) = .47, p < .001.

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Table . Regression analyses assessing the relationship between desires for drug questionnaire (DDQ) desire-and-intention and DDQ negative reinforcement subscale and drug use characteristics.

DV IV β B SE t-value

DDQ-Desire-and- Intention

OCDS-R . . . .∗∗ Pain severity . . . .∗ PMEQ-Pain Reduction . . . . ASI-Psychiatric status . . . . ASI-Drug use − . − .. − .

DDQ-Negative Reinforcement

OCDS-R . . . .∗ Pain severity . . . . PMEQ-Pain Reduction . . . .∗ ASI-Psychiatric status . . . . ASI-Drug use − . − . . − .

DDQ-Desire-and-Intention F(,) = ., p <., adjusted R = .; DDQ- Negative Reinforcement F(,) = ., p <., adjusted R = .; ∗∗p < .; ∗p < .;

Abbreviations: DV—Dependent Variable; IV—Independent Variable; OCDS- R—Obsessive Compulsive Drinking Scale-Revised; PMEQ—Pain Medication Expectancy Questionnaire; ASI—Addiction Severity Index.

Both psychiatric status, r(101) = .26, p < .01, and drug use severity, r(103) = .21, p < .05, were significantly asso- ciated with Desire-and-Intention scores. Although psy- chiatric status was significantly associated with Negative Reinforcement scores, r(101) = .33, p < .001, drug use severity was not, r(103) = .17, p > .05.

Regression analyses assessing unique associations between craving and selected pain and drug use characteristics Results of regression analyses revealed a significant model for DDQ-Desire-and-Intention scores, F(5,95) = 8.80, p <.001, adjusted R2 = .28 (see Table 4). Specifically, obses- sive thoughts and compulsive behaviors (β = .33), and pain severity scores (β = .20) were significantly positively associated with DDQ-Desire-and-Intention scores. This indicates that obsessive thoughts and compulsive behav- iors related to prescription opioids were the strongest cor- relate of desire-and-intention to use prescription opioids, although pain severity was also significantly associated with this type of craving.

For the regression with DDQ-Negative Reinforcement scores as the dependent variable, the overall model was significant, F(5,96) = 7.74, p <.001, adjusted R2 = .25. Obsessive thoughts and compulsive behaviors (β = .24) and the outcome expectancy of pain reduction (β = .29) were significantly associated with DDQ-Negative Rein- forcement scores (see Table 4). This suggests that greater craving to reduce negatives states was associated with obsessive thoughts and compulsive behaviors related to prescription opioids and greater expectancies of prescrip- tion opioids to relieve pain when controlling for the vari- ance explained by the other key characteristics.

Discussion

The current findings indicate that desire-and-intention to use prescription opioids and, to a lesser extent, craving for relief from negative states, were significantly asso- ciated with a number of pain-related characteristics, including having experienced pain over the past three months, pain severity, number of pain locations, and pain interference. When included in a regression model, the significant association between pain severity and desire- and-intention persisted after including key substance use characteristics (i.e., pain medication expectancies, obsessive thoughts and compulsive behaviors related to prescription opioids, drug use severity). This lat- ter finding is important because it suggests that those theoretically-driven substance use characteristics did not account for the relationship between desire-and-intention to use and pain severity.

This study provides further evidence that pain and craving are associated among addiction treatment patients (Rosenblum et al., 2003) and may provide an explanation for the inconsistent results in previous research on the relationship between pain and craving. This study examined the relationship between craving and pain using a multi-dimensional measure of craving, which provides a more nuanced evaluation of prescrip- tion opioid craving. Previous research has largely utilized single-item scales and respondents may find it difficult to characterize a complex phenomenon using a single numeral (Rosenberg, 2009). This finding highlights the importance of using a more sophisticated measure of craving among chronic pain and opioid-addicted patients.

The results of the current study provide partial sup- port for the hypothesis that pain would be associated with craving for prescription opioids to relieve negative states. Although this relationship was significant in the bivari- ate analysis, it was no longer significant after adjusting for other substance use-related variables. This is perhaps surprising given that addicted individuals might take pre- scription opioids for pain and/or other associated nega- tive thoughts or emotions (Garland et al., 2013; Martel, Dolman, et al., 2014; Martel, Jamison, Wasan, & Edwards, 2014). One possibility for the relatively weak relationship in this study was that the wording of the statements on the Negative Reinforcement subscale did not adequately assess the negative experiences of those with co-occurring pain and addiction. The Negative Reinforcement sub- scale consists of statements about general life problems (e.g., “I would feel as if all the bad things in my life had disappeared if I used prescription opioids right now”) and negative experiences focused on pain-related nega- tive experiences (e.g., anxiety, physical pain/discomfort,

1518 L. ASHRAFIOUN

pain catastrophizing) may better capture their experi- ences. Another possibility is that people’s beliefs about the effects of prescription opioids are more important than their pain severity. This would be consistent with the finding that pain reduction outcome expectancies were associated with craving to relieve negative states and pain severity was not. Additional research is needed to assess pain reduction outcome expectancies as a poten- tial mediator of pain and craving for relief from negative states.

Another novel contribution to the pain and craving lit- erature is that obsessive thoughts and compulsive behav- iors related to prescription opioids appear to be another key factor when considering craving for prescription opi- oids. This was among the strongest correlates of desire- and-intention to use prescription opioids and craving to relieve negative states, which is consistent with pre- vious research with heroin (Franken, 2002) and alco- hol (Bohn, Krahn, & Staehler, 1995; Flannery, Volpicelli, & Pettinati, 1999; Rosenberg & Mazzola, 2007). While these obsessive thoughts and compulsive behaviors may be conceptualized as craving, researchers have indicated that the construct measured in the OCDS is a “cogni- tive correlate” of craving that seems to be examining a different aspect of substance use dependence that is largely independent of craving (Anton, Moak, & Latham, 1996). This distinction is consistent with Franken’s model of drug craving, which posits that obsessive thoughts are one of several factors that are affected by and can affect one’s level of craving (Franken, 2003). Specifi- cally, he proposed that attentional bias to drug cues can elicit or enhance existing craving which, once acti- vated, can increase attentional bias, obsessive thoughts, and the likelihood of relapse (Franken, 2003).Further research is needed to better understand how pain sever- ity specifically may contribute to the relationship between obsessive thoughts, attentional bias, and current craving among individuals with chronic pain who are addicted to opioids.

These findings should be taken in consideration in the context of several limitations. For example, many of the participants were African American which may affect ratings of pain severity and craving. Carter et al. (2010) found that African Americans reported lower craving to smoke cigarettes compared to Caucasian counterparts. Furthermore, Riley and colleagues (2002) found that African Americans report greater emotional responses to pain and unpleasantness relative to Caucasians. These studies suggest that results observed in the current study may differ with a sample with a smaller proportion of African Americans. However, it is important to note that there were no differences in craving as a function of race in this study. Another limitation is that the majority of the

sample was receiving opioid maintenance therapy and no information was collected on the dosing or when those participants last took their medication. This is significant given that size and timing of the last dose of methadone can impact craving (Ilgen, Jain, Kim, & Trafton, 2008). In addition, withdrawal from opioids can impact pain severity given that symptoms include back and muscle aches, cramps, and joint pain among others. The inter- pretation of the results is also complicated by the varying time points in which the variables were measured (e.g., current craving, past year drug use severity, three-month pain scores, past-week obsessive thoughts and compul- sive behaviors). For example, assessing one’s craving in the past three months may depict a different relationship with pain intensity in the past three months compared to one’s current craving. In addition, this study was lim- ited in its sample size, which restricted the number of variables that could be accounted for in the multivariate analyses.

When considering the findings of this investigation in the context of the extant literature on pain and craving, this study does not provide definitive evidence for the pain-craving relationship but does provide some impor- tant insights. This adds to the evidence that pain and craving are associated among patients involved in opioid maintenance programs. In this study, pain and craving were both measured as continuous variables rather than dichotomous or categorical variables, which decrease loss of variability subsumed within groups, effect size, power, spurious statistical significance, and measurement reliability. Nonetheless, perhaps setting may be impor- tant such that substance use disorder treatment centers are places in which patients have their drug of choice (e.g., oxycodone, hydrocodone) taken away thus increas- ing their pain and craving for it. On the other hand, pain clinics, where several studies have recruited par- ticipants, may be viewed as a place in which patients receive their drug of choice and thus their craving and pain is reduced with receipt of the opioids. The current study also encourages further research recruiting African Americans, given that previous research was primarily in Caucasians. Furthermore, it also encourages further use of multi-dimensional measures, such as the DDQ. Single-item measures are advantageous due to their brevity; however, the DDQ takes minutes to complete and can provide more specific information. Nonetheless, the modest relationship between pain severity and crav- ing after accounting for only select substance use char- acteristics highlights that clinicians should be cognizant of not overestimating the relationship between pain and craving. Clinicians and patients may be better served by addressing the relationship between craving and pain medication expectancies and/or obsessive thoughts and

SUBSTANCE USE & MISUSE 1519

compulsive behaviors given the more robust relationships with these other substance use factors compared to pain. Future research should also consider other pain-related factors, such as pain condition and cognitive-behavioral constructs of pain. Research has found a significant rela- tionship between pain catastrophizing and craving (Mar- tel, Jamison, et al., 2014) and studies could also assess the association between craving and use and pain-related coping skills and pain avoidance. In addition, although research has demonstrated that craving prospectively pre- dicts prescription opioid use (Tsui, Anderson, Strong, & Stein, 2014), less is known regarding longitudinal trajec- tories of opioid and nonopioid pain interventions on crav- ing. This type of research could provide useful informa- tion regarding the relative effectiveness of various pain treatments on craving and the onset of prescription opi- oid dependence. This may also provide an opportunity to understand provider contributions to patient prescrip- tion opioid outcome expectancies (e.g., patient knowledge of opioid-induced hyperalgesia and withdrawal pain). In sum, this study found that pain severity was associ- ated with desire-and-intention to use prescription opi- oid after accounting for key substance use characteristics. For future studies, multi-dimensional craving measures should be used and pain-related factors should also be considered.

Glossary

Craving: An intense subjective desire to use a substance. Negative reinforcement craving: Craving for the relief from neg-

ative states. Obsessive compulsive substance use: Frequent and distressing

preoccupation with using substances that interferes with daily activity and is associated with little control over drug use.

Pain interference: The extent to which pain interferes with var- ious aspects of one’s life such as mood, engagement in daily activities, etc.

Declaration of interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of the article.

Funding

This work was funded by the American Psychological Associ- ation, the APF/COGDOP, and the Katzner Graduate Student Research and Professional Development Award.

Notes on contributor

Lisham Ashrafioun, PhD, is a post-doctoral fellow at the Department of Veterans Affairs VISN 2 Center of Excellence for Suicide Prevention and the Department of Psychiatry at the University of Rochester Med- ical Center. Dr. Ashrafioun’s research interests are related to the intersection between sui- cidal thoughts and behaviors, substance use, and pain.

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  • Abstract
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  • References
 

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