, Volume 231, Issue 12, pp 2449–2459 | Cite as

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

  • J. M. Thomas
  • C. T. Dourish
  • J. W. Tomlinson
  • Z. Hassan-Smith
  • S. Higgs
Original Investigation



The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development.


The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood.


Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings.


mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB.


The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.


Experimental medicine Anti-obesity drugs mCPP 5-HT2C ETB UEM Appetite Food intake Satiation quotient Emotional processing Memory 



The research was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would like to thank the staff at the facility for their support during the study. This work was funded by P1vital and the BBSRC1

Conflicts of interest

Dr Colin Dourish is an employee and shareholder of P1vital Ltd., Dr Suzanne Higgs is a member of P1vital's Advisory Panel, and Jason Michael Thomas is funded by the Steve Cooper P1vital—BBSRC PhD Studentship.


  1. AMA (2013) AMA adopts new policies on second day of voting at annual meeting.
  2. Anderson NH (1968) Likableness ratings of 555 personality-trait words. J Pers Soc Psychol 9:272–279PubMedCrossRefGoogle Scholar
  3. Anderson IM, Clark L, Elliott R, Kulkarni B, Williams SR, Deakin JF (2002) 5-HT(2C) receptor activation by m-chlorophenylpiperazine detected in humans with fMRI. Neuroreport 13:1547–1551PubMedCrossRefGoogle Scholar
  4. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571PubMedCrossRefGoogle Scholar
  5. Browning M, Reid C, Cowen PJ, Goodwin GM, Harmer CJ (2007) A single dose of citalopram increases fear recognition in healthy subjects. J Psychopharmacol 21:684–690PubMedCrossRefGoogle Scholar
  6. Butler H, Korbonits M (2009) Cannabinoids for clinicians: the rise and fall of the cannabinoid antagonists. Eur J Endocrinol 161:655–662PubMedCentralPubMedCrossRefGoogle Scholar
  7. Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology 92:14–24PubMedCrossRefGoogle Scholar
  8. Cowen PJ, Sargent PA, Williams C, Goodall EM, Orlikov AB (1995) Hypophagic, endocrine and subjective responses to m-chlorophenylpiperazine in healthy men and women. Hum Psychopharm 10:385–391CrossRefGoogle Scholar
  9. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB (1999) Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 281:235–242PubMedCrossRefGoogle Scholar
  10. Dawson GR, Craig KJ, Dourish CT (2011) Validation of experimental medicine methods in psychiatry: the P1vital approach and experience. Biochem Pharmacol 81:1435–1441PubMedCrossRefGoogle Scholar
  11. Dourish CT, Wilding JPH, Halford JCG (2008) Anti-obesity drugs: from animal models to clinical efficacy. In: McArthur RA, Borsini F (eds) Animal and translational models for CNS drug discovery. Vol 3–Reward deficit disorders. Academic, New York, 271–315Google Scholar
  12. Ekman P, Friesen WV (1976) Pictures of facial affect. Consulting Psychologists Press, Palo AltoGoogle Scholar
  13. Eysenck HJ, Eysenck SBG (1975) Manual of the Eysenck personality questionnaire (adult and junior). Hodder, LondonGoogle Scholar
  14. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M (2011) National, regional, and globaltrends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1million participants. Lancet 377:557–567PubMedCrossRefGoogle Scholar
  15. Foltin RW, Danysz W, Bisaga A (2008) A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine. Psychopharmacology 199:583–592PubMedCentralPubMedCrossRefGoogle Scholar
  16. Green SM, Delargy HJ, Joanes D, Blundell JE (1997) A satiety quotient: a formulation to assess the satiating effect of food. Appetite 29:291–304PubMedCrossRefGoogle Scholar
  17. Halford JCG, Boyland E, Cooper SJ, Dovey TD, Huda MSB, Dourish CT, Dawson G, Wilding JPH (2010) The effects of sibutramine on the microstructure of feeding behaviour as measured by the Universal Eating Monitor (UEM). J Psychopharmacol 24:99–109PubMedCrossRefGoogle Scholar
  18. Harmer CJ, Bhagwagar Z, Cowen PJ, Goodwin GM (2002) Acute administration of citalopram facilitates memory consolidation in healthy volunteers. Psychopharmacology 163:106–110PubMedCrossRefGoogle Scholar
  19. Harmer CJ, Bhagwagar Z, Perrett DI, Vollm BA, Cowen PJ, Goodwin GM (2003) Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 28:148–152PubMedCrossRefGoogle Scholar
  20. Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 161:1256–1263PubMedCrossRefGoogle Scholar
  21. Harmer CJ, O’Sullivan U, Favaron E, Massey-Chase R, Ayres R, Reinecke A, Goodwin GM, Cowen PJ (2009) Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry 166:1178–1184PubMedCrossRefGoogle Scholar
  22. Hayward G, Goodwin GM, Cowen PJ, Harmer CJ (2005) Low-dose tryptophan depletion in recovered depressed patients induces changes in cognitive processing without depressive symptoms. Biol Psychiatry 57:517–524PubMedCrossRefGoogle Scholar
  23. Heal DJ, Gosden J, Smith SL (2012) What is the prognosis for new centrally-acting anti-obesity drugs? Neuropharmacology 63:132–146PubMedCrossRefGoogle Scholar
  24. Hewitt KN, Lee MD, Dourish CT, Clifton PG (2002) Serotonin 2C receptor agonists and the behavioural satiety sequence in mice. Pharmacol Biochem Behav 71:691–700PubMedCrossRefGoogle Scholar
  25. Higgs S, Donohoe J (2011) Focusing on food during lunch enhances lunch memory and decreases later snack intake. Appetite 57:202–206PubMedCrossRefGoogle Scholar
  26. Horder J, Cowen PJ, Di Simplicio M, Browning M, Harmer CJ (2009) Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers. Psychopharmacology 205:85–91PubMedCrossRefGoogle Scholar
  27. Horder J, Harmer CJ, Cowen PJ, McCabe C (2010) Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers. Int J Neuropsychopharmacol 13:1103–1113PubMedCrossRefGoogle Scholar
  28. Kahn RS, Wetzler S, Asnis GM, Kling MA, Suckow RF, van Praag HM (1990) Effects of m-chlorophenylpiperazine in normal subjects: a dose–response study. Psychopharmacology 100:339–344PubMedCrossRefGoogle Scholar
  29. Kennett GA, Wood MD, Glen A, Grewal S, Forbes I, Gadre A, Blackburn TP (1994) In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. Br J Pharmacol 111:797–802PubMedCentralPubMedCrossRefGoogle Scholar
  30. Khaliq S, Haider S, Saleem S, Memon Z, Haleem DJ (2012) Influence of serotonergic 5-HT2C receptor antagonist mesulergine in the reversal of memory deficits induced by mCPP. J Coll Physicians Surg Pak 22:75–79PubMedGoogle Scholar
  31. Kissileff HR, Klingsberg G, Van Itallie TB (1980) Universal eating monitor for continuous recording of solid or liquid consumption in man. Am J Physiol 238:R14–R22PubMedGoogle Scholar
  32. Kitchener SJ, Dourish CT (1994) An examination of the behavioural specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats. Psychopharmacology 113:369–377PubMedCrossRefGoogle Scholar
  33. Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–716PubMedCrossRefGoogle Scholar
  34. Li MF, Cheung BMY (2009) Pharmacotherapy for obesity. Br J Clin Pharmacol 68:804–810PubMedCentralPubMedCrossRefGoogle Scholar
  35. Matsumoto D, Ekman P (1988) Japanese and Caucasian facial expressions of emotion (JACFEE). Intercultural and Emotion Research Laboratory. Department of Psychology, San Francisco State University, San FranciscoGoogle Scholar
  36. Miskowiak K, Papadatou-Pastou M, Cowen PJ, Goodwin GM, Norbury R, Harmer CJ (2007) Single dose antidepressant administration modulates the neural processing of self-referent personality trait words. Neuroimage 37:904–911PubMedCrossRefGoogle Scholar
  37. Mogg K, Bradley BP (2002) Selective orienting of attention to masked threat faces in social anxiety. Behav Res Ther 40:1403–1414PubMedCrossRefGoogle Scholar
  38. Murphy SE, Downham C, Cowen PJ, Harmer CJ (2008) Direct effects of diazepam on emotional processing in healthy volunteers. Psychopharmacology 199:503–513PubMedCentralPubMedCrossRefGoogle Scholar
  39. Nelson HE (1982) The National Adult Reading Test (NART): test manual. NFER-NelsonGoogle Scholar
  40. Parsons CG, Stoffler A, Danysz W (2007) Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system—too little activation is bad, too much is even worse. Neuropharmacology 53:699–723PubMedCrossRefGoogle Scholar
  41. Sargent PA, Sharpley AL, Williams C, Goodall EM, Cowen PJ (1997) 5-HT2C receptor activation decreases appetite and body weight in obese subjects. Psychopharmacology 133:309–312PubMedCrossRefGoogle Scholar
  42. Sassi F (2010) Obesity and the economics of prevention: fit not fat.,3343,en_2649_33929_45999775_1_1_1_1,00.html. Accessed 11 Aug 2012
  43. Sayburn A (2010) Withdrawal of sibutramine leaves European doctors with just one obesity drug. BMJ 340:C477PubMedCrossRefGoogle Scholar
  44. Silverstone PH, Cowen PJ (1994) The 5-HT3 antagonist, BRL 46470 does not attenuate m-chlorophenylpiperazine (mCPP)-induced changes in human volunteers. Biol Psychiatry 36:309–316PubMedCrossRefGoogle Scholar
  45. Smith KA, Oldman AD, Goodall EM, Walsh AES, Williams C, Odontiadis J, Cowen PJ (1994) Effects of meta-chlorophenylpiperazine on neuroendocrine responses and food intake in healthy female volunteers. J Serotonin Res 1:127–132Google Scholar
  46. Spielberger CD (1983) Manual for the state-trait anxiety inventory. Consulting Psychologists Publishing, Palo AltoGoogle Scholar
  47. Spitzer RL, Williams JB, Gibbon M, First MB (2004) Structured clinical interview for the DSM-IV (SCID-I/P)Google Scholar
  48. Stunkard AJ, Messick S (1985) The three-factor eating questionnaire to measure dietary restraint disinhibition and hunger. J Psychosom Res 29:71–83PubMedCrossRefGoogle Scholar
  49. von Zerssen D, Strian F, Schwarz D (1974) Evaluation of depressive states, especially in longitudinal studies. Mod Probl Pharmacopsychiatry 7:189–202CrossRefGoogle Scholar
  50. Walsh AE, Smith KA, Oldman AD, Williams C, Goodall EM, Cowen PJ (1994) m-Chlorophenylpiperazine decreases food intake in a test meal. Psychopharmacology 116:120–122PubMedCrossRefGoogle Scholar
  51. Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54:1063–1070PubMedCrossRefGoogle Scholar
  52. WHO (2012) Obesity and overweight, Fact sheet N°311. World Health Organization. Accessed 11 Aug 2012
  53. Yeomans MR (1996) Palatability and the microstructure of eating in humans: the appetiser effect. Appetite 27:119–133PubMedCrossRefGoogle Scholar
  54. Yeomans MR (2000) Rating changes over the course of meals: what do they tell us about motivation to eat? Neurosci Biobehav Rev 24:249–259PubMedCrossRefGoogle Scholar
  55. Young AW, Rowland D, Calder AJ, Etcoff NL, Seth A, Perrett DI (1997) Facial expression megamix: tests of dimensional and category accounts of emotion recognition. Cognition 63:271–313PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • J. M. Thomas
    • 1
  • C. T. Dourish
    • 2
  • J. W. Tomlinson
    • 3
  • Z. Hassan-Smith
    • 3
  • S. Higgs
    • 1
  1. 1.School of PsychologyUniversity of BirminghamBirminghamUK
  2. 2.P1vitalWallingfordUK
  3. 3.Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental MedicineUniversity of BirminghamBirminghamUK

Personalised recommendations