Nature-themed video intervention may improve cardiovascular safety of psilocybin-assisted therapy for alcohol use disorder.

Introduction: Psychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking. Methods: This was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25 mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the "ascent" and "descent" phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress. Results: Nineteen of 20 (95%) randomized participants (mean age 49 ± 11 years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9 min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups. Discussion: In this open-label pilot study, viewing Visual Healing videos during preparation and psilocybin dosing sessions was feasible, safe, and well-tolerated among participants with AUD. Preliminary findings suggest that Visual Healing has potential to reduce the cardiovascular risks of psychedelic therapy, without interfering with the psychedelic experience or alcohol-related treatment outcomes. Studies to replicate our findings as well as studies of different set and setting interventions with other psychedelic medications and indications are warranted.

Investigating possible syndemic relationships between structural and drug use factors, sexual HIV transmission and viral load among men of colour who have sex with men in Los Angeles County.

INTRODUCTION AND AIMS: Past research investigating syndemic factors and HIV-related outcomes has overlooked the impact of structural conditions on behaviours linked with HIV transmission and disease progression. Given prevalent substance use among our sample, we explored whether four structural conditions indicative of social marginalisation and previously correlated with increased risk for HIV infection demonstrated syndemic (additive/synergistic) effects on: (i) HIV viral suppression; and (ii) self-reported involvement in sexual HIV transmission behaviours among a prospective cohort mostly comprising men of colour who have sex with men (MCSM; i.e. Latino/Hispanic and African American/black men) in Los Angeles County. DESIGN AND METHODS: Data were collected between August 2014 and March 2017. The structural conditions of interest were: current unemployment, recent (≤6 months) incarceration history, 'unstable' accommodation (past month) and remote (>6 months) contact with health-care providers. Generalised estimating equations assessed possible additive effects of experiencing multiple structural conditions, and possible synergistic effects on the HIV-related outcomes. RESULTS: Of 428 participants, nearly half (49%) were HIV-positive at baseline. Involvement in sexual HIV transmission risk behaviours varied over follow-up (22-30%). Reporting ≥2 structural syndemic conditions was significantly associated with reporting sexual HIV transmission risk behaviours among HIV-negative participants, and detectable viral load among HIV-positive participants. Frequent methamphetamine use was consistently associated with the HIV-related outcomes across the final multivariate models. DISCUSSION AND CONCLUSIONS: When developing initiatives to address HIV transmission among marginalised sub-populations including MCSM, we must holistically consider systemic and structural issues (e.g. unemployment and homelessness), especially in the context of prevalent substance use.

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder.

Methamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve neurocognition and treatment outcomes in MA use disorder. We performed a randomized, placebo-controlled trial to determine the safety and efficacy of ibudilast (IBUD), a phosphodiesterase inhibitor that reduces neuroinflammation, for the treatment of MA use disorder. Treatment-seeking volunteers with MA use disorder were randomly assigned to receive 12 weeks of IBUD 50 mg twice daily (N = 64) or placebo (N = 61) with medication management counseling. Participants visited the outpatient research clinic twice weekly to provide urine specimens for drug screens and undergo study assessments. The primary outcome was end of treatment MA-abstinence (EOTA) during weeks 11 and 12 of treatment. Serum IBUID levels were measured for IBUD participants during week 3 of treatment. There was no difference in EOTA for IBUD (14%) versus placebo (16%, p > 0.05). There was no correlation between serum IBUD levels and MA use during treatment and mean IBUD levels for participants with (mean = 51.3, SD = 20.3) and without (mean = 54.7, SD = 33.0, p = 0.70) EOTA. IBUD was well tolerated. IBUD did not facilitate MA abstinence in this outpatient trial. Whether targeting neuroinflammation, either with IBUD in other subgroups of MA users or clinical trial designs, or with other anti-inflammatory medications, is an effective strategy for treating MA use disorder is not clear. Graphical Abstract The proportion of urine drug screens negative for methamphetamine (MA) during the two week lead-in period (weeks -2 and - 1) and the 12 week medication treatment period (weeks 1-12) for ibudilast versus placebo.

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder.

BACKGROUND: Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α. OBJECTIVE: The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients. METHODS: This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion. RESULTS: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion. CONCLUSIONS: Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.

Glial and neuroinflammatory targets for treating substance use disorders.

BACKGROUND: The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. METHODS: Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. RESULTS: Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. CONCLUSIONS: The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

Volatility and change in chronic pain severity predict outcomes of treatment for prescription opioid addiction.

BACKGROUND AND AIMS: Buprenorphine-naloxone (BUP-NLX) can be used to manage prescription opioid addiction among persons with chronic pain, but post-treatment relapse is common and difficult to predict. This study estimated whether changes in pain over time and pain volatility during BUP-NLX maintenance would predict opioid use during the taper BUP-NLX taper. DESIGN: Secondary analysis of a multi-site clinical trial for prescription opioid addiction, using data obtained during a 12-week BUP-NLX stabilization and 4-week BUP-NLX taper. SETTING: Community clinics affiliated with a national clinical trials network in 10 US cities. PARTICIPANTS: Subjects with chronic pain who entered the BUP-NLX taper phase (n = 125) with enrollment occurring from June 2006 to July 2009 (52% male, 88% Caucasian, 31% married). MEASUREMENTS: Outcomes were weekly biologically verified and self-reported opioid use from the 4-week taper phase. Predictors were estimates of baseline severity, rate of change and volatility in pain from weekly self-reports during the 12-week maintenance phase. FINDINGS: Controlling for baseline pain and treatment condition, increased pain [odds ratio (OR) = 2.38, P = 0.02] and greater pain volatility (OR = 2.43, P = 0.04) predicted greater odds of positive opioid urine screen during BUP-NLX taper. Increased pain (IRR = 1.40, P = 0.04) and greater pain volatility [incidence-rate ratio (IRR) = 1.66, P = 0.009] also predicted greater frequency of self-reported opioid use. CONCLUSIONS: Adults with chronic pain receiving out-patient treatment with buprenorphine-naloxone (BUP-NLX) for prescription opioid addiction have an elevated risk for opioid use when tapering off maintenance treatment. Those with relative persistence in pain over time and greater volatility in pain during treatment are less likely to sustain abstinence during BUP-NLX taper.

Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.

BACKGROUND: Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. METHODS: Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. RESULTS: Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. CONCLUSIONS: Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study.

BACKGROUND: Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans. METHODS: Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS). RESULTS: As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo. CONCLUSIONS: Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy.

Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder.

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders.

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain.

Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use.

AIMS: Two previous randomized trials found an effect for bupropion in reducing methamphetamine use in the subgroup with lower frequency of methamphetamine use at baseline. This study aimed to replicate these results by comparing bupropion versus placebo in methamphetamine-dependent participants with less than daily methamphetamine use at baseline. METHODS: Methamphetamine-dependent volunteers reporting methamphetamine use on ≤29 of past 30 days were randomized to bupropion 150 mg twice daily (n = 41) or placebo (n = 43) and out-patient counseling for 12 weeks. The primary outcome was the proportion achieving end-of-treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus placebo. A post-hoc analysis compared EOT abstinence by medication adherence assessed via plasma bupropion/hydroxybupropion level. RESULTS: There was no significant difference in EOT abstinence between bupropion (29%, 12 of 41) and placebo (14%, six of 43; P = 0.087). Among participants receiving bupropion, EOT abstinence was significantly higher in participants assessed as medication adherent by plasma bupropion/hydroxybupropion levels (54%, seven of 13) compared to non-adherent participants (18%, five of 28; P = 0.018). Medication adherence by plasma levels was low (32%). CONCLUSIONS: Bupropion may be efficacious for reducing methamphetamine in people with less than daily baseline methamphetamine use, but the evidence remains inconclusive.

Pharmacotherapy of amphetamine-type stimulant dependence: an update.

ISSUES: Methamphetamine- or amphetamine-type stimulants are the second most frequently used illicit drug worldwide, second only to cannabis. Behavioural treatments are efficacious, but their impact is limited underscoring the need for other treatment options, notably, pharmacotherapy. APPROACH: A review of randomised controlled trials of pharmacotherapies for methamphetamine- or amphetamine-type stimulants was performed using PubMed and Google Scholar databases. Evidence for efficacy of medications is reported. KEY FINDINGS: Clinical trials have yielded no broadly effective pharmacotherapy. Promising signals have been observed for methylphenidate, naltrexone, bupropion and mirtazapine in subgroups of patients in reducing stimulant use (e.g. patients with less severe dependence at baseline and men who have sex with men), though none has produced an unambiguous, replicable signal of efficacy. IMPLICATIONS: Problems in Phase II trials, including high dropout rates, missing data and a lack of agreement on outcomes, complicate efforts to find a broadly effective pharmacotherapy for amphetamine-type stimulant disorders. Efforts to address these problems include calls for better validation of pharmacological target exposure, receptor binding and functional modulation. As well, there is a need for agreement in using findings from preclinical and early phases of the medication development process for selecting better pharmacotherapy candidates. CONCLUSION: After over 20 years of efforts worldwide to develop a broadly effective medication for dependence on methamphetamine- or amphetamine-type stimulants, no candidate has emerged. This highlights the need for new compounds, consistent and stringent research methods, better integration between preclinical and clinical stages of medication development, and improved collaboration between government, industry and researchers.

Pilot randomized trial of bupropion for adolescent methamphetamine abuse/dependence.

PURPOSE: To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents. METHODS: Nineteen adolescents with methamphetamine abuse (n = 2) or dependence (n = 17) were randomly assigned to bupropion SR 150 mg twice daily or placebo for 8 weeks with outpatient substance abuse counseling. RESULTS: Bupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Adolescents receiving bupropion and females provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo (p = .043) and males (p = .005) respectively. CONCLUSIONS: Results do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes.

Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment.

INTRODUCTION AND AIMS: Cigarette smoking occurs frequently among individuals with methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested that the common co-abuse of MA and cigarettes represents a pharmacologically meaningful pattern. METHODS: The present study is a secondary analysis of a randomised, placebo-controlled trial of bupropion treatment for MA dependence (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers. Among smokers, relations between cigarettes smoked and MA use were assessed. RESULTS: Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of MA use during the same time period. This effect was not observed in the bupropion condition. DISCUSSION AND CONCLUSIONS: Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and MA use. The effect was modest and a precise pharmacological mechanism remains elusive. Cholinergic systems may be relevant for MA use outcomes. Future studies should continue to assess the role of smoking in MA treatment outcomes.

Placebo-group responders in methamphetamine pharmacotherapy trials: the role of immediate establishment of abstinence.

Treatment responses of placebo groups in addiction medicine trials have important implications for research methodology and clinical practice, however studies examining placebo group responses in addiction medicine are scarce. Extant data suggest the importance of early treatment responsiveness for long-term outcomes. Among methamphetamine-(MA) dependent individuals randomized to placebo pill plus behavioral support conditions in pharmacotherapy development trials, we hypothesized that immediate abstinence would be a necessary but insufficient predictor for end-of-trial (EOT) abstinence. The study is a secondary analysis of participants (n = 184; 36% female) in the placebo condition of three randomized, placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver operating characteristic (ROC) curve analyses assessed the predictive power of initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence. Sixty percent of individuals with complete abstinence in the first two weeks of treatment were abstinent at EOT, while 18% of people who failed to meet this standard were abstinent at EOT. Early response was related to retention at EOT and 12-month follow-up. Findings suggest that the inability to achieve at least three MA negative screenings in the first two weeks is associated with greater than 90% likelihood of treatment failure. A third week of screening added minimally to the prediction of EOT outcomes. The prediction of treatment failure was more precise than the prediction of treatment success. The absence of a clinical response in the first two weeks of treatment among participants in the placebo group signals high risk of treatment failure. The majority of information regarding response in the placebo group from a 12-week trial is obtained early in the trial.

A retrospective analysis of two randomized trials of bupropion for methamphetamine dependence: suggested guidelines for treatment discontinuation/augmentation.

BACKGROUND: Two clinical trials have shown efficacy for bupropion in treating methamphetamine (MA) dependence among those with moderate baseline MA use. However, treatment response is highly variable and it is unclear what duration of treatment is necessary to determine if maintaining the treatment course is indicated or if discontinuation or augmentation is appropriate. The present study assessed the relationship among early bupropion treatment response for moderate MA users and end-of-treatment (EOT) abstinence. These data provide estimates of the duration of treatment and the degree of responsiveness required to persist in bupropion treatment. METHODS: Participants with moderate baseline MA use in the bupropion condition of two randomized double-blind placebo controlled trials were included. The relationship between early treatment response and EOT outcomes was assessed with Receiver Operating Characteristic (ROC) curves. RESULTS: With thrice weekly urine drug testing, excellent predictive power was established in the first two weeks of treatment. The inability to achieve at least three MA negative samples in the first two weeks is associated with greater than 90% likelihood of treatment failure. More closely approximating clinical settings, once-weekly testing featured reliable predictive power within three weeks, suggesting that the failure to produce at least two clean samples in the first three weekly visits confers high risk of treatment failure. DISCUSSION: The findings provide preliminary evidence to guide clinical decisions for moderate MA users receiving bupropion. The results are consistent with data from the smoking cessation literature and may highlight the importance of early response in addiction treatment.

Gender, brain-derived neurotrophic factor Val66Met, and frequency of methamphetamine use.

BACKGROUND: Frequency of pretreatment methamphetamine (MA) use is an important predictor of outcomes of treatment for MA dependence. Preclinical studies suggest females self-administer more MA than males, but few clinical studies have examined potential sex differences in the frequency of MA use. Estrogen increases expression of brain-derived neurotrophic factor (BDNF), which has effects on MA-induced striatal dopamine release and protects against MA-induced neurotoxicity. OBJECTIVE: We examined potential effects of sex, the Val66Met polymorphism in BDNF, and their interaction on frequency of MA use among 60 Caucasian MA-dependent volunteers screening for a clinical trial. METHODS: Data was taken from 60 Caucasian MA-dependent volunteers screening for a clinical trial. RESULTS: Females reported significantly more pretreatment days with MA use in the past 30 days than males. There was a significant interaction between sex and BDNF Val66Met, with the highest frequency of MA use among females with Val/Val genotype. CONCLUSIONS: These results, although preliminary, add to the literature documenting sexual dimorphism in response to stimulants, including MA, and suggest a potential biological mechanism involving BDNF that might contribute to these differences. Additional research characterizing the biological basis of altered response to MA among females is warranted.

Clinical correlates of health-related quality of life among opioid-dependent patients.

PURPOSE: Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services. METHODS: We tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users in a clinical trial. Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, we tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36. RESULTS: Most hypothesized relationships were significant, and model fit was good. The model explained 36% of the variance in mental HRQOL and 34% of the variance in physical HRQOL. CONCLUSIONS: The conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Analysis of longitudinal data would help to evaluate more rigorously the adequacy of the model for explaining HRQOL in opioid withdrawal.