Associations between smoking and pain in early recovery in residential substance use treatment-seekers.

INTRODUCTION: A growing literature indicates bidirectional associations between pain and tobacco use. Cigarette smokers are at increased risk for chronic pain, and observational and experimental studies indicate that pain increases motivation to smoke. Tobacco use disorder frequently co-occurs with other substance use disorders, which are also associated with chronic pain vulnerability. Despite evidence that pain significantly predicts smoking and relapse, associations between smoking history/trajectory and changes in pain over the course of treatment have not been characterized. The objective of the study was to determine the association between in-treatment smoking trajectory, pack-years (i.e., number of cigarette packs smoked per day multiplied by smoking duration), pain-related interference in daily activities, and pain intensity over the course of residential treatment. METHODS: In this study, 280 adult smokers in a residential SUD treatment center in North Central Florida completed questionnaires assessing cigarette use, pain intensity, and pain interference at treatment entry and discharge (Mean = 80.3 days, SD = 25.6). Most participants were diagnosed with alcohol use disorder (66.1 %). Opioid (27.9 %) and cannabis use disorders (29.6 %) were also common. Participants were grouped by whether their smoking increased (n = 36), decreased (n = 46), or stayed the same (n = 133) from entry to discharge. RESULTS: Analyses indicated a positive association between pack-years and pain intensity at both baseline (r = 0.185, p = 0.018) and discharge (r = 0.184, p = 0.019). Smoking trajectory was associated with pack-years, with those decreasing smoking having greater pack-years than those sustaining or increasing use [F(2,136) = 8.62, p < 0.01, η2p = 0.114]. Mixed general linear models indicated pain intensity [F(1,274) = 44.15, p < 0.0001, η2p = 0.138] and interference in day-to-day activities [F(1,276) = 31.79, p < 0.0001, η2p = 0.103] decreased significantly over time. However, there was no main effect of smoking trajectory on pain intensity [F(2,212) = 2.051, p = 0.131, η2p = 0.019] or of smoking trajectory by time interaction [F(2, 212) = 1.228, p = 0.295, η2p = 0.011]. CONCLUSIONS: Overall, findings provide evidence that smoking behavior influences pain within the context of residential substance use treatment. Given that pain is associated with urge to use substances and risk of return to use, more consistent and rigorous assessment of pain and proactive pain management is likely to enhance substance use treatment outcomes among people who smoke.

Pain Predicts Dropout From Substance Use Treatment.

OBJECTIVE: This project aimed to characterize the relationship between physical pain experienced at time of entry to residential treatment for substance use disorders (SUDs) and the frequency of treatment dropout. We hypothesized that both endorsement of recent pain and higher magnitude of endorsed pain intensity would be associated with higher dropout rates. We further hypothesized that these effects would be exacerbated among patients with opioid use disorder (OUD). METHOD: Participants included 1,095 individuals in residential treatment for SUD. Data were collected within 24 hours of treatment entry. Analyses were conducted using logistic regression with dropout as the dependent variable. Dropout was operationally defined as leaving treatment against medical advice or being discharged from treatment because of use of substances. Pain (including endorsement and intensity) was the primary independent variable in all analyses. Analyses included demographic and affective covariates and included both main effects of OUD and interaction terms between OUD and pain. RESULTS: Pain endorsement was associated with greater frequency of dropout (odds ratio [OR] = 1.49, p = .04). Higher levels of pain intensity predicted increased rates of dropout (OR = 1.13, p < .01). In contrast with our hypothesis, no interactions between OUD and pain were observed. CONCLUSIONS: These results underscore the import of integrating pain monitoring and pain interventions as core components of treatment for SUD. Our findings are highly consistent with a growing literature recognizing the impact of pain across a constellation of important treatment outcomes and provide novel data strongly suggesting that pain predicts early cessation of treatment.

Urine and hair drug test results associated with daily consumption of codeine-predominant poppy seed food products.

This study examined the urine and hair opiate profiles associated with the daily consumption of presumptive codeine-predominant poppy seed food products. Ten participants consumed one of five food products at breakfast for 10 consecutive days. Baseline urine and hair samples were collected on Day 1. The urine samples were collected 4, 8 and 12 h following poppy seed consumption on Days 1 and 10, and the first morning void urine samples were collected on Days 2-10. A second hair specimen was collected on Day 20 ± 2. Urine drug test results: Three of the food products were associated with opiate-negative urine drug test results at all time points at a 300 ng/mL cut-off. Two of the food products were associated with opiate-positive drug test results at all non-baseline time points at a 300 ng/mL cut-off. Of these, all samples (n = 60) were codeine-positive, and 27 (45%) were morphine-positive. Codeine concentrations exceeded morphine concentrations in every sample and always by multiples. Thirty-nine of the 60 samples (65%) were codeine-positive at a 2,000 ng/mL cut-off, while none of these samples were morphine-positive at this cut-off. None of the 60 samples reached an opiate threshold of 15,000 ng/mL, although one participant produced a maximum codeine concentration of 13,161 ng/mL (13,854 ng/mg creatinine). There was no clear trend toward increasing urinary opiate concentrations over the course of the study. Hair drug test results: The hair samples of two participants produced quantifiable codeine (41 pg/mg and 51 pg/mg), but no sample reached a common reporting threshold of 200 pg/mg for codeine or morphine.

Co-occurring pain and addiction: prognostic implications for healthcare professionals in residential treatment for substance use disorder.

Objectives: Chronic pain is both an important antecedent and consequence of substance use. Although evidence suggests healthcare professionals may be uniquely vulnerable to chronic pain, this vulnerability remains largely unexamined in the context of recovery from substance use disorders (SUDs). We characterized pain in a sample of treatment-seeking individuals, examined potential differences in pain trajectories between healthcare professionals and non-healthcare patients, and interrogated potential pain-related vulnerabilities in treatment outcomes between these groups. Methods: Patients with SUDs (n = 663; 251 women) completed questionnaires indexing pain intensity, craving, and abstinence self-efficacy (including self-efficacy in pain-related contexts). Assessments were conducted at treatment entry, 30 days, and discharge. Analyses included chi-square and longitudinal mixed models. Results: The proportion of healthcare and non-healthcare patients endorsing recent pain was equivalent (χ2=1.78, p=.18). Healthcare professionals reported lower pain intensity (p = 0.02) and higher abstinence self-efficacy (p < 0.001). Profession by pain interactions (ps <.040) revealed that among medical professionals, associations between pain and all three treatment outcomes of interest were more robust relative to the non-healthcare group. Conclusions: Results suggest that although healthcare professionals endorse similar rates of pain and lower average pain intensity, they may be uniquely vulnerable to pain-related disruptions in craving and abstinence self-efficacy.

The association between adverse childhood experiences and treatment response for adults with alcohol and other drug use disorders.

BACKGROUND AND OBJECTIVES: Adverse events during childhood increase the risk for the development of substance use disorders (SUDs). This study examined the association between adverse childhood experiences (ACEs) and SUD treatment response. METHODS: This cohort analysis included data from longitudinal clinical assessments extracted from the records of 438 consenting individuals undergoing SUD treatment (63% male; 88.8% White). Mixed effects models evaluated the relationship between scores on the ACE questionnaire and indicators of treatment response (i.e., alcohol and drug abstinence self-efficacy; symptoms of depression, anxiety, and posttraumatic stress disorder) for individuals with alcohol-related (n = 332) and other drug-related (n = 275) diagnoses, with some participants included in both groups. RESULTS: Treatment response varied as a function of ACEs, with the magnitude of differences varying across time in treatment. Relative to those with no ACE history, those who experienced ≥2 ACEs reported worse depression, anxiety, PTSD symptoms, and alcohol/drug abstinence self-efficacy at baseline, with many differences remaining at the 30-day assessment. All differences abated by discharge, with the exception of PTSD symptoms among those in the drug use group with a history of ≥4 ACEs. Male gender and older age were generally associated with lower symptomology and higher abstinence self-efficacy. DISCUSSION AND CONCLUSIONS: Assessing ACE history early in SUD treatment may improve treatment planning and prognosis. Future studies should evaluate the role of trauma-informed programming and individual interventions to improve treatment response. SCIENTIFIC SIGNIFICANCE: This study demonstrates the association between adverse childhood experiences and symptom severity among patients across participation in SUD treatment.

Blood Phosphatidylethanol (PEth) Concentrations following Intensive Use of an Alcohol-based Hand Sanitizer.

Alcohol use disorders are prevalent in the USA and throughout the world. Monitoring for alcohol abstinence is useful in several clinical and forensic contexts. The direct alcohol biomarkers have the requisite sensitivity and specificity for abstinence monitoring. The relatively new direct biomarker phosphatidylethanol (PEth), measured in blood, is gaining increasing acceptance in monitoring abstinence from beverage alcohol consumption, but there remains little research addressing the potential for PEth formation consequent to incidental alcohol exposures. In the midst of the coronavirus disease 2019 pandemic, high-alcohol content hand sanitizer is a particularly important source of nonbeverage alcohol exposure. To assess the extent of alcohol absorption and subsequent formation of blood PEth related to intensive use of high alcohol content hand sanitizer, we recruited 15 participants to use a 70% ethyl alcohol-based hand sanitizer 24-100 times daily, for 12-13 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography--tandem mass spectrometry. Our hypothesis that blood PEth concentrations would fail to reach a 20 ng/mL threshold was confirmed. This work adds to the nascent literature on the effects of incidental alcohol exposures on blood PEth formation.

Patient experiences with tobacco use during substance use disorder treatment and early recovery: a mixed method analysis of phone interview responses.

Tobacco use and related mortality remain disproportionately high among individuals with substance use disorders (SUDs). Though engagement in tobacco cessation interventions is associated with improved long-term recovery, many individuals in SUD treatment do not participate. The goal of the present study was to better understand patient views regarding tobacco use/cessation during residential SUD treatment, in order to decrease barriers for this vulnerable population. This study utilized a cross-sectional design and mixed methods analysis. Following discharge from residential SUD treatment, individuals who reported any use of tobacco were invited to participate in a brief phone interview. Forty-one of the 60 who were reached (68%) agreed to participate. Responses were quantified for analysis when appropriate, and descriptive statistics were calculated for quantitative data. Thematic analysis was used to analyze qualitative responses. Most respondents (83%) reported that tobacco cessation was an important goal and were open to tobacco cessation treatment. The vast majority (85%) did not think tobacco use interfered with their recovery from other SUDs. Respondents noted the socially-reinforcing nature of tobacco use in treatment, and indicated a desire for increased access to cessation services. Results suggest increased patient education and changes to treatment center tobacco policies may assist individuals recovering from SUD with tobacco cessation.

Poppy Seed Consumption May Be Associated with Codeine-Only Urine Drug Test Results.

Consumption of poppy seed-containing food products can result in opiate-positive urine drug test results and may pose challenges in distinguishing poppy seed consumption from opiate administration. In this context, guidance has suggested that codeine concentrations exceeding 300 ng/mL coupled with morphine-to-codeine ratios <2 are indicative of codeine consumption and, therefore, exclude poppy seed consumption as a legitimate explanation for the test result. In recent years, we performed independent medical examinations of three individuals who produced codeine-positive/morphine-negative (300 ng/mL) forensic urine drug test results but denied codeine administration, attributing their test results to the consumption of specific poppy seed-containing food products. In the present study, 11 participants consumed one of the 10 unique poppy seed-containing food products, including the three implicated food products. Six of 33 non-baseline urine samples (18%)-representing three food products-were positive for codeine and negative for morphine at 300 ng/mL cut-offs (and therefore featured morphine-to-codeine ratios <2). This study adds to a small literature indicating that consumption of poppy seed-containing food products cannot reliably be distinguished from codeine administration based on previously published urinary opiate concentrations and ratios. An important caveat is that in none of these cases did maximum urinary codeine concentrations exceed 1,300 µg/g creatinine.

Longitudinal associations between pain and substance use disorder treatment outcomes.

INTRODUCTION: Pain is commonly reported among those in treatment for substance use disorders (SUD) and is associated with poorer SUD treatment outcomes. The current study examined the trajectory of pain over the course of SUD treatment and associations with substance use outcomes. METHODS: This observational study included adults seeking treatment for alcohol, cannabis, or opioid use disorders (N = 811). Participants completed a battery of assessments at treatment admission, 30 days post admission, and at discharge, including measures of demographics, pain, quality of life, abstinence self-efficacy, and craving. RESULTS: Analyses indicated linear reductions in pain intensity and interference over time. Significant interactive effects were observed for opioid use disorder (OUD) and time, such that participants with OUD had greater reductions in pain intensity and interference over time compared to those without OUD. Elevated pain intensity was associated with negative treatment outcomes, including reduced quality of life and abstinence self-efficacy, and greater craving and negative affect. CONCLUSIONS: Reductions in pain occur over the course of SUD treatment, particularly for those with OUD. Greater pain was also associated with adverse SUD treatment outcomes. Results suggest that treatment and associated abstinence may be beneficial for those with co-occurring pain and SUD, highlighting an additional benefit of improving access to SUD treatment for patients and health care systems. Future research should replicate these findings among diverse samples and further characterize the trajectory of pain during and after SUD treatment.

Blood Phosphatidylethanol Concentrations Following Regular Exposure to an Alcohol-Based Mouthwash.

Direct biomarkers of ethanol are used to monitor individuals who are required to abstain from ethanol consumption. In recent years, blood phosphatidylethanol (PEth) has gained acceptance in clinical and forensic contexts as an abstinence marker. Its elimination half-life of several days provides a window of detection of days to weeks. However, there is no research addressing the extent of PEth formation related to extraneous ethanol exposures. To assess the degree of ethanol absorption and subsequent formation of blood PEth related a common extraneous exposure, regular use of an ethanol-containing mouthwash, we recruited 16 participants to gargle with an alcohol-based mouthwash (21.6% ethanol) 4 times daily, for 12 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography-tandem mass spectrometry. Our hypothesis that blood PEth concentrations would not equal or exceed 20 ng/mL was confirmed. Although the data suggest that regular use of mouthwash is unlikely to result in suprathreshold PEth concentrations, this work highlights the importance of considering extraneous ethanol exposures in clinical decision-making and in future research.

The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs.

Direct alcohol biomarkers, including urinary ethyl glucuronide (EtG), urinary ethyl sulfate (EtS), and blood phosphatidylethanol (PEth), are used to monitor alcohol abstinence in individuals who are mandated to abstain. In this consecutive case series study, we examined 1000 forensic reports of participants enrolled in a professionals health program who were contractually obligated to abstain from alcohol and who underwent recovery status evaluations. We identified 52 evaluations in which urinary EtG, EtS, and blood PEth were measured and which produced a positive result for at least one of these analytes. PEth, at a cutoff concentration of 20 ng/mL, revealed alcohol use more frequently than EtG or EtS at our laboratory's cutoff concentrations of 100 and 25 ng/mL, respectively. This was true, as well, at alternative EtG/EtS cutoff concentrations of 200/50, 300/75, and 400/100 ng/mL. PEth was more likely than EtG/EtS to be positive in participants previously diagnosed with alcohol use disorders (AUD), whereas EtG/EtS was more likely than PEth to be positive in participants without AUD. In this study, blood PEth was the most sensitive biomarker for evidencing alcohol use.

Persistent Urinary Ethyl Sulfate in the Absence of Urinary Ethyl Glucuronide in a Patient with Alcohol Use Disorder Who Claimed Abstinence.

A 48-year-old nurse with an alcohol use disorder history was being monitored in a professional health program. She consistently produced low-to-moderate urinary ethyl sulfate (EtS) concentrations in the absence of detectable urinary ethyl glucuronide (EtG), blood phosphatidylethanol and breath alcohol. She denied intentional ethanol consumption. After prolonged monitoring in a drug treatment program, including a period in a controlled environment, we concluded that this individual's urinary EtS likely resulted from anatomical and microbial factors related to Roux-en-Y gastric bypass surgery, with possible contributions from hidden dietary sources of ethanol. We have no definitive explanation for the lack of urinary EtG.

Neuropsychological impairment associated with substance use by physicians.

Physicians and other healthcare professionals are at increased risk for the development of substance use disorders when compared to the general population. Substance use is associated with impairment in neuropsychological functioning, which may impact physicians' ability to practice with reasonable skill and safety. This review describes common neurocognitive deficits observed following use of various substance classes, including stimulants, benzodiazepines, cannabis, alcohol, and opioids. It also reviews the neurocognitive impact of pharmaceutical treatments for opioid use disorder. Clinical implications, including evaluation, treatment, and planning for return-to-work, are discussed. The importance of continued testing/monitoring following the acute treatment phase is emphasized. A case example highlights important issues that must be considered when a physician is referred due to suspected impairment.

The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the Dots for Recovery.

There are some who suggest that alcoholism and drug abuse are not diseases at all and that they are not consequences of a brain disorder as espoused recently by the American Society of Addiction Medicine (ASAM). Some would argue that addicts can quit on their own and moderate their alcohol and drug intake. When they present to a treatment program or enter the 12 Step Program & Fellowship, many addicts finally achieve complete abstinence. However, when controlled drinking fails, there may be successful alternatives that fit particular groups of individuals. In this expert opinion, we attempt to identify personal differences in recovery, by clarifying the molecular neurobiological basis of each step of the 12 Step Program. We explore the impact that the molecular neurobiological basis of the 12 steps can have on Reward Deficiency Syndrome (RDS) despite addiction risk gene polymorphisms. This exploration has already been accomplished in part by Blum and others in a 2013 Springer Neuroscience Brief. The purpose of this expert opinion is to briefly, outline the molecular neurobiological and genetic links, especially as they relate to the role of epigenetic changes that are possible in individuals who regularly attend AA meetings. It begs the question as to whether "12 steps programs and fellowship" does induce neuroplasticity and continued dopamine D2 receptor proliferation despite carrying hypodopaminergic type polymorphisms such as DRD2 A1 allele. "Like-minded" doctors of ASAM are cognizant that patients in treatment without the "psycho-social-spiritual trio," may not be obtaining the important benefits afforded by adopting 12-step doctrines. Are we better off with coupling medical assisted treatment (MAT) that favors combining dopamine agonist modalities (DAM) as possible histone-deacetylase activators with the 12 steps followed by a program that embraces either one or the other? While there are many unanswered questions, at least we have reached a time when "science meets recovery," and in doing so, can further redeem joy in recovery.

Ethyl glucuronide, ethyl sulfate, and ethanol in urine after intensive exposure to high ethanol content mouthwash.

To determine the degree of ethanol absorption and the resultant formation and urinary excretion of its conjugated metabolites following intensive use of high ethanol content mouthwash, 10 subjects gargled with Listerine(®) antiseptic 4 times daily for 3» days. First morning void urine specimens were collected on each of the four study days and post-gargle specimens were collected at 2, 4, and 6 h after the final gargle of the study. Urine ethanol, ethyl glucuronide (EtG), ethyl sulfate (EtS), and creatinine were measured. Ethanol was below the positive threshold of 20 mg/dL in all of the urine specimens. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (6 and 82 ng/mL; 16 and 83 µg/g creatinine). Only one specimen contained detectable EtG (173 ng/mL; 117 µg/g creatinine). EtS was detected in the urine of seven study subjects, but was not detected in the single specimen that had detectable EtG. The maximum EtS concentrations were 104 ng/mL and 112 µg/g creatinine (in different subjects). Three subjects produced a total of eight (non-baseline) urinary EtS concentrations above 50 ng/mL or 50 µg/g creatinine and three EtS concentrations exceeding 100 ng/mL or 100 µg/g creatinine. In patients being monitored for ethanol use by urinary EtG and EtS concentrations, currently accepted EtG and EtS cutoffs of 500 ng/mL are adequate to distinguish between ethanol consumption and four times daily use of high ethanol content mouthwash.

Ethyl glucuronide, ethyl sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer.

To assess the degree of ethanol absorption and subsequent formation of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) following sustained application of hand sanitizer, 11 volunteers cleansed their hands with Purell(™) hand sanitizer (62% ethanol) every 5 min for 10 h on three consecutive days. Urine specimens were obtained at the beginning and end of each day of the study, and on the morning of the fourth day. Urinary creatinine, ethanol, EtG, and EtS concentrations were measured. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (73 and 37 ng/mL). None of the pre-study specimens had detectable ethanol. The maximum EtG and EtS concentrations over the course of the study were 2001 and 84 ng/mL, respectively, and nearly all EtG- and EtS-positive urine specimens were collected at the conclusion of the individual study days. Only two specimens had detectable EtG at the beginning of any study day (96 and 139 ng/mL), and only one specimen had detectable EtS at the beginning of a study day (64 ng/mL), in addition to the two with detectable EtS prior to the study. Creatinine-adjusted maximum EtG and EtS concentrations were 1998 and 94 µg/g creatinine, respectively. In patients being monitored for ethanol use by urinary EtG concentrations, currently accepted EtG cutoffs do not distinguish between ethanol consumption and incidental exposures, particularly when urine specimens are obtained shortly after sustained use of ethanolcontaining hand sanitizer. Our data suggest that EtS may be an important complementary biomarker in distinguishing ethanol consumption from dermal exposure.