Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.

BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.

Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. Methods: Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05). Results: Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.

Factors affecting seizure outcome after epilepsy surgery: an observational series.

IMPORTANCE: Surgical treatment can bring seizure remission in people with focal epilepsy but requires careful selection of candidates. OBJECTIVES: To determine which preoperative factors are associated with postoperative seizure outcome. DESIGN: We audited seizure outcome of 693 adults who had resective epilepsy surgery between 1990 and 2010 and used survival analysis to detect preoperatively identifiable risk factors of poor seizure outcome. RESULTS: Seven factors were significantly associated with increased probability of recurrence of seizures with impaired awareness postsurgery: MRI findings (eg, HR adjusted for other variables in the model 2.5; 95% CI 1.6 to 3.8 for normal MRI compared with hippocampal sclerosis), a history of secondarily generalised convulsive seizures (2.3; 95% CI 1.7 to 3.0 for these seizures in the previous year vs never), psychiatric history (1.3; 95% CI 1.1 to 1.7), learning disability (1.8; 95% CI 1.2 to 2.6) and extratemporal (vs temporal) surgery (1.4; 95% CI 1.02, 2.04). People with an older onset of epilepsy had a higher probability of seizure recurrence (1.01; 95% CI 1.00, 1.02) as did those who had used more antiepileptic drugs (1.05; 95% CI 1.01 to 1.09). Combinations of variables associated with seizure recurrence gave overall low probabilities of 5-year seizure freedom (eg, a normal MRI and convulsive seizures in the previous year has a probability of seizure freedom at 5 years of approximately 0.19). CONCLUSIONS AND RELEVANCE: Readily identified clinical features and investigations are associated with reduced probability of good outcome and need consideration when planning presurgical evaluation.

Does health information exchange reduce unnecessary neuroimaging and improve quality of headache care in the emergency department?

BACKGROUND: Health information exchange (HIE) is advocated as an approach to reduce unnecessary testing and improve quality of emergency department (ED) care, but little evidence supports its use. Headache is a specific condition for which HIE has theoretical benefits. OBJECTIVE: To determine whether health information exchange (HIE) reduces potentially unnecessary neuroimaging, increases adherence with evidence-based guidelines, and decreases costs in the emergency department (ED) evaluation of headache. DESIGN: Longitudinal data analysis SUBJECTS: All repeat patient-visits (N = 2,102) by all 1,252 adults presenting with headache to a Memphis metropolitan area ED two or more times between August 1, 2007 and July 31, 2009. INTERVENTION: Use of a regional HIE connecting the 15 major adult hospitals and two regional clinic systems by authorized ED personnel to access the patient's record during the time period in which the patient was being seen in the ED. MAIN MEASURES: Diagnostic neuroimaging (CT, CT angiography, MRI or MRI angiography), evidence-based guideline adherence, and total patient-visit estimated cost. KEY RESULTS: HIE data were accessed for 21.8 % of ED patient-visits for headache. 69.8 % received neuroimaging. HIE was associated with decreased odds of diagnostic neuroimaging (odds ratio [OR] 0.38, confidence interval [CI] 0.29-0.50) and increased adherence with evidence-based guidelines (OR 1.33, CI 1.02-1.73). Administrative/nursing staff HIE use (OR 0.24, CI 0.17-0.34) was also associated with decreased neuroimaging after adjustment for confounding factors. Overall HIE use was not associated with significant changes in costs. CONCLUSIONS: HIE is associated with decreased diagnostic imaging and increased evidence-based guideline adherence in the emergency evaluation of headache, but was not associated with improvements in overall costs. Controlled trials are needed to test whether specific HIE enhancements to increase HIE use can further reduce potentially unnecessary diagnostic imaging and improve adherence with guidelines while decreasing costs of care.

Examination of costs for a lay health educator-delivered translation of the Diabetes Prevention Program in senior centers.

OBJECTIVE: Older adults in the U.S. have high rates of obesity. Despite the demonstrated efficacy of lifestyle interventions among older adults, lifestyle interventions are not widely implemented in community settings. Program delivery by lay health educators (LHEs) might support greater dissemination because of lower delivery cost and greater accessibility. We examined the costs of a LHE-delivered translation of the Diabetes Prevention Program (DPP) evidence-based lifestyle intervention for older adults in Arkansas senior centers. METHODS: This examination of costs used data from a cluster randomized control trial (conducted 2008-2010) in which 7 senior centers (116 participants) were randomized to implement a LHE-delivered 12-session translation of the DPP lifestyle intervention. We compiled direct lifestyle intervention implementation costs, including training, recruitment, materials, and ongoing intervention implementation support. Weight loss data (at 4-month follow-up) were collected from participants. RESULTS: Participant weight loss averaged 3.7kg at 4-months. The total estimated cost to implement the lifestyle intervention is $2731 per senior center, or $165 per participant. The implementation cost per kilogram lost is $45. CONCLUSIONS: A LHE-delivered DPP translation in senior centers is effective in achieving weight loss at low cost and offers promise for the dissemination of this evidence-based intervention.

Health information exchange reduces repeated diagnostic imaging for back pain.

STUDY OBJECTIVE: This study seeks to determine whether health information exchange reduces repeated diagnostic imaging and related costs in emergency back pain evaluation. METHODS: This was a longitudinal data analysis of health information exchange patient-visit data. All repeated emergency department (ED) patient visits for back pain with previous ED diagnostic imaging to a Memphis metropolitan area ED between August 1, 2007, and July 31, 2009, were included. Use of a regional health information exchange by ED personnel to access the patient's record during the emergency visit was the primary independent variable. Main outcomes included repeated lumbar or thoracic diagnostic imaging (radiograph, computed tomography [CT], or magnetic resonance imaging [MRI]) and total patient-visit estimated cost. RESULTS: One hundred seventy-nine (22.4%) of the 800 qualifying repeated back pain visits resulted in repeated diagnostic imaging (radiograph 84.9%, CT 6.1%, and MRI 9.5%). Health information exchange use in the study population was low, at 12.5%, and health care providers as opposed to administrative/nursing staff accounted for 80% of the total health information exchange use. Health information exchange use by any ED personnel was associated with reduced repeated diagnostic imaging (odds ratio 0.36; 95% confidence interval 0.18 to 0.71), as was physician or nurse practitioner health information exchange use (odds ratio 0.47; 95% confidence interval 0.23 to 0.96). No cost savings were associated with health information exchange use because of increased CT imaging when health care providers used health information exchange. CONCLUSION: Health information exchange use is associated with 64% lower odds of repeated diagnostic imaging in the emergency evaluation of back pain. Health information exchange effect on estimated costs was negligible. More studies are needed to evaluate specific strategies to increase health information exchange use and further decrease potentially unnecessary diagnostic imaging and associated costs of care.

Potentially avoidable hospitalizations in Tennessee: analysis of prevalence disparities associated with gender, race, and insurance.

OBJECTIVES: We determined (1) the relative rates of potentially avoidable hospitalizations (PAHs) in Tennessee; (2) relative rates of PAHs among gender, race, and insurance subgroups; and (3) adjusted population-based relative rates of PAHs, taking into account the influences of unobservable factors such as patient preferences, physician practice patterns, and availability of hospital beds that can also affect PAHs. METHODS: We applied the Agency for Healthcare Research and Quality's definitions of ambulatory care sensitive conditions (ACSCs) to Tennessee hospitalization records to identify PAHs. Patient discharge records for 2002 came from Tennessee's Hospital Discharge Data System. Population estimates came from the U.S. Census Current Population Survey. Hospital discharges with a complete record from all nonfederal acute-care hospitals in Tennessee were considered. RESULTS: The relative rates of PAHs in Tennessee were higher than the U.S. rates in each of the ACSC categories. The relative rates were sensitive to adjustment for unmeasured factors such as patient preferences, physician practice patterns, and the physician supply that were reflected implicitly in the hospitalization rates of each subgroup for all discharge conditions. Within Tennessee, the type of insurance each person held was the greatest determinant of the likelihood of having a PAH, particularly for a chronic condition. CONCLUSIONS: The results indicate poor health of the general population in Tennessee and suggest opportunities to improve the provision of primary care for specific ACSCs and population subgroups to reduce PAHs, particularly the uninsured and individuals enrolled in Tennessee's Medicaid managed care program.

Frontal lobe dysfunction as a predictor of depression and anxiety following temporal lobe epilepsy surgery.

OBJECTIVE: Predictors of psychiatric outcome following TLE surgery have proved elusive and represent a current challenge in the practice of TLE surgery. This prospective study investigated whether frontal lobe dysfunction is predictive of poorer psychiatric outcomes. METHODS: Forty-nine unilateral TLE surgical patients were assessed using the Beck Depression Inventory-Fast Screen (BDI-FS) and Beck Anxiety Inventory (BAI) preoperatively and 6 and 12 months postoperatively. Measures of intellectual function, semantic knowledge, memory and executive function were completed preoperatively, at 6 and 12 months following surgery. RESULTS: Preoperatively, 33 (67%) patients had minimal depressive symptoms, 8 (16%) were mildly depressed, 2 (4%) were moderately depressed, and 6 (12%) reported severe depressive morbidity. Twenty-three (47%) patients reported minimal anxiety, 18 (37%) were mildly anxious, 6 (12%) were moderately anxious and 2 (4%) patients reported severe anxiety symptoms. A mixed-model repeated-measures analysis was performed on the BDI-FS and BAI scores, adjusting for pertinent covariates identified in univariable analyses. At a year following TLE surgery, anxiety symptoms significantly improved but depressive morbidity did not. Indicators of frontal lobe dysfunction moderated the magnitude and direction of mood change. Specifically, pre-surgical cognitive measures of frontal lobe dysfunction predicted increased depression and anxiety symptoms following surgery. There was no relationship between preoperative BDI-FS or BAI scores and seizure outcome at 12 months or change in affective morbidity and seizure outcome. SIGNIFICANCE: This is the first longitudinal study to provide evidence that specific pre-surgical cognitive and behavioural indices of frontal dysfunction are predictive of poorer psychiatric outcome following TLE surgery. In addition, our findings highlight the potential utility of a dysexecutive behavioural rating scale (DEX) as an assessment tool in epilepsy. Examination of executive functioning in pre-surgical evaluations may lead to an increase in the power of prognostic models used to predict the psychiatric outcome of TLE surgery.

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

RATIONALE: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. OBJECTIVES: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. METHODS: In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. RESULTS: Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). CONCLUSIONS: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.