Please use this link to access this publication. Abstract Cannabis and cannabinoid drugs are central agents that are used widely recreationally and are employed broadly for treating psychiatric conditions. Cannabinoids primarily act by stimulating presynaptic CB1 receptors (CB1Rs), the most abundant G-protein-coupled receptors in brain. CB1R activation decreases neurotransmitter release by inhibiting presynaptic Ca2+ channels and induces long-term plasticity by decreasing cellular cAMP levels. Here we identified an unanticipated additional mechanism of acute cannabinoid signaling in presynaptic terminals that regulates the size of synaptic vesicle pools available for neurotransmitter release. Specifically, we show that activation of CB1Rs in human and mouse neurons rapidly recruits...

Please use this link to access this publication. Abstract Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in...

Please use this link to access this publication. Abstract Cannabis and cannabinoid-based products are increasingly being accepted and commodified globally. Yet there is currently limited understanding of the effect of the varied cannabinoid compounds on the brain. Exogenous cannabinoids interact with the endogenous cannabinoid system that underpins vital functions in the brain and body, and they are thought to perturb key brain and cognitive function. However, much neuroimaging research has been confined to observational studies of cannabis users, without examining the specific role of the various cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, etc.). This review summarizes the brain structural imaging evidence to date associated with cannabis use,...

Please use this link to access this publication. Abstract Cannabis has been used for hundreds of years, with its ability to dampen feelings of anxiety often reported as a primary reason for use. Only recently has the specific role cannabinoids play in anxiety been thoroughly investigated. Here we discuss the body of evidence describing how endocannabinoids and exogenous cannabinoids are capable of regulating the generation and termination of anxiety states. Disruption of the endogenous cannabinoid (eCB) system following genetic manipulation, pharmacological intervention or stress exposure reliably leads to the generation of an anxiety state. On the other hand, upregulation of eCB signaling is capable...

Please use this link to access this publication. Abstract Background The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. Methods This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. Results Results...

Please use this link to access this publication. Abstract Endocannabinoid system has been extensively studied in recent decades, particularly the cannabinoid receptors CB1 and CB2, due to their important role in neuroinflammation. Among these, CB2 has gained prominence due to its selective overexpression in glial cells during neuroinflammation. In contrast to CB1 agonists, CB2 agonists have no side effects such as ataxia, hypothermia, euphoria, psychological, or addiction liabilities. CB2 and its selective agonists' above-mentioned unique properties have become a research focus in neurodegenerative disorders such as Alzheimer's disease (AD). The review discusses the neuroprotective role of CB receptors, particularly CB2, in AD, as well...

Please use this link to access this publication. Abstract Converging lines of evidence from epidemiological, preclinical, and experimental studies indicate that the endocannabinoid system may be involved in the pathophysiology of schizophrenia and suggest that the cannabinoid CB1 receptor may be a potential therapeutic target. In view of this, we first provide an overview of the endocannabinoid system and systematically review the evidence for CB1 receptor alterations in animal models of schizophrenia and clinical studies in schizophrenia. MEDLINE, EMBASE, PsycArticles, and PsycINFO were systematically searched from inception until January 7, 2020. Of 1187 articles, 24 were included in the systematic review, including 8 preclinical...

Please use this link to access this publication. Abstract Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous mouse studies have investigated the role of ECS in several behavioral domains; however, none of them has performed an extensive assessment of social and communication behaviors, that is, the main core features of ASD. This study employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and characterized ultrasonic communication and social interaction in CB1−/−, CB1+/−, and CB1+/+ males and females. Quantitative and qualitative alterations in ultrasonic vocalizations (USVs) were observed in CB1...

Simple Summary Recent research has suggested that the endocannabinoid system offers several pharmacotherapeutic targets for drug administration as new options for the treatment and prophylaxis of skin cancer. This review focused on the anticarcinogenic mechanisms of cannabinoids at the different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy. Abstract Drugs targeting the endocannabinoid system are of interest as potential systemic chemotherapeutic treatments and for palliative care in cancer. In this context, cannabinoid compounds have been successfully tested as a systemic therapeutic option in preclinical models over the past decades. Recent...

Abstract The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe...