Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults.

BACKGROUND: Cannabis is the most used illicit drug worldwide. The long-standing consequences for the central nervous system associated with frequent cannabis use have not been well delineated and should be determined. OBJECTIVE: To review recent studies on the effects of regular cannabis use regarding its effects on cognition, brain structure, and function in adults. METHODS: A systematic literature review was conducted by performing electronic searches in the PubMed, LILACS, and SciELO databases (2010-2016). The initial search identified 898 records. They were evaluated for relevance according to the inclusion and exclusion criteria and 56 studies were included. RESULTS: The neuropsychological studies provide evidence for subtle cognitive deficits at least 7 days after heavy cannabis use. The structural neuroimaging studies show growing evidence of abnormalities in hippocampus volume and gray matter density of cannabis users relative to controls; however, morphological changes in other brain regions are more controversial. The functional neuroimaging studies suggest an altered pattern of brain activity associated with cannabis use. CONCLUSION: Although there are several limitations for study comparison and substantial heterogeneity in the findings, the present review suggests that regular cannabis use is associated with mild cognitive changes in addition to structural and functional alterations in the brain in adults. The morphological alterations could ultimately affect brain organization and function, but the associated time course for neuronal recovery as well as the real impact on cognitive functioning remain unknown. Also, it is still unclear whether the identified alterations are as a consequence of or precede cannabis use.

Pro-inflammatory cytokines, IL-1ß and TNF-α, produce persistent compromise in tonic immobility defensive behaviour in endotoxemia guinea-pigs.

AIM: Sepsis has been associated with acute behavioural changes in humans and rodents, which consists of a motivational state and an adaptive response that improve survival. However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (TI) defensive behaviour remains a literature gap. Our purposes were to characterize the TI defensive behaviour in endotoxemia guinea-pigs at acute phase and after recovery from the initial inflammatory challenge. Furthermore, we investigated whether peri-aqueductal grey matter (PAG) exists as a brain structure related to this behaviour and also pro-inflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1ß, act at this mesencephalic nucleus. METHODS: Endotoxemia was induced by lipopolysaccharide (LPS) administration in guinea-pigs. The parameters evaluated included TI defensive behaviour, survival, cytokines production, as well as neuronal activation and apoptosis in the PAG. RESULTS: Endotoxemia guinea-pigs exhibited a reduction in the duration of TI episodes, starting at 2 h after LPS administration and persisting throughout the experimental period evaluated over 7 days. Moreover, endotoxemia increased the c-FOS immunoreactivity of neurones in the ventrolateral PAG (vlPAG), as well as the caspase-3 expression. The LPS microinjection into vlPAG reproduces the same compromise, that is a decrease in the duration of TI defensive behaviour, observed after the peripheral administration. The immunoneutralization against IL-1ß and TNF-α into vlPAG reverts all the effects produced by peripheral LPS administration. CONCLUSION: Our findings confirm that vlPAG is an important brain structure involved in the behavioural alterations induced by endotoxemia, possibly changing the neuronal activity caused by pro-inflammatory cytokines produced peripherally.