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Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

ABSTRACT: Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications.

SUBMITTER: Silveira MM

PROVIDER: S-EPMC5350061 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

Silveira Mason M MM Arnold Jonathon C JC Laviolette Steven R SR Hillard Cecilia J CJ Celorrio Marta M Aymerich María S MS Adams Wendy K WK

Neuroscience and biobehavioral reviews 20160914 Pt B

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating ...[more]

PMID: 27639448

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Project description:AimA systematic review was performed to summarize the key findings of the peer influence on cannabis use through Social Network Analysis (SNA) studies and identify limitations and gaps with the purpose of informing future research and practice. Longitudinal studies were included since they provide robust information about social relationships change over time.BackgroundAdolescents' cannabis use is a global problem, which has awakened an interest in its determinants such as social influences. Research has shown the importance of these influences on cannabis uptake and use. SNA is an useful relational approach to examine socialization mechanisms related to the onset of cannabis use in adolescents.MethodA search was conducted in PyscINFO, PubMed, Scopus and Web of Science for longitudinal articles published until February 2023, to examine cannabis use and peer's social networks. We focus on peers' influence of peers on cannabis use. Additionally, information about effect of cannabis use for peer selection was collected.ResultsThe results of the included studies (n = 8) showed that friends' cannabis use was most often/strongly associated with cannabis use. There was also an increase of cannabis use when the adolescent did not feel close to the school's peers, had a higher proportion of friendships relative to the total number of ties in the neighborhood, had a central position, did not belong to any group but had ties to members of two or more groups, had cannabis user friends (especially in early ages), and lived in a neighborhood where cannabis was used.ConclusionCannabis use is mainly related to friends' use. Yet, future studies are warranted to control for relevant selection effects to further knowledge on network effects on cannabis use, improving the design, and improving the modeling of the network. This systematic review may inform about the critical aspects of preventing cannabis use among adolescents, taking into consideration their complex social environment.

Project description:Retrograde messengers adjust the precise timing of neurotransmitter release from the presynapse, thus modulating synaptic efficacy and neuronal activity. 2-Arachidonoyl glycerol, an endocannabinoid, is one such messenger produced in the postsynapse that inhibits neurotransmitter release upon activating presynaptic CB(1) cannabinoid receptors. Cognitive decline in Alzheimer's disease is due to synaptic failure in hippocampal neuronal networks. We hypothesized that errant retrograde 2-arachidonoyl glycerol signalling impairs synaptic neurotransmission in Alzheimer's disease. Comparative protein profiling and quantitative morphometry showed that overall CB(1) cannabinoid receptor protein levels in the hippocampi of patients with Alzheimer's disease remain unchanged relative to age-matched controls, and CB(1) cannabinoid receptor-positive presynapses engulf amyloid-?-containing senile plaques. Hippocampal protein concentrations for the sn-1-diacylglycerol lipase ? and ? isoforms, synthesizing 2-arachidonoyl glycerol, significantly increased in definite Alzheimer's (Braak stage VI), with ectopic sn-1-diacylglycerol lipase ? expression found in microglia accumulating near senile plaques and apposing CB(1) cannabinoid receptor-positive presynapses. We found that microglia, expressing two 2-arachidonoyl glycerol-degrading enzymes, serine hydrolase ?/?-hydrolase domain-containing 6 and monoacylglycerol lipase, begin to surround senile plaques in probable Alzheimer's disease (Braak stage III). However, Alzheimer's pathology differentially impacts serine hydrolase ?/?-hydrolase domain-containing 6 and monoacylglycerol lipase in hippocampal neurons: serine hydrolase ?/?-hydrolase domain-containing 6 expression ceases in neurofibrillary tangle-bearing pyramidal cells. In contrast, pyramidal cells containing hyperphosphorylated tau retain monoacylglycerol lipase expression, although at levels significantly lower than in neurons lacking neurofibrillary pathology. Here, monoacylglycerol lipase accumulates in CB(1) cannabinoid receptor-positive presynapses. Subcellular fractionation revealed impaired monoacylglycerol lipase recruitment to biological membranes in post-mortem Alzheimer's tissues, suggesting that disease progression slows the termination of 2-arachidonoyl glycerol signalling. We have experimentally confirmed that altered 2-arachidonoyl glycerol signalling could contribute to synapse silencing in Alzheimer's disease by demonstrating significantly prolonged depolarization-induced suppression of inhibition when superfusing mouse hippocampi with amyloid-?. We propose that the temporal dynamics and cellular specificity of molecular rearrangements impairing 2-arachidonoyl glycerol availability and actions may differ from those of anandamide. Thus, enhanced endocannabinoid signalling, particularly around senile plaques, can exacerbate synaptic failure in Alzheimer's disease.

Dataset Information

Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

Publications

Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

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