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BACKGROUND: The development of alcohol use disorder (AUD) is a major concern in public health, and cognitive impairments caused by alcohol are involved in this process. Emerging neurobiological evidence suggests that donepezil, an anticholinesterase agent, may improve AUD treatment outcomes by enhancing neurocognitive functioning. Previous research has also suggested that cognitive remediation therapy (CRT) could potentially improve cognitive function and AUD treatment outcomes. We present the rationale and design of a trial to evaluate the combination of donepezil and cognitive remediation therapy (donepezil + CRT) as an intervention for AUD. METHODS: We propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as an intervention for AUD. The main goal of the study is to evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking days and improving neurocognitive functioning. A total of 160 patients (4 groups, 40 per each group) with AUD between the ages of 18-80 years will be recruited at Yale University and the VA Connecticut Healthcare System. Primary outcome measures include 1) heavy drinking by Timeline Follow Back (TLFB) over 13 weeks and 2) global neurocognitive functioning by a global index of neurocognitive function score at 7 and 13 weeks. DISCUSSION: This protocol paper describes the rationale and proposed methods for the randomized controlled trial for improving AUD treatment outcomes. This project has significant clinical potential to help patients suffering from AUD by improving their cognition and reducing alcohol consumption. TRIAL REGISTRATION: NCT05042102.
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Opioid use disorder (OUD) and chronic pain are commonly co-occurring disorders which can exacerbate each other. Sex/gender differences have been shown in aspects of the clinical course and biological underpinnings of both OUD and chronic pain. The purpose of this scoping review is to summarize literature which has addressed sex/gender differences in relation to the confluence of OUD and chronic pain. This review focused on peer-reviewed journal articles with human subjects and addressing (a) opioid misuse, chronic opioid use or opioid use disorder (OUD), (b) chronic or persistent pain and (c) sex/gender differences in relation to OUD and/or chronic pain. Of the 146 papers identified by the search strategy, 30 met the criteria for inclusion. Charting focused on a priori themes of chronic pain, opioid misuse/OUD and sex/gender in sample, predictor and outcome variables, and key study findings. The majority of research identified was cross-sectional in nature, and sex/gender differences and treatment effects were largely included as post-hoc analyses. Together, the results of this early work align with higher prevalence for OUD in men/males and chronic pain in women/females, while adding critical information with respect to potential sex/gender differences in the development and treatment of their co-occurrence across a range of biological and psychosocial factors. Findings underline the importance of considering sex and gender in the intersection of the development and treatment of OUD and chronic pain.
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INTRODUCTION: Attentional bias (AB) is believed to be an important factor in the development and maintenance of both opioid use disorder (OUD) and chronic pain. Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), produce analgesic effects via processes that are potentially relevant to AB and is commonly used by persons with OUD. This exploratory study investigated if THC influences AB towards pain and opioid cues individuals with OUD. METHODS: Using a within-subject, crossover design, 27 adults receiving methadone were randomly assigned to receive single doses of oral THC (10 mg, 20 mg administered as dronabinol) or placebo across three, 5-h sessions. During each session, a visual probe task was used to measure AB to pain and opioid cues at baseline and 120 min post-THC administration. RESULTS: Mixed-effects models examined main effects of THC dose, time, and their interaction across all participants; findings were then stratified by methadone dose (low dose <90 mg/day and high dose ≥90 mg/day). Among individuals receiving high doses of methadone, a significant interaction was observed such that AB towards opioids increased following 10 mg THC administration and decreased following 20 mg THC administration. Additionally, participants receiving low doses of methadone showed significant increases in the variability of opioid-related AB post THC administration. CONCLUSION: We provide preliminary evidence showing that THC may cause dose-dependent effects on selective attention for opioid cues among methadone patients. These results underscore the need for further clinical investigation into the effects of cannabinoids and other substances with potential analgesic and addictive properties among persons with OUD.
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RATIONALE: No previous studies examined the discriminative stimulus effects of intravenous (IV) nicotine in humans. OBJECTIVES: To evaluate a pulsed IV nicotine infusion procedure designed to mimic inhaled nicotine delivery and to identify a range of nicotine doses that may capture the threshold doses for the subjective and discriminative stimulus effects of nicotine. By determining these thresholds, we can gain valuable insights into the addictive threshold of nicotine. METHODS: Eleven participants had 2 Test Sessions following overnight abstinence from smoking. Test Session 1 examined participants' ability to discriminate 0.1 mg nicotine/pulse nicotine from saline. Test Session 2 examined if participants can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline. These nicotine doses were delivered as a cluster of 4 pulsed-nicotine infusions of 2-second duration with a 28-second interval between each pulse. RESULTS: The lowest doses of nicotine that produced greater responses than saline for discrimination, subjective effects, and heart rate ranged from 0.05 to 0.1 mg nicotine/pulse. CONCLUSIONS: These findings support the validity of our pulsed-infusion procedure as a model for nicotine delivery by smoking and its utility in examining factors that may impact the addictive threshold of nicotine.
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Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca , Nicotina , Humanos , Nicotina/administración & dosificación , Masculino , Adulto , Femenino , Infusiones Intravenosas , Adulto Joven , Frecuencia Cardíaca/efectos de los fármacos , Fumar , Agonistas Nicotínicos/administración & dosificación , Agonistas Nicotínicos/farmacología , Discriminación en Psicología/efectos de los fármacosRESUMEN
INTRODUCTION: Avoidance is a well-documented risk factor for poor mental and physical health outcomes. However, limited research has explored this relationship specifically among trauma-exposed veterans, a population known to be particularly prone to avoidance behavior. Conceptually, avoidance is often divided into two distinct but overlapping constructs - experiential avoidance (resisting distressing internal states) and behavioral avoidance (avoiding or changing experiences that elicit distress). In this exploratory survey study, we examined associations between behavioral and experiential avoidance and mental, physical, and cognitive functioning, as well as quality of life. METHODS: Veterans with a trauma history (N = 89) completed a 121-item survey containing validated assessments to examine several mental and physical health and wellness-related variables. Correlations between experiential avoidance and outcome measures, and behavioral avoidance and outcome measures, were explored. Multivariable linear regression analyses were conducted to explore the association between experiential and behavioral avoidance on mental health outcomes. In addition, we conducted exploratory analyses in which we investigated these correlations in those who screened positive for PTSD versus those who did not, and between different types of behavioral avoidance and major outcomes. RESULTS: Experiential avoidance was moderately correlated with distress from depressive symptoms, distress related to past trauma, and health-related and cognitive dysfunction. Experiential Avoidance was weakly correlated with distress from anxiety symptoms and poorer quality of life. Behavioral avoidance was moderately correlated with distress from depressive and anxiety symptoms, distress related to past trauma, and cognitive dysfunction, and was weakly correlated with health-related dysfunction and poorer quality of life. Results from multivariable analyses revealed that experiential avoidance was associated with greater distress related to depressive symptoms and past trauma, and behavioral avoidance was associated with greater distress related to anxiety symptoms, depressive symptoms, and past trauma. CONCLUSIONS: Results suggest that avoidance negatively influences major domains of mental and physical health as well as functioning and health-related quality of life in trauma-exposed veterans. They further indicate that behavioral and experiential avoidance may be differentially linked to mental health outcomes. The results support the idea that avoidance may be an important marker for psychosocial functioning and may serve as a treatment target in trauma-exposed veterans.
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Reacción de Prevención , Trastornos por Estrés Postraumático , Veteranos , Humanos , Veteranos/psicología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trastornos por Estrés Postraumático/epidemiología , Reacción de Prevención/fisiología , Calidad de Vida , Trauma Psicológico , Depresión , AncianoRESUMEN
Chronic pain and opioid use disorder (OUD) are major public health problems, with rising opioid-related overdose deaths linked to increased opioid prescriptions for pain management. Novel treatment approaches for these commonly comorbid disorders are needed. Growing evidence supports a role for glial activation for both chronic pain and substance use disorders, including OUD. This review provides an overview of glial modulators as a novel treatment approach for comorbid pain and OUD. We aim to synthesize clinical studies investigating the efficacy of glial modulators in treating these comorbid disorders. We conducted a literature search of PubMed and Google Scholar databases in October 2023 to identify relevant clinical trials. The included studies varied in terms of patient population, study methodology and outcomes assessed, and were often limited by small sample sizes and other methodological issues. Additionally, several glial modulators have yet to be studied for chronic pain and OUD. Despite these limitations, these studies yielded positive signals that merit further investigation. Both chronic pain and OUD remain significant public health problems, with many treatment challenges. Glial modulators continue to hold promise as novel therapeutics for comorbid pain and OUD, given positive indications that they can improve pain measures, and reduce addiction-related outcomes. As our understanding of the mechanisms underlying the contributions of glial modulators to pain and addiction behaviours deepens, we will be better equipped to identify more specific therapeutic targets for chronic pain and OUD.
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The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.
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BACKGROUND: Chronic pain is common among individuals with opioid use disorder (OUD) who are maintained on medications for OUD (MOUD; eg, buprenorphine or methadone). Chronic pain is associated with worse retention and higher levels of substance use. Treatment of individuals with chronic pain receiving MOUD can be challenging due to their increased clinical complexity. Given the acute and growing nature of the opioid crisis, MOUD is increasingly offered in a wide range of settings, where high-quality, clinician-delivered, empirically validated behavioral treatment for chronic pain may not be available. Therefore, digital treatments that support patient self-management of chronic pain and OUD have the potential for wider implementation to fill this gap. OBJECTIVE: This study aims to evaluate the efficacy of Integrating the Management of Pain and Addiction via Collaborative Treatment (IMPACT), an interactive digital treatment program with asynchronous coach feedback, compared to treatment as usual (TAU) in individuals with chronic pain and OUD receiving MOUD. METHODS: Adult participants (n=160) receiving MOUD and reporting bothersome or high-impact chronic pain will be recruited from outpatient opioid treatment programs in Connecticut (United States) and randomized 1:1 to either IMPACT+TAU or TAU only. Participants randomized to IMPACT+TAU will complete an interactive digital treatment that includes 9 modules promoting training in pain and addiction coping skills and a progressive walking program. The program is augmented with a weekly personalized voice message from a trained coach based on daily participant-reported pain intensity and interference, craving to use opioids, sleep quality, daily steps, pain self-efficacy, MOUD adherence, and engagement with IMPACT collected through digital surveys. Outcomes will be assessed at 3, 6, and 9 months post randomization. The primary outcome is MOUD retention at 3 months post randomization (ie, post treatment). Secondary outcomes include pain interference, physical functioning, MOUD adherence, substance use, craving, pain intensity, sleep disturbance, pain catastrophizing, and pain self-efficacy. Semistructured qualitative interviews with study participants (n=34) randomized to IMPACT (completers and noncompleters) will be conducted to evaluate the usability and quality of the program and its outcomes. RESULTS: The study has received institutional review board approval and began recruitment at 1 site in July 2022. Recruitment at a second site started in January 2023, with a third and final site anticipated to begin recruitment in January 2024. Data collection is expected to continue through June 2025. CONCLUSIONS: Establishing efficacy for a digital treatment for addiction and chronic pain that can be integrated into MOUD clinics will provide options for individuals with OUD, which reduce barriers to behavioral treatment. Participant feedback on the intervention will inform updates or modifications to improve engagement and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05204576; https://clinicaltrials.gov/ct2/show/NCT05204576. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54342.
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AIMS: Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross-over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose. METHODS: Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4-h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min. RESULTS: Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P = .006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self-reported pain revealed a three-way interaction between dosing condition, craving and time (F(5,197) = 2.39, P = .039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P-range = .004-.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P = .050). CONCLUSIONS: These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose.
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INTRODUCTION: Childhood trauma is known to be associated with nicotine dependence, yet limited smoking outcomes have been examined and few studies have assessed associations between specific trauma subscales and smoking. Additionally, sex differences in trauma-smoking relations are understudied. This study examined associations between childhood trauma and several smoking-related outcomes in adults who smoke after overnight abstinence. AIMS AND METHODS: People who smoke (N = 205) completed self-report and biochemical assessments evaluating childhood trauma, affect, nicotine dependence, smoking urges, withdrawal, and plasma cortisol and cotinine levels. Smoking outcomes were compared between those with and without a history of moderate to severe childhood trauma among the total sample and by sex. RESULTS: Relative to those with no to minimal abuse, those with moderate to severe abuse had higher negative affect, withdrawal severity, and plasma cotinine levels. Exploratory analyses revealed that women were more likely than men to have urges to smoke for negative reinforcement and have higher withdrawal severity, but no interactions between abuse group and sex were observed. Examining specific trauma subscales, the moderate to severe emotional abuse group had more severe nicotine dependence, negative affect, and withdrawal compared to the no to minimal group. The moderate to severe sexual abuse group had more severe nicotine dependence and withdrawal compared to the no to minimal group. CONCLUSIONS: Exposure to childhood trauma is associated with more severe nicotine dependence, negative affect, withdrawal, and higher plasma cotinine levels. Findings also indicate that different types of trauma may differentially affect smoking behaviors. IMPLICATIONS: This study of adults who smoke finds that childhood trauma history may be a marker for smoking susceptibility and suggests that individuals with experiences of emotional and sexual abuse may require targeted forms of smoking cessation interventions. Moreover, findings suggest that smoking risks may differ for men and women. Findings inform public health interventions intended to reduce cigarette use in individuals with exposure to childhood trauma.
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Experiencias Adversas de la Infancia , Cese del Hábito de Fumar , Síndrome de Abstinencia a Sustancias , Tabaquismo , Adulto , Humanos , Femenino , Masculino , Niño , Tabaquismo/epidemiología , Tabaquismo/psicología , Cese del Hábito de Fumar/psicología , Síndrome de Abstinencia a Sustancias/psicología , Cotinina , Uso de TabacoRESUMEN
BACKGROUND AND OBJECTIVES: Childhood trauma (CT) increases addiction vulnerability. We examined CT's impact on delta-9-tetrahydrocannabinol (THC) effects. METHODS: This is a post-hoc analysis of a randomized, placebo-controlled, crossover trial investigating the effects of oral THC (10, 20 mg) among 25 persons receiving methadone for opioid use disorder (OUD). RESULTS: Greater CT was associated with lower aversive effects from higher THC doses (20 mg) (p = .006). DISCUSSION AND CONCLUSIONS: CT may reduce the subjective aversive effects of THC, potentially leading to greater cannabis use in individuals with OUD. SCIENTIFIC SIGNIFICANCE: These findings offer insights into THC's risks versus benefits in OUD subgroups and emphasize assessing CT in OUD treatment and research.
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The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta-9-tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within-subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5-h test sessions. Measures of experimental and self-reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed-effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low-dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk-benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.
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Dronabinol , Trastornos Relacionados con Opioides , Humanos , Femenino , Masculino , Dronabinol/farmacología , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Metadona/uso terapéutico , DolorRESUMEN
BACKGROUND: Despite high co-occurrence, chronic pain is often unaddressed in treatment for opioid use disorder (OUD) and little is known about mechanisms that may underlie associations between pain and opioid use. Using an attentional bias (AB) task with both pain and opioid cues, we evaluated a cognitive bias modification (CBM) task administered during regularly scheduled medications for OUD (mOUD) dosing visits. The current study evaluated the feasibility, acceptability, and preliminary efficacy of the CBM task. Outcomes for AB tasks used traditional mean-based score and trial-level bias scores (TLBS). METHODS: In a double-blind, randomized controlled trial, 28 individuals with OUD and chronic pain engaged in mOUD were randomized to either CBM or an AB control condition and completed up to three tasks per week for four weeks. Standard AB task was completed at baseline and post-treatment. Participants completed feasibility and acceptability measures, and preliminary efficacy (i.e., change in AB) was assessed using ANOVA models. RESULTS: Participants attended 83.3% of scheduled sessions and generally reported the task was enjoyable, credible, and easy to complete. Preliminary results demonstrated a condition by time interaction highlighting a reduction in AB in the CBM group but not the control group in opioid TLBS variability (F[1,26]=5.01, p = .034) and pain TLBS towards (F[1,26]=6.42, p = .018) and pain TLBS variability (F[1,26]=5.24, p = .03). CONCLUSIONS: The current study supports integrating brief, computer-based tasks designed to reduce AB into mOUD clinical care. The preliminary results suggest that TLBS outcomes may be more sensitive to capture changes in AB; however, larger studies are required.
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Buprenorfina , Dolor Crónico , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Señales (Psicología) , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/psicología , Estudios de Factibilidad , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/psicología , Cognición , Buprenorfina/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Metadona/uso terapéuticoRESUMEN
OBJECTIVE: Although the efficacy of evidence-based treatments for posttraumatic stress disorder (PTSD) has been well established, high rates of treatment dropout and/or nonresponse or under-response to treatment suggest a need to explore novel treatment approaches. Most current research has focused on DSM-based categorical outcomes as primary indicators of treatment response, which may obscure the phenotypic heterogeneity of PTSD and limit the ability to map symptoms to underlying neurobiology. This systematic review aimed to identify intermediate phenotypes (IPs) of PTSD and evaluate IP sensitivity to PTSD treatments. METHOD: Five databases were searched for empirical studies published in English between January 1, 2010 and August 1, 2022 examining behavioral and pharmacological PTSD treatment effects on biobehavioral PTSD outcomes. RESULTS: Twenty-two studies met the inclusion criteria. Most studies evaluated behavioral treatment outcomes (n = 20), while only two studies evaluated pharmacological interventions. Five PTSD IPs were identified, including "impairments in working memory," "alterations in cognitive control," "unstable threat processing," "heightened fear or startle response," and "disturbances in sleep and wakefulness." This review offers preliminary support to suggest the utility of IP measures in assessing treatment efficacy; however, risk of bias and methodological limitations constrain the validity and generalizability of the results. CONCLUSIONS: The paucity of research combined with the heterogeneity of study methodologies and significant study limitations makes it difficult to draw strong conclusions regarding IP sensitivity to treatment. However, the existing body of research incorporating this framework shows potential for the IP approach to improve the translation of treatment efficacy from clinical trials to clinical settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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INTRODUCTION: Large racial disparities exist in the prevention and treatment of smoking-related diseases, and minoritized populations carry a heavier burden of smoking-related morbidity and mortality. To date, most studies investigating smoking-related illnesses have been conducted in samples in which the majority, or totality, self-identified as White or Caucasian. While Black individuals who smoke tend to have a lower rate of nicotine clearance, in part due to the use of mentholated cigarettes, less is known about how slower clearance affects their acute subjective and physiologic responses in response to either overnight abstinence or subsequent nicotine administration. This study aimed to investigate differences between the experiences of Black and White individuals who smoke across these outcomes after a period of short-term abstinence and after IV nicotine infusion. METHODS: The study included 206 smokers (N = 103 Black, N = 103 White, by self-report). The study investigated self-report, physiological, and biochemical smoking-related outcomes following confirmed overnight abstinence followed by IV nicotine infusion. The outcome measures were separately analyzed with repeated-measures mixed-models. RESULTS: Black individuals had lower rates of nicotine clearance and were more likely to smoke mentholated cigarettes than White individuals. Despite these differences, no differences in withdrawal, cravings, or physiological outcomes were observed between the two groups. There were some trends toward differences in subjective experiences, in that an interaction with trend level significance between race and dose was observed for negative subjective drug effects, with White smokers trending towards endorsing higher levels of negative affect after abstinence and nicotine infusion. We also observed that Black individuals trended towards experiencing more negative drug effects in response to initial nicotine delivery than to saline, whereas White individuals had no differences in negative drug effects across saline or nicotine doses. CONCLUSIONS: Despite slower nicotine clearance, Black participants exhibited withdrawal and urges to smoke as severe as White participants, and did not have blunted physiological responses to overnight abstinence or administration of nicotine, which were contrary to our hypotheses. Our findings suggest minimal differences across races in the acute pharmacologic effects of nicotine. We observed trend-level differences in subjective and affective responses to nicotine. Greater insight into these differences may lead to improved prevention and treatment strategies for smoking-related illnesses for Black individuals who smoke.
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Nicotina , Fumadores , Humanos , Población Negra , Factores Raciales , Fumadores/psicología , Fumar/epidemiología , Población BlancaRESUMEN
A recent study demonstrated that during a single sampling period, 0.1 mg of intravenous (IV) nicotine (vs. placebo) was found to be the threshold for subjective and physiological drug effects. The present study is a secondary analysis evaluating whether the threshold for subjective and physiological effects is similar when the subject has repeated opportunities to choose blinded doses of nicotine versus placebo. We also examined whether cigarette craving, withdrawal, and rate of nicotine metabolism affected nicotine reinforcement, defined by a greater number of nicotine choices than placebo. Young adult (n = 34; 68% male), daily smokers had five laboratory sessions after overnight abstinence. After sampling an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg/70 kg) versus saline (placebo), participants completed a nicotine self-administration (NSA) procedure that included 10 opportunities to self-administer IV dose of nicotine or placebo. The threshold for subjective positive effects of nicotine during the NSA was equal to or lower than the sampling period, 0.05-0.1 mg versus 0.1 mg. The threshold for nicotine-induced heart rate increase was higher during the NSA than during the sampling period (0.2 mg vs. 0.1 mg). Higher baseline craving and nicotine metabolite ratio (NMR) were associated with nicotine reinforcement at 0.2 mg and 0.1 mg doses, respectively (p < .05). The results suggest that subjective effects during NSA are reported at doses lower than the sampling period. Taken together, tobacco products thought to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Cese del Hábito de Fumar , Productos de Tabaco , Tabaquismo , Adulto Joven , Masculino , Humanos , Femenino , Nicotina , Cese del Hábito de Fumar/métodos , NicotianaRESUMEN
To address the ongoing opioid epidemic, there has been an increased focus on the treatment and evaluation of opioid use disorder (OUD). OUD and chronic pain (CP) frequently co-occur; however, little is known about the additional comorbidities that present when they occur together as compared to when either condition presents alone. Using data from Fiscal Year 2012 Veteran's Health Administration, all veterans diagnosed with both OUD + CP were compared to those diagnosed with OUD or CP alone on socioenvironmental characteristics, medical and mental health diagnoses, and Veterans Affairs (VA) clinical service use. Veterans with OUD + CP (n = 33,166), compared to those with OUD only (n = 12,517), had higher numbers of medical conditions. Compared to those with CP only (n = 2,015,368), veterans with OUD + CP had higher rates of homelessness and substance use diagnoses. Most mental health diagnoses, numbers of psychotropic medication fills, opioid prescriptions, and use of all other services were higher in the OUD + CP group than in either single disorder group. Multinomial regression analysis revealed stronger effects for medical disorders and medical-surgical outpatient service use in the comparison of OUD + CP with OUD only and stronger effects for substance use and mental health disorders and use of prescription opiates in the comparison with CP only. These findings suggest that concurrent OUD + CP imposes exceptional disease and clinical service burdens that likely require the development of simultaneous, integrated approaches to treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Dolor Crónico , Trastornos Relacionados con Opioides , Veteranos , Humanos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/psicología , Veteranos/psicología , Atención a la Salud , Costo de Enfermedad , Analgésicos Opioides/uso terapéuticoRESUMEN
The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment.
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Analgésicos no Narcóticos , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides , Analgésicos no Narcóticos/uso terapéutico , Manejo del Dolor , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/epidemiología , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects. METHODS: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality. RESULTS: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline. CONCLUSIONS: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.
Asunto(s)
Cannabinoides , Cannabis , Alucinógenos , Síndrome de Abstinencia a Sustancias , Humanos , Masculino , Femenino , Dronabinol/efectos adversos , Cannabinoides/efectos adversos , Agonistas de Receptores de Cannabinoides/uso terapéutico , Alucinógenos/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéuticoRESUMEN
Introduction: There are no approved medications for the treatment of cocaine use disorder (CUD). Modafinil, a cognitive-enhancer with weak stimulant-like effects, has shown promise in initial studies as a treatment for CUD. Its potential efficacy has not been examined in individuals dually dependent on cocaine and opioids. Methods: This study examined the efficacy of modafinil, in combination with contingency management (CM), for reducing cocaine and opioid use and improving cognitive function in methadone-stabilized individuals with opioid and cocaine dependence. We conducted a 17-week, double-blind, randomized controlled trial in which participants were randomized to one of four conditions: 1) modafinil + CM; 2) modafinil + yoked-control (YC); 3) placebo +CM; or 4) placebo + YC. Additionally, all subjects received platform treatments of cognitive behavioral therapy (CBT) and methadone. While the original planned sample size was N=160, a total of 91 participants were randomized. The two primary cocaine use outcomes were percentage of urine specimens positive for cocaine and percent of days of self-reported abstinence from cocaine during treatment. Cognitive function, opioid use, and secondary cocaine use outcomes were also considered. Results: Modafinil was well-tolerated with minimal reports of adverse effects. Modafinil was no more effective than placebo in reducing cocaine or opioid use or improving cognitive performance. Conclusions: In the context of a trial with robust control conditions and platform treatments, findings did not provide support for the efficacy of modafinil treatment for the treatment of CUD in methadone-stabilized individuals with dual opioid and cocaine dependence.