Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume (11C-SL25.
View Article and Find Full Text PDFBackground And Aim: A central goal of the Cannabis Act (October 17, 2018) - Canada's national cannabis legalization framework - aimed to reduce cannabis-related criminalization and consequent impact on the Canadian criminal justice system. We assessed whether Canada's cannabis legalization was associated with changes in adult police-reported cannabis-related, property, or violent criminal incidents.
Design: Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models evaluated relations between legalization and adult cannabis-related, property, and violent crimes, using criminal incident data from the Canadian Uniform Crime Reporting Survey (UCR-2; January 1, 2015-December 31, 2021).
Introduction: Oxidative stress has been implicated in psychiatric disorders, including posttraumatic stress disorder (PTSD). Currently, the status of glutathione (GSH), the brain's most abundant antioxidant, in PTSD remains uncertain. Therefore, the current study investigated brain concentrations of GSH and peripheral concentrations of blood markers in individuals with PTSD vs.
View Article and Find Full Text PDFImportance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition.
Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC.
Background: Preclinical evidence suggests that increasing levels of the major endocannabinoid anandamide decreases anxiety and fear responses potentially through its effects in the amygdala. Here we used neuroimaging to test the hypothesis that lower fatty acid amide hydrolase (FAAH), the main catabolic enzyme for anandamide, is associated with a blunted amygdala response to threat.
Methods: Twenty-eight healthy participants completed a positron emission tomography (PET) scan with the radiotracer for FAAH, [C]CURB, as well as a block-design functional magnetic resonance imaging session during which angry and fearful faces meant to activate the amygdala were presented.
Background: We previously reported that the 2018 Canadian Cannabis Act, allowing youth to possess up to 5 g dried cannabis or equivalent for personal use/sharing, was associated with short-term (76 days) post-legalization reduction in police-reported cannabis-related crimes among youth. To establish whether the change might be sustained, we now estimate this association during a much longer time period by including an additional three years of post-legalization data.
Methods: Using national daily police-reported criminal incident data from January 1, 2015-December 31, 2021 from the Canadian Uniform Crime Reporting Survey (UCR-2), the study employed Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models to assess the associations between legalization and youth (12-17 years) cannabis-related offenses (male, n = 34,508; female, n = 9529).
Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD.
View Article and Find Full Text PDFIntroduction: Although there is momentum towards legalising adult recreational cannabis use worldwide, the extent of youth cannabis-related harm associated with legalisation is still uncertain. The current study aimed to assess whether the initial implementation of Canada's cannabis legalisation (via the Cannabis Act) on 17 October 2018 might be associated with youth harm, as assessed by emergency department visits for cannabis-related disorders/poisoning.
Methods: We used Ontario and Alberta, Canada emergency department data from 1 April 2015 to 31 December 2019.
Background: Reductions in fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid anandamide, may play a role in drinking behavior and risk for alcohol use disorder. We tested the hypotheses that lower brain FAAH levels in heavy-drinking youth are related to increased alcohol intake, hazardous drinking, and differential response to alcohol.
Methods: FAAH levels in the striatum, prefrontal cortex, and whole brain were determined using positron emission tomography imaging of [C]CURB in heavy-drinking youth (N = 31; 19-25 years of age).
Introduction: Preclinical data suggest methamphetamine (MA), a widely used stimulant drug, can harm the brain by causing oxidative stress and inflammation, but only limited information is available in humans. We tested the hypothesis that levels of glutathione (GSH), a major antioxidant, would be lower in the brains of chronic human MA preferring polysubstance users. We also explored if concentrations of peripheral immunoinflammatory blood biomarkers were related with brain GSH concentrations.
View Article and Find Full Text PDFObjective: Cannabis legalization in many jurisdictions worldwide has raised concerns that such legislation might increase the burden of transient and persistent psychotic illnesses in society. Our study aimed to address this issue.
Methods: Drawing upon emergency department (ED) presentations aggregated across Alberta and Ontario, Canada records (April 1, 2015-December 31, 2019), we employed Seasonal Autoregressive Integrated Moving Average (SARIMA) models to assess associations between Canada's cannabis legalization (via the implemented on October 17, 2018) and weekly ED presentation counts of the following ICD-10-CA-defined target series of cannabis-induced psychosis (F12.
Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that results from exposure to traumatic event(s). Decreased astrocyte-related proteins (e.g.
View Article and Find Full Text PDFBackground: Worldwide momentum toward legalization of recreational cannabis use has raised a common concern that such policies might increase cannabis-impaired driving and consequent traffic-related harms, especially among youth. The current study evaluated this issue in Canada.
Methods: Utilizing provincial emergency department (ED) records (April 1, 2015-December 31, 2019) from Alberta and Ontario, Canada, we employed Seasonal Autoregressive Integrated Moving Average (SARIMA) models to assess associations between Canada's cannabis legalization (via the Cannabis Act implemented on October 17, 2018) and weekly provincial counts of ICD-10-CA-defined traffic-injury ED presentations.
Aims: Canada's 2018 Cannabis Act allows youth (age 12-17 years) to possess up to 5 g of dried cannabis (or equivalent) for personal consumption/sharing. This study assessed whether the Cannabis Act was associated with changes in police-reported cannabis offences among youth in Canada.
Design: Time series model using national daily criminal incident data from January 1, 2015-December 31, 2018 from the Canadian Uniform Crime Reporting Survey (UCR-2).
Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO V), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans.
View Article and Find Full Text PDFObjective: To establish in an exploratory neuroimaging study whether γ-hydroxybutyrate (sodium oxybate [SO]), a sedative, anti-narcoleptic drug with abuse potential, transiently inhibits striatal dopamine release in the human.
Methods: Ten healthy participants (30 years; 6M, 4F) and one participant with narcolepsy received a baseline positron emission tomography scan of [C-11]raclopride, a D2/3 dopamine receptor radioligand sensitive to dopamine occupancy, followed approximately one week later by an oral sedative 3g dose of SO and two [C-11]raclopride scans (1 h, 7 h post SO). Plasma SO levels and drowsiness duration were assessed.
Background: Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control.
Methods: Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans.
Background: Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether this inherited difference in endocannabinoid metabolism relates to alcohol use disorder etiology and patterns of alcohol use in youth is unknown.
View Article and Find Full Text PDFBackground: In almost all of the literature examining the relation between cannabis use and cannabis-related harms, researchers have neglected to include quantity measures of cannabis use. The study aims to assess whether cannabis: (1) quantity predicts harms; and (2) quantity might interact with other key variables (age, gender, and frequency of use) vis-à-vis the outcomes.
Method: Using the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), the current study (n = 36,309; n = 3,339 past-year cannabis users) employed a logistic-regression approach to assess the cross-sectional relations between the continuous variables of cannabis-use quantity and frequency and two Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5) DSM-5-based outcomes: past-year cannabis-use disorder (CUD) and past-year cannabis-related problems (CRP).
Psychopharmacology (Berl)
September 2020
Rationale: The long-held speculation that the brain serotonin system mediates some behavioral effects of the psychostimulant cocaine is supported in part by the high affinity of cocaine for the serotonin transporter (SERT) and by reports that the serotonin transporter (SERT), estimated by SERT binding, is increased in brain of human chronic cocaine users. Excessive SERT activity and consequent synaptic serotonin deficiency might cause a behavioral (e.g.
View Article and Find Full Text PDFBackground: Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO V), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO V in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder.
View Article and Find Full Text PDFActivation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)-seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high-dose MA, but microglial status in human MA users is uncertain, with one positron emission tomography (PET) investigation reporting massively and globally increased translocator protein 18 kDa (TSPO; [C-11](R)-PK11195) binding, a biomarker for microgliosis, in MA users. Our aim was to measure binding of a second-generation TSPO radioligand, [F-18]FEPPA, in brain of human chronic MA users.
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