Please use this link to access this publication. Abstract Background The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV + ) and HIV-negative (HIV–) individuals. Methods Participants (HIV+, n = 48; HIV–, n = 29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e., < 20 copies/mL), and all were on a stable regimen of cART. Results For HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal...

Please use this link to access this publication. Abstract Regular cannabis use is associated with adverse cognitive and mental health outcomes that have been ascribed to aberrant neuroanatomy in brain regions densely innervated with cannabinoid receptors. Neuroanatomical differences between cannabis users and controls have been assessed in multiple structural magnetic resonance imaging (sMRI) studies. However, there is heterogeneity in the results leading to cautious interpretation of the data so far. We examined the sMRI evidence to date in human cannabis users, to establish more definitely whether neuroanatomical alterations are associated with regular cannabis use. The regional specificity and association with cannabis use indices (i.e....

Abstract Background: Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. Aim: To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Methods: Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Results: Experimental studies find that CBD reduces the overall level of alcohol...

Abstract The increasing use of medical marijuana highlights the importance of developing a better understanding of cannabinoid metabolism. Phytocannabinoids, including ∆9-tetrahydrocannabinol (THC), are metabolized and inactivated by cytochrome P450 enzymes primarily within the liver. The lipophilic nature of cannabinoids necessitates mechanism(s) to facilitate their intracellular transport to metabolic enzymes. Here, we test the central hypothesis that liver-type fatty acid binding protein (FABP1) mediates phytocannabinoid transport and subsequent inactivation. Using X-ray crystallography, molecular modeling, and in vitro binding approaches we demonstrate that FABP1 accommodates one molecule of THC within its ligand binding pocket. Consistent with its role as a THC carrier, biotransformation of THC was reduced in...

Please use this link to access this publication. Abstract The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood–brain barrier (BBB). TRPV2 expression and its role on Ca2+ cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Intracellular Ca2+ levels were increased by heat and...

Abstract Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics...

Abstract Background: The potential benefits of cannabis and its major non-intoxicating component cannabidiol (CBD) are attracting attention, including as a potential treatment in neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the neural action of CBD, and its relevance to ASD, remains unclear. We and others have previously shown that response to drug challenge can be measured using functional magnetic resonance imaging (fMRI), but that pharmacological responsivity is atypical in ASD. Aims: We hypothesized that there would be a (different) fMRI response to CBD in ASD. Methods: To test this, task-free fMRI was acquired in 34 healthy men (half with ASD) following oral...

Abstract Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in humans has been linked to subsequent vulnerability to psychiatric disorders such as addiction and schizophrenia. Here, we investigated in a rat model the effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), a psychoactive component of cannabis, on the morphological architecture and transcriptional profile of layer III pyramidal neurons—using cell type- and layer-specific high-resolution microscopy, laser capture microdissection and next-generation RNA-sequencing. The results confirmed known normal expansions in basal dendritic arborization and...

Please use this link to access this publication. Abstract Cannabis is the third most used psychoactive drug worldwide. Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means. Nevertheless, this substance is able to generate clear addiction syndromes in some individuals who use it, which are accompanied by brain alterations resembling those caused by other addictive drugs. Moreover, there is no available pharmacological treatment for this disorder. This fact motivates a deep study and...

Abstract Emotional dysregulation and anxiety are common in people at clinical high risk for psychosis (CHR) and are associated with altered neural responses to emotional stimuli in the striatum and medial temporal lobe. Using a randomised, double-blind, parallel-group design, 33 CHR patients were randomised to a single oral dose of CBD (600 mg) or placebo. Healthy controls (n = 19) were studied under identical conditions but did not receive any drug. Participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. Activation related to the CHR state and to the effects of CBD was examined using a region-of-interest approach. During fear processing, CHR...