PTSD

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Introduction

Posttraumatic stress disorder is considered a mental disorder caused after traumatic experiences like traffic accidents, violent circumstances, rape, warfare, etc. Typical symptoms include Anxiety, nightmares, flashbacks and trauma-related cues. cannabinoids could help to reduce PTSD-related symptoms and treat PTSD disease by recoding emotional memories in the brain.

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Post Traumatic Stress Disorder

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Prescription Advice

Clinical research has indicated THC and CBD may be beneficial in the treatment of PTSD.

Given the nature of the disorder, oral or sublingual application may be beneficial but smoking/inhalation also might help.

For inhalation, use until the symptoms subside or side-effects become intolerable.

For oral/sublingual application, please follow generic prescription advice.

Please note that, while based on preclinical and/or clinical research, this prescription advice is solely intended as a guideline to help physicians determine the right prescription. We intend to continuously update our prescription advice based on patient and/or expert feedback. If you have information that this prescription advice is inaccurate, incomplete or outdated please contact us here.

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Literature Discussion

The Endocannabinoid system has been shown to be implicated in the extinction and consolidation of aversive memories (Chhatwal, Davis, Maguschak, & Ressler, 2005; Marsicano et al., 2002; Pamplona, Bitencourt, & Takahashi, 2008; Shoshan & Akirav, 2017)

2-AG in the amygdala modulates stress resilience, which can modulate the response to trauma (Bluett et al., 2017)

Patients with PTSD have shown changes in plasma concentrations of endocannabinoids as well as increased CB1 receptors (Hauer et al., 2013; Hill et al., 2013; Neumeister et al., 2013)

Due to the emotional modulation properties of the Endocannabinoid system, it has been proposed as a target to treat PTSD (Trezza & Campolongo, 2013).

In fact, Pinna (2018), suggested that endocannabinoids as 2-AG, AEA, PEA and OEA could be helpful to find biomarkers for PTSD, acting mainly in PPAR-α.

PTSD has been linked to cannabis use, which could be used as a coping strategy for PTSD (Bonn-Miller, Babson, Vujanovic, & Feldner, 2010; Bonn-Miller, Vujanovic, Feldner, Bernstein, & Zvolensky, 2007; Bujarski et al., 2012; Cougle, Bonn-Miller, Vujanovic, Zvolensky, & Hawkins, 2011; Kevorkian et al., 2015)

Several studies shown that CBD, as well as THC and synthetic cannabinoids, facilitates extinction of fear memories in rats (Bitencourt, Pamplona, & Takahashi, 2008; Campos, Ferreira, & Guimarães, 2012; Do Monte, Souza, Bitencourt, Kroon, & Takahashi, 2013; Lemos, Resstel, & Guimarães, 2010; Levin et al., 2012; Morena et al., 2018; Resstel, Joca, Moreira, Corrêa, & Guimarães, 2006; Stern et al., 2015)

The effects of cannabinoids on fear extinction would be related to CB1 and 5HT1A receptors (Campos et al., 2012; de Oliveira Alvares, Pasqualini Genro, Diehl, Molina, & Quillfeldt, 2008; Levin et al., 2012; Lin, Mao, Su, & Gean, 2009; Simone, Green, Hodges, & McCormick, 2015)

CBD shows an effect on sleep processes, which could be helpful when targeting sleep disorders related to PTSD (Chagas et al., 2013; Hsiao, Yi, Li, & Chang, 2012)

The effects of CBD in fear memories extinction have been also proved in humans (Das et al., 2013)

The FAAH inhibitor URB597 showed improvement of PTSD related symptoms in rats, which confirms also the link between the Endocannabinoid system and PTSD (Fidelman, Mizrachi Zer-Aviv, Lange, Hillard, & Akirav, 2018)

In a pilot study, THC reduced PTSD-related nightmares and other symptoms severity in PTSD patients (Roitman, Mechoulam, Cooper-Kazaz, & Shalev, 2014)

Also, CBD reduced PTSD-related symptoms as Anxiety and sleep disorders in a case study of a child who was sexually abused (Shannon & Opila-Lehman, 2016).

In another case report, cannabis use reduced also PTSD-related symptoms as flashbacks and panic attacks (Passie, Emrich, Karst, Brandt, & Halpern, 2012)

In a retrospective study of 80 patients with PTSD, cannabis reduced PTSD-related symptoms (Greer, Grob, & Halberstadt, 2014)

Also, military veterans with PTSD reported that cannabinoids help them to manage PTSD symptoms (Betthauser, Pilz, & Vollmer, 2015)

For a detailed review on the topic see Bitencourt & Takahashi (2018)

References

Betthauser, K., Pilz, J., & Vollmer, L. E. (2015). Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharmacists, 72(15), 1279–1284. https://doi.org/10.2146/ajhp140523

Bitencourt, R. M., Pamplona, F. A., & Takahashi, R. N. (2008). Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 18(12), 849–859. https://doi.org/10.1016/j.euroneuro.2008.07.001

Bitencourt, R. M., & Takahashi, R. N. (2018). Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials. Frontiers in Neuroscience, 12, 502. https://doi.org/10.3389/fnins.2018.00502

Bluett, R. J., Báldi, R., Haymer, A., Gaulden, A. D., Hartley, N. D., Parrish, W. P., … Patel, S. (2017). Endocannabinoid signalling modulates susceptibility to traumatic stress exposure. Nature Communications, 8, 14782. https://doi.org/10.1038/ncomms14782

Bonn-Miller, M. O., Babson, K. A., Vujanovic, A. A., & Feldner, M. T. (2010). Sleep Problems and PTSD Symptoms Interact to Predict Marijuana Use Coping Motives: A Preliminary Investigation. Journal of Dual Diagnosis, 6(2), 111–122. https://doi.org/10.1080/15504261003751887

Bonn-Miller, M. O., Vujanovic, A. A., Feldner, M. T., Bernstein, A., & Zvolensky, M. J. (2007). Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users. Journal of Traumatic Stress, 20(4), 577–586. https://doi.org/10.1002/jts.20243

Bujarski, S. J., Feldner, M. T., Lewis, S. F., Babson, K. A., Trainor, C. D., Leen-Feldner, E., … Bonn-Miller, M. O. (2012). Marijuana use among traumatic event-exposed adolescents: posttraumatic stress symptom frequency predicts coping motivations for use. Addictive Behaviors, 37(1), 53–59. https://doi.org/10.1016/j.addbeh.2011.08.009

Campos, A. C., Ferreira, F. R., & Guimarães, F. S. (2012). Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. Journal of Psychiatric Research, 46(11), 1501–1510. https://doi.org/10.1016/j.jpsychires.2012.08.012

Chagas, M. H. N., Crippa, J. A. S., Zuardi, A. W., Hallak, J. E. C., Machado-de-Sousa, J. P., Hirotsu, C., … Andersen, M. L. (2013). Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. Journal of Psychopharmacology (Oxford, England), 27(3), 312–316. https://doi.org/10.1177/0269881112474524

Chhatwal, J. P., Davis, M., Maguschak, K. A., & Ressler, K. J. (2005). Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 30(3), 516–524. https://doi.org/10.1038/sj.npp.1300655

Cougle, J. R., Bonn-Miller, M. O., Vujanovic, A. A., Zvolensky, M. J., & Hawkins, K. A. (2011). Posttraumatic stress disorder and cannabis use in a nationally representative sample. Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors, 25(3), 554–558. https://doi.org/10.1037/a0023076

Das, R. K., Kamboj, S. K., Ramadas, M., Yogan, K., Gupta, V., Redman, E., … Morgan, C. J. A. (2013). Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology, 226(4), 781–792. https://doi.org/10.1007/s00213-012-2955-y

de Oliveira Alvares, L., Pasqualini Genro, B., Diehl, F., Molina, V. A., & Quillfeldt, J. A. (2008). Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction. Neuroscience, 154(4), 1648–1655. https://doi.org/10.1016/j.neuroscience.2008.05.005

Do Monte, F. H., Souza, R. R., Bitencourt, R. M., Kroon, J. A., & Takahashi, R. N. (2013). Infusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors. Behavioural Brain Research, 250, 23–27. https://doi.org/10.1016/j.bbr.2013.04.045

Fidelman, S., Mizrachi Zer-Aviv, T., Lange, R., Hillard, C. J., & Akirav, I. (2018). Chronic treatment with URB597 ameliorates post-stress symptoms in a rat model of PTSD. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 28(5), 630–642. https://doi.org/10.1016/j.euroneuro.2018.02.004

Greer, G. R., Grob, C. S., & Halberstadt, A. L. (2014). PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program. Journal of Psychoactive Drugs, 46(1), 73–77. https://doi.org/10.1080/02791072.2013.873843

Hauer, D., Schelling, G., Gola, H., Campolongo, P., Morath, J., Roozendaal, B., … Kolassa, I.-T. (2013). Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder. PloS One, 8(5), e62741. https://doi.org/10.1371/journal.pone.0062741

Hill, M. N., Bierer, L. M., Makotkine, I., Golier, J. A., Galea, S., McEwen, B. S., … Yehuda, R. (2013). Reductions in circulating Endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology, 38(12), 2952–2961. https://doi.org/10.1016/j.psyneuen.2013.08.004

Hsiao, Y.-T., Yi, P.-L., Li, C.-L., & Chang, F.-C. (2012). Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology, 62(1), 373–384. https://doi.org/10.1016/j.neuropharm.2011.08.013

Kevorkian, S., Bonn-Miller, M. O., Belendiuk, K., Carney, D. M., Roberson-Nay, R., & Berenz, E. C. (2015). Associations among trauma, posttraumatic stress disorder, cannabis use, and cannabis use disorder in a nationally representative epidemiologic sample. Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors, 29(3), 633–638. https://doi.org/10.1037/adb0000110

Lemos, J. I., Resstel, L. B., & Guimarães, F. S. (2010). Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behavioural Brain Research, 207(1), 105–111. https://doi.org/10.1016/j.bbr.2009.09.045

Levin, R., Almeida, V., Peres, F. F., Calzavara, M. B., da Silva, N. D., Suiama, M. A., … Abílio, V. C. (2012). Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in Schizophrenia. Current Pharmaceutical Design, 18(32), 4960–4965.

Lin, H.-C., Mao, S.-C., Su, C.-L., & Gean, P.-W. (2009). The role of prefrontal cortex CB1 receptors in the modulation of fear memory. Cerebral Cortex (New York, N.Y.: 1991), 19(1), 165–175. https://doi.org/10.1093/cercor/bhn075

Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., … Lutz, B. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418(6897), 530–534. https://doi.org/10.1038/nature00839

Morena, M., Berardi, A., Colucci, P., Palmery, M., Trezza, V., Hill, M. N., & Campolongo, P. (2018). Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats. Neuropsychopharmacology, 43(6), 1284–1296. https://doi.org/10.1038/npp.2017.305

Neumeister, A., Normandin, M. D., Pietrzak, R. H., Piomelli, D., Zheng, M. Q., Gujarro-Anton, A., … Huang, Y. (2013). Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry, 18(9), 1034–1040. https://doi.org/10.1038/mp.2013.61

Pamplona, F. A., Bitencourt, R. M., & Takahashi, R. N. (2008). Short- and long-term effects of cannabinoids on the extinction of contextual fear memory in rats. Neurobiology of Learning and Memory, 90(1), 290–293. https://doi.org/10.1016/j.nlm.2008.04.003

Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012). Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Testing and Analysis, 4(7–8), 649–659. https://doi.org/10.1002/dta.1377

Pinna, G. (2018). Biomarkers for PTSD at the Interface of the Endocannabinoid and Neurosteroid Axis. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.00482

Resstel, L. B. M., Joca, S. R. L., Moreira, F. A., Corrêa, F. M. A., & Guimarães, F. S. (2006). Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behavioural Brain Research, 172(2), 294–298. https://doi.org/10.1016/j.bbr.2006.05.016

Roitman, P., Mechoulam, R., Cooper-Kazaz, R., & Shalev, A. (2014). Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clinical Drug Investigation, 34(8), 587–591. https://doi.org/10.1007/s40261-014-0212-3

Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente Journal, 20(4), 108–111. https://doi.org/10.7812/TPP/16-005

Shoshan, N., & Akirav, I. (2017). The effects of cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala and hippocampus on the consolidation of a traumatic event. Neurobiology of Learning and Memory, 144, 248–258. https://doi.org/10.1016/j.nlm.2017.08.004

Simone, J. J., Green, M. R., Hodges, T. E., & McCormick, C. M. (2015). Differential effects of CB1 receptor agonism in behavioural tests of unconditioned and conditioned fear in adult male rats. Behavioural Brain Research, 279, 9–16. https://doi.org/10.1016/j.bbr.2014.11.012

Stern, C. A. J., Gazarini, L., Vanvossen, A. C., Zuardi, A. W., Galve-Roperh, I., Guimaraes, F. S., … Bertoglio, L. J. (2015). Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 25(6), 958–965. https://doi.org/10.1016/j.euroneuro.2015.02.001

Trezza, V., & Campolongo, P. (2013). The Endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Frontiers in Behavioral Neuroscience, 7, 100. https://doi.org/10.3389/fnbeh.2013.00100

Clinical Trials

CBD and THC were found to speed up/enhance fear extinction which should help prevent the development of PTSD (Das et al., 2013; Rabinak et al., 2013). In one open clinical trial the use of cannabis was found to provide significant relief of PTSD symptoms in most patients.

http://www.cannabis-med.org/studies/ww_en_db_study_show.php?s_id=481&&search_pattern=posttraumatic

More (controlled) clinical trials are required.

Literature:

Das, R.K., Kamboj, S.K., Ramadas, M., Yogan, K., Gupta, V., Redman, E., Curran, H.V., and Morgan, C.J.A. (2013). Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl.) 226, 781–792.

Rabinak, C.A., Angstadt, M., Sripada, C.S., Abelson, J.L., Liberzon, I., Milad, M.R., and Phan, K.L. (2013). cannabinoid facilitation of fear extinction memory recall in humans. Neuropharmacology 64, 396–402.