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A pilot study of the effects of cannabis on appetite hormones in HIV-infected adult men

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Abstract

The endocannabinoid system is under active investigation as a pharmacological target for obesity management due to its role in appetite regulation and metabolism. Exogenous cannabinoids such as tetrahydrocannabinol (THC) stimulate appetite and food intake. However, there are no controlled observations directly linking THC to changes of most of the appetite hormones. We took the opportunity afforded by a placebo-controlled trial of smoked medicinal cannabis for HIV-associated neuropathic pain to evaluate the effects of THC on the appetite hormones ghrelin, leptin and PYY, as well as on insulin. In this double-blind cross-over study, each subject was exposed to both active cannabis (THC) and placebo. Compared to placebo, cannabis administration was associated with significant increases in plasma levels of ghrelin and leptin, and decreases in PYY, but did not significantly influence insulin levels. These findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors, independent of glucose metabolism.

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... La insulina se eleva proporcionalmente con los niveles de THC 14 , ya que se ha reportado que la estimulación de los CB1 a nivel de las células β pancreáticas tiene la capacidad de estimular la liberación de insulina [16][17][18] , de manera que se genera un estímulo orexigénico. Además de su efecto sobre el consumo de alimentos, a largo plazo, la sobreexpresión grelina, una hormona que se libera en el estómago en situaciones de ayuno para informar a este núcleo vía humoral y a través del nervio vago, aumentando el apetito. ...
... Además de su efecto sobre el consumo de alimentos, a largo plazo, la sobreexpresión grelina, una hormona que se libera en el estómago en situaciones de ayuno para informar a este núcleo vía humoral y a través del nervio vago, aumentando el apetito. En el estudio de Riggs se hace una correlación entre los niveles de grelina, leptina e insulina en pacientes con VIH tras el consumo de marihuana, encontrando que la leptina tiene efectos anorexigénicos y tras el consumo de marihuana los niveles de leptina a nivel del plasma aumentan, sin embargo, tras esta primera fase, mientras aumentan los niveles de THC en sangre, disminuyen los de leptina 14 . Además, se observa una fuerte correlación negativa entre estas dos sustancias 14,15 . ...
... En el estudio de Riggs se hace una correlación entre los niveles de grelina, leptina e insulina en pacientes con VIH tras el consumo de marihuana, encontrando que la leptina tiene efectos anorexigénicos y tras el consumo de marihuana los niveles de leptina a nivel del plasma aumentan, sin embargo, tras esta primera fase, mientras aumentan los niveles de THC en sangre, disminuyen los de leptina 14 . Además, se observa una fuerte correlación negativa entre estas dos sustancias 14,15 . ...
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La marihuana es uno de los psicoactivos más consumidos en Colombia y el mundo. Se ha observado que tiene efectos sobre el sistema nervioso central y, en consecuencia, podría afectar al metabolismo y el estado nutricional de los individuos consumidores. Este artículo pretende evaluar si el consumo de marihuana y la activación del sistema cannabinoide tienen la capacidad de activar mecanismos fisiológicos mediante los cuales se afecte la ingesta de alimentos, el metabolismo de los nutrientes y el estado nutricional de los adultos adictos. Como resultado se encuentra que el consumo de la marihuana puede incrementar los estímulos orexigénicos y disminuir los anorexigénicos, incidiendo en el aumento de la ingesta y en cambios sobre la producción de enzimas importantes para el metabolismo de las grasas. Además, influye en la aparición de alteraciones del estado nutricional de los consumidores relacionadas con una disminución del índice de masa corporal (IMC), lo cual contrasta con los resultados observados a nivel de la ingesta, por lo tanto se resalta la importancia de efectuar estudios profundos que expliquen este cuestionamiento.
... 2,3 CB1R is widely expressed in the hypothalamus, which is the key region involved in the regulation of appetite and includes appetite hormones, such as leptin. 4 Leptin is a hormone released primarily from adipocytes. It reaches the brain through the bloodstream, binding to specific receptors. ...
... CB1R, which also controls leptin, causes it not to activate, since the cannabinoid system is under the negative control of leptin. 4,6 However, contradictory results have been observed about the interaction between cannabis and appetite hormones. Wagner et al. found that oral administration of a CB1R antagonist reduced plasma leptin levels in obese individuals. ...
... 2,7 However, Riggs et al. found significant changes in leptin levels after cannabis smoking, but not in placebo. 4 Other studies, moreover, have suggested that gender impacts the effects of cannabis use. Men consume cannabis in greater amounts and at higher rates than women. 1 On the other hand, Monteleone et al. demonstrated an inverse relationship between endogenous cannabinoid and circulating leptin in women. ...
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Objective: To evaluate the serum leptin levels in cannabis smokers. Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008). When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039). Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.
... 67 More studies indicated the synergistic effect of endocannabinoids and ghrelin. 68−70 Additionally, Riggs et al. 63 found that administration of medical cannabis by HIV-infected adult men decreased their plasma level of anorexic hormone peptide YY and had no effect on insulin level while another anorexic hormone leptin was increased in this case. One possible explanation of increased leptin is that the level of endogenous cannabinoids is inversely associated with leptin's plasma concentration. ...
... 71,72 However, the high levels of exogenous cannabinoid stimulation might feedback negatively on endogenous cannabinoid production, leading to increases in leptin. 63 On the contrary, in healthy adults instead of HIV-positive patients, consuming cannabis showed no significant or significant down-regulation effects on plasma leptin. 66,73 In parallel, the plasma concentrations of anorexic hormone GLP-1 in healthy volunteers were lower under cannabis consumption than in placebo condition, while the spike in blood insulin concentrations observed under the placebo condition due to food intake was blunted by cannabis administration. ...
Article
Cannabis is an excellent natural source of fiber and various bioactive cannabinoids. So far, at least 120 cannabinoids have been identified, and more novel cannabinoids are gradually being unveiled by detailed cannabis studies. However, cannabinoids in both natural and isolated forms are especially vulnerable to oxygen, heat, and light. Therefore, a diversity of cannabinoids is associated with their chemical instability to a large extent. The research status of structural conversion of cannabinoids is introduced. On the other hand, the use of drug-type cannabis and the phytocannabinoids thereof has been rapidly popularized and plays an indispensable role in both medical therapy and daily recreation. The recent legalization of edible cannabis further extends its application into the food industry. The varieties of legal edible cannabis products in the current commercial market are relatively monotonous due to rigorous restrictions under the framework of Cannabis Regulations and infancy of novel developments. Meanwhile, patents/studies related to the safety and quality assurance systems of cannabis edibles are still rare and need to be developed. Furthermore, along with cannabinoids, many phytochemicals such as flavonoids, lignans, terpenoids, and polysaccharides exist in the cannabis matrix, and these may exhibit prebiotic/probiotic properties and improve the composition of the gut microbiome. During metabolism and excretion, the bioactive phytochemicals of cannabis, mostly the cannabinoids, may be structurally modified during enterohepatic detoxification and gut fermentation. However, the potential adverse effects of both acute and chronic exposure to cannabinoids and their vulnerable groups have been clearly recognized. Therefore, a comprehensive understanding of the chemistry, metabolism, toxicity, commercialization, and regulations regarding cannabinoid edibles is reviewed and updated in this contribution.
... Total ghrelin blood levels were increased in chronic drug smoking HIV patients Chronic THC smokers Riggs et al. [217] Total ghrelin blood levels were increased after oral drug administration in healthy cannabis users Cannabis Farokhnia et al. [218] Total ghrelin blood levels were higher after oral drug administration in comparison to smoked and vaporized drug; no significant effects on acyl-ghrelin were found Cannabis Farokhnia et al. [219] Vaporized drug AUC was positively correlated with total ghrelin AUC and a similar positive correlation between drug AUC and acyl-ghrelin AUC was also indicated THC Farokhnia et al. [219] ...
... Human studies have explored the impact of cannabinoids on ghrelin blood levels. Increased blood levels of total ghrelin were observed in chronic THC-smoking HIV-infected men [217]. Furthermore, increased blood levels of total ghrelin were observed after the oral administration of cannabis in healthy adult cannabis users [218]. ...
Article
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Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin’s/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin’s/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.
... In line with this, animal work suggests that ECs may enhance appetitive motivation and food intake by interacting with several metabolic hormones. Human evidence is, however, limited, but a pilot study in HIV-infected men showed that chronically smoked THC increased plasma concentrations of ghrelin and leptin, whereas a decrease in PYY (peptide YY) and no effect on insulin were found (50). Furthermore, hedonic food intake in satiated normal-weight subjects increases plasma concentrations of the orexigenic hormone ghrelin and the EC 2-arachidonoylglycerol, indicating that both may be important in mediating the rewarding effects of palatable foods (12). ...
... However, we verified that baseline ghrelin concentrations were within physiological ranges and did not differ between THC and placebo, and that there were no other potential assay-related methodological issues that could have confounded our results. Moreover, it has to be noted that, to the best of our knowledge, so far no study has assessed the effect of acute cannabinoid administration on ghrelin concentrations to anticipatory food reward and human evidence on the effect of (chronically smoked) THC on plasma ghrelin concentrations is also mixed (more details in the Supplemental Information) (50,56). These divergent findings may be explained by differences in study paradigm (e.g., visual food cues compared with actual intake, a buffet meal compared with a single-drink meal), drug dosing, and route of administration as well as interspecies differences, and thus warrant further investigations. ...
Article
Background: The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans. Objective: We aimed to investigate the effect of oral Δ9-tetrahydrocannabinol (THC) on subjective and metabolic hormone responses to visual food stimuli and food intake. Methods: Seventeen healthy subjects participated in a single-blinded, placebo-controlled, 2 × 2 crossover trial. In each of the 4 visits, subjective "liking" and "wanting" ratings of high- and low-calorie food images were acquired after oral THC or placebo administration. The effect on food intake was quantified in 2 ways: via ad libitum oral intake (half of the visits) and intragastric infusion (other half) of chocolate milkshake. Appetite-related sensations and metabolic hormones were measured at set time points throughout each visit. Results: THC increased "liking" (P = 0.031) and "wanting" ratings (P = 0.0096) of the high-calorie, but not the low-calorie images, compared with placebo. Participants consumed significantly more milkshake after THC than after placebo during oral intake (P = 0.0005), but not intragastric infusion, of milkshake. Prospective food consumption ratings during the food image paradigm were higher after THC than after placebo (P = 0.0039). THC also increased plasma motilin (P = 0.0021) and decreased octanoylated ghrelin (P = 0.023) concentrations before milkshake consumption (i.e., in both oral intake and intragastric infusion test sessions), whereas glucagon-like peptide 1 responses to milkshake intake were attenuated by THC during both oral (P = 0.0002) and intragastric (P = 0.0055) administration. Conclusions: These findings suggest that the ECS drives food intake by interfering with anticipatory, cephalic phase, and metabolic hormone responses. This trial was registered at clinicaltrials.gov as NCT02310347.
... Besides BMI and body fat, levels of leptin are highly correlated with IGF-I [20] and urinary free cortisol (UFC) [21], suggesting that the physiological regulation of leptin is complex. Data from cannabis smoking HIV-infected adult men suggest that the secretion of leptin might also be modulated though the endogenous cannabinoid receptors [22]. In addition to leptin, adiponectin is an insulin-sensitising cytokine produced by adipose tissue, but in contrast to leptin, plasma adiponectin is normally decreased in obese subjects and elevated in lean subjects. ...
... However, with the exception of body weight, age and UFC, we were unable to detect any significant association between leptin and other measured clinical and hormonal parameters. In contrast with previous findings in cannabis-smoking HIV infected men [22], dronabinol intervention did not significantly predict a higher level of leptin than placebo. On the other hand, our findings cannot rule out the possibility that cannabinoid signalling nevertheless has indirectly influenced the secretion of leptin, as its levels tended to return to baseline 24 h after the last dronabinol dose. ...
... These findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors as previously concluded by [30], whose study results showed that cannabis administration was associated with significant increases in plasma levels of ghrelin and leptin, and decreases in PYY, but did not significantly influence insulin levels and these findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors, independent of glucose metabolism. ...
... Using the tools of PHI, models of Malaria outbreaks and vector habits have been developed [28,29]. In the United States, the use of GIS analysis has proven quite effective in identifying climate and habitat considerations conducive for the spread of the disease via deer ticks [24,25,30]. In closing, knowingly society has been adapting to the use of information technology usage in home, office, and public access areas. ...
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This study was performed to increase the understanding of the adverse reproductive effects associated with Laprol-604 animals exposed during gestation period of Wistar rats. Laprol-604 was administered to 75 pregnant dams once daily by gavage at doses of 0,125; 1,25 and 12,5 mg/kg, respectively is the 1-st; 2- nd and 3-rd group from the second gestation day (GD) to the twenty GD. The 4-th group (controls) consisted of 25 intact animals without Laprol-604 administration. Laprol-604 showed dosage dependent reproductive toxicity when the pregnant rats were exposed. It led to reduced statistically significant body weight of pregnant dams. Above this physiological change, significant elevations of hepatic weight were found in the 3-rd group as much as twofold over the corresponding the rat of control group. The small increase in the relative liver weight in the 0,125 mg/kg dosage group largely reflected the reduction of body weight, rather than a net increase of liver weight. Nevertheless, the high sensitivity to Laprol-604-induced liver toxicity in the rat of 3-rd group should be noted and the liver weight increase estimated at 1,7 times. Liver enlargement associated with biochemical disturbances is another feature seen after exposure to Laprol-604 to pregnant rats led to significant increase the levels of aminotransferases (alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and alkaline phosphates (ALP), in the liver homogenates. Additionally, the sorbitol dehydrogenase activity in the serum of rats 3-rd group appeared to reach the highest concentration compared with control, 2-nd and 1-rst groups. There was a significant reduction in total protein level, decrease level of glycogen and increase of total lipid level in liver homogenates of Laprol-604 administration rats when compared to the control group. Nonionic surfactants are known to catalyze oxidative stress as activation of protein catabolism [18, 19, 24] which is probably the reason for the decrease in content protein in liver homogenates. The adverse effect of Laprol-604 was indicated by the activation of protein catabolism, as seen, the elevation of low-molecular proteins concentration in the blood serum. Keywords: Laprol-604, polyols, surfactant, modeling, rats, reproductive toxicity, gestation day.
... Continuing on the subject of cannabis as medicine, there have been claims that either smoked or ingested cannabis containing the psychoactive component THC, and those that are natural or synthetic in origin (dronabinol), improves the appetites of people with AIDS, increases weight gain and lifts mood, thereby improving the quality of life. In a doubleblind cross-over study [40], compared to placebo, cannabis administration was associated with significant increases in plasma levels of appetite controlling hormones, ghrelin and leptin, but did not significantly influence insulin levels, suggesting that the modulation of appetite hormones is mediated through endogenous cannabinoid receptors, independent of glucose metabolism. In an elegant NIDA-funded randomized, cross-over, double-blind, placebo-controlled study, Farokhnia et al. [41] investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. ...
... Regarding the impact of cannabis on sexually transmitted infections (STIs), the data show that there were fewer STIs and lower risk of sexual engagement among HIV-infected MSMs who smoked cannabis as compared to those who did not smoke cannabis [72]. On the positive side of cannabis use, research shows that cannabis improves appetite, food intake, and metabolism, possibly via the endocannabinoid system, which, in turn, activates appetite stimulating hormones such as ghrelin and leptin [40,41]. ...
Article
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Cannabis continues to be the most used drug in the world today. Research shows that cannabis use is associated with a wide range of adverse health consequences that may involve almost every physiological and biochemical system including respiratory/pulmonary complications such as chronic cough and emphysema, impairment of immune function, and increased risk of acquiring or transmitting viral infections such as HIV, HCV, and others. The review of published research shows that cannabis use may impair immune function in many instances and thereby exerts an impact on viral infections including human immune deficiency virus (HIV), hepatitis C infection (HCV), and human T-cell lymphotropic type I and II virus (HTLV-I/II). The need for more research is also highlighted in the areas of long-term effects of cannabis use on pulmonary/respiratory diseases, immune dysfunction and the risk of infection transmission, and the molecular/genetic basis of immune dysfunction in chronic cannabis users.
... In the only published human study, to our knowledge, looking at appetitive and metabolic hormones, smoked medicinal cannabis (as a treatment for neuropathic pain) was tested in adult men positive for human immunodeficiency virus (HIV). In this pilot, crossover, double-blind study, cannabis administration increased blood concentrations of ghrelin and leptin, decreased peptide YY (PYY) concentrations, and had no significant effects on insulin 48 . The goal of the present study was to explore the effects of cannabis administration on peripheral concentrations of endocrine markers related to appetite and metabolism in a sample of cannabis users and to build the foundation for future studies in this regard. ...
... A pilot human study found a positive correlation between blood concentrations of an endocannabinoid (2-AG) and ghrelin during hedonic eating 85 . In another pilot human study, administration of smoked medicinal cannabis, compared to placebo, significantly increased blood ghrelin concentrations in HIV-infected adult men 48 . While the aforementioned findings are consistent with our results, it is hard to interpret why the effects on ghrelin in the present study were limited to specific routes of cannabis administration. ...
Article
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As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.
... It was found also that cannabis smoking had modulated the statistically significant inverse correlation between plasma AgRP concentrations and BMI in non cannabis smokers to be insignificant inversely correlation between them. These findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors as previously concluded by [30], whose study results showed that cannabis administration was associated with significant increases in plasma levels of ghrelin and leptin, and decreases in PYY, but did not significantly influence insulin levels and these findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors, independent of glucose metabolism. ...
... 86 Medical cannabis and THC, specifically, are known to boost appetite in humans and laboratory animals. 85,[87][88][89][90][91][92] Overall, studies assessing the effects of cannabis or phytocannabinoids on appetite in cancer patients have shown benefits, although there appears to be a placebo effect, and a 2017 report found insufficient evidence to support or refute its use. 73 In one study in 469 patients with advanced cancer and documented weight loss or reduced food intake, 93 and another in 243 patients with advanced cancer and cancer-related anorexia-cachexia syndrome (CACS), 94 appetite increased in all groups including comparison groups treated with dronabinol (synthetic THC), megestrol acetate, 93 cannabis extract, and placebo, 94 suggesting that cannabis-derived products are no better than a placebo. ...
Article
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Cannabis has the potential to modulate some of the most common and debilitating symptoms of cancer and its treatments, including nausea and vomiting, loss of appetite, and pain. However, the dearth of scientific evidence for the effectiveness of cannabis in treating these symptoms in patients with cancer poses a challenge to clinicians in discussing this option with their patients. A review was performed using keywords related to cannabis and important symptoms of cancer and its treatments. Literature was qualitatively reviewed from preclinical models to clinical trials in the fields of cancer, human immunodeficiency virus (HIV), multiple sclerosis, inflammatory bowel disease, post-traumatic stress disorder (PTSD), and others, to prudently inform the use of cannabis in supportive and palliative care in cancer. There is a reasonable amount of evidence to consider cannabis for nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments. There is promising evidence to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is thus far too limited to recommend cannabis for these symptoms. Scant, yet more controversial, evidence exists in regard to cannabis for cancer- and treatment-related cognitive impairment, anxiety, depression, and fatigue. Adverse effects of cannabis are documented but tend to be mild. Cannabis has multifaceted potential bioactive benefits that appear to outweigh its risks in many situations. Further research is required to elucidate its mechanisms of action and efficacy and to optimize cannabis preparations and doses for specific populations affected by cancer.
... Moreover, the increase in caloric intake was hypothesized to be closely linked with the concomitant increase in alcohol consumption [13]. Activation of CB 1 is widely thought to be the culprit for such polyphagic behavior through the stimulation of plasma ghrelin and leptin [14,15]. It is interesting to note that prevalence of obesity was lower in chronic cannabis users compared to non-users [16]. ...
Article
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Cannabis use in the US is rising with increased legalization. It has been noted that there is a five-fold increase risk of Myocardial Infarctions (MI) in the first hour after cannabis use. Traditional risk factors for MI include diabetes, hypertension and dyslipidemia. The rising use of cannabis may have ushered in an additional MI risk factor to be added to the list; that is cannabis. In this review, we discuss the growing use of cannabis and potential link with MI, highlighting the common pathogenic hypotheses linking these risk factors.
... The first report of increase in appetite was reported in AD 300. Smoking cannabis in patients with the history of HIV was shown to modulate leptin and ghrelin but not insulin levels demonstrating their effect on hormones [60]. They were also prescribed as appetite enhancing medicine in patients with AIDS and cancer [61,18]. ...
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... Theologically, the chronic administration of Δ 9 -THC may affect both central nerve system and immune system and, therefore, potentially modulate disease progression especially among patients infected with neurotropic HIV-1. This is a critical issue because the man-made Marinol, whose active ingredient is Δ 9 -THC, has been approved by the Food and Drug Administration as an appetite stimulant for the treatment of HIV-1-associated anorexia and weight loss (Abrams 1998;Riggs et al. 2012). HIV-1-positive marijuana smokers produced substantial and comparable increases in food intake (Haney 2002;Haney et al. 2007). ...
Article
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Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin.
... Cannabis administration, as compared to placebo, significantly increased ghrelin concentrations in this study. In addition, leptin and PYY levels were, respectively, increased and decreased, but no impact on insulin levels was found (Riggs et al., 2012). ...
Chapter
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In the past years, a significant volume of research has implicated the appetitive hormone ghrelin in the mechanisms underlying drug use and addiction. From a neuroscientific standpoint, ghrelin modulates both reward and stress pathways, two key drivers of substance use behaviors. Previous investigations support a connection between the ghrelin system and alcohol, stimulants, and tobacco use in both animals and humans, while the research on opioids and cannabis is scarce. In general, upregulation of the ghrelin system seems to enhance craving for drugs as well as substances use. On the other hand, acute and chronic exposure to drugs of abuse influences the ghrelin system at different levels. This chapter summarizes the literature on the relationship between the ghrelin system and substance-related behaviors. We also review recent work investigating the ghrelin system as a potential pharmacological target for treating substance use disorders and discuss the need for additional research.
... 3,4 On the basis of research carried out on pharmaceuticalgrade synthetic and herbal cannabinoids and, in some cases, marijuana itself, cannabinoids likely have utility in ameliorating symptoms that commonly afflict cancer patients including pain, nausea, vomiting, poor appetite, low mood, and disrupted sleep. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] MM may also offer certain advantages over pharmaceutical cannabinoids. First, it is available in a wider variety of preparations; it may be eaten, drunk, applied topically, smoked, or vaporized. ...
Article
Background: Expansion of medical marijuana (MM) laws in the United States may offer oncology new therapeutic options. However, the scientific evidence for MM remains in infancy. This study qualitatively explored professional opinion around the role of MM in cancer care. Methods: Semi-structured interviews were administered to a sample of individuals with expertise at the interface of MM and oncology nationally. Key informant criteria included an oncologic clinical or research background and any of the following: publications, research, or lectures on cannabinoids or cancer symptoms; involvement in the development of MM dispensaries or legislation; early adoption of state MM certification procedures. A gold-standard grounded, inductive approach was used to identify underlying themes. Results: Participants (N = 15) were predominantly male, in their sixth decade, working in academic settings. Themes ranged from strong beliefs in marijuana's medical utility to reservations about this notion, with calls for expansion of the scientific evidence base and more stringent MM production standards. All participants cited nausea as an appropriate indication, and 13 out of 15 pain. Over one-third believed MM to have a more attractive risk profile than opioids and benzodiazepines. Conclusions: Expert opinion was divided between conviction in marijuana's medicinal potential to guardedness in this assertion, with no participant refuting MM's utility outright. Emergent themes included: that MM ameliorates cancer-related pain and nausea and is safer than certain conventional medications. Participants called for enhanced purity and production standards, and further research on MM's utility.
... A study by Riggs et al. (2012) evaluated whether smoking cannabis leads to changes in appetiterelated hormones among HIV-infected male patients. Seven patients were administered cannabis joints 4 times daily for a period of 5 days, each with an individualized dose which was optimized during an initial titration session (using joints with a concentration range between 1% to 8% THC). ...
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In 2010 a review by Hazekamp and Grotenhermen covered controlled clinical trials of the years 2006-2009 on cannabis-based medicines, which followed the example of the review by Ben Amar (2006). The current review reports on the more recent clinical data available from 2010-2014. A systematic search was performed in the scientific database of PubMed, focused on clinical studies that were randomized, (double) blinded, and placebo-controlled. The key words used were: cannabis, marijuana, marihuana, hashish, cannabinoid(s), tetrahydrocannabinol, THC, CBD, dronabinol, Marinol, nabilone, Cannador, nabiximols and Sativex. For the final selection, only properly controlled clinical trials were retained. Open-label studies were excluded, except if they were a direct continuation of a study discussed here. Thirty-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Based on the clinical results, cannabinoids present an interesting therapeutic potential mainly as analgesics in chronic neuropathic pain and spasticity in multiple sclerosis. But a range of other indications also seem promising. CBD (cannabidiol) emerges as another valuable cannabinoid for therapeutic purposes besides THC.
... Moreover, if marijuana and alcohol are substitutes (Anderson, Hansen, and Rees 2014;Crost and Guerrero 2012;Kelly and Rasul, 2014;DiNardo and Lemieux, 2001) and MMLs cause individuals to substitute toward marijuana and away from alcohol, a relatively high-calorie beverage, then this reduction in calories could reduce body weight. On the other hand, if marijuana use induces greater lethargy (Pesta et al., 2013) or stimulates appetite (Riggs et al., 2012;Soria-Gómez et al., 2014), or if marijuana and alcohol are complements (Williams et al., 2004;Wen et al., 2014), then MMLs could increase body weight. ...
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This study is the first to examine the effects of medical marijuana laws (MMLs) on body weight, physical wellness, and exercise. Using data from the 1990 to 2012 Behavioral Risk Factor Surveillance System and a difference-in-difference approach, we find that the enforcement of MMLs is associated with a 2% to 6% decline in the probability of obesity. We find some evidence of age-specific heterogeneity in mechanisms. For older individuals, MML-induced increases in physical mobility may be a relatively important channel, while for younger individuals, a reduction in consumption of alcohol, a substitute for marijuana, appears more important. These findings are consistent with the hypothesis that MMLs may be more likely to induce marijuana use for health-related reasons among older individuals, and cause substitution toward lower-calorie recreational 'highs' among younger individuals. Our estimates suggest that MMLs induce a $58 to $115 per-person annual reduction in obesity-related medical costs. Copyright © 2015 John Wiley & Sons, Ltd.
... 192 When smoked medicinal cannabis was used in HIV-infected adult men, PYY was decreased, and ghrelin levels increased. 193 In 1994, Nelson et al. 194 evaluated the effect of tetrahydrocannabinol on appetite in 18 patients with cancer. Appetite was improved in 13 patients. ...
Article
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Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.
... Cannabis sativa is recognized as an orexigenic herb in Iranian traditional medicine. Little evidences are available about its influence on energy intake and its mechanism (Riggs et al., 2012, Fride et al., 2005. Their results showed that the extract of cannabis sativa meaningfully increased energy intake and total ghrelin levels were significantly increased in the Cannabis sativa group. ...
Article
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Abstract A kind of growth hormone secretagogue (GHS), ghrelin, was first isolated from the rat stomach and plays a major role in the activation of the growth hormone secretagogue receptor 1a (GHS-R1a) resulting the release of growth hormone (GH). The preproghrelin gene is placed on chromosome 3, at locus 3p25 –2 in humans and constitutes five exons and three introns. Ghrelin is most plentifully expressed in particular cells in the oxyntic glands of the gastric epithelium, initially named X/A-like cells. Almost 60-70% of circulating ghrelin is secreted by the stomach. Plasma ghrelin concentration alters throughout the day. Ghrelin has been suggested to act as a meal initiator because of its appetite-stimulating influences in free feeding rats in short period. In addition to ghrelin’s function as a meal motivator, it seems to contribute in long-term energy balance and nutritional status. In addition, many studies have been carried out in order to investigate the effects of natural and medicinal plants and botanical extracts on appetite, food intake, energy hemostasis, and the level of related hormones including ghrelin. Due to the importance of ghrelin in nutritional and medical sciences, this review was performed to understand new aspects of this hormone’s function.
... It has been suggested that drug use, such as the use of cannabis, plays a role in the development and progression of HIV by its immunomodulatory and neuromodulatory effects. Studies have examined the function of cannabinoids and their receptors in HIV replication, pathogenesis, and immuneregulation [Gurwitz and Kloog, 1998;Wang and Ho, 2011;Riggs et al., 2012]. The endocannabinoid system also has an important connection to HIV-associated dementia [Bari et al., 2010]. ...
Article
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Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
... Both dronabinol and smoked marijuana increase the number of eating occasions [22,25], and smoked marijuana may also affect weight gain and calorie intake by modulating appetite hormones [28]. Importantly, weight gain in one study was greater than would have been expected based on increased calorie consumption alone [23], which may be particularly relevant for those who have impaired food intake and/or nausea. ...
Article
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The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.
... Two randomized, placebo-controlled trials found that 28% of patients with HIV-SN achieved a clinically and statistically significant pain reduction (≥30% from baseline) with smoked Cannabis products, with a necessary number for treatment (NNT) of 4 [138][139][140]. Studies show that even smoked or ingested Cannabis, containing the THC component, is capable of improving appetite, weight, and mood, thus improving quality of life [142]. Despite this, recent studies have shown that chronic Cannabis smoking weakens the immune system leading to increased symptoms of chronic bronchitis, cough, sputum production, and wheezing [143][144][145]. ...
Article
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Medical case reports suggest that cannabinoids extracted from Cannabis sativa have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of its major component, Δ9-tetrahydrocannabinol (THC). The new scientific discoveries related to the endocannabinoid system, including new receptors, ligands, and mediators, allowed the development of new therapeutic targets for the treatment of several pathological disorders minimizing the undesirable psychotropic effects of some constituents of this plant. Today, FDA-approved drugs, such as nabiximols (a mixture of THC and non-psychoactive cannabidiol (CBD)), are employed in alleviating pain and spasticity in multiple sclerosis. Dronabinol and nabilone are used for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Dronabinol was approved for the treatment of anorexia in patients with AIDS (acquired immune deficiency syndrome). In this review, we highlighted the potential therapeutic efficacy of natural and synthetic cannabinoids and their clinical relevance in cancer, neurodegenerative and dermatological diseases, and viral infections.
... It was found also that cannabis smoking had modulated the statistically significant inverse correlation between plasma AgRP concentrations and BMI in non cannabis smokers to be insignificant inversely correlation between them. These findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors as previously concluded by [30], whose study results showed that cannabis administration was associated with significant increases in plasma levels of ghrelin and leptin, and decreases in PYY, but did not significantly influence insulin levels and these findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors, independent of glucose metabolism. ...
... 12 Patient-reported sleep benefits are likely related to these sedative effects. While cannabis (containing both 9-Δ-THC and CBD) has been indicated for use as an appetite stimulant in HIV-affected patients with cachexia, 22,23 it remains unclear if CBD alone has significant appetite stimulating effects beyond placebo. Long-term side effects were not analysed in this current audit and future study is still needed to clarify chronic effects of CBD administration. ...
Article
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Background: Cannabidiol (CBD) is the non-euphoriant component of cannabis. In 2017, the New Zealand Misuse of Drugs Regulations (1977) were amended, allowing doctors to prescribe CBD. Therapeutic benefit and tolerability of CBD remains unclear. Aim: To review the changes in self-reported quality of life measurements, drug tolerability, and dose-dependent relationships in patients prescribed CBD oil for various conditions at a single institution. Design & setting: An audit including all patients (n = 400) presenting to Cannabis Care, New Zealand, between 7 December 2017 and 7 December 2018 seeking CBD prescriptions METHOD: Indications for CBD use were recorded at baseline. Outcomes included EuroQol quality of life measures at baseline and after 3 weeks of use, patient-reported satisfaction, incidence of side effects, and patient-titrated dosage levels of CBD. Results: Four hundred patients were assessed for CBD and 397 received a prescription. Follow-up was completed on 253 patients (63.3%). Patients reported a mean increase of 13.6 points (P<0.001) on the EQ-VAS scale describing overall quality of health. Patients with non-cancer pain and mental-health symptoms achieved improvements to patient-reported pain and depression and anxiety symptoms (P<0.05). There were no major adverse effects. Positive side effects included improved sleep and appetite. No associations were found between CBD dose and patient-reported benefit. Conclusion: There may be analgesic and anxiolytic benefits of CBD in patients with non-cancer chronic pain and mental health conditions such as anxiety. CBD is well tolerated, making it safe to trial for non-cancer chronic pain, mental health, neurological, and cancer symptoms.
... Patricia K y su equipo en un estudio incluyeron a 28 pacientes adultos masculinos portadores de VIH, en ellos se analizaron hormonas de la conducta alimentaria y la influencia que ejerce el cannabis sobre éstas demostrando que la ghrelina aumenta 42% por las mañanas al compararla contra placebo, la leptina aumenta 67.1% comparada contra placebo, con respecto al PPY, éste disminuye en el grupo de intervención y tiende a aumentar en el grupo placebo en 23.2%; la significancia estadística presenta una p < 0.001. Éste es uno de los primeros ensayos clínicos donde se involucran marcadores biológicos de la conducta de la alimentación con respecto a la administración de un derivado cannabinoide (37) . ...
Article
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Introducción: La caquexia es un síndrome asociado al cáncer avanzado, VIH, pacientes en quimioterapia y quienes tienen seguimiento en cuidados paliativos. La prevalencia es de 25% de los pacientes con diagnóstico de cáncer, 26% en quienes reciben quimioterapia y de 14 a 38% de pacientes con VIH. Un pilar para el manejo es el cannabis debido al efecto del delta-9-tetrahidrocanabinol (THC), del cual se derivó el dronabinol, un fármaco desarrollado para estimular apetito y ganancia de peso. El objetivo de esta revisión bibliográfica es obtener la información sobre los cannabinoides y la evidencia más sólida existente con respecto al uso del dronabinol en pacientes que han presentado pérdida de peso y apetito. Material y métodos: Revisión de la bibliografía con buscador PubMed con las palabras clave Palliative care (cuidados paliativos), Cannabinoids (cannabinoides), cachexia (caquexia), Dronabinol (dronabinol), Appetite (apetito), de 1990 a 2018, limitado a humanos, obteniendo 259 artículos, eliminando 222 por repetirse o tener poca relevancia, dejando 37 artículos para análisis. Resultados: De 37 artículos revisados, nueve fueron estudios experimentales, 10 revisiones sistematizadas, un metaanálisis y 16 artículos de recomendaciones y sugerencias de manejo. Conclusión: El manejo del apetito y pérdida de peso en pacientes en cuidados paliativos, VIH, ancianos o en quimioterapia debe ser multidisciplinario, involucrando nutriólogos, psicólogos y médicos, ajustando el manejo a las características individuales que manifiesten. El dronabinol es un fármaco de primera elección para el manejo de dichos síntomas cuando la historia natural de la enfermedad se acompaña de náusea, vómito o dolor.
... Another research revealed that a single intravenous leptin injection in rats decreased the levels of the endocannabinoids, anandamide, and 2-arachidonylglycerol (2-AG) in the hypothalamus 22 . Also, cannabis smoking was associated with significant changes in leptin levels 23 . Moreover, gender differences have been detected on serum leptin levels in response to biological signals of cannabis smoking 24 . ...
... Welldesigned trials are needed to determine whether researchers can predict patient response and whether cannabis can improve appetite stimulation, improve the enjoyment of food (152), or improve QOL in patients with advanced cancer. Mechanistically, crosstalk of cannabinoids with neuroendocrine effectors such as ghrelin, leptin, and serotonin is warranted (153,154). ...
Article
Cannabis and cannabinoids are increasingly being accessed and used by patients with advanced cancer for various symptoms and general quality of life. Specific symptoms of pain, nausea and vomiting, loss of appetite and cachexia, anxiety, sleep disturbance, and medical trauma are among those that have prompted patients with cancer to use cannabis. This conference report from the National Cancer Institute’s “Cannabis, Cannabinoid and Cancer Research Symposium” on the topic of “Cancer Symptom/Treatment Side Effect Management” is an expert perspective of cannabis intervention for cancer and cancer treatment-related symptoms. The purpose of the symposium was to identify research gaps, describe the need for high-quality randomized prospective studies of medical cannabis for palliative care in patients with cancer, and evaluate the impact of medical cannabis on cancer survivors’ quality of life. Further, education of clinicians and affiliated health-care providers in guiding cancer patients in using cannabis for cancer care would benefit patients. Together, these steps will further aid in refining the use of cannabis and cannabinoids for symptom palliation and improve safety and efficacy for patients.
... Prior to conducting functional studies, we sought to evaluate the tolerance of BEVs by U937 monocytes by assessing cellular viability upon treatment with different concentrations (20,40, and 100 μg) of BEVs. Cells seeded atop collagen-coated 96-well plates were treated with different concentrations of VEH/SIV or THC/SIV BEVs, while PBS-treated cells served as negative controls. ...
Article
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Blood extracellular vesicles (BEVs) carry bioactive cargo (proteins, genetic materials, lipids, licit, and illicit drugs) that regulate diverse functions in target cells. The cannabinoid drug delta-9-tetrahydrocannabinol (THC) is FDA approved for the treatment of anorexia and weight loss in people living with HIV. However, the effect of THC on BEV characteristics in the setting of HIV/SIV infection needs to be determined. Here, we used the SIV-infected rhesus macaque model of AIDS to evaluate the longitudinal effects of THC (THC/SIV) or vehicle (VEH/SIV) treatment in HIV/SIV infection on the properties of BEVs. While BEV concentrations increased longitudinally (pre-SIV (0), 30, and 150 days post-SIV infection (DPI)) in VEH/SIV macaques, the opposite trend was observed with THC/SIV macaques. SIV infection altered BEV membrane properties and cargo composition late in infection, since i) the electrostatic surface properties (zeta potential, ζ potential) showed that RM BEVs carried negative surface charge, but at 150 DPI, SIV infection significantly changed BEV ζ potential; ii) BEVs from the VEH/SIV group altered tetraspanin CD9 and CD81 levels compared to the THC/SIV group. Furthermore, VEH/SIV and THC/SIV BEVs mediated divergent changes in monocyte gene expression, morphometrics, signaling, and function. These include altered tetraspanin and integrin β1 expression; altered levels and distribution of polymerized actin, FAK/pY397 FAK, pERK1/2, cleaved caspase 3, proapoptotic Bid and truncated tBid; and altered adhesion of monocytes to collagen I. These data indicate that HIV/SIV infection and THC treatment result in the release of bioactive BEVs with potential to induce distinct structural adaptations and signaling cues to instruct divergent cellular responses to infection.
... Cannabis has been associated with significant increases in ghrelin and leptin, and decreases in PYY, consistent with the modulation of appetite hormones mediated through endocannabinoid receptors. 61 The Endocannabinoid System The endocannabinoid system encompasses a key interface between the gut microbiota, the immune system, and homeostasis of the human host. Two main endogenous cannabinoids, or endocannabinoids, are the brain-derived arachidonoyl ethanolamide, known as anandamide (AEA), and 2-arachidonoylglycerol (2-AG) derived from lipid precursors, such as arachidonic acid, that are synthesized on demand. ...
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People living with HIV infection (PWH) disclose that cannabis is an effective strategy for alleviating symptoms associated with HIV disease. However, some medical providers feel ill-informed to engage in evidence-based conversations. HIV leads to alterations in the gut microbiome, gut-brain axis signaling, and chronic inflammation. The endocannabinoid system regulates homeostasis of multiple organ systems. When deficient, dysregulation of the gut-brain axis can result in chronic inflammation and neuroinflammation. Cannabis along with the naturally occurring endocannabinoids has antioxidant and anti-inflammatory properties that can support healing and restoration as an adjunctive therapy. The purpose of this literature review is to report the physiologic mechanisms that occur in the pathology of HIV and discuss potential benefits of cannabinoids in supporting health and reducing the negative effects of comorbidities in PWH.
... 4 Cannabis has been additionally pointed as interacting with opioid receptors, 5 and it present itself as an alternative to opioids. 6 Further, while loss of appetite and anorexia are common troubling symptoms which are common among cancer patients, 7 cannabis is known to boost appetite, 8,9 and observational data additionally supports such benefit among cancer patients. 10 To a certain extent, there is evidence to support the potential of cannabis for additional symptoms that impact cancer patients, such as gastrointestinal distress, 10 peripheral neuropathy, 11,12 as well as depression and anxiety. ...
Article
Objectives To assess the motivation of cancer survivors to consume medical cannabis and to assess the patterns of use, perceived efficacy, as well as side and adverse effects. Methods Cross-sectional survey among 190 Israeli cancer survivors who were licensed to use medical cannabis in a single institution. In addition to demographic information, the questionnaire examined patterns of use (including dosage, type of cannabis and way of administration), motivation for medical cannabis consumption, perceived efficacy, adverse and side effects, motivation for ceasing cannabis consumption, and tobacco smoking. Results The mean monthly dosage of cannabis consumed was 42.4 grams; 95.8% of respondents reported not consuming cannabis regularly before being diagnosed with cancer; the most common way of administration was smoking, and most of the participants reported taking cannabis throughout the day. The most common symptoms for which participants took medical cannabis were pain (n = 169, 88.9%), sleeping disorder (n = 144, 75.8%) and anxiety (n = 79, 41.6%). Twenty patients (10.5%) reported on mild side (or adverse) effects. Conclusions This study indicates that cancer survivors may indeed consume cannabis for symptom relief, and not merely for recreational purposes. Although our findings point to perceived safety and efficacy of medical cannabis for cancer survivors, more research is needed to study the adequate role that cannabis may have for treating symptoms associated with cancer survivorship.
... The mechanisms of a proposed marijuana and type 2 diabetes association, suggest that THC stimulates appetite through activation of CB1 (Riggs et al., 2012), and thus may play a role in eating behaviors among persons who use marijuana. Studies have shown significantly higher caloric intake in marijuana users compared with nonusers (Foltin et al., 1988;Ngueta et al., 2015;Rodondi et al., 2006;Smit and Crespo, 2001). ...
Article
Introduction: Marijuana use is common among persons living with HIV, but whether its use increases the risk of type 2 diabetes in this population has not been explored. Objective: To determine whether self-reported marijuana use is associated with incident type 2 diabetes in women and men living with and at risk for HIV. Methods: We analyzed data from the Women’s Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), between 2000-2017 (WIHS) and 1999-2017 (MACS). The association between self-reported marijuana use and incident type 2 diabetes was analyzed using time-dependent Cox regression models among 3,578 and 2,682 participants in the WIHS and MACS respectively. Results: Over the follow-up period, 452 (WIHS) and 326 (MACS) incident type 2 diabetes cases occurred. In multivariable models, the hazard ratios, collectively indicate a reduced risk of type 2 diabetes, in marijuana users compared to none users, although all associations were not statistically significant. The results were similar for HIV-positive and HIV-negative participants in both cohorts. Conclusions: In this prospective analysis of nearly 20 years of data for women and men with and at risk for HIV in the WIHS and MACS, although we found a pattern of reduced risk of type 2 diabetes among self-reported marijuana users, the associations were not statistically significant. To better inform clinical decisions and legal policy regarding marijuana use in this population, further longitudinal investigations that biologically quantify marijuana use to assess risk for incident diabetes is warranted.
... This compound, dronabinol, along with smoked cannabis, is effective at stimulating appetite to combat HIV-associated anorexia [45] and improve weight gain [46]. This is likely accomplished by stimulation of the appetite hormones ghrelin and leptin [47]. However, a more recent Cochrane systematic review indicated that longer studies would be necessary to truly evaluate the consistency and significance of dronabinol's reported benefits [48]. ...
Article
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The persistence of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) in the era of effective antiretroviral therapy suggests that modern HIV neuropathogenesis is driven, at least in part, by mechanisms distinct from the viral life cycle. Identifying more subtle mechanisms is complicated by frequent comorbidities in HIV+ populations. One of the common confounds is substance abuse, with cannabis being the most frequently used psychoactive substance among people living with HIV. The psychoactive effects of cannabis use can themselves mimic, and perhaps magnify, the cognitive deficits observed in HAND; however, the neuromodulatory and anti-inflammatory properties of cannabinoids may counter HIV-induced excitotoxicity and neuroinflammation. Here, we review our understanding of the cross talk between HIV and cannabinoids in the central nervous system by exploring both clinical observations and evidence from preclinical in vivo and in vitro models. Additionally, we comment on recent advances in human, multi-cell in vitro systems that allow for more translatable, mechanistic studies of the relationship between cannabinoid pharmacology and this uniquely human virus.
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Background: HIV/SIV-associated periodontal disease (gingivitis/periodontitis) (PD) represents a major comorbidity affecting people living with HIV (PLWH) on combination anti-retroviral therapy (cART). PD is characterized by chronic inflammation and dysbiosis. Nevertheless, the molecular mechanisms and use of feasible therapeutic strategies to reduce/reverse inflammation and dysbiosis remain understudied and unaddressed. Methods: Employing a systems biology approach, we report molecular, metabolome and microbiome changes underlying PD and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (Δ9-THC)] in uninfected and SIV-infected rhesus macaques (RMs) untreated (VEH-untreated/SIV) or treated with vehicle (VEH/SIV) or Δ9-THC (THC/SIV). Findings: VEH- untreated/SIV but not THC/SIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-β, NFκB, RIG-1, and JAK-STAT signaling. We focused on the anti-microbial DUOX1 and immune activation marker IDO1 that were reciprocally regulated in the gingiva of VEH-untreated/SIV RMs. Both proteins localized to the gingival epithelium and CD163+ macrophages, and showed differential expression in the gingiva of THC/SIV and VEH/SIV RMs. Additionally, inflammation-associated miR-21, miR-142-3p, miR-223, and miR-125a-5p showed significantly higher expression in the gingiva of VEH/SIV RMs. In human primary gingival epithelial cells, miR-125a-5p post-transcriptionally downregulated DUOX1 and THC inhibited IDO1 protein expression through a cannabinoid receptor-2 mediated mechanism. Interestingly, THC/SIV RMs showed relatively reduced plasma levels of kynurenine, kynurenate, and the neurotoxic quinolinate compared to VEH/SIV RMs at 5 months post SIV infection (MPI). Most importantly, THC blocked HIV/SIV-induced depletion of Firmicutes and Bacteroidetes, and reduced Gammaproteobacteria abundance in saliva. Reduced IDO1 protein expression was associated with significantly (p<0.05) higher abundance of Prevotella, Lactobacillus (L. salivarius, L. buchneri, L. fermentum, L. paracasei, L. rhamnosus, L. johnsonii) and Bifidobacteria and reduced abundance of the pathogenic Porphyromonas cangingivalis and Porphyromonas macacae at 5MPI. Interpretation: The data provides deeper insights into the molecular mechanisms underlying HIV/SIV-induced PD and more importantly, the anti-inflammatory and anti-dysbiotic properties of THC in the oral cavity. Overall, these translational findings suggest that phytocannabinoids may help reduce gingival/systemic inflammation, salivary dysbiosis and potentially metabolic disease/syndrome in PLWH on cART and those with no access to cART or do not suppress the virus under cART. Funding: Research reported in this publication was supported by the National Institutes of Health Award Numbers R01DA052845 (MM and SNB), R01DA050169 (MM and CO), R01DA042524 and R56DE026930 (MM), and P51OD011104 and P51OD011133. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive principle Δ9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. The apex of endocannabinoid research seems to have been reached with the clinical development, and in some cases also the marketing, of synthetic or natural pharmaceuticals targeting this signalling system, which followed the understanding of its physiological and pathological role in several conditions, a role that was investigated first in rodent experimental models and then in humans. We particularly take an interest in Manuscripts that report relevance of the endocannabinoid system. Original reports or Reviews describing the results of experimental evidence about the neurobiological role of the endocannabinoid system would be a great interest. Main topics include, but are not limited to: *The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution, their splicing variants and polymorphisms, and the possible implications of all this in determining different behaviours as well as various pathological conditions and the addiction to substances of abuse. *Pharmacological approaches describing the potential use in the central nervous system disorders of endocannabinoid-based drugs, such as cannabinoid receptor agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and even plant cannabinoids other than THC and with a molecular mechanism of action. *The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy.
Article
There is growing momentum to legalize medical cannabis across the United States. Positive public attitudes and permissive policies are based on growing anecdotal experiences and medical evidence that enumerate the health benefits of cannabis. Against this backdrop, Muslim stakeholders are (re)-evaluating their stance on the issue for Muslim patients who may benefit from such novel treatments, Muslim physicians who could incorporate the provision of cannabis into practices, and Muslim entrepreneurs who may seek to engage with the pharmaceutical and business aspects of the growing industry. Given this renewed interest, the Fiqh Council of North America (FCNA), a deliberative body comprised of Islamic jurists and medical consultants, examined the medical as well as religious evidence surrounding medical cannabis in order to furnish Muslim Americans with religious guidance. In 2018, they resolved that, while the use of intoxicating substances is proscribed by Islamic law, medical cannabis was permissible for Muslims to use with the following stipulations: Non-psychoactive preparations of cannabis are permitted to treat illnesses for which therapeutic effects of cannabis are certain, and psychoactive preparations are contingently permissible in cases of dire necessity. In this paper we first discuss the deliberative process and ethico-legal rationale brought to bear in furnishing the ruling, and then proceed to critically examine its conceptual gaps, practical limitations, and future implications. Clarifying the nuances around the religious permissibility of medical cannabis is important for Muslim patients and providers whose attitudes and behaviors may be informed by the ruling, as well for stakeholder groups within pharmaceutical and health policy circles who aim to address the needs of the global Muslim community that may stand to benefit from advances in medical cannabis research and therapeutics.
Article
Dronabinol (synthetic Δ(9)- tetrahydrocannabinol) is used in patients with nausea and vomiting from chemotherapy and in AIDS patients for appetite stimulation. Recently, dronabinol was used to successfully treat visceral hypersensitivity causing noncardiac chest pain. With widening uses of this medication, we aim to explore its effects on metabolic parameters in long-term dosing and hypothesize that it will not affect major metabolic parameters. A double-blind, placebo-controlled, 28-day trial was performed with patients 18 to 75 years old without cardiac disease. Patients had at least 2 weekly episodes of chest pain for the last 3 months and evidence of esophageal hypersensitivity after balloon distention testing. Prior use of pain medication, psychiatric diagnosis, or significant medical comorbidities precluded inclusion in the study. Patients were randomized to receive 5 mg dronabinol or placebo twice daily with metabolic parameters examined before and after the use of medication. Thirteen patients completed the study (7 with dronabinol [6 women and 1 man] and 6 with placebo [5 women and 1 man]). None of the measured values, including body mass index, HDL, triglycerides, calculated LDL, high-sensitivity C-reactive protein, glucose, insulin, leptin, aspartate aminotransferase, alanine aminotransferase, LDH, or non-HDL, differed significantly in either group before or after treatment. In general, treatment with dronabinol coincided with favorable trends in some parameters, although these trends were not statistically significant. Dronabinol administration does not significantly affect basic metabolic components after a period of 28 days. The implications of these findings are important because dronabinol may be able to be used in patients with metabolic disorders. The favorable trends observed here warrant further exploration into its long-term effects. ClinicalTrials.gov identifier: NCT01598207. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.
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Ghrelin and cannabinoids stimulate appetite, this effect possibly being mediated by the activation of hypothalamic AMP-activated protein kinase (AMPK), a key enzyme in appetite and metabolism regulation. The cannabinoid receptor type 1 (CB1) antagonist rimonabant can block the orexigenic effect of ghrelin. In this study, we have elucidated the mechanism of the putative ghrelin-cannabinoid interaction. The effects of ghrelin and CB1 antagonist rimonabant in wild-type mice, and the effect of ghrelin in CB1-knockout animals, were studied on food intake, hypothalamic AMPK activity and endogenous cannabinoid content. In patch-clamp electrophysiology experiments the effect of ghrelin was assessed on the synaptic inputs in parvocellular neurons of the hypothalamic paraventricular nucleus, with or without the pre-administration of a CB1 antagonist or of cannabinoid synthesis inhibitors. Ghrelin did not induce an orexigenic effect in CB1-knockout mice. Correspondingly, both the genetic lack of CB1 and the pharmacological blockade of CB1 inhibited the effect of ghrelin on AMPK activity. Ghrelin increased the endocannabinoid content of the hypothalamus in wild-type mice and this effect was abolished by rimonabant pre-treatment, while no effect was observed in CB1-KO animals. Electrophysiology studies showed that ghrelin can inhibit the excitatory inputs on the parvocellular neurons of the paraventricular nucleus, and that this effect is abolished by administration of a CB1 antagonist or an inhibitor of the DAG lipase, the enzyme responsible for 2-AG synthesis. The effect is also lost in the presence of BAPTA, an intracellular calcium chelator, which inhibits endocannabinoid synthesis in the recorded parvocellular neuron and therefore blocks the retrograde signaling exerted by endocannabinoids. In summary, an intact cannabinoid signaling pathway is necessary for the stimulatory effects of ghrelin on AMPK activity and food intake, and for the inhibitory effect of ghrelin on paraventricular neurons.
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Cannabinoid-1 (CB(1)) receptor antagonists exhibit pharmacological properties favorable to treatment of obesity, caused by both centrally mediated effects on appetite and peripherally mediated effects on energy metabolism. However, the relative contribution of these effects to the weight loss produced by CB(1) receptor antagonists remains unclear. Here, we compare food intake-related and independent effects of the CB(1)-selective antagonist 1-(7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-3-(methylamino) azetidine-3-carboxamide (PF-95453) in obese cynomolgus monkeys. Monkeys were divided into three study groups (n = 10 each) and treated once daily for 8 weeks with either vehicle or PF-95453 as follows: 1, fed ad libitum and dosed orally with vehicle; 2, fed ad libitum and dosed orally with PF-95453 (0.5 mg/kg weeks 1-3, 1.0 mg/kg weeks 4-8); and 3, fed an amount equal to the amount consumed by the drug-treated group and dosed orally with vehicle (pair-fed). PF-95453 treatment significantly reduced food consumption by 23%, body weight by 10%, body fat by 39%, and leptin by 34% while increasing adiponectin by 78% relative to vehicle-treated controls. Pair-fed animals did not exhibit reductions in body weight or leptin but did show significantly reduced body fat (11%) and increased adiponectin (15%) relative to vehicle-treated controls but markedly less than after PF-95453 treatment. Indeed, significant differences were noted between the drug-treated and pair-fed groups with respect to body weight reduction, body fat reduction, increased adiponectin, and leptin reduction. Similar to humans, monkeys treated with the CB(1) receptor antagonist exhibited decreased body weight and body fat, a substantial portion of which seemed to be independent of the effects on food intake.
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Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.
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Ghrelin, a peptide hormone predominantly produced by the stomach, was isolated as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is a potent stimulator of growth hormone (GH) secretion and is the only circulatory hormone known to potently enhance feeding and weight gain and to regulate energy homeostasis following central and systemic administration. Therapeutic intervention with ghrelin in catabolic situations may induce a combination of enhanced food intake, increased gastric emptying and nutrient storage, coupled with an increase in GH thereby linking nutrient partitioning with growth and repair processes. These qualities have fostered the idea that ghrelin-based compounds may have therapeutic utility in treating malnutrition and wasting induced by various sub-acute and chronic disorders. Conversely, compounds that inhibit ghrelin action may be useful for the prevention or treatment of metabolic syndrome components such as obesity, impaired lipid metabolism or insulin resistance. In recent years, the effects of ghrelin on glucose homeostasis, memory function and gastrointestinal motility have attracted considerable amount of attention and revealed novel therapeutic targets in treating a wide range of pathologic conditions. Furthermore, discovery of ghrelin O-acyltransferase has also opened new research opportunities that could lead to major understanding of ghrelin physiology. This review summarizes the current knowledge on ghrelin synthesis, secretion, mechanism of action and biological functions with an additional focus on potential for ghrelin-based pharmacotherapies.
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Leptin plays a vital role in the regulation of energy balance in rodent models of obesity. However, less information is available about its homeostatic role in humans. The aim of this study was to determine whether leptin serves as an indicator of short-term energy balance by measuring acute effects of small manipulations in energy intake on leptin levels in normal individuals. The 12-day study was composed of four consecutive dietary-treatment periods of 3 days each. Baseline (BASE) [100% total energy expenditure (TEE)] feeding, followed by random crossover periods of overfeeding (130% TEE) or underfeeding (70% TEE) separated by a eucaloric (100% TEE) washout (WASH) period. The study participants were six healthy, nonobese subjects. Leptin levels serially measured throughout the study period allowed a daily profile for each treatment period to be constructed and a 24-h average to be calculated; ad libitum intake during breakfast "buffet" following each treatment period was also measured. Average changes in mesor leptin levels during WASH, which were sensitive to energy balance effected during the prior period, were observed. After underfeeding, leptin levels during WASH were 88 +/- 16% of those during BASE compared with 135 +/- 22% following overfeeding (P = 0.03). Leptin levels did not return to BASE during WASH when intake returned to 100% TEE, but instead were restored (104 +/- 21% and 106 +/- 16%; not significant) only after subjects crossed-over to complementary dietary treatment that restored cumulative energy balance. Changes in ad libitum intake from BASE correlated with changes in leptin levels (r2 = 0.40; P = 0.01). Leptin levels are acutely responsive to modest changes in energy balance. Because leptin levels returned to BASE only after completion of a complementary feeding period and restoration of cumulative energy balance, leptin levels reflect short-term cumulative energy balance. Leptin seems to maintain cumulative energy balance by modulating energy intake.
Article
Ghrelin is an orexigenic hormone secreted by the stomach. Increased plasma ghrelin concentration was reported during diet-induced weight loss in obese humans, suggesting that ghrelin contributes to adaptive increment in appetite associated with caloric restriction. Leptin reduces spontaneous food intake and body weight in rodents. The current study tested the hypothesis that increased plasma leptin prevents the potential increase in plasma ghrelin concentration during moderate caloric restriction in lean rats. Six-month-old male rats (body weight, 367 +/- 9 grams) were randomly assigned to one of the following treatments (8 rats each) for 1 week: (1) leptin subcutaneous infusion to induce moderate hyperleptinemia and moderate caloric restriction (-26% of ad libitum), (2) vehicle infusion and pair feeding, and (3) vehicle infusion and ad libitum feeding. Leptin-treated (-19 +/- 5 grams) and pair-fed (-19 +/- 2) rats lost weight compared with ad libitum-fed rats (-3 +/- 1, P < 0.05). Compared with control (6.8 +/- 0.7 ng/mL), plasma leptin was higher in leptin-treated (18.6 +/- 0.9 ng/mL, P < 0.01) rats and lower in pair-fed rats (4.3 +/- 0.4 ng/mL, P < 0.05). Plasma ghrelin was substantially higher in calorie-restricted than control rats (2505 +/- 132 pg/mL vs. 1790 +/- 134 pg/mL, P < 0.01), and leptin treatment (1625 +/- 117 pg/mL) completely prevented this change. Plasma ghrelin concentration was negatively correlated with body weight changes in calorie-restricted and control (r = -0.75, P < 0.01) but not in leptin-treated rats (P > 0.8). Moderate hyperleptinemia prevents an increase of plasma ghrelin during moderate short-term caloric restriction. Satiety-inducing effects of leptin include suppression of gastric orexigenic signals and disruption of a potential feedback mechanism between body weight changes and plasma ghrelin in lean adult rats.
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The paraventricular nucleus (PVN) of the hypothalamus plays a key role in the control of appetite and energy balance. Both ghrelin and cannabinoid receptor agonists increase food intake when administered into this nucleus: this study investigated possible interactions between the two systems in relation to eating. The orexigenic effect of ghrelin (100 pmol) when infused in to the PVN was reversed by a small, systemic dose of the CB1 cannabinoid receptor antagonist SR141716 (1 mg kg−1). This is the first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems, and, although it needs to be further investigated, the effect of ghrelin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release. British Journal of Pharmacology (2004) 143, 520–523. doi:10.1038/sj.bjp.0705968
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Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.
Article
Appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion. Peripheral regulation includes satiety signals and adiposity signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal (GI) tract during a meal and, through the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC), where satiety signals are integrated with adiposity signals, namely leptin and insulin, and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits which finally elaborate the individual response to a meal. As for the neuropeptidergic system, ARC neurons secrete orexigenic substances, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Other brain areas involved in the control of food intake are located downstream the ARC: among these, the paraventricular nucleus (PVN), which produces anorexigenic peptides such as thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH). A great interest in endocannabinoids, important players in the regulation of food intake, has recently developed. In conclusion, the present work reviews the most recent insights into the complex and redundant molecular mechanisms regulating food intake, focusing on the most encouraging perspectives for the treatment of obesity.
Neurobiology Component
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Archibald, M.A., John Hesselink, M.D., Jacopo Annese, Ph.D., Michael J. Taylor, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Ian Everall, FRCPsych., FRCPath., Ph.D., Cristian Achim, M.D., Ph.D.; Neurovirology Component: Douglas Richman, M.D., (P.I.), David M. Smith, M.D.; Interna-tional Component: J. Allen McCutchan, M.D.,(P.I.);
Leptin-regulated endocannabinoids are involved in maintaining food intake
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The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis
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Cone, R.D., Cowley, M.A., Butler, A.A., Fan, W., Marks, D.L., Low, M.J., 2001. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), S63-S67.
Neurobiology Component Neurovirology Component International Component
  • M A Archibald
  • John Hesselink
  • M D Jacopo Annese
  • Ph D Michael
  • J Taylor
  • Ph D Douglas Richman
  • David M Smith
Archibald, M.A., John Hesselink, M.D., Jacopo Annese, Ph.D., Michael J. Taylor, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Ian Everall, FRCPsych., FRCPath., Ph.D., Cristian Achim, M.D., Ph.D.; Neurovirology Component: Douglas Richman, M.D., (P.I.), David M. Smith, M.D.; International Component: J. Allen McCutchan, M.D.,(P.I.); Developmental Component: Ian Everall, FRCPsych., FRCPath., Ph.D. (P.I.), Stuart Lipton, M.D.,Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Rodney von Jaeger,M.P.H.; Data Management Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman (Data Systems Manager); Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D., Reena Deutsch, Ph.D., Tanya Wolfson, M.A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.