Synaptic changes induced by cannabinoid drugs and cannabis use disorder

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

“… 68 It is shown that the negative effects of cannabinoids include dependence, delayed response, anxiety, and others, which depend on the administration method and dosage. 69 Cannabis-derived drugs are widely used in the world. However, legalizing and rationalizing these drugs are rapidly changing the research and use of cannabis.…”

Pediatric Brain on Cannabinoids: Adverse Effects of Cannabinoid Products in Children and Adolescents

“…The principal lipid ligands known as anandamide (AEA) and 2-arachidonyl glycerol (2-AG) are responsible for signal transduction but may also themselves be acted upon by specific and important enzymes during signal transduction. Although the components of the endocannabinoid system may remain consistent through life, its function is drastically different during nervous system development as eCB play important roles in neurodevelopment and synaptic plasticity [14,15]. Unfortunately, it is also under appreciated that brain development does not stop until late adolescence (18-24 years old) [16].…”

“…Adolescence is a critical time period for brain development which involves the eCB system and there is some evidence noted below that would indicate that this age group's mental health may be particularly vulnerable to the effects of exogenous THC. Some of the behavioral abnormalities that have been linked to cannabis use in younger people, before the age of 17, are schizophrenia, psychosis, bipolar disorders and addiction [15]. More specifically, Goggi and coworkers found that there was an association of cannabis use during adolescence (age < 18 years) and depression, suicidal ideation and suicide attempts [21].…”

“…In many regular cannabis users, cannabis withdrawal syndrome (CWS) may occur with cessation of cannabis use and is an indicator of CUD. Signs and symptoms of CWS include cravings, irritability, sleep disruption, aggression, weight loss, depression, anxiety, sweating, headaches, tremors and fatigue and may occur within days of stopping cannabis [15]. There are no approved medications for either CUD or CWS.…”

Voltage dependence of the cannabinoid CB1 receptor

“…The CB1 receptor is also involved in controlling the resting potential of excitable cells by activating and modulating several classes of ion channels ( Turu and Hunyady, 2010 ). The role of the CB1 receptor in long term potentiation (LTP) and other forms of activity-dependent plasticity in the brain is now quite established ( Carlson et al, 2002 ; Augustin and Lovinger, 2018 ; Winters and Vaughan, 2021 ; Augustin and Lovinger, 2022 ). Interestingly, some of these processes are known to be mediated by changes in membrane potential, e.g., depolarization-induced suppression of excitation and inhibition ( Kreitzer and Regehr, 2001 ; Straiker and Mackie, 2005 ).…”