“Cannabis is widely used in the United States with an estimated prevalence of 9.5%. Certain cannabinoids in Cannabis sativa, in particular, Δ9-tetrahydrocannabinol (THC), possess immune modulating and anti-inflammatory activity. Depending on the context, the anti-inflammatory activity of cannabinoids may be beneficial, such as in treating inflammatory diseases, or detrimental to normal immune defense against pathogens. The potential beneficial impact of cannabinoids on chronic neuroinflammation has gained recent attention. Monocyte migration to the brain has been implicated as a key event in chronic neuroinflammation and in the etiology of central nervous system diseases including viral infection (e.g., HIV-associated neurocognitive disorder). In the brain, monocytes can contribute to neuroinflammation through interactions with astrocytes, including inducing astrocyte secretion of cytokines and chemokines. In a human co-culture system, monocyte-derived IL-1β due to toll-like receptor 7 (TLR7)-activation, has been identified to promote astrocyte production of MCP-1 and IL-6. THC treatment of TLR7-stimulated co-culture suppressed monocyte secretion of IL-1β resulting in decreased astrocyte production of MCP-1 and IL-6. Furthermore, THC displayed direct inhibition of monocytes, as TLR7-stimulated monocyte monocultures treated with THC also showed suppressed IL-1β production. The cannabinoid receptor 2 (CB2) agonist, JWH-015, impaired monocyte IL-1β production similar to that of THC, suggesting THC is, in part, acting through CB2. THC also suppressed key elements of the IL-1β production pathway, including IL1B mRNA levels and caspase-1 activity. Collectively, this study demonstrates that the anti-inflammatory properties of THC suppress TLR7-induced monocyte secretion of IL-1β, through CB2, which results in decreased astrocyte secretion of MCP-1 and IL-6.
SIGNIFICANCE STATEMENT: As cannabis use is highly prevalent in the United States and has putative anti-inflammatory properties, it is important to investigate the effect of cannabinoids on immune cell function. Furthermore, cannabinoids have garnered particular interest due to their potential beneficial effects on attenuating viral-induced chronic neuroinflammation. This study utilized a primary human co-culture system to demonstrate that the major psychotropic cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC) and a cannabinoid receptor-2 (CB2) selective agonist, suppress specific monocyte-mediated astrocyte inflammatory responses. In the context of viral-induced chronic neuroinflammation, the findings presented here suggest that cannabinoids via CB2 ligation may have beneficial anti-inflammatory effects.”
https://www.ncbi.nlm.nih.gov/pubmed/31383729
http://jpet.aspetjournals.org/content/early/2019/08/05/jpet.119.260661
“In recent years, the use of 
“As more states enact laws liberalizing marijuana use and the U.S. opioid epidemic surges to unprecedented levels, understanding the relationship between marijuana and opioids is growing increasingly important.
“Δ9-tetrahydrocannabinol (Δ9-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous 
“Combat veterans are at elevated suicide risk. The goal of this study was to test the hypothesis that combat veterans who have made a suicide attempt post-deployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. For the latter, we focused on endogenous cannabinoids, neuroendocrine markers that are associated with stress. Demographic and clinical parameters of suicide attempters and non-attempters were assessed. Blood samples were assayed for anandamide (AEA), 2-arachidonoylglycerol (2-AG), and cortisol. Suicide attempters had higher Scale for Suicidal Ideation (SSI) scores in comparison to non-attempters. Controlling for gender, 2-AG levels were higher among suicide attempters in comparison to non-attempters. Cortisol levels positively correlated with 2-AG levels and negatively correlated with SSI scores among non-attempters but not among attempters. AEA levels negatively correlated with SSI scores among attempters but not among non-attempters. Our results indicate that there are psychological and biological differences between combat veterans with or without a history of suicidal attempt. Our findings also suggest that clinically observed differences between the groups may have a neurobiological basis.”
“The G-protein coupled cannabinoid receptor 2 (CB2) has been implicated in the regulation of adult neurogenesis in the hippocampus. The contribution of CB2 towards basal levels of proliferation and the number of neural progenitors in the subgranular zone (SGZ) of the dentate gyrus, however, remain unclear. We stained hippocampal brain sections of 16- to 17-week-old wildtype and CB2-deficient mice, for neural progenitor and immature neuron markers doublecortin (DCX) and calretinin (CR) and for the proliferation marker Ki67 and quantified the number of positive cells in the SGZ. The quantification revealed that CB2 deficiency neither altered overall cell proliferation nor the size of the DCX+ or DCX and CR double-positive populations in the SGZ compared to control animals. The results indicate that CB2 might not contribute to basal levels of adult neurogenesis in four-month-old healthy mice. CB2 signaling might be more relevant in conditions where adult neurogenesis is dynamically regulated, such as neuroinflammation.”
“As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of 