Role of endocannabinoid system in mental diseases

Abstract

In the last decade, a large number of studies using Delta9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation. Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports of the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions or psychiatric illness. On the other hand, cannabis abuse has been related to several psychiatric disorders such as dependence, anxiety, depression, cognitive impairment, and psychosis. Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabinoid system to novel opportunities for therapeutic intervention and its effects on the central nervous system.

Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex

“…Dysfunction of this system is thought to be involved in the development of affective disorders such as anxiety and depression. Cannabinoid receptors have been implicated in the regulation of anxiety-like behaviors (Berrendero and Maldonado, 2002;Chaperon and Thiebot, 1999;Degenhardt et al, 2001;Manzanares et al, 2004). For example, cannabinoid administration causes both anxiogenic and anxiolytic responses in animal studies (Rodriguez de Fonseca, Rubio et al 1996).…”

“…Long-term cannabis use has also been related to several affective disorders including anxiety, depression, cognitive impairment, and psychosis (Troisi, Pasini et al 1998;Arnold, Topple et al 2001;Degenhardt, Hall et al 2001;Berrendero and Maldonado 2002;Manzanares, Uriguen et al 2004). One longitudinal study reported that daily use of cannabis by teenagers was associated with a two-fold increased risk for depression and anxiety during their adult years (Patton, Coffey et al 2002).…”

Repeated cannabinoid administration increases indices of noradrenergic activity in rats

“…Repeated administration of cannabinoid agonists has been associated with activation of the stress-response system, anxiety, depression, and cognitive impairment (Arendt and MunkJorgensen 2004;Arnold et al 2001;Berrendero and Maldonado 2002;Degenhardt et al 2001;Manzanares et al 2004;Troisi et al 1998). The neural substrates underlying these effects remain to be elucidated.…”

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

“…19 Thus, cannabinoids, which are the main component of marijuana, act with exocannabinoids on the endocannabinoid system, which plays a significant role in vulnerability to development of addiction and other mental disturbances. 20 CNR2 may also be associated with addiction vulnerability as a modulator of the reward system. CNR2 has been observed in the brainstem, 21 cerebellum 22 and several other regions of the brain.…”