Dronabinol in Trichotillomania and Other Body Focused Repetitive Behaviors

Summary

The goal of the proposed study is to evaluate the efficacy and safety of dronabinol in trichotillomania and other body-focused repetitive behaviors such as skin-picking disorder. 50 subjects with DSM-5 trichotillomania or skin-picking disorder will receive 10 weeks of double-blind dronabinol or placebo. The hypothesis to be tested is that dronabinol will be effective and well tolerated in patients with trichotillomania and/or skin-picking disorder compared to placebo. The proposed study will provide needed data on the treatment of disabling disorders that currently lacks a clearly effective treatment.

Timeline

Start

2018-10-01

Primary completion

2021-07-20

Completion

2021-11-01

Publications

• Background Woods DW, Flessner CA, Franklin ME, Keuthen NJ, Goodwin RD, Stein DJ, Walther MR; Trichotillomania Learning Center-Scientific Advisory Board. The Trichotillomania Impact Project (TIP): exploring phenomenology, functional impairment, and treatment utilization. J Clin Psychiatry. 2006 Dec;67(12):1877-88. doi: 10.4088/jcp.v67n1207.
• Background Bloch MH, Landeros-Weisenberger A, Dombrowski P, Kelmendi B, Wegner R, Nudel J, Pittenger C, Leckman JF, Coric V. Systematic review: pharmacological and behavioral treatment for trichotillomania. Biol Psychiatry. 2007 Oct 15;62(8):839-46. doi: 10.1016/j.biopsych.2007.05.019. Epub 2007 Aug 28.
• Background Grant JE, Odlaug BL, Chamberlain SR, Kim SW. Dronabinol, a cannabinoid agonist, reduces hair pulling in trichotillomania: a pilot study. Psychopharmacology (Berl). 2011 Dec;218(3):493-502. doi: 10.1007/s00213-011-2347-8. Epub 2011 May 19.
• Background Chamberlain SR, Hampshire A, Menzies LA, Garyfallidis E, Grant JE, Odlaug BL, Craig K, Fineberg N, Sahakian BJ. Reduced brain white matter integrity in trichotillomania: a diffusion tensor imaging study. Arch Gen Psychiatry. 2010 Sep;67(9):965-71. doi: 10.1001/archgenpsychiatry.2010.109.
• Background Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6. doi: 10.1073/pnas.87.5.1932.
• Background Glass M, Felder CC. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci. 1997 Jul 15;17(14):5327-33. doi: 10.1523/JNEUROSCI.17-14-05327.1997.
• Background Gerdeman GL, Ronesi J, Lovinger DM. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci. 2002 May;5(5):446-51. doi: 10.1038/nn832.
• Background Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science. 2003 Oct 3;302(5642):84-8. doi: 10.1126/science.1088208.
• Background Khaspekov LG, Brenz Verca MS, Frumkina LE, Hermann H, Marsicano G, Lutz B. Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. Eur J Neurosci. 2004 Apr;19(7):1691-8. doi: 10.1111/j.1460-9568.2004.03285.x.
• Background De Chiara V, Angelucci F, Rossi S, Musella A, Cavasinni F, Cantarella C, Mataluni G, Sacchetti L, Napolitano F, Castelli M, Caltagirone C, Bernardi G, Maccarrone M, Usiello A, Centonze D. Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum. J Neurosci. 2010 Jun 16;30(24):8127-37. doi: 10.1523/JNEUROSCI.1683-10.2010.
• Background van der Stelt M, Di Marzo V. Cannabinoid receptors and their role in neuroprotection. Neuromolecular Med. 2005;7(1-2):37-50. doi: 10.1385/NMM:7:1-2:037.
• Background Rossi S, De Chiara V, Musella A, Kusayanagi H, Mataluni G, Bernardi G, Usiello A, Centonze D. Chronic psychoemotional stress impairs cannabinoid-receptor-mediated control of GABA transmission in the striatum. J Neurosci. 2008 Jul 16;28(29):7284-92. doi: 10.1523/JNEUROSCI.5346-07.2008.
• Background Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009 Jul;66(7):756-63. doi: 10.1001/archgenpsychiatry.2009.60.
• Background Bienvenu OJ, Wang Y, Shugart YY, Welch JM, Grados MA, Fyer AJ, Rauch SL, McCracken JT, Rasmussen SA, Murphy DL, Cullen B, Valle D, Hoehn-Saric R, Greenberg BD, Pinto A, Knowles JA, Piacentini J, Pauls DL, Liang KY, Willour VL, Riddle M, Samuels JF, Feng G, Nestadt G. Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):710-20. doi: 10.1002/ajmg.b.30897.
• Background Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage. 1995 Feb;10(2):89-97. doi: 10.1016/0885-3924(94)00117-4.
• Background Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, Morales JO, Murphy R, Powderly W, Plasse TF, Mosdell KW, Shepard KV. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage. 1997 Jul;14(1):7-14. doi: 10.1016/S0885-3924(97)00038-9.
• Background Swedo SE, Leonard HL, Rapoport JL, Lenane MC, Goldberger EL, Cheslow DL. A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling). N Engl J Med. 1989 Aug 24;321(8):497-501. doi: 10.1056/NEJM198908243210803.
• Background Keuthen NJ, O'Sullivan RL, Ricciardi JN, Shera D, Savage CR, Borgmann AS, Jenike MA, Baer L. The Massachusetts General Hospital (MGH) Hairpulling Scale: 1. development and factor analyses. Psychother Psychosom. 1995;64(3-4):141-5. doi: 10.1159/000289003.
• Background Grant JE, Chamberlain SR. Clinical correlates of symptom severity in skin picking disorder. Compr Psychiatry. 2017 Oct;78:25-30. doi: 10.1016/j.comppsych.2017.07.001. Epub 2017 Jul 8.
• Grant JE, Valle S, Chesivoir E, Ehsan D. Tetrahydrocannabinol fails to reduce hair pulling or skin picking: results of a double-blind, placebo-controlled study of dronabinol. Int Clin Psychopharmacol. 2022 Jan 1;37(1):14-20. doi: 10.1097/YIC.0000000000000382.
• Hoffman J, Williams T, Rothbart R, Ipser JC, Fineberg N, Chamberlain SR, Stein DJ. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD007662. doi: 10.1002/14651858.CD007662.pub3.

Drugs

Indications