Opioid Use Disorder, Cannabis Use Disorder, and a Mindfulness Intervention Affecting Pain-Related Neural Substrates

In DSM-5, the tolerance and withdrawal criteria have been removed for making the diagnosis of POUD for individuals that are appropriately taking their prescribed opiates. PRISM-5-OP, an assessment tool that was developed to better characterize POUD, allows for comparison of the following assessments: 1) meeting full DSM-5 criteria and maintaining the tolerance and withdrawal criteria; 2) meeting DSM-5 criteria but dropping tolerance and withdrawal if patients are appropriately taking opiates; and 3) “pain-adjusted” criteria in which tolerance and withdrawal criteria remain but the behavioral/subjective criteria are not met if the motivation to take opiates is solely for pain management. Hasin et al. (2) examine data from 606 patients from inpatient substance abuse treatment (N=258) and outpatient pain treatment facilities (N=348) who were assessed with the PRISM-5-OP. Findings across the entire sample demonstrated that 51% of patients met criteria for opiate use disorder when using the DSM-5 unadjusted criteria, 44.4% of patients met criteria when using the DSM-5 criteria dropping tolerance and withdrawal, and this further dropped to 30.4% when using the pain-adjusted criteria. As predicted, the use of the pain-adjusted criteria markedly reduced the number of chronic pain patients in the sample that met opioid use disorder criteria. Within the chronic pain patient group, the diagnosis of POUD decreased from 42.8% meeting the unadjusted DSM-5 criteria to 31.6% when dropping the tolerance and withdrawal criteria, and to 9.8% when using the pain-adjusted criteria. In addition, other validating measures were found to be more closely related to the pain-adjusted criteria. These findings highlight the prevalence of opiate use disorder in individuals prescribed opiates for chronic pain control, demonstrate the utility of the PRISM-5-OP as an assessment tool, and suggest that pain-adjusted criteria may be the most valid for diagnosing POUD. In their editorial, Drs. Mark Sullivan and Jane Ballantyne from the University of Washington (3) comment on the findings in relation to the biological effects of opiates. They conclude with the reminder that regardless of the motivation to take opiates, or the criteria that are used to determine opiate use disorder diagnoses, dose and duration of use are strong predictors of the long-term neurobiological adaptations that are characteristic of dependence, tolerance, and withdrawal.

With the motivation to increase access to treatments for opiate use disorder, Jutras-Aswad and colleagues (4) provide data that supports the use of buprenorphine/naloxone, primarily taken at home, as an effective and safe strategy for the treatment of POUD. This noninferiority study was performed in Canada and analyzed data from 271 DSM-5 opioid use disorder patients who were taking prescribed opiates. Study participants were randomized to 24 weeks of either home treatment with flexible sublingual buprenorphine/naloxone dosing or to methadone administered in a clinic setting. In this open-label study, patients in the buprenorphine/naloxone group were allowed to take their medication at home when they were deemed to be “clinically stable,” an average of 12.7 days after the study began. In the methadone group, home administration was allowed on average 85.2 days after initiation. Opioid-free urine drug screens obtained every 2 weeks were used as a primary outcome measure, with 24% opioid-free urine screens occurring in the buprenorphine/naloxone group compared to 18.5% in the methadone group. Overall retention rates for the study were low: 32 of 138 individuals in the buprenorphine/naloxone group and 45 of 133 individuals in the methadone group. Treatment-related increases in quality of life did not differ between the groups. In addition, both treatments had similar side effects and were generally safe. Taken together, the findings from this noninferiority clinical trial demonstrate the potential utility and safety of buprenorphine/naloxone home-based treatment programs for individuals with POUD, with implications for increasing access to treatment especially during such times as the COVID-19 pandemic. In her editorial, Dr. Elizabeth Saunders from Dartmouth University (5) discusses the relevance of the findings from this paper, emphasizing the importance of flexible treatment models for increasing access and improving outcomes for patients struggling with opiate use disorders.

The aim of the study by Lin et al. (6) was to characterize the effects of COVID-19 telehealth policy changes related to buprenorphine treatment on the treatment of opiate use disorder. Buprenorphine is a partial mu opiate agonist, which is commonly used as a replacement therapy for treating opiate use disorder. Using data from the Veterans Health Administration (VHA), the researchers compared data from the 1 year prior to the COVID-related policy changes, March 2019–February 2020, to data collected during the first year of the policy changes, March 2020–February 2021. Among these changes was dropping the condition that the initial buprenorphine appointment had to be in person. The numbers of patients treated with buprenorphine for opioid use disorder in the VA system increased by 14% over the period of study, coinciding with the COVID-related changes in telehealth policy. Not surprisingly, major differences were found in the delivery of care. Prior to the changes in the telehealth policy, 11.9% of the visits were performed using telehealth (telephone or video) compared to 82.6% during the year after the changes were implemented. Taken together, the data from this VHA study demonstrate that buprenorphine-related COVID-19 policy changes effectively facilitated the maintenance of care via telehealth for a patient population that otherwise would have faced marked barriers to access treatment.

Cannabis use disorder is on the rise, and its negative consequences can be quite significant. With the advent of more readily available increased potency cannabis and the importance of understanding the prevalence of cannabis use disorder in the VA population, Hasin and colleagues (7) used VHA data from 2005–2019 to characterize changes in the prevalence of cannabis use disorder diagnoses. Particular interest was focused on factors such as age, sex, race, and ethnicity. In 2005, cannabis use disorder was most common in patients less than 35 years of age, affecting 1.7% of veterans assessed from data in VHA electronic health records. By 2019, cannabis use disorder increased to 4.84% in this age group. In individuals 65 years of age or older, the diagnosis of cannabis use disorder increased from 0.03% in 2005 to 0.4% in 2019. In this predominantly male sample, across the entire time period males had a greater relative incidence of being diagnosed with cannabis disorder compared to females, as did Black individuals. In addition, in the less than 35 years of age group the rate of increase was greater in Black compared with White individuals. In their editorial, Drs. Ziva Cooper and Stephanie Lake from UCLA (8) discuss the potential reasons underlying the increase in the diagnosis of cannabis use disorder in VA patients, focusing on the increased rates in Black individuals as well as in older veterans.

Moving from opioid-related strategies for pain management toward understanding the potential efficacy and mechanisms underlying behavioral interventions, Wielgosz and colleagues (9) report the results of a randomized clinical trial aimed at assessing the effects of 8 weeks of mindfulness-based stress reduction training on subjective and neural responses to experimentally induced thermal pain. Participants naïve to meditation (N=115) and long-term meditators (N=30) were first assessed at baseline with fMRI revealing that the pain-related neural signatures selected for the study were a valid reflection of pain exposure. These neural signatures were previously derived with machine learning techniques and were demonstrated to reflect the stimulus-dependent features of pain such as pain intensity (Neurologic Pain Signature [NPS]) and the stimulus-independent features of pain such as psychological factors associated with experiencing pain (Stimulus Intensity Independent Pain Signature-1 [SIIPS1]). After collection of baseline data, 28 individuals underwent 8 weeks of mindfulness-based training, 32 individuals participated in a health enhancement program as an active comparator, and 31 individuals remained on a waiting list. Results demonstrated that compared with the active control, mindfulness training was associated with a significant reduction in the activation of NPS, and a nonsignificant reduction was found when compared to the waiting list group. Mindfulness training was also associated with nonsignificant reductions in SIIPS1 when compared with the active control and waiting list groups. Both mindfulness training and participation in the active control group resulted in significant reductions in subjective reports of unpleasantness. The long-term meditators reported lower levels of pain associated with the thermal stimulus when compared to the other individuals in the study but surprisingly did not differ from the other individuals in relation to their NPS or SIIPS1 responses. The results from this study demonstrate the potential utility of mindfulness-based stress reduction training as an intervention to aid in pain management. It is of interest that the effects of mindfulness training appeared to be more robust in relation to the activation of neural processes associated with the intensity of pain and less so in relation to the psychological aspects of experiencing pain. Drs. Ann Gillespie and Catherine Harmer from the University of Oxford contribute an editorial (10) that highlights the importance of using fMRI-derived “neural signatures” as objective measures of brain responses as well as their potential utility in studying other psychiatric disorders.

Opioid and cannabis use disorders are highly prevalent, and in many cases the use of these substances is initially related to “self-medication” strategies aimed at reducing one’s emotional or physical pain. Additionally, it is well recognized that taking prescribed opiates for pain management frequently progresses to patterns of misuse and subsequent addiction. Based on this, there is a clear rationale for increasing access to treatment for opioid use disorder patients and for developing effective nonopiate and nonpharmacological strategies for pain management. In this issue of the Journal we learn about 1) the high prevalence of opioid use disorder and current evidence for its management; 2) the effects of modifying the criteria for POUD on the prevalence rates for its diagnosis; 3) the efficacy of buprenorphine/naloxone home treatment for POUD, potentially enabling easier access to treatment; and 4) how buprenorphine treatment-related telehealth policy changes effectively reduce COVID-19 associated barriers to treatment. In relation to cannabis use disorder, we also learn that within the VA population its prevalence has been increasing, which is especially notable in Black individuals. Finally, Wielgosz and colleagues (9) introduce us to nonpharmacological approaches to pain management, demonstrating that mindfulness-based stress reduction training can modulate the perception of painful stimuli as well as the activation of underlying neural systems involved in pain processing.

Together, the papers in this issue of the Journal highlight the importance of developing new strategies for reducing the incidence of opioid use disorder and for its treatment. Decreasing the use of prescribed and illicit opiates is key and can potentially be accomplished by prioritizing the use of nonopiate strategies, including behavioral strategies, for chronic pain management. For individuals already struggling with opiate use disorder, decreasing barriers to treatment is a critical public health policy issue.