Category Archives: Anorexia

Limited Access to a High Fat Diet Alters Endocannabinoid Tone in Female Rats.

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“Emerging evidence suggest an impaired endocannabinoid activity in the pathophysiology of binge eating disorder (BED). Herein, we investigated whether endocannabinoid tone could be modified as a consequence of dietary-induced binge eating in female rats.

For this purpose, brain levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), as well as two endocannabinoid-like lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), were assessed in different brain areas involved in the hedonic feeding (i.e., prefrontal cortex, nucleus accumbens, amygdala, hippocampus, and hypothalamus).

The brain density of cannabinoid type-1 receptors (CB1) was also evaluated. Furthermore, we determined plasma levels of leptin, ghrelin, and corticosterone hormones, which are well-known to control the levels of endocannabioids and/or CB1 receptors in the brain.

To induce binge eating behavior, rats were subject to an intermittent and limited access to a high fat diet (HFD) (margarine). Three experimental groups were used, all with ad libitum access to chow: control (CTRL), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days/week; high restriction (HR), with 2 h margarine access 3 days/week. Bingeing was established when margarine intake in the HR group exceeded that of the LR group.

Our results show that, compared to CTRL, AEA significantly decreased in the caudate putamen, amygdala, and hippocampus of HR group. In contrast, 2-AG significantly increased in the hippocampus while OEA decreased in the hypothalamus. Similar to the HR group, AEA and OEA decreased respectively in the amygdala and hypothalamus and 2-AG increased in the hippocampus of LR group. Moreover, LR group also had AEA decreased in the prefrontal cortex and increased in the nucleus accumbens. In both groups we found the same reduction of CB1 receptor density in the prefrontal cortex compared to CTRL. Also, LR and HR groups showed alterations in both ghrelin and corticosterone levels, while leptin remained unaltered.

In conclusion, our findings show a modified endocannabinoid tone due to margarine exposure, in several brain areas that are known to influence the hedonic aspect of food. Even if not uniquely specific to binge eating, margarine-induced changes in endocannabinoid tone could contributes to the development and maintenance of this behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/29456490

https://www.frontiersin.org/articles/10.3389/fnins.2018.00040/full

Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders.

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“Eating Disorder (ED) is characterized by persistently and severely disturbed eating behaviours. They arise from a combination of long-standing behavioural, emotional, psychological, interpersonal, and social factors and result in insufficient nutrient ingestion and/or adsorption. The three main EDs are: anorexia nervosa, bulimia nervosa, and binge eating disorder. We review the role of peripheral endocannabinoids in eating behaviour.

DISCUSSION:

The neuronal pathways involved in feeding behaviours are closely related to catecholaminergic, serotoninergic and peptidergic systems. Accordingly, feeding is promoted by serotonin, dopamine, and prostaglandin and inhibited by neuropeptide Y, norepinephrine, GABA, and opioid peptides. The endocannabinoid system plays a role in EDs, and multiple lines of evidence indicate that the cannabinoid signalling system is a key modulatory factor of the activity in the brain areas involved in EDs as well as in reward processes.

CONCLUSION:

Besides their central role in controlling food behaviours, peripheral cannabinoids are also involved in regulating adipose tissue and insulin signalling as well as cell metabolism in peripheral tissues such as liver, pancreas, fatty tissue, and skeletal muscle. Altogether, these data indicate that peripheral cannabinoids can provide new therapeutic targets not only for EDs but also for metabolic disease.”

https://www.ncbi.nlm.nih.gov/pubmed/29437028

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

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“The discovery of endocannabinoid’s role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer’s disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington’s disease, Parkinson’s disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer’s disease and dementia, Huntington’s disease, and Tourette syndrome, and dyskinesia in Parkinson’s disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/29073741

http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2017.15.4.301

Cannabinoid CB1/CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

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British Journal of Pharmacology

“Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate.

Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients.

Our data show that subchronic treatment with both the CB1/CB2 receptor natural agonist Δ9-tetrahydrocannabinol and the synthetic CB1/CB2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioral effects were accompanied by an increase in leptin signaling and a decrease in plasma levels of corticosterone.

Taken together, our results further demonstrate EC system involvement in AN pathophysiology and that strategies which modulate EC signaling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance.”

https://www.ncbi.nlm.nih.gov/pubmed/28561272

http://onlinelibrary.wiley.com/doi/10.1111/bph.13892/abstract

Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus.

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“Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood.

Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations.

Our immunohistochemical and ultrastructural study demonstrates the morphological substrate for cannabinoid-conducted feeding behavior via retrograde dis-inhibition of hunger-promoting AgRP/NPY neurons.”

https://www.ncbi.nlm.nih.gov/pubmed/28377876

Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats.

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“Weight gain is an important side effect of most atypical antipsychotic drugs such as olanzapine. Moreover, although many animal models with metabolic side effects have been well defined, the interaction with other pathways has to be considered.

The endocannabinoid system and the CB1 receptor (CB1R) are among the most promising central and peripheral targets involved in weight and energy balance.

In this study we developed a rat model based 15-days treatment with olanzapine that shows weight gain and an alteration of the blood parameters involved in the regulation of energy balance and glucose metabolism. Consequently, we analysed whether, and by which mechanism, a co-treatment with the novel CB1R neutral antagonist NESS06SM, could attenuate the adverse metabolic effects of olanzapine compared to the reference CB1R inverse agonist rimonabant.

Our results showed alterations of the cannabinoid markers in the nucleus accumbens and of orexigenic/anorexigenic markers in the hypothalamus of female rats treated with olanzapine. These molecular modifications could explain the excessive food intake and the resulting weight gain. Moreover, we confirmed that a co-treatment with CB1R antagonist/inverse agonist compounds decreased food intake and weight increment and restored all blood parameters, without altering the positive effects of olanzapine on behaviour. Furthermore, rimonabant and NESS06SM restored the metabolic enzymes in the liver and fat tissue altered by olanzapine.

Therefore, CB1 receptor antagonist/inverse agonist compounds could be good candidate agents for the treatment of weight gain induced by olanzapine.”

https://www.ncbi.nlm.nih.gov/pubmed/28377074

Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.

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“Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting.

The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone.

Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids.

Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions.

As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.”

https://www.ncbi.nlm.nih.gov/pubmed/28207408

A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9-tetrahydrocannabinol, elicits hyperphagia in rats.

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“Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation.

We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats.

As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour.

CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of [INCREMENT]-tetrahydrocannabinol in the extract.”

https://www.ncbi.nlm.nih.gov/pubmed/28125508

Cannabinol and cannabidiol exert opposing effects on rat feeding patterns.

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“Increased food consumption following ∆(9)-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented.

However, possible non-∆(9)-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors.

Cannabinol induced a CB(1)R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior.

This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆(9)-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic.

Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/22543671

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

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“The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes.

These endogenous neuromodulators enhance appetite in animals.

The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug.

The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling.

In obese humans, it causes weight reduction.

Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.”

https://www.ncbi.nlm.nih.gov/pubmed/12182965