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PubMed1994

Cannabinoids and appetite stimulation.

Appetite stimulation by cannabinoids is highly variable. Four within-subject design studies explored the effects of age, gender, satiety status, route of drug administration, and dose on intake. One study involved a single oral administration of active drug (15 mg males, 10 mg females) or placebo to an age and gender stratified sample of 57 healthy, adult light marijuana users. Eleven subjects received single doses by oral, sublingual, and inhaled routes in a second study. In the third study, 10 subjects ingested a single oral dose in fasted and fed states. A 2.5 mg dose was administered b.i.d. for 3 days by oral and rectal suppository routes in the fourth study. Mean daily energy intake was significantly elevated following chronic dosing by rectal suppository, but not oral capsule, relative to all acute dosing regimens except inhalation. Total daily energy intake was comparable on fed and fasted days, suggesting satiety mechanisms were not impaired by the drug. Subject age, gender, reported "high," and plasma drug level were not significantly associated with drug effects on food intake.

Adult↗

PubMed1993

Appetite and appetite stimulants.

Poor appetite is a common symptom among cancer patients. It can lead to inadequate food intake, weight loss, physical debilitation and reduced tolerance to anti-neoplastic treatment. Although cancer-induced anorexia is not fully understood, there are some theories relating to its development. Interventions may be aimed at improving nutritional intake to prevent excessive weight loss when poor appetite exists, or it may concentrate on improving appetite by pharmacological means. Appetite should be considered alongside other aspects of symptom control and tackled aggressively when it is contributing to a poor quality of life.

Anorexia↗

PubMed2005

Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis.

Appetite stimulants have been used to help overcome decreased appetite and malnutrition in children and adults with various chronic illnesses, including cystic fibrosis (CF). Stimulants have included megestrol acetate (MA), cyproheptadine hydrochloride (CH), cannabinoids, hydrazine sulfate, anabolic hormones, and growth hormone. Many of these, including MA, have substantial side effects and may not be suitable for prolonged use. We previously studied the effects of CH on weight gain in a short-term (12 week) trial in CF with good results compared to placebo. Side effects were few, and weight gain was significant. In this study, we sought to determine the effects of CH over a longer term in order to assess its suitability for prolonged use. Sixteen CF children and adults enrolled in the original short-term study subsequently entered this study, and 12 completed the 9-month trial. All patients receiving placebo in the original short-term study received CH 4 mg up to four times a day in the long-term study continuation, and those receiving CH in the short-term study continued on the drug. No pill counts were done, and patients were queried at quarterly visits as to their CH use. Anthropometrics and spirometry were also done quarterly, and antibiotic use was quantified. Subjects who had changed from placebo (CH2 group) gained weight significantly over 3-6 months, and those continuing on CH (CH1 group) generally maintained previously gained weight over the duration of the study. Select spirometric measures improved in both groups but not significantly, and side effects were mild. CH appears to be an effective appetite stimulant in CF, and generally maintains its effect over time with an acceptable side-effect profile.

Adolescent↗

PubMed2000

The effect of propofol administered intravenously on appetite stimulation in dogs.

Anorexia is defined as diminished appetite or aversion to food. Clinical manifestations of anorexia have multiple etiologies, which include systemic illness, pain, fever, stress, metabolic disorders, and decreased palatability and learned aversion to food. Disorders of appetite are common in companion and laboratory animal medicine. Anecdotal evidence and personal experience suggest that propofol (2, 6-diisopropylphenol), when given intravenously at subhypnotic doses, causes acute appetite stimulation in dogs. The establishment of a dose-response effect could have important clinical applications; therefore, this study attempts to qualify and quantify the effect of propofol on appetite stimulation in healthy young adult dogs. Six purpose-bred male dogs (age, 6 months) were obtained from a Class A vendor. Dogs were housed individually and provided water ad libitum throughout the study period. All dogs were fed ad libitum to ensure that test conditions and degree of satiety were identical. Each dog was assigned randomly to either an experimental group or control each day of the study. The experimental groups received single bolus intravenous injections of propofol at different dosage levels (0.5, 1.0, 1.5, 2.0, or 3.0 mg/kg of body weight), and the control group received saline. The administrator was blinded to the animals identification and dose. Dosages greater than 3.0 mg/kg resulted in profound sedation and ataxia, which physically inhibited the dogs from obtaining the food; therefore 3.0 mg/kg was the highest dose tested. Dogs were weighed daily to ensure accurate dosing. Dosing was performed at the same time each day to minimize variability. Food intake amounts were recorded at 15, 30, 60, 120, and 1440 min after injection. Food intake was expressed as [food intake (g)/ body weight (kg)/ unit time (min)]. After a 1-w rest period, the study was repeated. Data were analyzed with a type RBF-65 randomized-block factoral design (ANOVA). Each dog served as its own control. The two experiments were analyzed separately, and a P-value of less than 0.05 was used to declare statistical significance. A significant (P, 0.05) increase in food consumption was observed solely during the 0-to-15-min time interval; no significant increase in food consumption was observed at any other time point. This data supports propofols appetite stimulating effect in the initial 15 min after injection. Additional studies are required to explore the mechanism for this effect and to determine whether it occurs in other species.

Anesthetics, Intravenous↗

PubMed2001

Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats.

This investigation reports the possible role of the endocannabinoid anandamide in modulating appetitive behaviour. Given that cannabinoids have been used clinically to stimulate appetite in HIV and cancer chemotherapy patients, there has been a renewed interest in the involvement of cannabinoids in appetite modulation. This is the first report on the administration of anandamide into the ventromedial hypothalamus. Pre-satiated rats received an intrahypothalamic injection of anandamide (50 ng x 0.5 microl(-1)) followed by measurement of food intake at 3 h post injection. Administration of anandamide induced significant hyperphagia. Pretreatment with the selective CB1 cannabinoid antagonist SR 141716 (30 microg x 0.5 microl(-1)), 30 min prior to anandamide injection resulted in an attenuation of the anandamide-induced hyperphagia (P<0.001). This study demonstrates that intrahypothalamic anandamide initiates appetite by stimulation of CB1 receptors, thus providing evidence on the involvement of hypothalamic endocannabinoids in appetite initiation.

Animals↗

PubMed2004

Cyproheptadine is an effective appetite stimulant in cystic fibrosis.

Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF). Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis. We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF. This was a 12-week, randomized, double-blind, controlled trial of CH vs. placebo. Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study. Subjects were seen at baseline and every 4 weeks. Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey. Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs. 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass. There were no changes or differences in PO or IV antibiotic use or spirometric changes. No significant side effects except transient mild sedation occurred in the CH group. Patient acceptance was good. In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF.

Adolescent↗

PubMed1993

[Essential obesity: an unresolved clinical problem. Considerations on central appetite stimulants and inhibitors].

The recent theories on the etiology of obesity have attributed more importance to the mechanisms of feeding control. The amount of calories taken daily seems to be under the control of a group of substances which stimulate or inhibit the appetite at the hypothalamic level. The hypothalamus is particularly rich in neurotransmitters or neurohormones which are biologically active and represent the connexion between the cells of the upper centers and the hypothalamus and they interfere in the regulation of feeding. The authors pass in review the more recent literature data regarding the main appetite stimulators as well as their site and their mechanism of action.

Adipose Tissue↗

PubMed2003

Cross talk between physical activity and appetite control: does physical activity stimulate appetite?

Physical activity has the potential to modulate appetite control by improving the sensitivity of the physiological satiety signalling system, by adjusting macronutrient preferences or food choices and by altering the hedonic response to food. There is evidence for all these actions. Concerning the impact of physical activity on energy balance, there exists a belief that physical activity drives up hunger and increases food intake, thereby rendering it futile as a method of weight control. There is, however, no evidence for such an immediate or automatic effect. Short (1-2 d)-term and medium (7-16 d)-term studies demonstrate that men and women can tolerate substantial negative energy balances of < or = 4 MJ energy cost/d when performing physical activity programmes. Consequently, the immediate effect of taking up exercise is weight loss (although this outcome is sometimes difficult to assess due to changes in body composition or fluid compartmentalization). However, subsequently food intake begins to increase in order to provide compensation for about 30% of the energy expended in activity. This compensation (up to 16 d) is partial and incomplete. Moreover, subjects separate into compensators and non-compensators. The exact nature of these differences in compensation and whether it is actually reflective of non-compliance with protocols is yet to be determined. Some subjects (men and women) performing activity with a cost of < or = 4 MJ/d for 14 d, show no change in daily energy intake. Conversely, it can be demonstrated that when active individuals are forced into a sedentary routine food intake does not decrease to a lower level to match the reduced energy expenditure. Consequently, this situation creates a substantial positive energy balance accompanied by weight gain. The next stage is to further characterize the compensators and non-compensators, and to identify the mechanisms (physiological or behavioural) that are responsible for the rate of compensation and its limits.

Anorexia↗

PubMed1994

A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.

PURPOSE: To evaluate the appetite-stimulating properties of delta-9-tetrahydrocannabinol (THC) in patients with anorexia due to advanced cancer. PATIENTS AND METHODS: Nineteen patients with various malignancies were entered. All had cancer-associated anorexia and a life expectancy greater than four weeks. Patients were started on THC 2.5 mg p.o. t.i.d. one hour after meals for four weeks. Evaluations for side effects, efficacy, acceptability and satisfaction were conducted at two and four weeks. RESULTS: 18 patients were evaluable. Ten patients completed the entire 28-day study. Four patients experienced grade I toxicity and three withdrew at their request. Thirteen patients reported an improved appetite. CONCLUSION: THC is an effective appetite stimulant in patients with advanced cancer. It is well tolerated at low doses. Further studies are needed to determine the most appropriate dose and the specific population most likely to respond.

Administration, Oral↗

PubMed2000

[Standards, Options and Recommendations (SOR) for the use of appetite stimulants in oncology. Work group. Federation of the French Cancer Centres (FNCLCC)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the use of appetite stimulants in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 55 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the use of appetite stimulants in oncology are: 1) Corticosteroids and the synthetic progestogens (megestrol acetate and medroxyprogesterone acetate) are appetite stimulants. 2) They can be useful in managing anorexia and weight loss in cancer patients, especially in the palliative setting, despite the potential side-effects of these agents. 3) The most effective way of using these drugs is not known. Inclusion in clinical trials is recommended. 4) Cyproheptadine, metoclopramide, nandrolone and pentoxif line should not be used outside prospective clinical trials. 5) Hydrazine sulfate should not be used.

Adrenal Cortex Hormones↗

PubMed1998

[Orexins--new hypothalamic peptides that stimulate appetite].

A family of novel hypothalamus-specific peptides called orexins have recently been discovered and characterized. The orexins stimulate appetite (the greek word orexis means appetite) when given intraventricularly to rats. Their genes are expressed bilaterally in the lateral hypothalamus, a region previously known to regulate food intake. The two peptides, orexin A (33 amino-acids) and orexin B (28 amino acids), are derived from a common prepro-orexin precursor. The peptides bind to specific G-protein-coupled orexin receptors termed OX-1R and OX-2R. The identification of the orexins will increase our understanding on how the brain regulates food intake.

Amino Acid Sequence↗

PubMed2005

Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls.

Ghrelin, a growth hormone (GH) secretagogue receptor ligand was isolated from the stomach and hypothalamus of rats and humans. In rodents, ghrelin exerts distinct orexigenic action, probably as counterpart of the anorexigenic leptin. In humans, ghrelin infusion enhances appetite. It is unknown whether single intravenous (i.v.) injections of ghrelin affect human eating behavior. Therefore, we investigated the influence of a single i.v. bolus injection of 100 microg ghrelin on appetite, ideas about food, hormone levels, and glucose concentration in young control subjects. In order to test gender differences, we included five women and four men. After ghrelin administration, appetite was enhanced in eight of nine subjects. Seven probands reported a vivid, plastic image of their preferred meal. Furthermore, ghrelin stimulated an immediate increase in plasma levels of GH (area under the curve, mean+/-SEM 35+/-16 ng/ml x min after placebo [P] to 2808+/-533 ng/ml x min after ghrelin [G]; p<0.001), cortisol (5908+/-984 ng/ml x min [P] to 10179+/-1293 ng/ml x min [G]; p<0.001), and ACTH (922+/-103 pg/ml x min [P] to 3030+/-763 pg/ml x min [G]; p<0.02), whereas leptin levels remained unchanged. Contrary to placebo, glucose concentration did not decrease markedly after administration of ghrelin. Our data suggest that i.v. ghrelin stimulates appetite and images of food in young women and men. Obviously, leptin is not involved in these effects.

Adrenocorticotropic Hormone↗

PubMed1978

Increased feeding in rats treated with chlordimeform and related formamidines: a new class of appetite stimulants.

Low doses of the formamidine pesticide, chlordimeform (CDM) induce voracious daytime feeding in non-food deprived rats. Following CDM (10 mg/kg), food intakes were five times control intakes after 3 h and 1.1 times control intakes after 24 h. Other selected formamidines, such as the N-demethylated metabolite of CDM, and amitraz, increased 3-h food intake by two and five times control intake, respectively. Anorexia accompanied by excessive CNS stimulation was noted with higher doses of CDM (above 40 mg/kg) and other formamidines. This contrasts with the sedation usually observed with high doses of other structurally diverse appetite stimulants. In addition, hyperphagia was not observed with other CNS stimulants or local anesthetics such as amphetamine, cocaine, and holocaine. Thus the formamidines constitute a new class of appetite stimulants, which should prove to be useful agents for the study of feeding behavior.

Amidines↗

PubMed2004

Clinical endocrinology and metabolism. Ghrelin, a novel growth-hormone-releasing and appetite-stimulating peptide from stomach.

Recent identification of novel appetite-regulating hormones has revealed the complex interactions of these humoral factors in the regulation of feeding behavior in mammals. One of these hormones, ghrelin, a natural ligand of the orphan receptor GHS-R, purified from stomach, is able to stimulate growth hormone release from pituitary cells. Ghrelin is a 28 amino acid peptide containing an n-octanoylated serine 3 residue that is essential for its activity. Ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, the region known to control food intake. As an orexigenic peptide, ghrelin is therefore an endogenous regulator of feeding behavior from the peripheral tissues to the central nervous system.

Amino Acid Sequence↗

PubMed2006

Does alcohol stimulate appetite and energy intake?

It has been anecdotally suggested that alcohol stimulates appetite and so increases energy intake in people who have poor appetite. This review sought to systematically review the evidence for this practice, using the mini-review approach (Griffiths, 2002). Among the eight studies reviewed, only one showed a significant difference in appetite ratings between the alcohol and no alcohol preload. However, significant differences were found in energy intake following a high-dose alcohol preload as opposed to a no-alcohol preload, in three out of the eight studies reviewed. One further study reported an increase in energy intake after the alcohol preload but this failed to reach statistical significance. In conclusion, the effect of alcohol on appetite appears largely unsubstantiated. Alcohol's effect on energy intake does appear significant, but further research is necessary owing to small sample sizes.

Adult↗

PubMed1997

Effect of the appetite stimulant cyproheptadine on deoxynivalenol-induced reductions in feed consumption and weight gain in the mouse.

Deoxynivalenol (DON, vomitoxin), a Fusarium mycotoxin, is suspected of inducing its anorectic/feed refusal activity through a serotoninergic (5HT) mechanism, possible via 5HT2-receptors. In this study the efficiency of cyproheptadine (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the adverse effect of DON was investigated in mice. CYP was administered in the feed for two days before animals began receiving the DON, which was also added to the feed. Both agents were administered concurrently thereafter for a 12-day period. Dosing levels included various combinations of the two compounds, ranging from 0-16 ppm DON and 0-20 ppm CYP.

Animals↗

PubMed2006

Lewis rats are more sensitive than Fischer rats to successive negative contrast, but less sensitive to the anxiolytic and appetite-stimulating effects of chlordiazepoxide.

Lewis rats show greater anticipatory contrast effects than Fischer 344 rats. Specifically, relative to Fischer rats, Lewis rats exhibit greater avoidance of a saccharin cue when it predicts the future availability of a preferred sucrose reward [Grigson, P.S., Freet, C.S. The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: evidence for the reward comparison hypothesis. Behav Neurosci 2000;114:353-363.]. Experiment 1 was designed to determine whether Lewis rats also would demonstrate greater contrast in another paradigm, successive negative contrast (SNC). The results demonstrated a tendency for greater SNC in Lewis rats and then slower recovery from the unexpected loss of reward relative to the Fischer rats. Pretreatment with the anxiolytic agent, chlordiazepoxide (CDP), effectively eliminated contrast in the Fischer rats, but served to prolong recovery from contrast in the Lewis rats. Finally, the results of Experiment 2 demonstrated that Fischer rats, but not Lewis rats, increase consumption of a 0.1 M sucrose solution following pretreatment with CDP. Together, the results show that, while both Lewis and Fischer rats demonstrate SNC, the effect is more sustained in the Lewis rats and these rats are insensitive to both the anxiolytic and the appetite-stimulating effects of CDP.

Animals↗

PubMed2006

Differences in the appetite-stimulating effect of orexin, neuropeptide Y and ghrelin among young, adult and old rats.

Aging is associated with a progressive decrease in appetite and food intake. The appetite-stimulating peptides orexin A, neuropeptide Y (NPY) and ghrelin are known to play a critical role in food intake. In this study, the stimulatory effect of intracerebroventricular administration of these peptides on food intake was compared among young (4 months old), adult (11 months old) and old (24-27 months old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses of orexin A (0.25-3 nmol), NPY and ghrelin (0.03-1 nmol) were injected into the left lateral ventricle without anesthesia. Food consumption was measured at 1, 2 and 4 h after injection. We also examined the plasma levels of acylated and desacyl ghrelin in young and old rats by ELISA. Intracerebroventricular administration of orexin A and NPY stimulated food intake in young and adult rats, but no effects were observed at any dose in old rats. Ghrelin increased food intake in a dose-dependent manner in all groups, and the effect of ghrelin was reduced with advancing age. Neither the acylated nor the desacyl plasma ghrelin level differed significantly between young and old rats. In conclusion, the orexigenic effect of the peptides orexin A, NPY and ghrelin decreased in old rats, and this reduction may have been responsible for the age-related decrease in food intake.

Aging↗