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  • ∆9-tetrahydrocannabinol (THC), Cannabis
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Chronic effects of cannabis use on the human reward system: An fMRI study

Please use this link to access this publication. Abstract Cannabis is one of the most used drugs of abuse. It affects the brain reward system in animals, and has proven rewarding and addictive potential in humans. We used functional MRI to measure brain activity during reward anticipation in a monetary reward task. Long-term cannabis users were compared to healthy controls. An additional control group consisting of nicotine users was included. Cannabis users showed attenuated brain activity during reward anticipation in the nucleus accumbens compared to non-smoking controls, but not compared to smoking controls. Cannabis users showed decreased reward anticipation activity in the caudate nucleus, compared to both...
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Δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

Please use this link to access this publication. Abstract We recently reported that Δ9-tetrahydrocannabinol (Δ9-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ9-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ9-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in...
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Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells

Abstract BACKGROUND AND PURPOSE Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. We previously showed that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways. EXPERIMENTAL APPROACH To characterize the transcriptional effects of CBD and THC, we treated BV-2 microglial cells with these compounds and performed comparative microarray analysis using the Illumina MouseRef-8 BeadChip platform. Ingenuity Pathway Analysis was performed to identify functional subsets of genes and networks regulated by CBD and/or...
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Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol

Please use this link to access this publication. Abstract This study was designed to test our hypothesis that an ultra-low dose of delta-9 tetrahydrocannabinol (THC) reverses age-dependent cognitive impairments in old mice and to examine the possible biological mechanisms that underlie this behavioral effect. Old female mice aged 24 months that had been injected once with 0.002 mg/kg THC (3–4 orders of magnitudes lower than doses that induce the conventional cannabinoid effects in mice) performed significantly better than vehicle-treated old mice and performed similarly to naive young mice aged 2 months, in 6 different behavioral assays that measured various aspects of memory and learning. The beneficial effect of THC lasted for at least 7 weeks. The single injection...
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Developmental Effects of Cannabidiol and Δ9-Tetrahydrocannabinol in Zebrafish

Abstract Cannabidiol (CBD) has gained much attention in the past several years for its therapeutic potential in the treatment of drug-resistant epilepsy, such as Dravet syndrome. Although CBD has shown anecdotal efficacy in reducing seizure frequency, little is known regarding the potential adverse side effects of CBD on physiology, development, organogenesis, or behavior. The goal of this project was to compare the relative morphological, behavioral, and gene expression phenotypes resulting after a developmental exposure to Δ9-tetrahydrocannabinol (THC) or CBD. Zebrafish were exposed from blastula through larval stage (96 h postfertilization [hpf]) to 0.3, 0.6, 1.25, 2.5, 5 mg/l (1, 2, 4, 8, 16 µM) THC or...
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Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines

Please use this link to access this publication. Abstract General population epidemiological studies have consistently found that cannabis use increases the risk of developing psychotic disorders in a dose-dependent manner. While the epidemiological signal between cannabis and psychosis has gained considerable attention, the biological mechanism whereby cannabis increases risk for psychosis remains poorly understood. Animal research suggests that delta-9-tetrahydrocannabinol (THC, the main psychoactive component of cannabis) increases dopamine levels in several regions of the brain, including striatal and prefrontal areas. Since dopamine is hypothesized to represent a crucial common final pathway between brain biology and actual experience of psychosis, a focus on dopamine may...
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Structural MRI Findings in Long-Term Cannabis Users: What Do We Know?

Please use this link to access this publication. Abstract In animal studies, tetrahydrocannabinol (THC) has been found to affect brain morphology, particularly within areas rich in cannabinoid receptors (e.g., hippocampus, cerebral cortex). While cannabis remains the most widely used illicit drug worldwide, there has been limited work investigating its effects on human brain tissue. In this paper, we conducted a systematic review of existing structural magnetic resonance imaging studies to examine whether cannabis use is associated with significant changes in brain anatomy. We identified only 13 structural neuroimaging studies, which were diverse in terms of sample characteristics (e.g., age of participants, duration and frequency...
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Cannabis with high cannabidiol content is associated with fewer psychotic experiences

Abstract Objective Cannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to Δ 9-tetrahydrocannabinol (Δ 9-THC). An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users. Methods In a web-based cross-sectional study we obtained detailed information about cannabis use and subclinical psychiatric experiences using the Community Assessment of Psychic Experiences (CAPE). Different types of cannabis (i.e. marijuana, hashish etc.) have distinctive...
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The Cannabinoid Receptor Agonist THC Attenuates Weight Loss in a Rodent Model of Activity-Based Anorexia

Abstract Anorexia nervosa (AN) is characterized by anhedonia whereby patients experience little pleasure or reward in many aspects of their lives. Reward pathways and the endocannabionid system have been implicated in the mediation of food intake. The potential to exploit these systems to reverse weight loss is investigated in a rodent model of activity-based anorexia (ABA). The effect of subchronic (6 days) Δ9-tetrahydrocannabinol (THC) treatment (0.1, 0.5, or 2.0 mg/kg/day) was assessed on chow and high-fat diet (HFD) intake, body weight, running wheel activity (RWA) as well as thermogenesis in brown adipose tissue (BAT) and lipid metabolism in white adipose tissue (WAT). Limited time availability...
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Prevalence and trends of suspected cannabinoid hyperemesis syndrome over an 11-year period in Northern California: An electronic health record study

Please use this link to access this publication. Abstract Background As access to cannabis has increased, there has been a rise in a condition called cannabinoid hyperemesis syndrome (CHS). This study estimates annual prevalence of suspected CHS at emergency department visits (ED) over an 11-year period in Northern California. Methods This retrospective observational cohort study used electronic health records from Kaiser Permanente Northern California. Two CHS case definitions were used to construct two cohorts of adults (18+) with ≥1 CHS visits from 2009 to 2019. The primary definition used a narrow definition based on past studies (CHS group 1) and an exploratory definition allowed...
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