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. 2025 May 26;29(6):e70048. doi: 10.1002/ejp.70048

The Mediating Role of Psychological Flexibility and Inflexibility Between Impulsivity and Opioid Misuse in People With Chronic Noncancer Pain

Victoria Barrado‐Moreno 1,2,✉, Rosa Esteve 1,2, Lance M McCracken 3, Carmen Ramírez‐Maestre 1,2
PMCID: PMC12105413  PMID: 40418088

ABSTRACT

Background

The prescription of opioid medication is a frequent therapeutic approach in chronic noncancer pain, as is misuse of prescribed opioids. There is previous evidence for associations between personal variables such as impulsivity and opioid misuse. Psychological flexibility and inflexibility have also been associated with pain‐related outcomes and opioid misuse. The aim of this cross‐sectional study was to examine the combined role of a dispositional variable (impulsivity) along with psychological factors (Psychological Flexibility and Inflexibility) in pain outcomes and opioid misuse.

Methods

The sample comprised 155 people with chronic noncancer pain. A hypothetical model was tested using correlation and structural equation modelling analyses.

Results

The results show significant associations between impulsivity and Psychological Flexibility, Psychological Inflexibility and opioid misuse. Psychological Flexibility and Inflexibility were related to pain intensity, interference and opioid misuse. Structural equation modelling showed significant associations between impulsivity, Psychological Inflexibility and pain interference, and opioid misuse. Associations between Psychological Flexibility and pain interference and opioid misuse were nonsignificant. These results support the hypothesis that impulsivity and Psychological Inflexibility are factors that contribute to pain interference and opioid misuse, but do not support the hypothesis that Psychological Flexibility reduces opioid misuse.

Conclusions

It is recommended to assess these psychological aspects prior to the prescription of opioid medication, and, if necessary, offering Acceptance and Commitment and Mindfulness Based Therapies could be desirable.

Significance

The results of this study provide further evidence of the role of trait impulsivity as a transdiagnostic antecedent variable in opioid misuse, both by a direct association and through psychological inflexibility. It can be drawn from these results that psychological transdiagnostic variables, rather than pain outcomes alone, would be key factors influencing opioid misuse. These findings underscore the need for comprehensive psychological assessments prior to the prescription of opioids.

Chronic pain is a complex and major public health problem that requires a multidisciplinary treatment approach (Bruun et al. 2023; Cohen et al. 2021).

Pharmacological treatment including opioid analgesics has increased over the last decades for chronic pain conditions (Tormo‐Molina et al. 2017), as has the controversy regarding its adverse side effects and risks (Chou et al. 2015; Els et al. 2018). Misuse of prescribed opioids is frequent in long‐term opioid treatments, with prevalence rates estimated between 20% and 30% (Vowles et al. 2015). It is defined as the use of opioids differently from prescribed (Vowles et al. 2015), including overuse (Martel et al. 2020).

Risk of prescription opioid misuse has been linked to different psychological factors in people with chronic noncancer pain (CNCP), including dispositional transdiagnostic variables such as trait impulsivity (Marino et al. 2013; Ramírez‐Maestre et al. 2024; Ramesh and Evans 2018; Vest et al. 2016). Impulsivity is defined as a predisposition to unplanned rapid actions regardless of the potential negative consequences (Moeller et al. 2001).

Transdiagnostic factors such as psychological flexibility and inflexibility, key processes in Acceptance and Commitment Therapy (ACT) (Hayes et al. 2012), have also been linked to opioid misuse. Psychological flexibility is defined as the ability to be consciously in contact with inner experiences while adapting behaviour consistently with one's goals and values (Hayes et al. 2012). Conversely, psychological inflexibility implies a rigid pattern of behaviour guided by inner experiences rather than by personal values (Bond et al. 2011). There is cumulative evidence for the role of these transdiagnostic factors described here in relation to physical (e.g., pain intensity and physical functioning) and emotional functioning (e.g., anxiety, depression) of people with CNCP. Reviews assessing the efficacy of ACT randomised controlled trials have demonstrated small to large effects of ACT on the improvement of physical functioning, pain global impact, health and emotional well‐being (see Lai et al. 2023; McCracken 2024 for extensive reviews). Additionally, Ding and Zheng (2022) conducted a meta‐analysis analysing the associations between the six components of psychological flexibility and functioning in chronic pain samples. Their results showed small to large positive associations between mostly all the components of psychological flexibility and physical and psychological functioning.

Recent research has explored the role of psychological flexibility and inflexibility in opioid misuse in CNCP samples. Results show that components of psychological flexibility, such as present‐moment awareness and pain acceptance, serve as protective factors against misuse of opioids (Esteve et al. 2021; Priddy et al. 2018; Smit et al. 2023; Villarreal et al. 2020), while nonacceptance of pain and experiential avoidance are linked to opioid misuse beyond the influence of pain outcomes (Lin et al. 2015; McIntyre et al. 2021; Rhodes et al. 2021).

Despite the cumulative evidence for the role of psychological flexibility and psychological inflexibility in CNCP outcomes, research has been centred on specific components of psychological flexibility and inflexibility separately. To our knowledge, no study has examined the role of both psychological flexibility and inflexibility on pain outcomes and opioid misuse by measuring simultaneously all their components. Moreover, although both trait impulsivity and psychological inflexibility are risk factors for opioid misuse, few studies have examined how these variables interact. For instance, Levin et al. (2018) found that experiential avoidance mediated the relationship between impulsivity and mental health problems. Regarding opioid misuse, Esteve et al. (2024) conducted a study to analyse psychological profiles based on opioid misuse, trait impulsivity, acceptance of pain and other variables in people with CNCP. Their results showed that people forming the ‘severe problems group’ in terms of higher misuse, withdrawal and craving, exhibited higher trait impulsivity, and lower pain acceptance compared to those who formed the ‘mild problems group’. These results suggest that higher levels of impulsivity (vulnerability variable) along with lower acceptance of pain (protective variable) are related to higher opioid medication misuse.

The relationship between impulsivity and pain outcomes remains unclear since few studies have examined their relationship (Esteve et al. 2024; Ramírez‐Maestre et al. 2024; Vest et al. 2016). Correlation analyses showed a nonsignificant association between this dispositional variable and pain intensity (Esteve et al. 2024; Ramírez‐Maestre et al. 2024), though there was a significant correlation between impulsivity and pain interference (Ramírez‐Maestre et al. 2024). However, testing the role of impulsivity in a structural equation model, Ramírez‐Maestre et al. (2024) found that this dispositional variable played an important role as an antecedent variable not only in opioid misuse, but also in adjustment to pain in CNCP people (e.g., pain acceptance, pain intensity and pain impairment and functioning). When considering dimensions of impulsivity, Vest et al. (2016) found a small significant correlation between urgency (i.e., the tendency to act impulsively while experiencing negative emotions) and pain intensity and interference. This evidence suggests that not only dispositional variables, but also additional psychological factors (e.g., psychological flexibility and inflexibility) interact to play a role not only in opioid misuse, but also in CNCP outcomes.

The aim of this cross‐sectional study was to test a hypothetical model where impulsivity, as an antecedent variable, is associated with lower psychological flexibility and higher psychological inflexibility. Psychological flexibility and inflexibility would act as mediators related to pain intensity and interference, and opioid misuse (Figure 1).

FIGURE 1.

FIGURE 1

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Hypothetical model. Observed variables are represented by squares. PF, psychological flexibility; PI, psychological inflexibility.

1. Methods

1.1. Participants

Participants were recruited from the pain units of three general hospitals. Inclusion criteria were as follows: 18 years of age or more; diagnosis of non‐oncologic chronic pain; receiving treatment with opioid medication for at least 90 days, which is considered long‐term opioid therapy (Chou et al. 2015); able to understand information about the study and sign informed consent; no active symptomatology of major mental health disorders or other disorders that could hinder understanding the questions; average pain intensity score > 3; and fluency in written and spoken Spanish.

Kline (2005) recommended a 10:1 ratio of sample size to the number of estimated parameters to conduct Structural Equation Modelling (SEM). Since we hypothesised 8 parameters (see Figure 1), a minimum of 80 participants would be appropriate. The final sample comprised 155 participants with non‐oncologic chronic pain. In total, 562 people were invited to take part in the study. Of these, 85 were excluded due to not meeting the inclusion criteria and 318 refused to participate. The reasons for declining were as follows: not answering the phone (n = 81); expressly refusing (n = 128); not being able to travel to the hospital for the assessment (n = 63); and not attending the appointment (n = 46). Four participants were excluded as they quit the assessment before completing half of the questionnaires included in the study protocol because of fatigue.

1.2. Procedure

All the procedures were conducted in accordance with the Helsinki Declaration of 1975 and its later amendments (World Medical Association, Ethics Unit 2007). This study is part of a research project on the study of predictive psychological variables of prescription opioid misuse in patients with CNCP (see Ramírez‐Maestre et al. 2021 for more information) which was approved by the Ethics Committee of the University of Málaga (CEUMA 2013‐0016‐H) and by the Research Ethics Committee of the Province of Málaga (CEIP‐281021).

We met the recruiting physicians to describe the eligibility criteria and the procedures of the study. At the end of visits, the doctors informed people who fulfilled the eligibility criteria about the study aims and invited them to participate. They left their contact details to set an appointment on another day. Psychologists in charge of the assessment contacted them by telephone, checked whether they met the inclusion criteria and whether they agreed to participate. If so, they made an appointment to conduct the assessment at the hospital where the participants usually received regular medical attention. The recruitment process lasted from September 2023 to July 2024. Prior to data collection, participants were informed of the aims of the study and provided signed informed consent. They also were aware that the information collected was confidential and linked to a number alone and not to their personal data. A clinical psychologist then conducted a semi‐structured interview to obtain clinical and demographic data along with a battery of questionnaires administered in the same order as described in the following section. Interviews lasted an average of 70 min. Neither the participants nor the participating physicians received any form of compensation or incentive for their participation.

1.3. Measures

1.3.1. Demographics and Clinical Characteristics

Participants were asked to provide demographic information regarding gender, age, relationship status, level of education and work status. They also provided clinical information on pain diagnosis, pain duration and pain sites.

1.3.2. Opioid Use

We assessed opioid use by asking participants about their current pain medications, dosages, frequency of intake and the time when they started treatment. We calculated the daily dose of opioids and converted it to oral morphine milligram equivalents (MME) following the methods recommended by Dowell et al. (2022).

1.3.3. Brief Pain Inventory‐Short Form (BPI‐SF)

The BPI‐SF (Badia et al. 2003; Cleeland and Ryan 1991) is a widely used measure to assess pain intensity and pain interference. Intensity of pain is assessed using four items referred to current pain, the least, average and worst pain in the last 24 h, rated on a scale ranging from 0 (‘No pain’) to 10 (‘Worst possible pain’). The mean of the four items is calculated as a measure of overall pain intensity. In the current sample, Cronbach's alpha for the Pain Intensity subscale was 0.86.

Pain interference is assessed using seven items related to different domains of daily living (general activity, mood, walking, work ability, relationships with others, sleep and enjoyment of life), rated on a scale ranging from 0 (‘Does not interfere’) to 10 (‘Completely interferes’). The responses to the items are averaged to compute a score of pain interference. Internal consistency for the Pain Interference subscale was acceptable in the current sample (α = 0.76).

1.3.4. Multidimensional Psychological Flexibility Inventory‐24 (MPFI‐24)

The MPFI‐24 (Barrado‐Moreno et al. 2025; Rolffs et al. 2016) is a 24‐item measure of psychological flexibility and inflexibility and their 12 components. Each subscale is composed of two items rated on a 6‐point scale ranging from 1 (‘Never true’) to 6 (‘Always true’). The dimensions assessed include: Acceptance (e.g., ‘I was receptive to observing unpleasant thoughts and feelings without interfering with them’), present‐moment awareness (e.g., ‘I was attentive and aware of my emotions’), self‐as‐context (e.g., ‘Even when I felt hurt or upset, I tried to maintain a broader perspective’), defusion (e.g., ‘I was able to let negative feelings come and go without getting caught up in them’), contact with values (e.g., ‘I was very in‐touch with what is important to me and my life’), and committed action (e.g., ‘Even when I stumbled in my efforts, I didn't quit working toward what is important’); experiential avoidance (e.g., ‘When I had a bad memory, I tried to distract myself to make it go away’), lack of contact with the present moment (e.g., I did most things on ‘automatic’ with little awareness of ‘what I was doing’), self‐as‐content (e.g., ‘I thought some of my emotions were bad or inappropriate and I shouldn't feel them’), fusion (e.g., ‘Negative thoughts and feelings tended to stick with me for a long time’), lack of contact with values (e.g., ‘My priorities and values often fell by the wayside in my day to day life’), and inaction (e.g., ‘Negative feelings often trapped me in inaction’). Items can be averaged to represent each of the 12 processes of psychological flexibility and inflexibility, or global composites of psychological flexibility and inflexibility. The MPFI has been tested in its long (Sundström et al. 2023) and short‐form (Lavefjord et al. 2025) in two studies focused on people with chronic pain, and has demonstrated satisfactory validity and reliability. Internal consistency for both psychological flexibility and inflexibility composites was good in the current study (α = 0.81).

1.3.5. Current Opioid Misuse Measure (COMM)

The COMM (Butler et al. 2007; Reyes‐Pérez et al. 2022) is a 17‐item self‐report measure to monitor chronic pain patients on opioid therapy and to detect their adherence to their prescribed opioid treatment in the past 30 days. The COMM assess problematic medication use behaviours such as searching for more medication than prescribed (e.g., ‘In the past 30 days, how often have you had to go to someone other than your prescribing physician to get sufficient pain relief from medications?’ [i.e., another doctor, the Emergency Room, friends, street sources)], opioid medication misuse (e.g., ‘In the past 30 days, how often have you taken your medications differently from how they are prescribed?’), or emergency visits (e.g., ‘In the past 30 days, how often have you had to visit the Emergency Room?’). Items are rated on a 5‐point scale ranging from 0 (‘Never’) to 4 (‘Very often’). Item scores are summed, with higher scores indicating more risk for opioid misuse. In the current sample, Cronbach's alpha value was 0.80.

1.3.6. Barratt Impulsiveness Scale (BIS‐11)

The BIS‐11 (Oquendo et al. 2001; Patton et al. 1995; Quintana et al. 2003) is a 30‐item instrument used to measure impulsivity. Items are rated on a 4‐point scale ranging from 1 (‘Rarely or never’) to 4 (‘Almost always or always’). Item scores are summed, with higher scores indicating higher levels of impulsivity. Internal consistency of the global score of the scale in the current sample was acceptable (α = 0.70).

1.4. Statistical Analysis

The variable distributions were tested for kurtosis, symmetry and normality. Four outliers were detected using a cut‐off score of three standard deviations in regard to scale scores. Outliers were not removed as effects on the data appeared negligible. The missing data rate was acceptable (ranging from 0.6% to 1.3%), and we assumed that they were missing at random; therefore, we replaced them by applying the multiple imputation method at the item level (Mazza et al. 2015). Descriptive statistics were calculated for the demographic, clinical and other study variables. We conducted a series of analyses to test our hypothesis. First, we computed Pearson correlation coefficients between the observed variables included in the model. Correlations were interpreted following Cohen's (1988) guidelines: values between 0.10 and 0.29 were interpreted as low correlations, values between 0.30 and 0.49 as moderate and values between 0.50 and 1 as large. These analyses were conducted using IBM SPSS Statistics version 25.0.

Structural Equation Modelling (SEM) analyses were conducted to test the hypothetical model (see Figure 1) using LISREL 8.30 software package (Jöreskog and Sörbom 1993). Due to some of the data deviating from normality, we used the Maximum Likelihood estimation method on the covariance matrix and we provided the asymptotic covariance matrix. This method is effective for any data distribution if the analyses are performed on covariance matrices (Batista Foguet and Coenders Gallart 2000). Several goodness‐of‐fit indexes (GFIs) were used to test the adequacy of the model. The Satorra‐Bentler chi‐square (Bentler 2006) is a chi‐square index that corrects the statistic under distributional violations. The index is divided by the degrees of freedom to reduce the sensitivity of chi‐square to sample size. Ratios of 3 or less indicate acceptable fit (Kline 2016). The root‐mean‐square error of approximation (RMSEA) is an absolute misfit index in which values < 0.08 indicate an adequate fit, and < 0.06 a good fit (Hu and Bentler 1999). The Comparative Fit Index (CFI; Bentler 1990) and the Non‐normed Fit Index (NNFI; Bentler and Bonett 1980) measure the proportional improvement in fit by comparing a hypothesized model with a more restricted baseline model (e.g., a null model). Values of both indexes range between 0 and 1, and values close to 1 indicate the best fit (Hu and Bentler 1999).

Five observable variables were related in the hypothetical model (see Figure 1). The exogenous variable was Impulsivity, and Psychological Flexibility, Psychological Inflexibility, Pain Intensity, Pain Interference and Opioid Misuse were the endogenous variables. As shown in Figure 1, we hypothesized negative associations between psychological flexibility and impulsivity, pain intensity, pain interference, opioid misuse and psychological inflexibility. Conversely, we hypothesized positive associations between psychological inflexibility and impulsivity, pain‐related variables and opioid misuse.

2. Results

2.1. Participants

The final sample included 155 participants (58.7% females) with a mean age of 56.38 years (SD = 11.27). See Table 1 for more details. The most reported diagnoses of pain were as follows: secondary musculoskeletal pain (57.4%), primary widespread chronic pain (19.4%), secondary postsurgical or post‐traumatic pain (12.3%) and secondary neuropathic pain (7.1%). The mean pain duration was 224.33 months (SD = 184.90), and the mean MME dose per day was moderate (68.68; SD = 84.74) according to Dowell et al. (2022). See Table 2 for more detailed information.

TABLE 1.

Frequency data for the demographic variables (N = 155).

Variables M (min/max) SD
Age (years) 56.38 (23/84) 11.27
N %
Sex
Female 91 58.7
Male 64 41.3
Relationship status
Single 25 16.1
Married/Unmarried couple 101 65.2
Divorced/Separated 21 13.5
Widowed 8 5.2
Education
Reading and writing 19 12.3
Primary school 47 30.3
High school 66 42.6
University education 23 14.8
Work status
Housekeeping 1 0.6
Working 51 32.9
Unemployed 22 14.2
Retired 81 52.3
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Abbreviations: M = mean, SD = standard deviation.

TABLE 2.

Frequency data for clinical variables (N = 155).

Variables N %
Diagnosis
Chronic primary pain
Widespread chronic pain 30 19.4
Complex regional pain syndrome 2 1.3
Primary musculoskeletal pain 2 1.3
Chronic secondary pain
Postsurgical/post‐traumatic pain 19 12.3
Neuropathic pain 11 7.1
Visceral pain 2 1.3
Secondary musculoskeletal pain 89 57.4
Medication
Opioids a
Tramadol 56 36.1
Tramadol plus paracetamol 42 27.1
Oxycodone 35 22.6
Tapentadol 29 18.7
Fentanyl 24 15.5
Morphine 9 5.8
Buphrenorphine 4 2.6
Metadone 3 1.9
Paracetamol plus codeine 3 1.9
Tramadol plus dexketoprofen 2 1.3
Hydromorphone 1 0.6
Adjuvant medications for treating pain
Benzodiazepines 123 79.4
Antidepresants 99 63.9
Antiepileptic drugs 91 58.7
Hypnotics 9 5.8
M (min/max) SD
Time in pain 224.33 (6/792) 184.90
Pain intensity 6.50 (3/10) 1.62
Daily MME/d 68.68 (0.59/520) 84.74
Time in treatment with opioids (months) 51.56 (3/240) 51.41
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Abbreviations: M = mean, MME = morphine milligram equivalents, SD = standard deviation.

a

34.2% of the participants took more than one opioid.

2.2. Correlation Analysis

Table 3 shows the means, standard deviations and Pearson correlation coefficients of the variables included in the hypothesised model. Statistically significant moderate correlations in the expected direction were observed between impulsivity and psychological flexibility, inflexibility and opioid misuse. The associations between both psychological flexibility and inflexibility and opioid misuse were moderate and in the expected direction. Small correlations in the expected direction were observed between both psychological flexibility and inflexibility and pain interference. Finally, the associations between pain intensity and pain interference, and opioid misuse were small and moderate, respectively, and in the expected direction. No statistically significant correlations were found between pain intensity and the psychological variables (i.e., impulsivity, psychological flexibility and inflexibility).

TABLE 3.

Means, standard deviations and correlations between the model variables.

Mean SD Min/Max 1 2 3 4 5 6
1. Impulsivity 47.71 12.31 18/83 1
2. PF 4.22 0.85 1.92/6 −0.39 a 1
3. PI 3.5 0.94 1.33/5.33 0.46 a −0.32 a 1
4. Pain Intensity 6.5 1.62 3/10 0.11 −0.07 0.12 1
5. Pain Interference 7.48 1.77 2.14/10 0.15 −0.20 b 0.29 a 0.52 a 1
6. Opioid misuse 16.1 10.1 0/58 0.41 a −0.33 a 0.47 a 0.19 b 0.40 a 1
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Note: Pearson's correlations.

Abbreviations: PF = psychological flexibility, PI = psychological inflexibility, SD = standard deviation.

a

p < 0.001.

b

p < 0.05.

2.3. Evaluation of the Hypothesized Model

The initial model is represented in Figure 2. To obtain a parsimonious model, paths of the original model that were not statistically significant were deleted. Thus, paths from both psychological flexibility and psychological inflexibility to pain intensity were removed. As a result, pain intensity was excluded from the model. The nonsignificant path from psychological flexibility to pain interference was also removed. Additionally, two relationships suggested by the modification indexes were added: two paths from both impulsivity and pain interference to opioid misuse. The addition of these paths seemed plausible given previous evidence (Esteve et al. 2024; Ramírez‐Maestre et al. 2024; Rhodes et al. 2021). Finally, a correlation between the unexplained variance of psychological flexibility and inflexibility was allowed. This latter allowance was made in accordance with previous research that has suggested that psychological flexibility and inflexibility are related but distinct constructs (Rolffs et al. 2016); moreover, both were measured with the same instrument (MPFI‐24).

FIGURE 2.

FIGURE 2

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Initial model. Observed variables are represented by squares. Straight lines with arrows represent presumed paths, and values above the arrows represent standardised coefficients (a p < 0.05). PF, psychological flexibility; PI, psychological inflexibility.

Table 4 shows the GFIs of the initial and final models. The GFIs calculated for the initial model indicated that it did not provide a good fit to the data. Following the aforementioned modifications made to the model, the final model (see Figure 3) provided an adequate fit to the data and accounted for 35% of the variance of scores on opioid misuse. As hypothesised, the findings show a significant moderate relationship in the expected direction between impulsivity and psychological flexibility and inflexibility, as well as a significant positive low relationship between psychological inflexibility and opioid misuse. However, contrary to our hypotheses, psychological flexibility was not associated with pain interference. Moreover, after the adjustments suggested by the modification indexes, the association between psychological flexibility and opioid misuse was no longer significant, and the path was removed in the final model. Additionally, although in line with previous findings, significant positive associations that were not included in our hypothesised model emerged between both impulsivity and pain interference and opioid misuse.

TABLE 4.

Goodness‐of‐fit indices.

χ 2/df RMSEA CFI NNFI
Initial model 9.95 0.24 0.73 0.42
Final model 1.74 0.07 0.99 0.96
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Abbreviations: CFI = Comparative Fit Index, df = degrees of freedom, NNFI = Non‐Normed Fit Index, RMSEA = root mean square error of approximation, χ 2 = Satorra‐Bentler scaled chi‐square.

FIGURE 3.

FIGURE 3

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Final model. Observed variables are represented by squares. Straight lines with arrows represent presumed paths, and values above the arrows represent standardised coefficients (a p < 0.05), and the curved line represents the covariance between the errors of the variables. PF, psychological flexibility; PI, psychological inflexibility.

3. Discussion

The aim of this cross‐sectional study was to test a hypothetical model to explain opioid misuse and pain‐related outcomes in CNCP people. This hypothesized model included trait impulsivity as an antecedent variable, and psychological flexibility and inflexibility as mediators. The results of the correlational analysis showed significant associations in the expected direction between the variables included in the model, ranging from low to large. However, contrary to expectation, pain intensity was not related to any of the mediator variables. The results of the SEM analyses partially supported our hypotheses. Thus, the final model suggests that impulsivity is a dispositional variable that might make people with CNCP more likely to misuse prescribed opioids, both by a direct association and by increasing psychological inflexibility. These results are consistent with previous research that linked impulsivity with addiction behaviour in people with (Esteve et al. 2024; Marino et al. 2013; Ramírez‐Maestre et al. 2024; Ramesh and Evans 2018; Vest et al. 2016) and without CNCP (Lee et al. 2019). The association between psychological inflexibility and opioid misuse is also consistent with cumulative previous evidence regarding its role in the onset and maintenance of addiction behaviour (Albal and Buzlu 2021; Levin et al. 2012; Rhodes et al. 2021). Despite the empirical evidence regarding the close link between these variables and maladaptive substance use behaviours, to our knowledge, this is the first study exploring their simultaneous influence on opioid misuse in a CNCP sample. The results of this study suggest that trait impulsivity, which involves a lack of behavioural inhibition, impaired attentional focus and planning, and a preference for immediate rewards, would lead to a maladaptive pattern of behaviour known as psychological inflexibility (Hayes et al. 2012). Psychological inflexibility is aimed at avoiding unpleasant inner experiences at the expense of long‐term valuable and meaningful gains. Psychological inflexibility also involves impaired attentional processes, which are focused and fixed on negative experiences, leading to an inability to attend and respond to contextual cues (Hayes et al. 2006; Marín‐Romero and García‐Lecumberri 2023). Thus, people with CNCP who exhibit impulsive traits would be more vulnerable to an inability to shift their attentional focus from pain and its negative consequences to other valuable aspects of their daily lives, and to engage in a pattern of pain‐avoidance behaviour neglecting other valuable aspects. This would result in the misuse of opioid prescribed medication as an attempt to immediately alleviate these negative experiences (e.g., pain intensity, beliefs and feelings), regardless of the long‐term consequences.

Additionally, although previous research has shown a link between pain intensity and opioid misuse (Goesling et al. 2015; Griffin et al. 2016), our results show that only pain interference, which is enhanced by psychological inflexibility, is positively associated with opioid misuse. These results support previous evidence suggesting that people with CNCP misuse opioids not only due to high pain intensity but because of psychological factors (Martel et al. 2020; Rhodes et al. 2021; Rogers et al. 2020). Moreover, our findings underscore the importance of psychological factors in self‐reported pain interference (Rambla et al. 2023), reinforcing previous evidence regarding the more intimate relationship between pain coping styles and pain interference compared to pain intensity (Adams et al. 2018; Osborne et al. 2007). Therefore, the results in this study highlight that psychological inflexibility involves a maladaptive pattern of coping with chronic pain that comprises topographically different behaviours to avoid or control pain: (1) misusing opioids; and (2) giving up valuable daily activities, resulting in greater pain interference (Vowles et al. 2014), and consequently misusing opioids as an attempt to cope with these limitations and/or avoid the negative thoughts and emotions derived from them.

The negative relationship between impulsivity and psychological flexibility confirms our hypothesis and is congruent with the definitions of both constructs. In contrast to impulsivity and psychological inflexibility, psychological flexibility is the ability to be in contact with unpleasant experiences and to adapt behaviour to the context demands according to one's long‐term personal goals (McCracken and Morley 2014). We also hypothesized a significant association between psychological flexibility and both pain interference and opioid misuse. However, although significant Pearson's correlations were found between these variables, nonsignificant associations were found in the SEM analysis. This is an unexpected result given previous evidence on the negative association between pain acceptance and pain impairment (Ramírez‐Maestre et al. 2014; Smit et al. 2023), and the protective role of the different components of psychological flexibility against opioid misuse (Esteve et al. 2021; Lin et al. 2015). Thus, several studies have confirmed that acceptance of pain is related to lower medication intake (Esteve et al. 2020; Esteve et al. 2024), and opioid misuse (Lin et al. 2015; Smit et al. 2023). Regarding other components of psychological flexibility, several studies demonstrated that present‐moment awareness was inversely associated to opioid misuse (Parisi et al. 2023; Priddy et al. 2018; Villarreal et al. 2020), and inconsistence with personal values increased the probability of a frequent intake of opioids (Rosen et al. 2020). It is noteworthy that some of these studies have analysed the effect of each component alone. Discrepancies in the results emerged when analysing several components simultaneously. For example, Parisi et al. (2023) showed that when considering both pain acceptance and present‐moment awareness as predictors of opioid misuse, only the latter significantly predicted opioid misuse.

The lack of statistical significance of psychological flexibility in predicting opioid misuse in the current study is consistent with previous evidence suggesting that psychological inflexibility is a stronger predictor of psychological distress than psychological flexibility in nonclinical samples (Stabbe et al. 2019; Thomas et al. 2021), and of patient functioning in chronic pain samples (McCracken and Samuel 2007; McCracken and Vowles 2007). However, this result regarding psychological flexibility could be because we used a measure that is not specific to chronic pain, unlike pain acceptance; or because the relationship between psychological flexibility and opioid misuse could be mediated by other psychological variables that have not been included in our model, such as depression and anxiety (Esteve et al. 2021).

The model examined here explained 35% of the variance of opioid misuse, so further research is needed to explore the potential influence of other psychological variables related to pain and opioid misuse, such as anxiety sensitivity (Ramírez‐Maestre et al. 2024), pain catastrophizing (Elphinston et al. 2022; López‐Martínez et al. 2023; Martel et al. 2020) or pain acceptance (Esteve et al. 2021; Lin et al. 2015; Smit et al. 2023). Nonetheless, relevant conclusions relevant to clinical management of pain can be drawn from the findings in this study. First, prior to prescription of opioid medication, it would be relevant to assess not only pain‐related variables such as pain intensity and interference, but also psychological variables such as trait impulsivity, psychological flexibility and inflexibility, to identify those who may be at risk of misusing opioids. Clinical guidelines have recommended psychological assessments of patients with CNCP before prescribing opioids to decide the most appropriate intervention given their characteristics (Chou et al. 2009; Passik and Kirsh 2003). Second, given the relevance of impulsivity and psychological inflexibility in opioid misuse, and their shared mechanisms, psychological interventions aimed to target both variables could be useful not only to prevent misuse, but also to treat maladaptive opioid use behaviours. In this sense, ACT and Mindfulness‐based therapies (MBTs) have demonstrated promising results in the reduction of impulsivity in substance use disorder samples because of their emphasis on attentional processes (mindfulness), acceptance and goal‐directed behaviour (Moniz‐Lewis et al. 2023). Moreover, ACT and MBTs interventions have proven to be beneficial approaches for CNCP in terms of physical and emotional functioning (Lai et al. 2023; McCracken 2024; Veehof et al. 2016). Therefore, people seeking treatment for CNCP could benefit from the utility of ACT and MBTs both to reduce the risk of opioid misuse and to improve emotional and physical aspects related to chronic pain.

The results of this study should be considered in the context of several limitations. First, this study was cross‐sectional, which does not allow causal conclusions. Future longitudinal research should investigate the role of the variables included in the model in predicting future opioid dependence. Second, the generalizability of the results could be limited due to our sample including more women than men, more than half of the sample being retired, and the fact that we did not consider other demographic variables such as ethnicity or income. Further research could focus on the potential interactions between demographic factors such as work status, psychological flexibility and inflexibility, and opioid misuse. Third, we relied on self‐report measures that could be biased by social desirability, despite the fact that participants were informed that their answers would be confidential and that their participation in the study would not affect their current treatment. Future research could include clinical interviews to assess opioid misuse behaviours or Opioid Use Disorder indicators. Additionally, it is noteworthy that benzodiazepines were prescribed along with opioid medication in the majority of the sample; future research could explore the potential impact of psychological flexibility and inflexibility in benzodiazepine use.

Despite some limitations, this is the first study testing an explicative model of opioid misuse and pain‐related outcomes that includes transdiagnostic dispositional variables (trait impulsivity) and transdiagnostic mediators (psychological flexibility and psychological inflexibility) in people with CNCP. The findings underline the potential value of psychological assessment prior to the prescription of opioid medication for chronic pain (Chou et al. 2009; Ramírez‐Maestre et al. 2024; Rhodes et al. 2021), as well as the relevance of acceptance or mindfulness‐based psychological treatments not only to improve pain outcomes but also to target risk factors for opioid misuse.

Author Contributions

This study was designed by Victoria Barrado‐Moreno, Rosa Esteve and Carmen Ramírez‐Maestre. Data were collected by Victoria Barrado‐Moreno and analysed by Victoria Barrado‐Moreno, Rosa Esteve and Carmen Ramírez‐Maestre. The results were examined and discussed by all the authors. Victoria Barrado‐Moreno had a primary role in preparing the manuscript, which was revised and edited by Rosa Esteve, Lance M. McCracken, and Carmen Ramírez‐Maestre. All authors have approved the final version of the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding: This study received Grants PRE2020‐093204 and PID2019‐106086RB‐I00 funded by MCIN/AEI /10.13039/501100011033 by ‘ESF Investing in your future’, and the Regional Government of Andalusia (HUM‐566).

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