The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study

<b><i>Introduction:</i></b> Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. <b><i>Methods:</i></b> We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. <b><i>Results:</i></b> There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. <b><i>Discussion/Conclusion:</i></b> We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

EFFECTS OF HAZARDOUS ALCOHOL AND DRUG USE ON ANTIRETROVIRAL ADHERENCE AND HIV VIRAL SUPPRESSION: A MEDIATION ANALYSIS

Background: Little is known regarding the degree to which substance and alcohol use effects on HIV viral suppression are mediated through medication adherence. We hypothesized that the total effects of such use are mediated through adherence. Methods: We included patients with HIV (PWH) receiving care at an urban academic HIV clinic between 2014 and 2018. Eligible patients were those prescribed antiretroviral therapy who completed both patient reported outcome (PRO) questionnaires, and had subsequent plasma viral load (pVL) measurements. Measures included assessments of alcohol use (AUDIT-C), drug use (ASSIST), and self-reported adherence. Substances found in bivariate analysis to predict detectable pVL were modeled separately for mediation effects through adherence. We report natural direct (NDE) and indirect effect (NIE), marginal total effect (MTE) and percentage mediated. Results: Among 3125 Patients who met eligibility criteria, percentages of current use by category were: hazardous alcohol 25.8%, cannabis 27.1%, amphetamines 13.1%, inhalants 11.9%, cocaine 5.3%, sedative-hypnotics 4.5%, opioids 2.9%, and hallucinogens 2.3%. Excellent adherence was reported in 58% and 10% had detectable pVL. Except for sedatives use of other ascertained substances was significantly associated with worse adherence. Bivariate predictors of detectable pVL were [OR(95% CI)]: amphetamine use 2.4 (1.8 -3.2 ) and opioid use 2.3 (1.3 - 4.0) . The percentage mediated by adherence was 36% for amphetamine use, 26.5% for opioid use, and 39% for multiple substance use. Conclusion: Use of amphetamines, opioids, and multiple substances predicted detectable pVL. However, less than 40% of effects were mediated by self-reported adherence.

The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review

Background Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD. Methods We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes. Results Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples. Conclusions Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.

Co-exposure of cannabinoids with amphetamines and biological, behavioural and health outcomes: a scoping review of animal and human studies

Rationale The growing prevalence of psychostimulant (including amphetamine) use and associated health harms, with limited treatment options, present a global challenge. There is an increasing availability and medical applications of cannabinoids, and growing interest in their therapeutic potential for addictive disorders. Objectives The objective of this study is to review available data regarding cannabis/cannabinoid co-use or exposure on amphetamine-related outcomes. Methods Towards the present scoping review, we systematically searched four databases (Medline, Web-of-Science, CINAHL Plus and PsycInfo) using cannabis/cannabinoid and amphetamine text-terms identifying peer-reviewed, English-language studies published in 2000–2020 involving multiple methods approaches among both human and animal study samples, assessing the association of co-use/administration of cannabis/cannabinoids products with non-medical amphetamines on biological, behavioural or health outcomes. Results Twenty-five articles were included. Pre-clinical studies (n = 15) found mostly protective effects of single or repeated cannabinoids administration on rodents in amphetamine addiction models, amphetamine-induced models of human mental disorders (e.g. schizophrenia) and amphetamine-induced neurotoxicity. Human studies (n = 10) were more heterogeneously designed (e.g. cross-sectional, case–control, longitudinal) and assessed natural ongoing cannabis and methamphetamine use or dependence, showing mostly enhanced harms in a diversity of outcomes (e.g. mental health, methamphetamine use, cognition). Conclusions While human studies suggest cannabis use as an adverse risk factor among non-medical amphetamine users, pre-clinical studies suggest therapeutic potential of cannabinoids, especially cannabidiol, to alleviate amphetamine addiction and harms, including treatment outcomes. Given increasing psychostimulant harms but lack of care options, rigorous, high-quality design studies should aim to translate and investigate pre-clinical study results for potential therapeutic benefits of cannabinoids for amphetamine use/abuse in human subjects.

Levels of Impulsivity, Hyperactivity, and Inattention and the Association with Mental Health and Substance Use Severity in Opioid-Dependent Patients Seeking Treatment with Extended-Release Naltrexone

The level of impulsivity, hyperactivity, and inattention (IHI) is higher among patients with substance use disorder (SUD) than in the general population. However, the prevalence of such symptoms in patients seeking treatment with an opioid antagonist, such as extended-release naltrexone (XR-NTX), is unknown. We screened 162 patients with opioid use disorder (OUD) seeking treatment with XR-NTX in Norway using the Adult ADHD Self-Report Scale (ASRS) to estimate the prevalence of IHI alongside an assessment of mental and physical health and substance use. Sixty-six patients scored above the clinical cut-off on the ASRS. Higher levels of IHI were significantly associated with a longer history of frequent amphetamine use, current alcohol use, and greater mental distress. Mental distress was the strongest factor associated with higher levels of IHI. The introduction of screening for IHI and mental distress in opioid maintenance treatment and XR-NTX would likely improve the quality of care and enable clinicians to tailor interventions to the needs of patients with high levels of IHI to prevent treatment discontinuation.

Risicofactoren van psychotische symptomen en hun causaliteit: een overzicht

Risk factors of psychotic symptoms and their causality: an overview. Psychotic symptoms exist on a continuum in both clinical and non-clinical populations. The purpose of this review article is to provide a concise overview of the most studied risk factors ensuring a person moves along the continuum and exhibits more psychotic symptoms. A possible causal relationship is evaluated for every risk factor using the Bradford Hill criteria for causation. This literature study could show a strong association, dose-response relationship and temporal relationship between cannabis use and psychotic symptoms on the one hand and amphetamine use and psychotic symptoms on the other. Furthermore, a few biologically plausible mechanisms could be withheld, whereby a causal relationship seems likely in both cases. Regarding sleep problems, childhood victimization, urbanicity and demographic factors, there was sufficient scientific evidence in the literary study for this article to withhold an association with psychotic symptoms.

Risk and Protective Factors of Lifetime Cocaine-Associated Chest Pain

Introduction: Cocaine users often present with repetitive events of cocaine-associated chest pain (CACP), clinically resembling acute coronary syndromes. The aim of the study is to describe the specific risk factors for CACP.Method: Cocaine users (n = 316) were recruited for a multicenter cross-sectional study. Lifetime CACP history, sociodemographic factors, and lifetime use of cocaine and other substances were assessed. Thirty single nucleotide polymorphisms (SNPs) of NOS3, ROCK2, EDN1, GUCY1A3, and ALDH2 genes, suggested by the literature on coronary spasms, were selected. The associations with CACP history were tested using the chi-square test, Student's t-test and logistic regression.Results: Among the 316 subjects [78.5% men, mean age 37.5 years, (standard-deviation ±8.7)], 190 (60.1%) were daily cocaine users and 103 (32.6%) reported a lifetime CACP history. Among those with a lifetime CACP history, the median was 10 events per individual. In multivariate analysis, lifetime CACP history was associated with daily cocaine use [odds-ratio (OR) 3.24; 95% confidence intervals (1.29–9.33)], rapid route of cocaine use [OR 2.33 (1.20–4.64) vs. intranasal use], and lifetime amphetamine use [daily amphetamine use: OR 2.80 (1.25–6.32) and non-daily amphetamine use: OR 2.14 (1.15–4.04) vs. never used]. Patients with lifetime opioid maintenance treatment (OMT) reported significantly less lifetime CACP history [OR 0.35 (0.16–0.76)]. None of the selected SNPs was associated with CACP history after multiple testing corrections.Conclusions: Clinical variables describing the intensity of stimulant use were positively associated with lifetime CACP history, while OMT was negatively associated with it. Specific harm reduction strategies can target these risk factors.