Effects Of Cannabinoids On The Central Serotonergic System

Serotonin content and metabolism in the brain are affected by acute peripheral administration of A9-THC. For example, a single administration of A9-THC increases the concentration of serotonin in brains of adult mice (Holtzman et al., 1969) and rats (Sofia et al., 1971 Molina-Holgado et al., 1993 Egashira et al., 2002). In mice, increases in the whole-brain levels of serotonin occur following injections with doses of A9-THC higher than 5 mg kg. At a dose of 10 mg kg, the increase in the amount...

Multiple Sclerosis

Among all the neurodegenerative diseases discussed within this chapter, perhaps the most compelling evidence for a primary role for cannabinoid-based treatments exists for MS. MS is characterized by a loss of myelin, which normally forms an outer cover or insulation layer around nerve fibers, and axonal loss. This results in an inability of the neurons to conduct nerve impulses efficiently. Demyelination is considered to occur as a consequence of a chronic inflammation (Noseworthy et al., 2000)...

Maternal Exposure To Cannabinoids And Its Effects On The Serotonergic System

The cannabinoids may affect the fetus by crossing the placenta during gestation (Vardaris et al., 1976 Martin et al., 1977 Bailey et al., 1987) and interacting with cannabinoid receptors located on the placenta membranes (Buckley et al., 1998 Kenney et al., 1999 Park et al., 2003). Postnatal exposure to A9-THC can also occur through the milk during lactation (Jakubovic et al., 1973). Several studies indicate interactions of cannabinoids with the serotonergic system during development. For...

Regulation of Intracellular cAMP Levels

Modulation of cAMP production was the first second messenger system convincingly demonstrated to be mediated by cannabinoids via the CB1 receptor. Both exo- and endocannabinoids inhibit adenylyl cyclase via G proteins. Numerous studies have shown the involvement of cannabinoids in the modulation of cAMP levels in cells of various types in culture, as well as in homogenates of brain regions. In the neuroblastoma (N18TG2) or neuroblastoma X glioma (NG108-15) cell lines, cannabinoid-induced...

Implication For The Medical Use Of Marijuana

The use of cannabis for both recreational and medicinal purposes dates back for thousands of years. In recent times, there has been increased attention that marijuana should be legalized for medicinal use in AIDS, cancer, obesity, multiple sclerosis, and other medical conditions where patients might benefit from the pharmacological effects of cannabis. Synthetic cannabinoids such as dronabinol, marinol, and nabilone already have an established use as antiemetics in nausea and vomiting...

Interactions Between Cannabinoids And Dopamine At The Corticolimbic Structures

Mesocorticolimbic dopaminergic neurons subserve cognitive processes (Nieoullon, 2002), motivated behavior (McAllister, 2000), the central stress response (Koob and Le Moal, 1997), and the pleasure produced by natural (i.e., sex, food) or unnatural (i.e., drugs of abuse) reinforcers, or by compulsive activities such as gambling, overeating, and sex dependence (for reviews, see Comings and Blum, 2000 Gardner, 2002). In fact, dopamine is possibly the neurotransmitter more studied as a potential...

Regulation of Ion Channels

The recent discovery that endocannabinoids serve as retrograde messengers in multiple brain regions has allowed for the integration of past data concerning endocannabinoid influence on ion currents into a specific unit in a complete functional neurotransmitter circuit (Ohno-Shosaku et al., 2001 Kreitzer and Regehr, 2001 Wilson and Nicoll, 2001). Many important initial studies laid the foundation for these pathways, as detailed in the following paragraphs. Inhibition of Voltage-Dependent Calcium...

Concluding Remarks

Cannabinoid receptors are widely distributed among various mammalian tissues and cells. It is becoming evident that cannabinoid receptors play physiologically essential roles in diverse biological systems such as the nervous system and the immune system. Studies on endogenous cannabinoid receptor ligands, i.e., endocannabinoids, are therefore essential. Numerous studies have already been carried out on endocannabinoids. Nevertheless, the physiological significance as well as the detailed...

Marijuana Use In Cell Survival Neurogenesis And Apoptosis

Marijuana use and the effects of exogenous synthetic cannabinoid administration, including the activation of endocannabinoids and multiple signaling capabilities, have been shown to control cell survival and death by inhibiting or stimulating cell growth. Thus, cannabinoids induce growth arrest or apoptosis in a number of transformed neural and nonneural cells in culture (Guzman et al., 2002). Cannabinoids of all classes also have the ability to protect neurons from a variety of insults that...

Endocannabinoids And Neuroprotection

Exogenous cannabinoids inhibit glutamate release upon binding to presynaptic CBj receptors in vitro (116,117). Endocannabinoids are increasingly believed to be inhibitors of neurotransmitter release via binding to presynaptic CBj receptors following their retrograde transport from a postsynaptic locus of synthesis. This retrograde endocannabinoid function has been demonstrated to modulate GABA release (118-120) and glutamate release (121-124) in different brain regions of the rat. Activation of...

Motivational Processes

The activation of the mesolimbic DA neurons is a common feature of drugs of abuse (i.e., cocaine, opioids, amphetamine), and it appears that cannabinoids indirectly activate the same dopaminergic pathways. Endocannabinoids in the Reward Pathway The endocannabinoid system has closed connections with the dopaminergic systems, and this may account for several of its effects. The mesocorticolimbic DA system, and in particular the NAcc, is known to play an important role in the establishment of...

Use Of Endocannabinoidbased Substances In Animal Models Of Disorders

The potential therapeutic value of Cannabis sativa and of its major components, THC and canna-bidiol, is currently being reevaluated (Hall and Degenhardt, 2003). In the case of THC and its synthetic analogs capable of activating cannabinoid CB1 receptors in the brain, the possible therapeutic applications are limited by their psychotropic side effects. For this reason, the possibility that substances capable of activating cannabinoid CB1 receptors indirectly, by enhancing endocan-nabinoid...

Endocannabinoid Dependent DSI and DSE at Cerebellar Synapses

At the same time that studies were elucidating a role for endocannabinoids at hippocampal synapses, other groups were investigating similar mechanisms in the cerebellum, another brain area known to be rich in CBj receptors (Herkenham et al., 1990). As mentioned previously (Table 9.1 Levenes et al., 1998 Takahashi and Linden, 2000), both excitatory and inhibitory cerebellar synapses were known to be sensitive to exogenously applied cannabinoids, thereby providing a physiological explanation for...

The Endocannabinoid System

The CE3 receptor is one of the most abundant neuromodulatory receptors in the brain and is expressed at high levels in the hippocampus, cortex, cerebellum, and basal ganglia (Herkenham et al., 1991 Matsuda et al., 1993 Tsou et al., 1998 Wilson and Nicoll, 2001 Wilson and Nicoll, 2002). Recently, the endogenous cannabinoids, AB Mnd 2-AG ) have been proposed to be retrograde signaling molecules that mediate the suppression of GABA release from presynaptic terminals following depolarization of a...

References

Adashi, E.Y., Jones, PB.C., and Hsueh, A.J.W. (1983) Direct antigonadal activity of cannabinoids suppression of rat granulose cell functions. Am J Physiol 244 E177-185. Andersson, K.E. (2001) Pharmacology of penile erection. Pharmacol Rev 53 417-450. Arevalo, C., de Miguel, R., and Hernandez-Tristan, R. (2001) Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. Pharmacol Biochem Behav 70 123-131. Arletti, R., Benelli, A., and Bertolini, A. (1990) Oxytocin...

An Endocannabinoid Hypothesis Of Substance Abuse

There is accumulating evidence indicating a central role of an EPCS in the regulation of the rewarding effects of abused substances. Thus, a role for the EPCS in addiction has been proposed, based on the assumption of a role of the EPCS in brain reward mechanisms. The ubiquitous effects of cannabinoids and therefore marijuana use on almost any biochemical system support this hypothesis. Specifically, it appears that manipulation of some components of the EPCS might be effective at attenuating...

Endocannabinoids And Gl Motility

In Vitro Studies on Intestinal, Longitudinal, and Circular Muscle Preparations Over the past three decades, Pertwee and his coinvestigators have been the leading contributors to the understanding of the in vitro effects of A9-THC, its synthetic analogs, and anandamide on intestinal motility functions (Pertwee, 2001). Their studies evolved from the observation that A9-THC inhibits the contractile response produced by electrically evoked contractions of isolated whole ileum or isolated myenteric...

Endocannabinoids in the modulation of pain

Convergence between Opioid, Cannabinoid, and Vanilloid Systems in Pain Pathways One major therapeutic indication of cannabinoids is analgesia, but it may be limited by their psychotropic effects. Over the years, strong evidence of the physiological and biochemical basis of the involvement of the EPCS in pain has emerged. The antinociceptive effects of CB receptor agonists have been demonstrated in animal models of acute, inflammatory, and nerve injury-induced pain, following peripheral,...

Concluding Remarks And Future Directions

The recent significant progress in marijuana-cannabinoid research has led to a new understanding about the biological effects and the unique therapeutic possibilities of targeting the EPCS, which is activated by THC and marijuana use. In just a few years since the discovery of endocannabinoids that serve as cannabinoids in vivo, these lipid-signaling molecules and endolipids have been shown to participate in a broad array of physiological and pathological processes. However, the impact of...

Conclusions

Marijuana and Sex Strange Bed Partners was the title of a major review article written by Powell and Fuller (1983). The evidence summarized in this review shows that an intimate association exists at the molecular level between endocannabinoid signaling and a broad spectrum of reproductive processes in humans and other organisms. Elucidation of these phenomena requires additional experimentation and will enhance our understanding of normal reproductive biology, clarify certain currently...

Interactions Between Cannabinoids And 5ht Receptors

In addition to the effects of cannabinoids on the serotonergic metabolism, cannabinoids may affect the function of 5-HT receptors. The receptors for serotonin include seven distinct classes (5-HT1 to 5-HT7), with multiple members in each class (Hoyer et al., 2002). Although most of these receptors are G protein-coupled, the 5-HT3 receptor is the only ion channel receptor for serotonin in mammals (Derkach et al., 1989). Among the seven 5-HT receptors, only 5-HT2 and 5-HT3 receptors have to date...

Possible Effects Of Endocannabinoids On Gi Secretions

To date, there is no direct evidence on the effects of endocannabinoids on GIT secretions. However, a number of studies provide indirect evidence for possible antisecretory effects of endocannabinoids. For example, the selective cannabinoid CB1 SR141716A - but not the CB2 SR144528 -receptor antagonist is able to increase intestinal fluid volume Izzo, Mascolo, Borrelli, et al., 1999 and fecal water content Izzo, Mascolo, Pinto, et al., 1999 in rats. One possible explanation offered for these...

Cannabinoids And Movement Disorders

Cannabinoid receptors in the brain appear to be intimately involved in the control of movement. For example, the administration of plant-derived, synthetic, or endogenous cannabinoids produces a complex pattern of movement disorders with low-dose cannabinoids producing hyperactivity, whereas high doses produce a marked catalepsy. This effect is paralleled by changes in the levels of a range of neurotransmitters in basal ganglia, including GABA, dopamine, and glutamate Romero et al., 1995 Maneuf...