A Systematic Review and Meta-Analysis of Cognitive Performance among People with Chronic Use of Opioids for Chronic Non-Cancer Pain.

OBJECTIVE: Opioids, often prescribed for chronic non-cancer pain, may adversely affect cognition. Research has not been synthesized in recent years, during which time academic interest has increased. This study presents meta-analyses on cognitive performance in people taking opioids for chronic non-cancer pain (CNCP). METHODS: We ran systematic literature searches in EMBASE, Medline, and PsycINFO. Eligible studies included people taking opioids for CNCP, an opioid-free group (i.e., case-control) or session (e.g., pre-post), and objective cognitive assessments. Using random-effects meta-analyses, we computed pooled effect sizes for differential task performance for each study design across five domains (motor performance, attention, working memory, executive functions, memory). RESULTS: Seventeen studies were included. Case-control studies covered three control types (healthy, CNCP, taper-off). Pre-post studies were grouped into five follow-ups (four to six and six to nine weeks; three, six, and 12 months). Effect sizes ranged from 0.02-0.62. Cases showed small magnitude impairments in attention and memory compared with healthy controls. Although limited by small sample sizes, there was no clear evidence of impairment in cases compared with opioid-free controls with CNCP. Cases showed some cognitive improvements from opioid-free baseline to follow-up. Effects were strongest for attention and working memory and were apparent from four weeks to six months follow-up. Other effects were small and nonsignificant. CONCLUSIONS: Opioid therapy for CNCP did not worsen cognitive performance and improved it for some domains. People who take opioids for CNCP may evidence deficits in attention and memory, but this is unlikely to translate to global impairment and likely relates to pain more so than opioids.

Naloxone cascade of care among people who regularly inject drugs in Australia, 2020-2022.

BACKGROUND: Examining take-home naloxone (THN) uptake using a 'cascade of care' framework could help identify targets for increasing THN training and carriage among people who may witness or experience opioid overdose. We describe the THN cascade and factors associated with engagement among people who inject drugs. METHODS: People aged ≥18 years in Australia who inject drugs were interviewed from 2020 to 2022, reporting lifetime THN awareness and acquisition and past-month carriage. We examined factors associated with engagement using multivariable logistic regression. RESULTS: Of 2,149 participants (64 % men, mean age 44.5), 85 % had heard of naloxone, of whom 76 % were aware of THN programs. Of these, 72 % had ever participated in THN training/brief education, 92 % of whom had acquired THN. Of those who had ever acquired THN and reported past-month opioid use, 63 % always/often carried THN when using opioids. Past six-month opioid agonist treatment (OAT) (adjusted odds ratio [AOR] 2.55; 95 %CI 1.91-3.42) and ≥daily injecting (1.32; 1.01-1.73) were associated with awareness. OAT (1.79; 1.38-2.33), past-year opioid overdose (1.68; 1.18-2.42) and older age (1.02; 1.00-1.03) were associated with acquisition. Primarily injecting methamphetamine (versus heroin) in the past month was associated with lower awareness (0.43; 0.31-0.58) and acquisition (0.59; 0.44-0.78). Reporting no accommodation (squatting/sleeping rough) was associated with reduced odds of carriage (0.46; 0.24-0.88). CONCLUSION: Participants reported high THN awareness and acquisition, with lower carriage. Future efforts should focus on improving THN access and reducing barriers to carriage, particularly for people experiencing homelessness or who primarily inject non-opioids.

Trends and psychosocial correlates of same day polysubstance use among people who inject drugs in Australia, 2012-2022.

BACKGROUND: Polysubstance use is associated with negative health and social outcomes among people who inject drugs. We aimed to describe trends in polysubstance use and identify psychosocial correlates and associated drug use risk behaviours. We defined polysubstance use as intentional same day use of more than one of three drug classes: opioids, other non-opioid depressants (hereafter 'depressants'), and stimulants. METHODS: We used 10 years (2012-2022, excluding 2020) of data from annual surveys in Australian capital cities with people who inject drugs (N=5657) to construct five mutually exclusive polysubstance use profiles: opioid-depressant, opioid-stimulant, stimulant-depressant, opioid-stimulant-depressant, and single drug class use. We examined time trends using the Mann Kendall test and identified correlates using multinomial logistic regression. RESULTS: Same day polysubstance use was relatively common among this sample (43.6%). Opioid-depressant use was the most frequent polysubstance use profile, but this decreased over the study period (32.6% to 13.3%, p<0.001). This aligned with observed decreases in use of pharmaceutical opioids (p<0.001), opioid agonist treatment (p=0.007), and benzodiazepines (p=0.001). There was no evidence for any trend in the other polysubstance use profiles, although single drug class use increased (51.9% to 64.7%, p=0.031). The different polysubstance use profiles were variously associated with psychosocial factors, including unstable housing and very high psychological distress, and other drug use risk behaviours, including non-fatal overdose, receptive and/or distributive needle sharing, and reusing one's own needles. CONCLUSION: Same day polysubstance use has remained relatively common among this sample over time, although the typology has changed. Collectively, our findings point to diverse drug use patterns among people who inject drugs and reiterate the need for a range of harm reduction, treatment, and support options.

Dopamine, endocannabinoids and their interaction in fear extinction and negative affect in PTSD.

There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder. Based on current evidence, we outline an early, preliminary model that links re-experiencing and negative cognitions and mood in PTSD by invoking the interaction between endocannabinoid and dopaminergic signalling in the brain. These interactions between PTSD, dopamine and endocannabinoids may have implications for future therapies for treatment-resistant and comorbid PTSD patients.

Cognitive outcomes associated with long-term, regular, recreational cannabis use in adults: A meta-analysis.

Despite research advances, it remains unclear if long-term, regular cannabis use harms cognition once intoxication has passed. Our meta-analysis aimed to investigate the association between cognitive functioning and long-term (mean ≥2 years), regular (mean ≥4 days/week), recreational cannabis use in adults during abstinence (mean ≥12 hr). We searched PubMed, PsycINFO, CINAHL, Scopus, and Dissertations and Theses International for English-language articles from the date each database began until May 22, 2019. We identified study inclusion by completing abstract and full text screening using predetermined criteria and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We classified cognitive performance into 6 cognitive domains (attention, executive function, learning and memory, decision making, information processing, and working memory), and included a global measure. Effect sizes were calculated for each domain using univariate meta-analyses. There were 30 studies with a total 849 participants who used cannabis (M = 30.7-years-old, SD = 5.5-years-old) and 764 control participants (M = 30.3-years-old, SD = 5.9-years-old). Cannabis was associated with significant but small-magnitude deficits in executive function, learning and memory, and global cognition, while decision making had moderate deficits. There were small-magnitude and nonsignificant group differences for information processing, working memory, and attention. Cannabis use duration, age of onset, and prolonged abstinence (≥25 days) did not influence outcomes, except group differences in executive function were nonsignificant in analyses of prolonged abstinence. Our results suggest that long-term, regular cannabis use is associated with small to moderate deficits in some cognitive domains. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Nature versus intensity of intoxication: Co-ingestion of alcohol and energy drinks and the effect on objective and subjective intoxication.

BACKGROUND: We report a series of studies examining the effect of alcohol mixed with energy drinks (AmEDs) versus alcohol on objective intoxication (breath alcohol concentration; BrAC), intensity, and nature of intoxication. We also aimed to disentangle the role of energy drink (ED) ingredients in any effects. METHOD: Three within-subject double-blind placebo-controlled studies measured BrAC, subjective intoxication and impairment ('intensity of intoxication'), stimulation and sedation ('nature of intoxication') following administration of ED, Cola, Caffeine+Sugar, and Placebo with alcohol (Study 1, n=18); ED, Caffeine-only, Sugar-only and Placebo with alcohol (Study 2, n=20); and ED and Placebo with alcohol (Study 3, n=27). RESULTS: Significant moderate-to-large magnitude BrAC decrements and delayed time to peak BrAC were observed after ED administration versus Placebo. However, no meaningful BrAC differences between ED and other active conditions were observed in Study 1 and 2. After BrAC adjustment, moderate-to-large magnitude reductions in intoxication and impairment ratings were observed after ED versus Placebo on the ascending limb in all studies and at peak in Study 2 and 3. No meaningful differences were observed in intoxication and impairment ratings between ED and Caffeine+Sugar and Cola conditions (Study 1); ratings were lower after ED versus Sugar-only (Study 2). Stimulation and sedation ratings did not differ between ED and Placebo. CONCLUSION: Reductions in objective intoxication and perceived intensity of intoxication, but not nature of intoxication, were observed after AmED consumption. However, effects may be common to alcohol mixers containing sugars (objective intoxication) and caffeine (intensity of intoxication) and specific to a laboratory setting.