Abstract Marijuana and hashish, from the plant Cannabis sativa L, are the illicit drugs most frequently used worldwide. Cannabis is well known for its recreational effects being popular among adolescents and young adults and is often perceived as harmless. Cannabis, however, impairs working and short-term memory and is associated with decline in academic functioning, impaired driving skills, cognitive impairment, and progression to other illicit substance use. Cannabis use has also been linked to a propensity for developing psychotic events while neuroimaging studies indicated brain volume changes in heavy and chronic users. Cannabis effects are ascribed to its major psychoactive constituent delta-9- tetrahydrocannabinol (Δ9-THC) acting...

Abstract Cannabis is the most widely used illicit drug worldwide. Evidence indicated negative impact for cannabis on the brain. Animal research and in vitro studies using delta-9-THC (THC) or cannabis extracts with high THC content provided evidence for a detrimental effect on neuronal integrity with DNA damage, cell shrinkage, atrophy and apoptosis. The mechanisms by which herbal cannabis affects brain structure and function are not clear but impaired mitochondrial functioning, reduced glucose availability and inhibition of brain energetic metabolism by cannabis have been shown. Clinical studies investigating the effects of cannabis in humans found raised serum levels of proinflammatory cytokines in chronic cannabis users....

Please use this link to access this publication Abstract Cannabinoid use has increased among aging individuals. However, little information on age-related differences in the behavioral effects of these agents is available. To explore potential differences in the behavioral effects of cannabinoids, we determined effects of Δ9-tetrahydrocannabinol (THC, 1–10 mg/kg) or rimonabant (0.3–3.2 mg/kg) on operant fixed-ratio responding (FR10) for food in young adult (6 months) and aged (29 months) rats. THC dose-dependently decreased responding for food. Rimonabant alone had little or no effect on responding up to 1.0 mg/kg, but disrupted responding following a 3.2 mg/kg dose. Rimonabant (1.0 mg/kg) partially antagonized response disruption by THC. These effects were similar in young...

Abstract Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood. Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The...

Abstract During adolescence, frequent and heavy cannabis use can lead to serious adverse health effects and cannabis use disorder (CUD). Rodent models of adolescent exposure to the main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), mimic the behavioral alterations observed in adolescent users. However, the underlying molecular mechanisms remain largely unknown. Here, we treated female and male C57BL6/N mice with high doses of THC during early adolescence and assessed their memory and social behaviors in late adolescence. We then profiled the transcriptome of five brain regions involved in cognitive and addiction-related processes. We applied gene coexpression network analysis and identified gene coexpression modules, termed cognitive...

Please use this link to access publication Abstract Adolescence is a gradual transition period between childhood and adulthood, characterized by greater sensitivity to rewarding stimuli. Consistently, demographic studies have shown that teenagers show a high prevalence of rewarding drugs use, mainly nicotine-containing products and cannabis. Clinical researches have associated the adolescence consume of nicotine and cannabis with a higher vulnerability to develop neuropsychiatric diseases in adulthood such as depression, schizophrenia, and drug addiction. Despite these evidence, it is difficult to conclusively prove causal relationships with longitudinal and retrospective clinical research in humans. Accordingly, preclinical animal models are indispensable tools to determine the causal relationship...

Please use this link to access publication Abstract Introduction: The hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF) is well known to stimulate proliferation of blood stem/progenitor cells of the leukocyte lineage, but is also recognized as a neurotrophic factor involved in brain self-repair processes. G-CSF administration has been shown to promote recovery from experimental models of traumatic brain injury (TBI) and to modulate components of the endocannabinoid system (eCS). Conversely, Δ9-tetrahydrocannabinol (Δ9THC) treatment of normal mice has been shown to increase blood levels of G-CSF in the periphery. Hypothesis: Administration of the phytocannabinoid Δ9THC will enhance brain repair following controlled cortical impact (CCI) by upregulating G-CSF and other...

Abstract Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular, the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Aims: To examine effects of THC, CBD, and THC + CBD on functional connectivity of striatal sub-divisions (associative, limbic and sensorimotor). Method: Resting-state functional Magnetic Resonance Imaging (fMRI) was used across two within-subjects, placebo-controlled, double-blind...

Please use this link to access publication Abstract Hypothesis: Administration of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. Materials and Methods: C57BL/6J mice underwent CCI and were treated for 3 days with Δ9-THC 3 mg/kg intraperitoneally (i.p.). Short-term working memory was determined using the spontaneous alternations test during exploratory behavior in a Y-maze. Locomotor function was measured as latency to fall from a rotating drum (rotometry). These behaviors...

Abstract Introduction: Cannabis abuse during adolescence is a risk factor for cognitive impairments in psychiatric disorders later in life. To date, the possible causal relationship between cannabinoids, kynurenic acid (KYNA; i.e., a neuroactive metabolite of tryptophan degradation) and cognition has not been investigated in adolescence. Early exposure to delta 9-tetrahydrocannabinol (THC; i.e., the main psychotropic component of cannabis) causes enduring cognitive deficits, which critically involve impaired glutamatergic function in the prefrontal cortex (PFC). In addition, prenatal cannabis exposure results in enduring increases in PFC KYNA levels. Based on these findings, the effects of chronic THC exposure in rats, during another critical period of neurodevelopment particularly...