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Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder

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Abstract

Background and Objectives

Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ9-tetrahydrocannabinol (THC) for chronic PTSD.

Methods

Ten outpatients with chronic PTSD, on stable medication, received 5 mg of Δ9-THC twice a day as add-on treatment.

Results

There were mild adverse effects in three patients, none of which led to treatment discontinuation. The intervention caused a statistically significant improvement in global symptom severity, sleep quality, frequency of nightmares, and PTSD hyperarousal symptoms.

Conclusions

Orally absorbable Δ9-THC was safe and well tolerated by patients with chronic PTSD.

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References

  1. Stein DJ, Ipser J, McAnda N. Pharmacotherapy of posttraumatic stress disorder: a review of meta-analyses and treatment guidelines. CNS Spectr. 2009;14(1 Suppl 1):25–31.

    PubMed  Google Scholar 

  2. Bonn-Miller MO, Vujanovic AA, Drescher KD. Cannabis use among military veterans after residential treatment for posttraumatic stress disorder. Psychol Addict Behav. 2011;25(3):485–91.

    Article  PubMed  Google Scholar 

  3. Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58(3):389–462.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Passie T, Emrich HM, Karst M, Brandt SD, Halpern JH. Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Test Anal. 2012;4(7–8):649–59.

    Article  CAS  PubMed  Google Scholar 

  5. Pierre JM. Psychosis associated with medical marijuana: risk vs. benefits of medicinal cannabis use. Am J Psychiatry. 2010;167(5):598–9.

    Article  PubMed  Google Scholar 

  6. Musty RE, Rossi R. Effects of smoked Cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. J Cannabis Therapy. 2001;1:30.

    Article  Google Scholar 

  7. Crippa JA, Zuardi AW, Martin-Santos R, Bhattacharyya S, Atakan Z, McGuire P, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol. 2009;24(7):515–23.

    Article  CAS  PubMed  Google Scholar 

  8. Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, et al. Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep. J Acquir Immune Defic Syndr. 2007;45(5):545–54.

    Article  CAS  PubMed  Google Scholar 

  9. Fraser GA. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci Ther. 2009;15(1):84–8.

    Article  PubMed  Google Scholar 

  10. Greer GR, Grob CS, Halberstadt AL. PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program. J Psychoact Drugs. 2014;46(1):73–7.

    Article  Google Scholar 

  11. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418(6897):530–4.

    Article  CAS  PubMed  Google Scholar 

  12. Rabinak CA, Angstadt M, Sripada CS, Abelson JL, Liberzon I, Milad MR, et al. Cannabinoid facilitation of fear extinction memory recall in humans. Neuropharmacology. 2013;64:396–402.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, et al. Elevated brain cannabinoid CB receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry. 2013;18(9):6.

    Google Scholar 

  14. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, et al. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995;8(1):75–90.

    Article  CAS  PubMed  Google Scholar 

  15. Guy GW. The Clinical Global Impression Scale. In: ECDEU assessment manual for psychopharmacology–revised. Bethesda; US Department of Health, Education and Welfare; 1976: pp 218–222.

  16. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.

    Article  CAS  PubMed  Google Scholar 

  17. Krakow B. Nightmare frequency in sexual assault survivors with PTSD. J Anxiety Disord. 2002;16(2):175–90.

    Article  PubMed  Google Scholar 

  18. Krakow B, Hollifield M, Schrader R, Koss M, Tandberg D, Lauriello J, et al. A controlled study of imagery rehearsal for chronic nightmares in sexual assault survivors with PTSD: a preliminary report. J Trauma Stress. 2000;13(4):589–609.

    Article  CAS  PubMed  Google Scholar 

  19. Guy GW. A phase 1, double blind, three-way crossover study to assess the pharmacokinetic profile of cannabis based medicine extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers. J Cannabis Ther 2003;3:31.

  20. Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006;15(5):349–53.

    Article  PubMed  Google Scholar 

  21. Haroutiunian S, Rosen G, Shouval R, Davidson E. Open-label, add-on study of tetrahydrocannabinol for chronic nonmalignant pain. J Pain Palliat Care Pharmacother. 2008;22(3):213–7.

    Article  PubMed  Google Scholar 

  22. Grotenhermen F, Muller-Vahl K. The therapeutic potential of cannabis and cannabinoids. Deutsches Arzteblatt Int. 2012;109(29–30):495–501.

    Google Scholar 

  23. Bonn-Miller MO, Babson KA, Vandrey R. Using cannabis to help you sleep: heightened frequency of medical cannabis use among those with PTSD. Drug Alcohol Depend. 2014;1(136):162–5.

    Article  Google Scholar 

  24. Schierenbeck T, Riemann D, Berger M, Hornyak M. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med Rev. 2008;12(5):381–9.

    Article  PubMed  Google Scholar 

  25. Bremner JD, Southwick SM, Darnell A, Charney DS. Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. Am J Psychiatry. 1996;153(3):369–75.

    CAS  PubMed  Google Scholar 

  26. Ursano RJ, Zhang L, Li H, Johnson L, Carlton J, Fullerton CS, et al. PTSD and traumatic stress from gene to community and bench to bedside. Brain Res. 2009;26(1293):2–12.

    Article  Google Scholar 

  27. Ashton CH, Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand. 2011;124(4):250–61.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Raphael Mechoulam has consulted to GW Pharmaceuticals, UK.

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Authors and Affiliations

  1. Department of Psychiatry, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Pablo Roitman & Arieh Shalev

  2. Institute for Drug Research, Hebrew University School of Pharmacy, Jerusalem, Israel

    Raphael Mechoulam

  3. Psychiatry Department, Clalit Health Services, Jerusalem, Israel

    Rena Cooper-Kazaz

  4. Department of Psychiatry, Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury, New York University Langone Medical Center, New York, NY, USA

    Arieh Shalev

  5. Ha Zait st. 259, Moshav Mata, 99870, Mate Yehuda, Israel

    Pablo Roitman

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  1. Pablo Roitman
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  2. Raphael Mechoulam
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  3. Rena Cooper-Kazaz
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  4. Arieh Shalev
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Correspondence to Pablo Roitman.

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Roitman, P., Mechoulam, R., Cooper-Kazaz, R. et al. Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder. Clin Drug Investig 34, 587–591 (2014). https://doi.org/10.1007/s40261-014-0212-3

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  • DOI: https://doi.org/10.1007/s40261-014-0212-3

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