title: Changes in IGF-I, urinary free cortisol and adipokines during dronabinol therapy in anorexia nervosa: Results from a randomised, controlled trial.
abstract: OBJECTIVE
  Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved in energy metabolism have not been previously described in humans. Therefore we found it of interest to assess interactions between the synthetic cannabinoid agonist dronabinol and insulin-like growth factor I (IGF-I), urinary free cortisol (UFC) and adipokines in patients with chronic AN.
  
  
  METHODS
  This was a prospective, double-blind randomised crossover study, conducted at a specialised care centre for eating disorders. The results are based on twenty-four adult women with chronic AN, who completed the study. The participants received dronabinol (oral capsules, 5mg daily) and matching placebo over four weeks, separated by a four-week washout period. Bioactive IGF was determined by a cell-based bioassay, whereas total IGF-I, IGFBP-2 and -3 and the two adipokines leptin and adiponectines were measured by immunoassays. The UFC excretion was determined by mass spectrometry.
  
  
  RESULTS
  As previously reported, dronabinol treatment caused a small, yet significant increase in BMI as compared to placebo (+0.23 kg/m(2); P = 0.04). This modest weight gain predicted a corresponding increase in bioactive IGF-I, while the amount of daily energy expenditure due to physical activity had a comparable but opposite effect. Nevertheless, neither IGF-I, bioactive IGF nor the IGFBPs levels changed significantly during dronabinol intervention as compared to placebo. Adiponectin also remained unaffected by the weight gain, whereas plasma leptin showed a transient increase at three weeks (P < 0.05). UFC levels were decreased during dronabinol intervention.
  
  
  CONCLUSIONS
  Our results showed that low-dosage therapy with the synthetic cannabinoid agonist dronabinol affected neither the concentration nor the activity of the circulating IGF-system in women with severe and chronic AN. However, our results suggest that such treatment may alleviate the increased hypothalamic-pituitary-adrenal axis activity seen in these patients.
authors.affiliation: Center for Eating Disorders, Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark. Electronic address: alin@dadlnet.dk.
authors.forename: Alin
authors.initials: A
authors.lastname: Andries
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.affiliation: Center for Eating Disorders, Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark.
authors.forename: René Klinkby
authors.initials: RK
authors.lastname: Støving
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000856:Anorexia Nervosa / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D011446:Prospective Studies; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D063386:Cannabinoid Receptor Agonists; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013759:Dronabinol; D006854:Hydrocortisone
keywords: Anorexia nervosa; Cortisol; Dronabinol; IGF-I; Leptin