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Effect of dronabinol therapy on physical activity in anorexia nervosa: a randomised, controlled trial

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Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Purpose

The level of physical activity is inappropriately high in up to 80 % of the patients suffering of anorexia nervosa (AN), as a result of conscious efforts to lose weight, affect regulation and biological adaptive changes to starvation induced by hypothermia and neuroendocrine mechanisms. The purposes of this paper were to (1) assess the effect of dronabinol—a synthetic cannabinoid agonist—on physical activity in patients with chronic and stable AN, and to (2) unravel the role of leptin and cortisol in this process.

Methods

This prospective, randomised, double-blind, crossover study was conducted at a specialised care centre for eating disorders. Twenty-four adult women with AN of at least 5-year duration received either the dronabinol-placebo or placebo-dronabinol sequence. Physical activity was monitored during the fourth week of each intervention. Body weight, leptin and urinary free cortisol excretion were measured repeatedly during the trial. Changes in behavioural dimensions related to AN were assessed by Eating Disorder Inventory-2.

Results

The total duration of physical activity did not change, while its average intensity increased by 20 % (P = 0.01) during dronabinol therapy, resulting in an increased energy expenditure with 68.2 kcal/day (P = 0.01) above placebo.

Conclusions

This randomised, double-blind study revealed that cannabinoid agonist treatment was associated with a modest increase in physical activity in adult women with severe and longstanding AN. Additionally, we detected a strong relationship between the circulating levels of leptin and physical activity in these chronically undernourished patients.

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Notes

  1. as recommended by the manufacturer: http://www.actigraphcorp.com/research-database/kcal-estimates-from-activity-counts-using-the-potential-energy-method/.

References

  1. Davis C, Katzman DK, Kaptein S, Kirsh C, Brewer H, Kalmbach K, Olmsted MP, Woodside DB, Kaplan AS (1997) The prevalence of high-level exercise in the eating disorders: etiological implications. Compr Psychiatry 38(6):321–326

    Article  CAS  PubMed  Google Scholar 

  2. Beumont PJ, Arthur B, Russell JD, Touyz SW (1994) Excessive physical activity in dieting disorder patients: proposals for a supervised exercise program. Int J Eat Disord 15(1):21–36

    Article  CAS  PubMed  Google Scholar 

  3. Blinder BJ, Freeman DM, Stunkard AJ (1970) Behavior therapy of anorexia nervosa: effectiveness of activity as a reinforcer of weight gain. Am J Psychiatry 126(8):1093–1098

    Article  CAS  PubMed  Google Scholar 

  4. Falk JR, Halmi KA, Tryon WW (1985) Activity measures in anorexia nervosa. Arch Gen Psychiatry 42(8):811–814

    Article  CAS  PubMed  Google Scholar 

  5. Bratland-Sanda S, Sundgot-Borgen J, Ro O, Rosenvinge JH, Hoffart A, Martinsen EW (2010) Physical activity and exercise dependence during inpatient treatment of longstanding eating disorders: an exploratory study of excessive and non-excessive exercisers. Int J Eat Disord 43(3):266–273. doi:10.1002/eat.20769

    PubMed  Google Scholar 

  6. Carter JC, Blackmore E, Sutandar-Pinnock K, Woodside DB (2004) Relapse in anorexia nervosa: a survival analysis. Psychol Med 34(4):671–679. doi:10.1017/S0033291703001168

    Article  CAS  PubMed  Google Scholar 

  7. Strober M, Freeman R, Morrell W (1997) The long-term course of severe anorexia nervosa in adolescents: survival analysis of recovery, relapse, and outcome predictors over 10–15 years in a prospective study. Int J Eat Disord 22(4):339–360

    Article  CAS  PubMed  Google Scholar 

  8. Penas-Lledo E, Vaz Leal FJ, Waller G (2002) Excessive exercise in anorexia nervosa and bulimia nervosa: relation to eating characteristics and general psychopathology. Int J Eat Disord 31(4):370–375. doi:10.1002/eat.10042

    Article  PubMed  Google Scholar 

  9. Casper RC (2006) The ‘drive for activity’ and “restlessness” in anorexia nervosa: potential pathways. J Affect Disord 92(1):99–107. doi:10.1016/j.jad.2005.12.039

    Article  PubMed  Google Scholar 

  10. Stoving RK, Hangaard J, Hagen C (2001) Update on endocrine disturbances in anorexia nervosa. J Pediatr Endocrinol Metab 14(5):459–480

    CAS  PubMed  Google Scholar 

  11. Mastorakos G, Pavlatou M, Diamanti-Kandarakis E, Chrousos GP (2005) Exercise and the stress system. Hormones 4(2):73–89

    PubMed  Google Scholar 

  12. Focker M, Timmesfeld N, Scherag S, Buhren K, Langkamp M, Dempfle A, Sheridan EM, de Zwaan M, Fleischhaker C, Herzog W, Egberts K, Zipfel S, Herpertz-Dahlmann B, Hebebrand J (2011) Screening for anorexia nervosa via measurement of serum leptin levels. J Neural Transm 118(4):571–578. doi:10.1007/s00702-010-0551-z

    Article  CAS  PubMed  Google Scholar 

  13. Hebebrand J, Bulik CM (2011) Critical appraisal of the provisional DSM-5 criteria for anorexia nervosa and an alternative proposal. Int J Eat Disord 44(8):665–678. doi:10.1002/eat.20875

    Article  PubMed  Google Scholar 

  14. Holtkamp K, Herpertz-Dahlmann B, Mika C, Heer M, Heussen N, Fichter M, Herpertz S, Senf W, Blum WF, Schweiger U, Warnke A, Ballauff A, Remschmidt H, Hebebrand J (2003) Elevated physical activity and low leptin levels co-occur in patients with anorexia nervosa. J Clin Endocrinol Metab 88(11):5169–5174

    Article  CAS  PubMed  Google Scholar 

  15. Exner C, Hebebrand J, Remschmidt H, Wewetzer C, Ziegler A, Herpertz S, Schweiger U, Blum WF, Preibisch G, Heldmaier G, Klingenspor M (2000) Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa. Mol Psychiatry 5(5):476–481

    Article  CAS  PubMed  Google Scholar 

  16. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J (2006) Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA J Am Med Assoc 295(7):761–775

    Article  CAS  Google Scholar 

  17. Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10(2):89–97

    Article  CAS  PubMed  Google Scholar 

  18. Andries A, Frystyk J, Flyvbjerg A, Stoving RK (2014) Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. Int J Eat Disord 47(1):18–23. doi:10.1002/eat.22173

    Article  PubMed  Google Scholar 

  19. Sanudo-Pena MC, Romero J, Seale GE, Fernandez-Ruiz JJ, Walker JM (2000) Activational role of cannabinoids on movement. Eur J Pharmacol 391(3):269–274

    Article  CAS  PubMed  Google Scholar 

  20. Hill MN, Tasker JG (2012) Endocannabinoid signaling, glucocorticoid-mediated negative feedback, and regulation of the hypothalamic–pituitary–adrenal axis. Neuroscience 204:5–16. doi:10.1016/j.neuroscience.2011.12.030

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Klein DA, Mayer LE, Schebendach JE, Walsh BT (2007) Physical activity and cortisol in anorexia nervosa. Psychoneuroendocrinology 32(5):539–547. doi:10.1016/j.psyneuen.2007.03.007

    Article  CAS  PubMed  Google Scholar 

  22. Aguirre CA, Castillo VA, Llanos MN (2012) Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice. Diabetol Metab Syndr 4(1):35. doi:10.1186/1758-5996-4-35

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. McLaughlin PJ, Thakur GA, Vemuri VK, McClure ED, Brown CM, Winston KM, Wood JT, Makriyannis A, Salamone JD (2013) Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054. Pharmacol Biochem Behav 109:16–22. doi:10.1016/j.pbb.2013.04.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Verty AN, Evetts MJ, Crouch GJ, McGregor IS, Stefanidis A, Oldfield BJ (2011) The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology 36(7):1349–1358. doi:10.1038/npp.2011.19

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Stoving RK, Andries A, Brixen K, Bilenberg N, Horder K (2011) Gender differences in outcome of eating disorders: a retrospective cohort study. Psychiatry Res 186(2–3):362–366. doi:10.1016/j.psychres.2010.08.005

    Article  PubMed  Google Scholar 

  26. Stoving RK, Andries A, Brixen KT, Bilenberg N, Lichtenstein MB, Horder K (2012) Purging behavior in anorexia nervosa and eating disorder not otherwise specified: a retrospective cohort study. Psychiatry Res. doi:10.1016/j.psychres.2011.10.009

    PubMed  Google Scholar 

  27. Freedson PS, Melanson E, Sirard J (1998) Calibration of the computer science and applications, Inc. accelerometer. Med Sci Sports Exerc 30(5):777–781

    Article  CAS  PubMed  Google Scholar 

  28. Asferg C, Mogelvang R, Flyvbjerg A, Frystyk J, Jensen JS, Marott JL, Appleyard M, Jensen GB, Jeppesen J (2010) Leptin, not adiponectin, predicts hypertension in the Copenhagen City Heart Study. Am J Hypertens 23(3):327–333. doi:10.1038/ajh.2009.244

    Article  CAS  PubMed  Google Scholar 

  29. Garner DM (1991) Eating Disorder Inventory-2: professional manual. Psychological Assessment Resources, Inc., Odessa, FL

    Google Scholar 

  30. Clausen L, Rokkedal K, Rosenvinge JH (2009) Validating the eating disorder inventory (EDI-2) in two Danish samples: a comparison between female eating disorder patients and females from the general population. Eur Eat Disord Rev 17(6):462–467. doi:10.1002/erv.945

    Article  PubMed  Google Scholar 

  31. Thiel A, Paul T (2006) Test–retest reliability of the Eating Disorder Inventory 2. J Psychosom Res 61(4):567–569. doi:10.1016/j.jpsychores.2006.02.015

    Article  PubMed  Google Scholar 

  32. Practice guideline for the treatment of patients with eating disorders (revision). American Psychiatric Association Work Group on Eating Disorders. Am J Psychiatry 157(1 Suppl):1–39

  33. Senn S (2002) Cross-over trials in clinical research. Wiley, New York

    Book  Google Scholar 

  34. Rey AA, Purrio M, Viveros MP, Lutz B (2012) Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission. Neuropsychopharmacology 37(12):2624–2634. doi:10.1038/npp.2012.123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Viveros MP, Marco EM, File SE (2005) Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav 81(2):331–342. doi:10.1016/j.pbb.2005.01.029

    Article  CAS  PubMed  Google Scholar 

  36. Kawaguchi M, Scott KA, Moran TH, Bi S (2005) Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia. Am J Physiol Regul Integr Comp Physiol 288(6):R1800–R1805. doi:10.1152/ajpregu.00805.2004

    Article  CAS  PubMed  Google Scholar 

  37. Sutton RE, Koob GF, Le Moal M, Rivier J, Vale W (1982) Corticotropin releasing factor produces behavioural activation in rats. Nature 297(5864):331–333

    Article  CAS  PubMed  Google Scholar 

  38. Rivest S, Richard D (1990) Involvement of corticotropin-releasing factor in the anorexia induced by exercise. Brain Res Bull 25(1):169–172

    Article  CAS  PubMed  Google Scholar 

  39. Holtkamp K, Herpertz-Dahlmann B, Hebebrand K, Mika C, Kratzsch J, Hebebrand J (2006) Physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa. Biol Psychiatry 60(3):311–313. doi:10.1016/j.biopsych.2005.11.001

    Article  CAS  PubMed  Google Scholar 

  40. Zhang LN, Gamo Y, Sinclair R, Mitchell SE, Morgan DG, Clapham JC, Speakman JR (2012) Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice. Obesity 20(5):954–962. doi:10.1038/oby.2011.357

    Article  CAS  PubMed  Google Scholar 

  41. Zeeck A, Hartmann A, Buchholz C, Herzog T (2005) Drop outs from in-patient treatment of anorexia nervosa. Acta Psychiatr Scand 111(1):29–37

    Article  CAS  PubMed  Google Scholar 

  42. Bissada H, Tasca GA, Barber AM, Bradwejn J (2008) Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 165(10):1281–1288. doi:10.1176/appi.ajp.2008.07121900

    Article  PubMed  Google Scholar 

  43. Nysom K, Molgaard C, Hutchings B, Michaelsen KF (2001) Body mass index of 0 to 45-y-old Danes: reference values and comparison with published European reference values. Int J Obes Relat Metab Disord 25(2):177–184. doi:10.1038/sj.ijo.0801515

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the patients who participated in the trial; Charlotte Olsen, Lone Hansen and Merete Møller are thanked for helping with collecting samples and the leptin measurements. We would like to kindly thank to the team at the Department of Exercise epidemiology, University of Southern Denmark who developed the software Propero used for compiling accelerometer data. Claire Gudex is thanked for language editing of the manuscript.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Centre for Eating Disorders, Odense University Hospital, 5000, Odense, Denmark

    Alin Andries & René Klinkby Støving

  2. Psychiatry of Region Southern Denmark, University of Southern Denmark, Odense, Denmark

    Alin Andries & René Klinkby Støving

  3. Department of Clinical Research, Hospital of Southwest Denmark, Esbjerg, Denmark

    Bibi Gram

  4. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Bibi Gram

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  1. Alin Andries
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Correspondence to Alin Andries.

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Andries, A., Gram, B. & Støving, R.K. Effect of dronabinol therapy on physical activity in anorexia nervosa: a randomised, controlled trial. Eat Weight Disord 20, 13–21 (2015). https://doi.org/10.1007/s40519-014-0132-5

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  • DOI: https://doi.org/10.1007/s40519-014-0132-5

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