The endocannabinoid system (ECS), which is composed of the cannabinoid receptors types 1 and 2 (CB1 and CB2) for marijuana's psychoactive ingredient Δ9-tetrahydrocannabinol (Δ9-THC), the endogenous ligands (AEA and 2-AG) and the enzymatic systems involved in their biosynthesis and degradation, recently emerged as important modulator of emotional and non-emotional behaviors. For centuries, in addition to its recreational actions, several contradictory claims regarding the effects of Cannabis use in sexual functioning and behavior (e.g. aphrodisiac vs anti-aphrodisiac) of both sexes have been accumulated. The identification of Δ9-THC and later on, the discovery of the ECS have opened a potential therapeutic target for sexual dysfunctions, given the partial efficacy of current pharmacological treatment. In agreement with the bidirectional modulation induced by cannabinoids on several behavioral responses, the endogenous cannabinoid AEA elicited biphasic effects on sexual behavior as well. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of several aspects of sexuality in preclinical and human studies, highlighting their therapeutic potential.
BACKGROUND: n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. METHODOLOGY/PRINCIPAL FINDINGS: In a 'prevention study', C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ∼35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. CONCLUSIONS/SIGNIFICANCE: Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT.
- MeSH
- Analysis of Variance MeSH
- Adipose Tissue, White metabolism MeSH
- Biological Availability MeSH
- Diet, High-Fat MeSH
- Endocannabinoids MeSH
- Phospholipids metabolism MeSH
- Immunohistochemistry MeSH
- Liver drug effects metabolism MeSH
- Muscle, Skeletal metabolism MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Eicosapentaenoic Acid metabolism MeSH
- Docosahexaenoic Acids metabolism MeSH
- Metabolomics MeSH
- Microscopy MeSH
- Cannabinoid Receptor Modulators metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Obesity diet therapy prevention & control MeSH
- Fatty Acids, Omega-3 administration & dosage metabolism pharmacology MeSH
- Body Weight MeSH
- Triglycerides metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- MeSH
- Cannabinoid Receptor Antagonists MeSH
- Financing, Organized MeSH
- Cannabinoids pharmacology MeSH
- Anti-Obesity Agents pharmacology MeSH
- Humans MeSH
- Cannabinoid Receptor Modulators antagonists & inhibitors metabolism MeSH
- Obesity drug therapy metabolism MeSH
- Eating physiology drug effects MeSH
- Receptors, Cannabinoid metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comment MeSH
- Overall MeSH
Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabinoid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative illnesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and synthetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.
- MeSH
- Cannabis chemistry MeSH
- Cannabinoids pharmacology chemistry MeSH
- Plants, Medicinal chemistry MeSH
- Humans MeSH
- Cannabinoid Receptor Modulators metabolism MeSH
- Receptors, Cannabinoid metabolism drug effects MeSH
- Signal Transduction physiology MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Obezita se stává v současné době celosvětovou epidemií. Etiologie obezity je multifaktoriální. Hlavní příčinou obezity je převaha energetického příjmu nad energetickým výdejem. Genetické faktory se na rozvoji obezity podílejí z 40 až 70 % a jejich vliv je modulován faktory vnějšího prostředí, z nichž hlavní význam mají dietní návyky, pohybová aktivita, faktory sociální a psychické. Pro zvrácení dosavadního nepříznivého vývoje je rozhodující změnit stravovací návyky, zvýšit pohybovou aktivitu a zodpovědnost každého jedince za své zdraví. S uplatňováním preventivních opatření je třeba začít již od útlého dětství, kdy se vytvářejí životní návyky. Nezastupitelnou roli v prevenci obezity mají rodiče, škola a stát.
At present obesity is becoming a worldwide pandemic. There is a multifactor etiology of obesity. The main reason is an excess of energetic input. Genetic factors account for 40-70% of its development. These genetic factors are also influenced by external factors, of which the diet, physical activity, social and mental factors are of the greatest importance. For a reversal of the present adverse development a change of diet habits, an incerease of fitness and responsibility of each subject for their health are critical. It is necessary to start with the applying of preventive measures from early childhood when the lifestyle habits are formed. Parents, school and Government have their own unsubstitutable role in the prevention of obesity.
- MeSH
- Adiponectin physiology metabolism MeSH
- Insulin metabolism secretion MeSH
- Leptin metabolism MeSH
- Humans MeSH
- Cannabinoid Receptor Modulators pharmacokinetics metabolism MeSH
- Obesity etiology genetics prevention & control MeSH
- Socioeconomic Factors MeSH
- Adipose Tissue metabolism MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Endokanabinoidní systém tvořený u savců včetně člověka souborem specifických receptorů (kanabinoidních receptorů označovaných CB, existujících v několika podtypech) a endogenních látek fyziologicky je ovlivňujících (endokanabinoidů) získal svůj název od kanabinoidů známých jako více než 60 látek (z celkového počtu asi 420) izolovaných z konopí setého (Cannabis sativa). Nejznámějším kanabinoidem definovaným jako čistá substance se v roce 1964 stal d-9-tetrahydrokanabinol (THC) s psychotropním působením.
- MeSH
- Cannabinoid Receptor Antagonists MeSH
- Diabetes Mellitus drug therapy metabolism MeSH
- Financing, Organized utilization MeSH
- Glucose metabolism MeSH
- Cardiovascular Diseases drug therapy metabolism prevention & control MeSH
- Evidence-Based Medicine trends MeSH
- Lipid Metabolism drug effects MeSH
- Cannabinoid Receptor Modulators pharmacology metabolism MeSH
- Piperidines administration & dosage adverse effects therapeutic use MeSH
- Pyrazoles administration & dosage adverse effects therapeutic use MeSH
- Receptors, Cannabinoid metabolism drug effects MeSH
Endokanabinoidní systém je endogenní signální systém, který hraje důležitou roli v regulaci energetické homeostázy a metabolismu tuků a sacharidů, což může potenciálně ovlivnit kardiometabolické riziko. Endokanabinoidy jsou zapojeny v mechanismech ovlivňujících chuť k jídlu a tělesnou hmotnost. Centrální i periferní stimulace endokanabinoidního systému podporuje metabolické procesy vedoucí následně ke zvýšení hmotnosti, k lipogenezi, inzulínové rezistenci, dyslipidémii a porušené glukózové toleranci. Endokanabinoidní systém je trvale aktivnější u obézních jedinců. Endokanabinoidní systém se stává potenciálním mechanismem, který reguluje důležité aspekty kardiovaskulárních a metabolických funkcí.
The endocannabinoid system (ECS) is an endogenous signalling system that plays an important role in the regulation of energy homeostasis and lipid and glucose metabolism-all of which can influence cardiometabolic risk. Endocannabinoids are involved in the appetite and body weight regulation. Central or peripheral stimulation of ECS favours metabolic processes that lead to weight gain, lipogenesis, insulin resistance, dyslipidemia, and impaired glucose homeostasis. ECS is tonically overactive in obese individuals. ECS appears to be a promising novel mechanistic pathway that modulates important aspects of the cardiovascular and metabolic function.
- MeSH
- Animal Experimentation MeSH
- Financing, Organized MeSH
- Risk Assessment MeSH
- Homeostasis physiology MeSH
- Body Mass Index MeSH
- Cardiovascular Diseases etiology metabolism MeSH
- Rats metabolism MeSH
- Lipid Metabolism physiology MeSH
- Carbohydrate Metabolism genetics MeSH
- Cannabinoid Receptor Modulators metabolism MeSH
- Mice metabolism MeSH
- Obesity metabolism MeSH
- Eating physiology MeSH
- Body Weight Changes MeSH
- Animals MeSH
- Check Tag
- Rats metabolism MeSH
- Mice metabolism MeSH
- Animals MeSH
In the last 25 years data has grown exponentially dealing with the discovery of the endocannabinoid system consisting of specific cannabinoid receptors, their endogenous ligands, and enzymatic systems of their biosynthesis and degradation. Progress is being made in the development of novel agonists and antagonists with receptor subtype selectivity which should help in providing a greater understanding of the physiological role of the endocannabinoid system and perhaps also in a broad number of pathologies. This could lead to advances with important therapeutic potential of drugs modulating activity of endocannabinoid system as hypnotics, analgesics, antiemetics, antiasthmatics, antihypertensives, immunomodulatory drugs, antiphlogistics, neuroprotective agents, antiepileptics, agents influencing glaucoma, spasticity and other "movement disorders", eating disorders, alcohol withdrawal, hepatic fibrosis, bone growth, and atherosclerosis. The aim of this review is to highlight distribution of the CB1 and CB2 receptor subtypes in the nervous system and functional involvement of their specific ligands.
- MeSH
- Financing, Organized MeSH
- Cannabinoids therapeutic use MeSH
- Humans MeSH
- Ligands MeSH
- Cannabinoid Receptor Modulators metabolism MeSH
- Nervous System metabolism MeSH
- Receptor, Cannabinoid, CB1 agonists antagonists & inhibitors metabolism MeSH
- Receptor, Cannabinoid, CB2 agonists antagonists & inhibitors metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Review MeSH
Pokroky v pochopení mechanismů účinků kanabinoidů byly učiněny především po objevení kanabinoidních receptorů a nalezení jejich endogenních ligandů. Nové poznatky jsou získávány jak pomocí známých rostlinných kanabinoidů (fytokanabinoidů), tak i kanabinoidů endogenních a syntetických. V této práci jsou shrnuty základní informaci o účincích a mechanismech působení kanabinoidů a o úloze endokanabinoidního systému ve vzniku či léčbě závislostí, schizofrenie a poruch nálady. V závěru jsou uvedeny možnosti terapeutického využití kanabinoidů.
Progress in understanding the mechanisms of action of cannabinoids was made after discovery of cannabinoid receptors and finding their endogenous ligands. New findings are obtained using both plant cannabinoids (phytocannabinoids) and endogenous or synthetic cannabinoids. Basic information is summarized in the paper about mechanisms of action of cannabinoids, about role of endocannabinoid system in addiction, schizophrenia or mood disorders. Possible therapeutic use of cannabinoids is described at the close.
[6] s. : il. ; 30 cm
- MeSH
- Adiposity MeSH
- Diabetes Mellitus, Type 2 metabolism MeSH
- Cardiovascular Diseases MeSH
- Diabetes Complications drug therapy MeSH
- Disease Management MeSH
- Cannabinoid Receptor Modulators metabolism MeSH
- Risk Factors MeSH
- Publication type
- Meeting Abstract MeSH
- Collected Work MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- diabetologie
- kardiologie
