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Abstract
The endocannabinoid system (ECS) has been recently recognized as a prominent promoter of the emotional homeostasis, mediating the effects of different environmental signals including rewarding and stressing stimuli. The ECS modulates the rewarding effects of environmental stimuli, influencing synaptic transmission in the dopaminergic projections to the limbic system, and mediates the neurophysiological and behavioral consequences of stress. Notably, the individual psychosocial context is another key element modulating the activity of the ECS. Finally, inflammation represents an additional factor that could alter the cannabinoid signaling in the CNS inducing a “sickness behavior,” characterized by anxiety, anhedonia, and depressive symptoms. The complex influences of the ECS on both the environmental and internal stimuli processing, make the cannabinoid-based drugs an appealing option to treat different psychiatric conditions. Although ample experimental evidence shows beneficial effects of ECS modulation on mood, scarce clinical indication limits the use of cannabis-based treatments. To better define the possible clinical indications of cannabinoid-based drugs in psychiatry, a number of issues should be better addressed, including genetic variability and psychosocial factors possibly affecting the individual response. In particular, better knowledge of the multifaceted effects of cannabinoids could help to understand how to boost their therapeutic use in anxiety and depression treatment.
Highlights
Reviewed by: Wei Xiong, University of Science and Technology of China, China Luis F
The main eCBs, anandamide (AEA) and 2arachidonoyl-glycerol (2-AG), are degraded by distinct enzymes, the fatty-acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. eCBs interact with a number of different molecular targets (Howlett et al, 2002) as the two cannabinoid receptors (CBRs) (CB1R and CB2R) and with other G protein-coupled receptors (GPCRs) including GPR55 and GPR119, GPR18 which are expressed in different tissues, including the immune cells, and mediate a wide range of physiological functions (Chiang et al, 2015; Morales and Reggio, 2017)
These results suggest that IL-1β is involved in inflammation-induced mood alterations and play a key role in mediating responses to environmental stress (Koo and Duman, 2008; Goshen and Yirmiya, 2009; Norman et al, 2010)
Summary
The endocannabinoid system (ECS) consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), biosynthesizing, and degrading enzymes. ECBs interact with a number of different molecular targets (Howlett et al, 2002) as the two CBRs (CB1R and CB2R) and with other G protein-coupled receptors (GPCRs) including GPR55 and GPR119, GPR18 which are expressed in different tissues, including the immune cells, and mediate a wide range of physiological functions (Chiang et al, 2015; Morales and Reggio, 2017). As mood, cognition, feeding behavior and pain perception, are modulated by the ECS (Di Marzo et al, 1998; Di Marzo, 2009; Castillo et al, 2012; Pacher and Kunos, 2013). Different inflammatory mediators alter CB signaling in the CNS (Figure 1)
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