Top

Clinical Drug Investigation

Published in:

01-08-2014 | Short Communication

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

Authors: Pablo Roitman, Raphael Mechoulam, Rena Cooper-Kazaz, Arieh Shalev

Published in: Clinical Drug Investigation | Issue 8/2014

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.

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

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.PubMedCrossRef

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

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.PubMedCrossRef

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

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.CrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

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.PubMedCentralPubMedCrossRef

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.

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.PubMedCrossRef

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.PubMedCrossRef

17.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

22.

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

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.CrossRef

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.PubMedCrossRef

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.PubMed

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.CrossRef

27.

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

Title: Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder
Authors: Pablo Roitman
Raphael Mechoulam
Rena Cooper-Kazaz
Arieh Shalev
Publication date: 01-08-2014
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 8/2014
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.1007/s40261-014-0212-3

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background and Objectives

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2014

Pharmacokinetic Interaction Study of Ticagrelor and Cyclosporine in Healthy Volunteers

Biological Drugs for the Treatment of Moderate-to-Severe Psoriasis by Subcutaneous Route: Determining Statistical Equivalence According to Evidence-Based Methods

Investigation of the Effect of Macitentan on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects

Evaluation of Blood Pressure and Heart Rate in Patients with Hypertension Who Received Tapentadol Extended Release for Chronic Pain: A Post Hoc, Pooled Data Analysis

Long-Term Inhaled Granulocyte Macrophage–Colony-Stimulating Factor in Autoimmune Pulmonary Alveolar Proteinosis: Effectiveness, Safety, and Lowest Effective Dose

Negative Clinical Results from a Randomised, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy of Two Doses of Immunologically Enhanced, Grass Subcutaneous Immunotherapy Despite Dose-Dependent Immunological Response