Since the discovery of the cannabinoid receptors and their endogenous ligands, significant advances have been made in studying the physiological function of the endocannabinoid system. The presence of cannabinoid receptors on cells of the immune system and anecdotal and historical evidence suggesting that cannabis use has potent immuno-modulatory effects, has led to research directed at understanding the function and role of these receptors within the context of immunological cellular function. Studies from chronic cannabis smokers have provided much of the evidence for immunomodulatory effects of cannabis in humans, and animal and in vitro studies of immune cells such as T cells and macrophages have...

The active component of marijuana, D9 -tetrahydrocannabinol, activates the CB1 and CB2 cannabinoid receptors, thus mimicking the action of endogenous cannabinoids. CB1 is predominantly neuronal and mediates the cannabinoid psychotropic effects. CB2 is predominantly expressed in peripheral tissues, mainly in pathological conditions. So far the main endocannabinoids, anandamide and 2-arachidonoylglycerol, have been found in bone at ‘brain’ levels. The CB1 receptor is present mainly in skeletal sympathetic nerve terminals, thus regulating the adrenergic tonic restrain of bone formation. CB2 is expressed in osteoblasts and osteoclasts, stimulates bone formation, and inhibits bone resorption. Because low bone mass is the only spontaneous phenotype so far reported...

Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9 -tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the...

Abstract Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in...

Abstract Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects. The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis. Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions. This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.

Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system, much work has been done to investigate the main effects of these compounds. There is increasing evidence that the cannabinoid system may regulate neurodegenerative processes such as excessive glutamate production, oxidative stress and neuroinflammation. Neurodegeneration is a feature common to the various types of dementia and this has led to interest in whether cannabinoids may be clinically useful in the treatment of people with dementia. Recent studies have also shown that cannabinoids may have more specific effects in interrupting the pathological process in Alzheimer’s...

The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer. The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors, with their endogenous ligands and the enzymes related to the synthesis and degradation of these endocannabinoid compounds. Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses,...

Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabis relieves symptoms of mania and/or depression. The cannabinoids ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects....

Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data were extracted on lesion volume, outcome and quality, and analyzed using random effect models. Results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). In all, 144 experiments (34 publications) assessed CBs on infarct volume in 1,473 animals. Cannabinoids reduced infarct volume in transient (SMD − 1.41 (95% CI − 1.71), − 1.11) Po0.00001) and permanent...

Abstract Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too...