Role of the endogenous cannabinoid system in nicotine addiction: novel insights

Abstract

Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans. Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects. Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.

The neurobiology of social play and its rewarding value in rats

“…The mostly likely mechanism underlying such interaction is the modulation of the activity of ventral tegmental dopamine neurons by endocannabinoids, that alter the functional activity of the GABA and glutamate inputs received by dopaminergic cells (Gardner, 2005). Moreover, endocannabinoids have been implicated in the play-enhancing effects of nicotine and ethanol in rats (Trezza et al, 2009a), a finding in line with the role of the endocannabinoid system in the reinforcing effects of these drugs (Economidou et al, 2006; Gamaleddin et al, 2015; Pava and Woodward, 2012). …”

Metabolic effects of smoking cessation

“…The idea of treating tobacco dependence and obesity together is a provocative one. Rimonabant, a cannabinoid receptor antagonist, has been used to treat obesity 96 and nicotine dependence 97 , and is also effective against the metabolic syndrome 98 . However, rimonabant had adverse psychiatric effects and did not receive FDA approval 96 .…”

Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse

“…CB1 receptors are expressed at high levels in many of the brain regions implicated in addiction such as basal ganglia, cingulate cortex, frontal cortices and hippocampus, while moderate levels are found in many other addiction-relevant regions such as amygdala, basal forebrain and NAc (Mackie, 2005). Indeed, others have noticed the remarkable overlap in the expression of nAChRs and CB1 receptors in the mesolimbic dopamine system, amygdala, and hippocampus (Gamaleddin et al, 2015), which may underlie the interaction between endocannabinoid and cholinergic systems, especially in nicotine abuse/dependence (Narushima et al, 2007). Similarly for alcoholism, many groups have explored the relationship between alcohol exposure, alcohol addiction and the endocannabinoid system (e.g.…”

“…It seems that many studies have implicated the endocannabinoid system for their on demand presynaptic action in modulating dopamine release in both drug and natural rewards (Cheer et al, 2007). And, as has been reviewed for alcohol (Pava & Woodward, 2012) or nicotine (Gamaleddin et al, 2015) elsewhere, low CB1 levels are associated with a greater likelihood of developing an AUD (e.g. (Ortiz et al, 2004) while CB1 antagonism or deletion has been effective in reducing both alcohol and nicotine self-administration and other addiction relevant behaviors (e.g.…”

“…(Ortiz et al, 2004) while CB1 antagonism or deletion has been effective in reducing both alcohol and nicotine self-administration and other addiction relevant behaviors (e.g. (Castane et al, 2002; Cippitelli et al, 2005; Cohen et al, 2002; Freedland et al, 2001; Hungund & Basavarajappa, 2004; Hungund et al, 2003; Rodriguez de Fonseca et al, 1999; Simonnet et al, 2013); see also (Gamaleddin et al, 2015; Pava & Woodward, 2012) for more detailed review). Although there appear to be some similarities in how alcohol or nicotine alone affect the endocannabinoid system (e.g.…”