Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial.

Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.

Adjunct interventions to standard medical management of buprenorphine in outpatient settings: A systematic review of the evidence.

BACKGROUND: A growing body of research has examined adjunctive interventions supportive of engagement and retention in treatment among patients receiving buprenorphine for opioid use disorder (OUD). We conducted a systematic review of the literature addressing the effect on key outcomes of adjunctive interventions provided alongside standard medical management of buprenorphine in outpatient settings. METHODS: We included prospective studies examining adults receiving buprenorphine paired with an adjunctive intervention for the treatment of OUD in an outpatient setting. Data sources included Medline, Cochrane Central Register of Controlled Trials, CINAHL and PsycINFO from inception through January 2020. Two raters independently reviewed full-text articles, abstracted data and appraised risk of bias. Outcomes examined included abstinence, retention in treatment and non-addiction-related health outcomes. RESULTS: The final review includes 20 manuscripts, 11 randomized control trials (RCTs), three secondary analyses of RCTs and six observational studies. Most studies examined psychosocial interventions (n = 14). Few examined complementary therapies (e.g., yoga; n = 2) or technological interventions (e.g., electronic pill dispensation; n = 3); one study examined an intervention addressing structural barriers to care (patient navigators; n = 1). Low risk of bias RCTs found no evidence that adding psychosocial interventions to buprenorphine treatment improves substance use outcomes. CONCLUSIONS: Research is needed to identify adjunctive interventions with potential to support medication adherence and addiction-related outcomes for patients engaged in buprenorphine treatment. Data from clinical trials suggest that lack of ready access to psychosocial treatments should not discourage clinicians from prescribing buprenorphine.

Cannabis Use and Nonfatal Opioid Overdose among Patients Enrolled in Methadone Maintenance Treatment.

BACKGROUND: Some ecological studies found lower rates of opioid overdose in states with liberalized cannabis legislation, but results are mixed, and the association has not been analyzed in individuals. We quantified the association between cannabis use and nonfatal opioid overdose among individuals enrolled in methadone maintenance treatment (MMT) for opioid use disorder (OUD). METHODS: We recruited a convenience sample of individuals enrolled in four MMT clinics in Washington State and southern New England who completed a one-time survey.Descriptive statistics and multivariate logistic regression compared the prevalence and risk of nonfatal opioid overdose in the past 12 months between participants reporting frequent (at least weekly) or infrequent (once or none) cannabis use in the past month. RESULTS: Of 446 participants, 35% (n = 156) reported frequent cannabis use and 7% (n = 32) reported nonfatal opioid overdose in the past year. The prevalence of nonfatal opioid overdose was 3% among reporters of frequent cannabis use, and 9% among reporters of infrequent/no use (p = 0.02). After imputing missing data and controlling for demographic and clinical factors, the likelihood of self-reported nonfatal opioid overdose in the past year was 71% lower among reporters of frequent cannabis use in the past month (adjusted RR = 0.29, 95% CI 0.10-0.80, p = 0.02). CONCLUSIONS: Among individuals enrolled in MMT, frequent cannabis use in the past month was associated with fewer self-reported nonfatal opioid overdoses in the past year. Methodological limitations caution against causal interpretation of this relationship. Additional studies are needed to understand the prospective impact of co-occurring cannabis on opioid-related outcomes.

A pilot trial of collaborative care with motivational interviewing to reduce opioid risk and improve chronic pain management.

BACKGROUND AND AIMS: Opioid use and chronic pain are prevalent in the veteran population. Collaborative care enhances coordination between patients and their care teams, and motivational interviewing (MI) is a communication style designed to facilitate behavior change. This study evaluated the use of collaborative care with MI (CCMI) with patients with chronic pain and high-risk prescription opioid use. DESIGN: Small pilot study of a randomized controlled trial. SETTING: An urban Veterans Affairs (VA) Medical Center in the United States. PARTICIPANTS: One hundred adult veterans with chronic pain currently enrolled into primary care and receiving long-term opioid therapy. INTERVENTION AND COMPARATOR: During an initial 1-hour visit with a study primary-care physician (PCP), all veterans (n = 100) developed a personalized pain care plan, after which they were randomized to receive four sessions (at 4, 6, 8 and 12 weeks) of either CCMI (n = 51) or attention control psychoeducation (ACP; n = 49). Subsequently, participants had 30-minute follow-up visits with study PCPs and post-treatment assessment at 12 weeks. MEASUREMENTS: Co-primary outcomes measures assessed opioid risk and pain interference; secondary measures assessed pain severity, PCP rating of opioid risk and pain management goals. FINDINGS: At 12 weeks, intent-to-treat (ITT) analyses using multivariate mixed-effects linear regression were inconclusive regarding the between-group differences in primary and secondary outcomes at post-intervention (12 weeks). Bayes factors for opioid risk, pain interference, pain severity and PCP ratings were 1.96, 1.36, 0.45 and 0.82, respectively. Veterans in the CCMI group reported implementing more complementary integrative health (CIH) goals (e.g. yoga) than did those in the ACP group (d = 0.54). CONCLUSIONS: US veterans with chronic pain who received collaborative care with motivational interviewing reduced their high-risk opioid use and showed improved pain interference and severity after an intake with a primary-care provider involving shared decision-making and the creation of a personalized pain care plan.

Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation.

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care. DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis. SUMMARY: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel.

Prospective Investigation of Factors Associated with Prescription Opioid Dose Escalation among Patients in Integrated Health Systems.

BACKGROUND: Prior research has identified factors associated with prescription opioid initiation, but little is known about the prevalence or predictors of dose escalation among patients already prescribed long-term opioid therapy (LTOT). OBJECTIVE: This was a 2-year prospective cohort study to examine patient and clinician factors associated with opioid dose escalation. DESIGN: A prospective cohort study. Participants were seen at baseline and every 6 months for a total of 2 years. PARTICIPANTS: Patients prescribed a stable dose of LTOT for musculoskeletal pain were recruited from two integrated health systems (Kaiser Permanente and the Department of Veterans Affairs, respectively). MAIN MEASURES: The prescription opioid dose was based on pharmacy records and self-report. Administrative data were gathered on characteristics of the opioid-prescribing clinician and healthcare utilization. Participants completed measures of pain, functioning, and quality of life. KEY RESULTS: Of enrolled participants (n = 517), 19.5% had an opioid dose increase. In multivariate analyses, patient variables associated with dose escalation were lower opioid dose (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.79-0.94, for every 10-mg increase in baseline dose) and greater pain catastrophizing (HR = 1.03, 95% CI = 1.01-1.05). Other variables associated with dose escalation were as follows: receiving medications from a nurse practitioner primary care provider (HR = 2.10, 95% CI = 1.12-3.96) or specialty physician (HR = 3.18, 95% CI = 1.22-8.34), relative to a physician primary care provider, and having undergone surgery within the past 6 months (HR = 1.80, 95% CI = 1.10-2.94). Other variables, including pain intensity, pain disability, or depression, were not associated with dose escalation. CONCLUSIONS: In this 2-year prospective cohort study, variables associated with opioid dose escalation were lower opioid dose, higher pain catastrophizing, receiving opioids from a medical specialist (rather than primary care clinician) or nurse practitioner, and having recently undergone surgery. Study findings highlight intervention points that may be helpful for reducing the likelihood of future prescription opioid dose escalation.

Pharmacotherapy for the Treatment of Cannabis Use Disorder: A Systematic Review.

Background: Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options. Purpose: To review the benefits and risks of pharmacotherapies for the treatment of CUD. Data Sources: MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019. Study Selection: Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes. Data Extraction: Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria. Data Synthesis: Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found. Limitations: Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment. Conclusion: Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064).

Efficacy of Biofeedback for Medical Conditions: an Evidence Map.

BACKGROUND: Biofeedback is increasingly used to treat clinical conditions in a wide range of settings; however, evidence supporting its use remains unclear. The purpose of this evidence map is to illustrate the conditions supported by controlled trials, those that are not, and those in need of more research. METHODS: We searched multiple data sources (MEDLINE, PsycINFO, CINAHL, Epistemonikos, and EBM Reviews through September 2018) for good-quality systematic reviews examining biofeedback for clinical conditions. We included the highest quality, most recent review representing each condition and included only controlled trials from those reviews. We relied on quality ratings reported in included reviews. Outcomes of interest were condition-specific, secondary, and global health outcomes, and harms. For each review, we computed confidence ratings and categorized reported findings as no effect, unclear, or insufficient; evidence of a potential positive effect; or evidence of a positive effect. We present our findings in the form of evidence maps. RESULTS: We included 16 good-quality systematic reviews examining biofeedback alone or as an adjunctive intervention. We found clear, consistent evidence across a large number of trials that biofeedback can reduce headache pain and can provide benefit as adjunctive therapy to men experiencing urinary incontinence after a prostatectomy. Consistent evidence across fewer trials suggests biofeedback may improve fecal incontinence and stroke recovery. There is insufficient evidence to draw conclusions about effects for most conditions including bruxism, labor pain, and Raynaud's. Biofeedback was not beneficial for urinary incontinence in women, nor for hypertension management, but these conclusions are limited by small sample sizes and methodologic limitations of these studies. DISCUSSION: Available evidence suggests that biofeedback is effective for improving urinary incontinence after prostatectomy and headache, and may provide benefit for fecal incontinence and balance and stroke recovery. Further controlled trials across a wide range of conditions are indicated.

Marijuana Use Is Not Associated With Changes in Opioid Prescriptions or Pain Severity Among People Living With HIV and Chronic Pain.

BACKGROUND: People living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation). METHODS: Participants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation. RESULTS: Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation. CONCLUSIONS: We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

Correlates of Benzodiazepine Use and Adverse Outcomes Among Patients with Chronic Pain Prescribed Long-term Opioid Therapy.

OBJECTIVE: To examine the correlates and odds of receiving overlapping benzodiazepine and opioid prescriptions and whether co-prescription was associated with greater odds of falling or visiting the emergency department. DESIGN: Cross-sectional study. SETTING: A large private integrated health system and a Veterans Health Administration integrated health system. SUBJECTS: Five hundred seventeen adults with musculoskeletal pain and current prescriptions for long-term opioid therapy. METHODS: A multivariate logistic regression model examined correlates of having overlapping benzodiazepine and opioid prescriptions in the year before enrollment in the cross-sectional study. Negative binomial models analyzed the number of falls in the past three months and past-year emergency department visits. In addition to propensity score adjustment, models controlled for demographic characteristics, psychiatric diagnoses, medications, overall comorbidity score, and opioid morphine equivalent dose. RESULTS: Twenty-five percent (N = 127) of participants had co-occurring benzodiazepine and opioid prescriptions in the prior year. Odds of receiving a benzodiazepine prescription were significantly higher among patients with the following psychiatric diagnoses: anxiety disorder (adjusted odds ratio [AOR] = 4.71, 95% confidence interval [CI] = 2.67-8.32, P < 0.001), post-traumatic stress disorder (AOR = 2.24, 95% CI = 1.14-4.38, P = 0.019), and bipolar disorder (AOR = 3.82, 95% CI = 1.49-9.81, P = 0.005). Past-year overlapping benzodiazepine and opioid prescriptions were associated with adverse outcomes, including a greater number of falls (risk ratio [RR] = 3.27, 95% CI = 1.77-6.02, P = 0.001) and emergency department visits (RR = 1.66, 95% CI = 1.08-2.53, P = 0.0194). CONCLUSIONS: Among patients with chronic pain prescribed long-term opioid therapy, one-quarter of patients had co-occurring prescriptions for benzodiazepines, and dual use was associated with increased odds of falls and emergency department visits.

Clinician Response to Aberrant Urine Drug Test Results of Patients Prescribed Opioid Therapy for Chronic Pain.

OBJECTIVE: Urine drug testing (UDT) is recommended for patients who are prescribed opioid medications, but little is known about the various strategies clinicians use to respond to aberrant UDT results. We sought to examine changes in opioid prescribing and implementation of other risk reduction activities following an aberrant UDT. METHODS: In a national cohort of Veterans Affairs patients with new initiations of opioid therapy through 2013, we identified a random sample of 100 patients who had aberrant positive UDTs (results positive for nonprescribed/illicit substance), 100 who had aberrant negative UDTs (results negative for prescribed opioid), and 100 who had expected UDT results. We examined medical record data for opioid prescribing changes and risk reduction strategies in the 12 months following UDT. RESULTS: Following an aberrant UDT, 17.5% of clinicians documented planning to discontinue or change the opioid dose and 52.5% initiated another strategy to reduce opioid-related risk. In multivariate analyses, variables associated with a planned change in opioid prescription status were having an aberrant positive UDT (odds ratio [OR], 30.77; 95% confidence interval [CI], 5.92-160.10) and higher prescription opioid dose (OR, 1.01; 95% CI, 1.01-1.02). The only variable associated with implementation of other risk reduction activities was having an aberrant positive UDT (OR, 0.29; 95% CI, 0.16-0.55). DISCUSSION: The majority of clinicians enacted some type of opioid prescribing or other change to reduce risk following an aberrant UDT, and the action depended on whether the result was an aberrant positive or aberrant negative UDT. Experimental studies are needed to develop and test strategies for managing aberrant UDT results.

Provider reasons for discontinuing long-term opioid therapy following aberrant urine drug tests differ based on the type of substance identified.

OBJECTIVE: Urine drug testing (UDT) is increasingly performed as a means of identifying aberrant behavior that may be grounds for discontinuation of long-term opioid therapy (LTOT). Little is known, however, about the ways in which positive UDT results may differentially inform decisions to discontinue LTOT based on the type of substance for which the UDT screened positive. The aim of this study was to examine the likelihood of clinician-initiated discontinuation of LTOT attributed to positive UDT results across three discrete categories of substances: (1) cannabis, (2) alcohol or illicit substances (excluding cannabis), and (3) controlled prescription medications that were not prescribed. DESIGN: This retrospective study utilized the US Department of Veterans Affairs (VA) Health Care System. Corporate Data Warehouse to assemble a sample of 600 patients with substance use disorders and matched controls who were discontinued from LTOT in 2012. Comprehensive manual medical record review identified UDT results in the year prior to discontinuation and reason(s) for discontinuation. PATIENTS, PARTICIPANTS: Patients with one or more UDTs positive for a single substance (N = 185) comprised the study sample. MAIN OUTCOME MEASURE(S): Likelihood of clinician-initiated discontinuation attributed to a positive UDT across the three categories. RESULTS: Patients with one or more UDTs positive for cannabis were more likely to be discontinued from opioid therapy as a result of the positive UDT compared to those with one or more UDTs positive for nonprescribed prescription medication (adjusted odds ratio [OR] = 18.05, 95% CI = 7.29-44.66). Similarly, patients with UDTs positive for alcohol or illicit substances were more likely to be discontinued for the positive UDTs relative to patients who tested positive for nonprescribed prescription medications (adjusted OR = 13.10, 95% CI = 4.81-35.68). No difference in UDT-related discontinuation decisions was evident between patients with UDTs positive for alcohol/illicit substances versus cannabis (adjusted OR = 1.47, 95% CI = 0.57-3.77). CONCLUSIONS: High odds of UDT-related discontinuation were found in patients who tested positive for cannabis, alcohol, or illicit substances, relative to nonprescribed prescription medications.

Correlates of Use and Perceived Effectiveness of Non-pharmacologic Strategies for Chronic Pain Among Patients Prescribed Long-term Opioid Therapy.

OBJECTIVE: Non-pharmacologic treatments (NPTs) are recommended for chronic pain. Information is limited on patient use or perceptions of NPTs. We examined the frequency and correlates of use and self-rated helpfulness of NPTs for chronic pain among patients who are prescribed long-term opioid therapy (LTOT). METHODS: Participants (n = 517) with musculoskeletal pain who were prescribed LTOT were recruited from two integrated health systems. They rated the frequency and utility of six clinician-directed and five self-directed NPTs for chronic pain. We categorized NPT use at four levels based on number of interventions used and frequency of use (none, low, moderate, high). Analyses examined clinical and demographic factors that differed among groups for both clinician-directed and self-directed NPTs. RESULTS: Seventy-one percent of participants reported use of any NPT for pain within the prior 6 months. NPTs were rated as being helpful by more than 50% of users for all treatments assessed (range 51-79%). High users of clinician-directed NPTs were younger than non-users or low-frequency users and had the most depressive symptoms. In both clinician-directed and self-directed categories, high NPT users had significantly higher pain disability compared to non-NPT users. No significant group differences were detected on other demographic or clinical variables. In multivariable analyses, clinician-directed NPT use was modestly associated with younger age (OR = 0.97, 95% CI = 0.96-0.98) and higher pain disability (OR = 1.01, 95% CI = 1.00-1.02). Variables associated with greater self-directed NPT use were some college education (OR = 1.80, 95% CI = 1.13-2.84), college graduate or more (OR = 2.02, 95% CI = 1.20-3.40), and higher pain disability (OR = 1.01, 95% CI = 1.01-1.02). CONCLUSIONS: NPT use was associated with higher pain disability and younger age for both clinician-directed and self-directed NPTs and higher education for self-directed NPTs. These strategies were rated as helpful by those that used them. These results can inform intervention implementation and be used to increase engagement in NPTs for chronic pain.

Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy.

OBJECTIVE: Little is known about co-occurring long-term opioid therapy (LTOT) and medical cannabis use. We compared characteristics of patients prescribed LTOT who endorsed using medical cannabis for pain to patients who did not report cannabis use. METHOD: Participants (n=371) prescribed LTOT completed self-report measures about pain, substance use, and mental health. RESULTS: Eighteen percent of participants endorsed using medical cannabis for pain. No significant differences were detected on pain-related variables, depression, or anxiety between those who endorsed medical cannabis use and those who did not. Medical cannabis users had higher scores of risk for prescription opioid misuse (median=17.0 vs. 11.5, p<0.001), rates of hazardous alcohol use (25% vs. 16%, p<0.05), and rates of nicotine use (42% vs. 26%, p=0.01). Multivariable analyses indicated that medical cannabis use was significantly associated with risk of prescription opioid misuse (ß=0.17, p=0.001), but not hazardous alcohol use (aOR=1.96, 95% CI=0.96-4.00, p=0.06) or nicotine use (aOR=1.61, 95% CI=0.90-2.88, p=0.11). CONCLUSION: There are potential risks associated with co-occurring LTOT and medical cannabis for pain. Study findings highlight the need for further clinical evaluation in this population. Future research is needed to examine the longitudinal impact of medical cannabis use on pain-related and substance use outcomes.

Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review.

BACKGROUND: Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. PURPOSE: To identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. DATA SOURCES: MEDLINE, the Cochrane Library, and other sources from database inception to March 2017. STUDY SELECTION: English-language systematic reviews, trials, and observational studies with a control group that reported PTSD symptoms and adverse effects of plant-based cannabis use in adults with PTSD. DATA EXTRACTION: Study data extracted by 1 investigator was checked by a second reviewer; 2 reviewers independently assessed study quality, and the investigator group graded the overall strength of evidence by using standard criteria. DATA SYNTHESIS: Two systematic reviews, 3 observational studies, and no randomized trials were found. The systematic reviews reported insufficient evidence to draw conclusions about benefits and harms. The observational studies found that compared with nonuse, cannabis did not reduce PTSD symptoms. Studies had medium and high risk of bias, and overall evidence was judged insufficient. Two randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD are ongoing and are expected to be completed within 3 years. LIMITATION: Very scant evidence with medium to high risk of bias. CONCLUSION: Evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016033623).

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review.

BACKGROUND: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. PURPOSE: To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. DATA SOURCES: MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. STUDY SELECTION: Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes. DATA EXTRACTION: Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. DATA SYNTHESIS: From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient. LIMITATION: Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily. CONCLUSION: Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).

Substance Use Disorder Treatment Following Clinician-Initiated Discontinuation of Long-Term Opioid Therapy Resulting from an Aberrant Urine Drug Test.

BACKGROUND: It is unclear whether substance use disorder (SUD) treatment is offered to, or utilized by, patients who are discontinued from long-term opioid therapy (LTOT) following aberrant urine drug tests (UDTs). OBJECTIVE: To describe the proportion of patients who were referred to, and engaged in, SUD treatment following LTOT discontinuation and to examine differences in SUD treatment referral and engagement based on the substances that led to discontinuation. DESIGN: From a sample of 600 patients selected from a national cohort of Veterans Health Administration patients who were discontinued from LTOT, we used manual chart review to identify 169 patients who were discontinued because of a UDT that was positive for alcohol, cannabis, or other illicit or non-prescribed controlled substances. MAIN MEASURES: We extracted sociodemographic, clinical, and health care utilization data from patients' electronic medical records. KEY RESULTS: Forty-three percent of patients (n = 73) received an SUD treatment referral following LTOT discontinuation and 20% (n = 34) engaged in a new episode of SUD treatment in the year following discontinuation. Logistic regression models controlling for sociodemographic and clinical variables demonstrated that patients who tested positive for cannabis were less likely than patients who tested positive for non-cannabis substances to receive referrals for SUD treatment (aOR = 0.44, 95% CI = 0.23-0.84, p = 0.01) or engage in SUD treatment (aOR = 0.42, 95% CI = 0.19-0.94, p = 0.04). Conversely, those who tested positive for cocaine were more likely to receive an SUD treatment referral (aOR = 3.32, 95% CI = 1.57-7.06, p = 0.002) and engage in SUD treatment (aOR = 2.44, 95% CI = 1.00-5.96, p = 0.05) compared to those who did not have a cocaine-positive UDT. CONCLUSIONS: There may be substance-specific differences in clinician referrals to, and patient engagement in, SUD treatment. This suggests a need for more standardized implementation of clinical guidelines that recommend SUD care, when appropriate, following LTOT discontinuation.

Higher Prescription Opioid Dose is Associated With Worse Patient-Reported Pain Outcomes and More Health Care Utilization.

Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Participants were recruited from 2 large integrated health systems, Kaiser Permanente Northwest (n = 331) and VA Portland Health Care System (n = 186). To be included, participants had to have musculoskeletal pain diagnoses and be receiving stable doses of long-term opioid therapy. We divided participants into 3 groups on the basis of current prescription opioid dose in daily morphine equivalent dose (MED): low dose (5-20 mg MED), moderate dose (20.1-50 mg MED), and higher dose (50.1-120 mg MED) groups. A statistically significant trend emerged where higher prescription opioid dose was associated with moderately sized effects including greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization. Rates of potential alcohol and substance use disorders also differed among groups. Findings from this evaluation reveal significant differences in pain-related and substance-related factors on the basis of prescription opioid dose. PERSPECTIVE: This study included 517 patients who were prescribed long-term opioid therapy and compared differences on pain- and mental health-related variables on the basis of prescription opioid dose. Findings reveal small- to medium-sized differences on pain-related variables, alcohol and substance use, and health care utilization on the basis of the dose of opioid prescribed.

Treatment changes following aberrant urine drug test results for patients prescribed chronic opioid therapy.

BACKGROUND/OBJECTIVE: Urine drug testing (UDT) may be used to help screen for prescription opioid misuse. There are little data available describing usual pain care practices for patients who have aberrant UDT results. The goal of this research was to evaluate the clinical care for patients prescribed chronic opioid therapy (COT) and have an aberrant UDT. DESIGN: Retrospective cohort study. SETTING: VA Medical Center in the Pacific Northwest. PARTICIPANTS: Patients with chronic pain who were prescribed COT and had a UDT result that was positive for an illicit or nonprescribed substance. MAIN OUTCOME MEASURES: This was an exploratory study designed to document usual care practices. RESULTS: Participants' (n = 83) mean age was 49.5 (SD = 9.6) and 81.5 percent were male. The most common substances detected on UDT were marijuana (69 percent) or a nonprescribed opioid (25 percent); 18 percent had a UDT positive for two or more substances. Plans to modify treatment were documented in 69 percent of cases. The most common treatment change after aberrant UDT results was instituting more frequent UDTs, which occurred in 43 percent of cases. Clinicians documented plans to alter their opioid prescribing (eg, terminating opioids, requiring more frequent fills, changing opioid dose, or transitioning to another opioid) in 52 percent of cases, but implemented these changes in only 24 percent. DISCUSSION: Current methods for optimizing treatment after obtaining aberrant UDT results should be enhanced. To improve the utility of UDT to reduce prescription opioid misuse, additional interventions and support for clinicians need to be developed and tested.