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At least 37 records · Page 2Linked to original sources
PubMed2006

Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N-acetyltransferase activity without involvement of cannabinoid receptors.

Cannabinoids modulate neuronal and neuroendocrine circuits by binding to cannabinoid receptors acting upon cAMP/Ca(2+)-mediated intracellular signaling cascades. The rat pineal represents an established model to investigate intracellular signaling processes because a well defined input, the neurotransmitter norepinephrine, is transformed via cAMP/Ca(2+)-dependent mechanisms into an easily detectable output signal, the biosynthesis of melatonin. Here we investigated the impact of cannabinoids on norepinephrine-regulated melatonin biosynthesis in the rat pineal. We demonstrated that treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine-induced arylalkylamine N-acetyltransferase (AANAT) activity and melatonin biosynthesis. These effects were not mimicked by the cannabinoid receptor agonist WIN55,212-2 and were not blocked by cannabinoid 1 and 2 receptor antagonists. The cannabinoids used did not affect norepinephrine-induced increases in cAMP/Ca(2+) levels. Notably, cannabinoids were found to directly inhibit AANAT activity in lysates of the pineal gland. This effect was specific in so far as cannabinoids did not influence the activity of hydroxyindole-O-methyltransferase (HIOMT), the last enzyme in melatonin biosynthesis. Taken together, our data strongly suggest that cannabinoids inhibit AANAT activity and attenuate melatonin biosynthesis through intracellular actions without involvement of classical cannabinoid receptor-dependent signaling cascades.

Animals↗
PubMed2005

Cholesterol-dependent modulation of type 1 cannabinoid receptors in nerve cells.

Type 1 cannabinoid receptors (CB1R) are G-protein-coupled receptors that mediate several actions of the endocannabinoid anandamide (N-arachidonoylethanolamine; AEA) in the central nervous system. Here we show that cholesterol enrichment of rat C6 glioma cell membranes reduces by approximately twofold the binding efficiency (i.e., the ratio between maximum binding and dissociation constant) of CB1R and that activation of CB1R by AEA leads to approximately twofold lower [(35)S]GTPgammaS binding in cholesterol-treated cells than in controls. In addition, we show that CB1R-dependent signaling via adenylate cyclase and p42/p44 mitogen-activated protein kinase is almost halved by cholesterol enrichment. Unlike CB1R, the other AEA-binding receptor TRPV1, the AEA synthetase NAPE-PLD, and the AEA hydrolase FAAH are not modulated by cholesterol, whereas the catalytic efficiency (i.e., the ratio between maximal velocity and Michaelis-Menten constant) of the AEA membrane transporter AMT is almost doubled compared with control cells. These data demonstrate that, among the proteins of the "endocannabinoid system," only CB1R and AMT critically depend on membrane cholesterol content. This observation may have important implications for the role of CB1R in protecting nerve cells against (endo)cannabinoid-induced apoptosis.

Animals↗
PubMed2001

Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level.

Little is known about the expression and function of cannabinoid receptor type 1 (CB1) in the human pituitary gland. The aim of this study was to investigate CB1 expression in human normal and tumoral pituitaries by in situ hybridization and immunohistochemistry using an antibody against CB1. CB1 was found in corticotrophs, mammotrophs, somatotrophs, and folliculostellate cells in the anterior lobe of normal pituitary. After examination of 42 pituitary adenomas, CB1 was detected in acromegaly-associated pituitary adenomas, Cushing's adenomas, and prolactinomas, whereas faint or no expression was found in nonfunctioning pituitary adenomas. Experiments with cultured pituitary adenoma cells showed that the CB1 agonist WIN 55,212--2 inhibited GH secretion in most of acromegaly-associated pituitary adenomas tested and that the CB1 antagonist SR 141716A was generally able to reverse this effect. Moreover, WIN 55,212--2 was able to suppress GHRH-stimulated GH release, and this effect was not blocked by coincubation with SR 141716A, possibly indicating a non-CB1-mediated effect. In contrast, WIN 55,212--2 was ineffective on GH-releasing peptide-stimulated GH release. In four Cushing's adenomas tested, WIN 55,212--2 was not able to modify basal ACTH secretion. However, simultaneous application of CRF and WIN 55,212--2 resulted in a synergistic effect on ACTH secretion, and this effect could be abolished by SR 141716A, demonstrating a CB1-mediated effect. In the single case of prolactinomas tested, WIN 55,212--2 was able to inhibit basal secretion of PRL. Finally, the presence of endocannabinoids (anandamide and 2-arachidonoylglycerol) was investigated in normal and tumoral pituitaries. All tumoral samples had higher contents of anandamide and 2-arachidonoylglycerol compared with the normal hypophysis. Moreover, endocannabinoid content in the different pituitary adenomas correlated with the presence of CB1, being elevated in the tumoral samples positive for CB1 and lower in the samples in which no or low levels of CB1 were found. The results of this study point to a direct role of cannabinoids in the regulation of human pituitary hormone secretion.

Adenoma↗
PubMed2004

[Role of endogenous cannabinoids in cerebral reward mechanisms].

Central cannabinoid receptors (CB1 receptors) are densely located in the output nuclei of the basal ganglia (globus pallidus, substantia nigra pars reticulata). Endogenous cannabinoids appear to modulate transmitter systems (e.g. dopamine) within the basal ganglia. In the striatum, CB1 receptors are localized on the same neurons as Gi-coupled dopamine D2 receptors. Striatal CB1 receptors are also negatively linked to adenylcyase, and may modulate dopamine release. The presence of CB1 receptors in dopaminergic neurons strongly suggests that cannabinoids play a modulatory role in dopaminergic neuronal pathways. This co-localization may postulate "cross talk" between endocannabinoids and dopamine-dependent reward mechanisms.

Basal Ganglia↗
PubMed2005

Effects on the immune system.

Marijuana and other exogenous cannabinoids alter immune function and decrease host resistance to microbial infections in experimental animal models and in vitro. Two modes of action by which delta9-tetrahydrocannabinol (THC) and other cannabinoids affect immune responses have been proposed. First, cannabinoids may signal through the cannabinoid receptors CB1 and CB2. Second, at sites of direct exposure to high concentrations of cannabinoids, such as the lung, membrane perturbation may be involved. In addition, endogenous cannabinoids or endocannabinoids have been identified and have been proposed as native modulators of immune functions through cannabinoid receptors. Exogenously introduced cannabinoids may disturb this homoeostatic immune balance. A mode by which cannabinoids may affect immune responses and host resistance maybe by perturbing the balance of T helper (Th)1 pro-inflammatory versus Th2 anti-inflammatory cytokines. While marijuana and various cannabinoids have been documented to alter immune functions in vitro and in experimental animals, no controlled longitudinal epidemiological studies have yet definitively correlated immunosuppressive effects with increased incidence of infections or immune disorders in humans. However, cannabinoids by virtue of their immunomodulatory properties have the potential to serve as therapeutic agents for ablation of untoward immune responses.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Examination of the effect of the cannabinoid receptor agonist, CP 55,940, on electrically evoked transmitter release from rat brain slices.

In the present study we examined the effect of the cannabinoid receptor agonist, [[1 a,2-(R)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyc lohexyl]-phenol; CP 55,940] on [14C]acetylcholine and [3H]norepinephrine release from hippocampal slices and on [14C]acetylcholine release from striatal slices. CP 55,940 potently inhibited electrically evoked [14C]acetylcholine release from hippocampal slices, with an EC50 of 0.02 microM and a maximal inhibition of 61% at 1 microM. The inhibition of acetylcholine release by CP 55,940 was partially antagonized (60%) by the cannabinoid receptor antagonist, [[N-piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride; SR 141716A]. Alone, SR 141716A significantly enhanced stimulated [14C]acetylcholine release. In contrast to the effects of CP 55,940 on [14C]acetylcholine release, electrically evoked [3H]norepinephrine release from hippocampal slices and [14C]acetylcholine release from striatal slices were both unaffected by this compound. Similarly, hippocampal [3H]norepinephrine release and striatal [14C]acetylcholine release were not affected by SR 141716A. In conclusion, the results of this study extend our previous data indicating that cannabinoid receptors modulate acetylcholine release in the hippocampus. The effects of cannabinoid receptor activation on [3H]acetylcholine release in the hippocampus does not appear to extend to [3H]norepinephrine release from this region or to acetylcholine release from the striatum.

Acetylcholine↗
PubMed2003

Cannabinoids for gastrointestinal diseases: potential therapeutic applications.

Delta(9)-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) and CB(2) receptors. CB(1) receptors have been detected on enteric nerves, and pharmacological effects of their activation include gastroprotection, reduction of gastric and intestinal motility and reduction of intestinal secretion. The digestive tract also contains endogenous cannabinoids (i.e., the endocannabinoids anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e., endocannabinoids uptake and enzymatic degradation). Cannabinoid receptors, endocannabinoids and the proteins involved in endocannabinoids inactivation are collectively referred as the 'endogenous cannabinoid system'. A pharmacological modulation of the endogenous cannabinoid system could provide new therapeutics for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn's disease, secretory diarrhoea, paralytic ileus and gastroesophageal reflux disease. Some cannabinoids are already in use clinically, for example, nabilone and delta(9)-tetrahydrocannabinol are used as antiemetics.

Animals↗
PubMed2003

Cannabinoid receptor activation differentially modulates ion channels in photoreceptors of the tiger salamander.

Cannabinoid CB1 receptors have been detected in retinas of numerous species, with prominent labeling in photoreceptor terminals of the chick and monkey. CB1 labeling is well-conserved across species, suggesting that CB1 receptors might also be present in photoreceptors of the tiger salamander. Synaptic transmission in vertebrate photoreceptors is mediated by L-type calcium currents-currents that are modulated by CB1 receptors in bipolar cells of the tiger salamander. Presence of CB1 receptors in photoreceptor terminals would therefore be consistent with presynaptic modulation of synaptic transmission, a role seen for cannabinoids in other parts of the brain. Here we report immunohistochemical and electrophysiological evidence for the presence of functional CB1 receptors in rod and cone photoreceptors of the tiger salamander. The cannabinoid receptor agonist WIN 55212-2 enhances calcium currents of rod photoreceptors by 39% but decreases calcium currents of large single cones by 50%. In addition, WIN 55212-2 suppresses potassium currents of rods and large single cones by 44 and 48%, respectively. Thus functional CB1 receptors, present in the terminals of rod and cone photoreceptors, differentially modulate calcium and potassium currents in rods and large single cones. CB1 receptors are therefore well positioned to modulate neurotransmitter release at the first synapse of the visual system.

Ambystoma↗
PubMed2005

Structural requirements for cannabinoid receptor probes.

The discovery and cloning of CB1 and CB2, the two known G(i/o) protein-coupled cannabinoid receptors, as well as the isolation and characterization of two families of endogenous cannabinergic ligands represented by arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG), have opened new horizons in this newly discovered field of biology. Furthermore, a considerable number of cannabinoid analogs belonging to structurally diverse classes of compounds have been synthesized and tested, thus providing substantial information on the structural requirements for cannabinoid receptor recognition and activation. Experiments with site-directed mutated receptors and computer modeling studies have suggested that these diverse classes of ligands may interact with the receptors through different binding motifs. The information about the exact binding site may be obtained with the help of suitably designed molecular probes. These ligands either interact with the receptors in a reversible fashion (reversible probes) or alternatively attach at or near the receptor active site with the formation of covalent bonds (irreversible probes). This review focuses on structural requirements of cannabinoid receptor ligands and highlights their pharmacological and therapeutic potential.

Animals↗
PubMed2003

Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases.

Endocannabinoids are thought to function as retrograde messengers, which modulate neurotransmitter release by activating presynaptic cannabinoid receptors. Anandamide and 2-arachidonoylglycerol (2-AG) are the two best studied endogenous lipids which can act as endocannabinoids. Together with the proteins responsible for their biosynthesis, inactivation and the cannabinoid receptors, these lipids constitute the endocannabinoid system. This system is proposed to be involved in various neurodegenerative diseases such as Parkinson's and Huntington's diseases as well as Multiple Sclerosis. It has been demonstrated that the endocannabinoid system can protect neurons against glutamate excitotoxicity and acute neuronal damage in both in vitro and in vivo models. In this paper we review the data concerning the involvement of the endocannabinoid system in neurodegenerative diseases in which neuronal cell death may be elicited by excitotoxicity. We focus on the biosynthesis of endocannabinoids and on their modes of action in animal models of these neurodegenerative diseases.

Acute Disease↗
PubMed2004

Cannabinoid physiology and pharmacology: 30 years of progress.

Delta9-Tetrahydrocannabinol from Cannabis sativa is mimicked by cannabimimetic analogs such as CP55940 and WIN55212-2, and antagonized by rimonabant and SR144528, through G-protein-coupled receptors, CB1 in the brain, and CB2 in the immune system. Eicosanoids anandamide and 2-arachidonoylglycerol are the "endocannabinoid" agonists for these receptors. CB1 receptors are abundant in basal ganglia, hippocampus and cerebellum, and their functional activity can be mapped during behaviors using cerebral metabolism as the neuroimaging tool. CB1 receptors couple to G(i/o) to inhibit cAMP production, decrease Ca2+ conductance, increase K+ conductance, and increase mitogen-activated protein kinase activity. Functional activation of G-proteins can be imaged by [35S]GTPgammaS autoradiography. Post-synaptically generated endocannabinoids form the basis of a retrograde signaling mechanism referred to as depolarization-induced suppression of inhibition (DSI) or excitation (DSE). Under circumstances of sufficient intracellular Ca2+ (e.g., burst activity in seizures), synthesis of endocannabinoids releases a diffusible retrograde messenger to stimulate presynaptic CB1 receptors. This results in suppression of gamma-aminobutyric acid (GABA) release, thereby relieving the post-synaptic inhibition. Tolerance develops as neurons adjust both receptor number and cellular signal transduction to the chronic administration of cannabinoid drugs. Future therapeutic drug design can progress based upon our current understanding of the physiology and pharmacology of CB1, CB2 and related receptors. One very important role for CB1 antagonists will be in the treatment of craving in the disease of substance abuse.

Animals↗
PubMed2004

Differential effects of endogenous and synthetic cannabinoids on alpha7-nicotinic acetylcholine receptor-mediated responses in Xenopus Oocytes.

The effects of endogenous and synthetic cannabinoid receptor agonists, including 2-arachidonoylglycerol (2-AG), R-methanandamide, WIN55,212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], and CP 55,940 [1alpha,2beta-(R)-5alpha]-(-)-5-(1,1-dimethyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl-phenol], and the psychoactive constituent of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), on the function of homomeric alpha7-nicotinic acetylcholine (nACh) receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. The endogenous cannabinoid receptor ligands 2-AG and the metabolically stable analog of anandamide (arachidonylethanolamide), R-methanandamide, reversibly inhibited currents evoked with ACh (100 microM) in a concentration-dependent manner (IC50 values of 168 and 183 nM, respectively). In contrast, the synthetic cannabinoid receptor agonists CP 55,940, WIN55,212-2, and the phytochemical Delta9-THC did not alter alpha7-nACh receptor function. The inhibition of alpha7-mediated currents by 2-AG was found to be non-competitive and voltage-independent. Additional experiments using endocannabinoid metabolites suggested that arachidonic acid, but not ethanolamine or glycerol, could also inhibit the alpha7-nACh receptor function. Whereas the effects of arachidonic acid were also noncompetitive and voltage-independent, its potency was much lower than 2-AG and anandamide. Results of studies with chimeric alpha7-nACh-5-hydroxytryptamine (5-HT)3 receptors comprised of the amino-terminal domain of the alpha7-nACh receptor and the transmembrane and carboxyl-terminal domains of 5-HT3 receptors indicated that the site of interaction of the endocannabinoids with the alpha7-nAChR was not located on the N-terminal region of the receptor. These data indicate that cannabinoid receptor ligands that are produced in situ potently inhibit alpha7-nACh receptor function, whereas the synthetic cannabinoid ligands, and Delta9-THC, are without effect, or are relatively ineffective at inhibiting these receptors.

Analgesics, Non-Narcotic↗
PubMed2004

Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling.

Cannabinoids include not only plant-derived compounds (of which delta9-tetrahydrocannabinol is the primary psychoactive ingredient of cannabis), but also synthetic agents and endogenous substances termed endocannabinoids which include anandamide (2-arachidonoylethanolamide) and 2-arachidonoylglycerol. Cannabinoids act on specific, G-protein-coupled, receptors which are currently divided into two types, CB1 and CB2. Relatively selective agonists and antagonists for these receptors have been developed, although one agent (SR141716A) widely used as an antagonist at CB1 receptors has non-cannabinoid receptor-mediated effects at concentrations which are often used to define the presence of the CB1 receptor. Both cannabinoid receptors are primarily coupled to Gi/o proteins and act to inhibit adenylyl cyclase. Stimulation of CB1 receptors also modulates the activity of K+ and Ca2+ channels and of protein kinase pathways including protein kinase B (Akt) which might mediate effects on apoptosis. CB, receptors may activate the extracellular signal-regulated kinase cascade through ceramide signalling. Cannabinoid actions on the cardiovascular system have been widely interpreted as being mediated by CB1 receptors although there are a growing number of observations, particularly in isolated heart and blood vessel preparations, that suggest that other cannabinoid receptors may exist. Interestingly, the currently identified cannabinoid receptors appear to be related to a wider family of lipid receptor, those for the lysophospholipids, which are also linked to Gi/o protein signalling. Anandamide also activates vanilloid VR1 receptors on sensory nerves and releases the vasoactive peptide, calcitonin gene-related peptide (CGRP), which brings about vasodilatation through its action on CGRP receptors. Current evidence suggests that endocannabinoids have important protective roles in pathophysiological conditions such as shock and myocardial infarction. Therefore, their cardiovascular effects and the receptors mediating them are the subject of increasing investigative interest.

Animals↗
PubMed2006

Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids.

Cannabinoids are a structurally diverse group of mostly lipophilic molecules that bind to cannabinoid receptors. In fact, endogenous cannabinoids (endocannabinoids) are a class of signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids. They are synthesized from lipid precursors in plasma membranes via Ca(2+) or G-protein-dependent processes and exhibit cannabinoid-like actions by binding to cannabinoid receptors. However, endocannabinoids can produce effects that are not mediated by these receptors. In pharmacologically relevant concentrations, endocannabinoids modulate the functional properties of voltage-gated ion channels including Ca(2+) channels, Na(+) channels, various types of K(+) channels, and ligand-gated ion channels such as serotonin type 3, nicotinic acetylcholine, and glycine receptors. In addition, modulatory effects of endocannabinoids on other ion-transporting membrane proteins such as transient potential receptor-class channels, gap junctions and transporters for neurotransmitters have also been demonstrated. Furthermore, functional properties of G-protein-coupled receptors for different types of neurotransmitters and neuropeptides are altered by direct actions of endocannabinoids. Although the mechanisms of these effects are currently not clear, it is likely that these direct actions of endocannabinoids are due to their lipophilic structures. These findings indicate that additional molecular targets for endocannabinoids exist and that these targets may represent novel sites for cannabinoids to alter either the excitability of the neurons or the response of the neuronal systems. This review focuses on the results of recent studies indicating that beyond their receptor-mediated effects, endocannabinoids alter the functions of ion channels and other integral membrane proteins directly.

Animals↗
PubMed1995

Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process.

Previous studies have shown that cannabinoid receptor analogs increase voltage-dependent potassium A-current (IA) in cultured hippocampal cells. Because cannabinoid receptors inhibit adenylate cyclase, the present study explored whether cAMP played a role in mediating this effect on IA. The specific issue of whether cannabinoid receptor modulation of voltage-dependent IA acts via a cAMP-dependent process was investigated. The cAMP analog, 8-bromo-cAMP, as well as the adenylate cyclase stimulant forskolin, produced concentration-dependent shifts in IA that were opposite those produced by cannabinoid receptor ligands. Moreover, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also produced a marked negative shift in the steady-state voltage dependence of IA and increased the effect of forskolin on IA. As shown in previous studies, the cannabinoid agonist WIN 55,212-2 increased IA via a decrease in steady-state voltage-dependent inactivation of IA. WIN 55,212-2 also reversed the effects of forskolin on IA. The electrophysiological studies were paralleled by direct assays of cAMP in these cells, where cannabinoids inhibited forskolin-stimulated cAMP by 50% in a pertussis toxin-sensitive manner. The results confirmed that pertussis toxin-sensitive cannabinoid receptor-mediated changes in IA were probably the result of inhibition of adenylate cyclase. The findings are discussed in terms of modulation of IA conductance properties via cannabinoid receptor-mediated inhibition of cAMP levels within the cell.

1-Methyl-3-isobutylxanthine↗
PubMed2004

Cannabinoids and gene expression during brain development.

Cannabis is the most commonly used illicit drug in western societies, in particular among young people. It is consumed even by women during pregnancy and lactation, which result in a variety of disturbances in the development of their offspring, because, like other habit-forming drugs, cannabinoids, the psychoactive ingredients of marijuana, can cross the placental barrier and be secreted in the maternal milk. Through this way, cannabinoids affect the ontogeny of various neurotransmitter systems leading to changes in different behavioral patterns. Dopamine and endogenous opioids are among the neurotransmitters that result more affected by perinatal cannabinoid exposure, which, when animals mature, produce changes in motor activity, drug-seeking behavior, nociception and other processes. These disturbances are likely originated by the capability of cannabinoids to influence the expression of key genes for both neurotransmitters, in particular, the enzyme tyrosine hydroxylase and the opioid precursor proenkephalin. In addition, cannabinoids seem to be also able to influence the expression of genes encoding for neuron-glia cell adhesion molecules, which supports a potential influence of cannabinoids on the processes of cell proliferation, neuronal migration or axonal elongation in which these proteins are involved. In support of this possibility, CB1 receptors, which represent the major targets for the action of cannabinoids, are abundantly expressed in certain brain regions, such as the subventricular areas, which have been involved in these processes during brain development. Finally, cannabinoids might also be involved in the apoptotic death that occurs during brain development, possibly by influencing the expression of Bcl-2/Bax system. Also in support of this option, CB1 receptors are transiently expressed during brain development in different group of neurons which do not contain these receptors in the adult brain. This paper will review all evidence relating cannabinoids to the expression of key genes for neural development, trying to establish the future research addressed to elucidate the mechanisms involved in the epigenetic action of cannabinoids during brain development.

Brain↗
PubMed2002

[The pharmacology of cannabinoid derivatives: are there applications to treatment of pain?].

OBJECTIVE: To present the cannabinoid system together with recent findings on the pharmacology of these compounds in the treatment of pain. DATA SOURCES: Search through Medline database of articles published in French and English since 1966. Also use of other publications such as books on cannabis. STUDY SELECTION: All the relevant documents within the theme of this review were used. DATA EXTRACTION: All the data linked to the present topic were searched. DATA SYNTHESIS: Recent advances have dramatically increased our understanding of cannabinoid pharmacology. The psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors and ligands. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio. CONCLUSION: The cannabinoid system is a major target in the treatment of pain and its therapeutic potential should be assessed in the near future by the performance of new clinical trials.

Analgesics, Non-Narcotic↗