Abstract Background: Previous studies have demonstrated abnormal white matter (WM) microstructure in recreational cannabis consumers; however, the long-term impact of medical cannabis (MC) use on WM coherence is unknown. Accordingly, this study assessed the longitudinal impact of MC treatment on WM coherence. Given results from preclinical studies, we hypothesized that MC treatment would be associated with increased fractional anisotropy (FA) and reduced mean diffusivity (MD). Methods: As part of a larger, longitudinal investigation, patients interested in treating at least one medical condition with commercially available MC products of their choosing were assessed before initiating MC use (baseline n=37; female=25, male=12) and following three (n=31) and six (n=22) months of...

Abstract Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes...

Abstract Due to differences in potency, efficacy, and affinity for CB1 receptors, similarities and differences in psychoactive effect profiles of natural cannabis and synthetic cannabinoids (SCs) cannot reliably be derived from equipotent dose comparisons. Instead, the current study proposes to compare the intrinsic psychoactive effects of natural cannabis (THC) and an SC, JWH-018, at psychotropic dose equivalence. Participants from two placebo-controlled studies were matched for their levels of subjective high to compare neurocognitive and psychotomimetic effects of THC and JWH-018. At equal subjective intoxication levels, both drugs impaired psychomotor, divided attention, and impulse control, with no significant difference between the two drugs. Both drugs...

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...