Clinical Efficacy of Cannabinoids in PTSD Management: A Systematic  Review Overcoming Limitations of Prior Evidence

Santosh Ramesh  Achwani; Ramya  Rachamanti; Sumana  Sen; Abida  Khan; Ashwin Kumar A; V S S S Gupta  Atyam; Rajkumar Krishnan  Vasanthi; Sovan Bagchi

Authors

Santosh Ramesh Achwani Department of Family Medicine, Al Bateen Health care Center, Abu Dhabi Health Services Company, United Arab Emirates https://orcid.org/0009-0006-9271-2460
Ramya Rachamanti Department of Pharmacology, Guntur Medical College, Guntur Andhra Pradesh, India https://orcid.org/0000-0002-8927-8679
Sumana Sen Department of Pharmacology, Apollo institute of medical sciences and research, Hyderabad-96, India https://orcid.org/0000-0003-2640-5877
Abida Khan Center for Health Research, Northern Border University, Arar, Saudi Arabia https://orcid.org/0000-0001-5261-4010
Ashwin Kumar A Department of Radiology, Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education and Research, Chennai, India https://orcid.org/0000-0001-5640-2656
V S S S Gupta Atyam 6Department of Pharmacology, Joginpally B.R. Pharmacy College, Hyderabad, India https://orcid.org/0000-0003-1811-6733
Rajkumar Krishnan Vasanthi 7Faculty of Health and Life Sciences, INTI International University, Nilai, Negeri Sembilan, Malaysia https://orcid.org/0000-0001-6866-8224
Sovan Bagchi Department of Biomedical Sciences, College of Medicine, Gulf Medical University, United Arab Emirates https://orcid.org/0000-0003-3507-1944

Keywords:

post-traumatic stress disorder, cannabinoids, medical cannabis, Systematic Review, psychiatric treatment

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition that affects the entire population, with a higher prevalence among military veterans. It is characterized by the re-experiencing of traumatic events, the avoidance of trauma-related stimuli, and persistent hyperarousal. PTSD is widely regarded as a disorder marked by impaired memory processing. Current therapy mostly comprises trauma-focused psychotherapies and pharmacological agents, including selective serotonin reuptake inhibitors (SSRIs) and monoamine receptor antagonists. However, currently access to specialized therapies is constrained, and pharmaceutical results remain inadequate, highlighting the necessity for innovative therapeutic approaches. Cannabinoids have surfaced as prospective therapy alternatives; however, previous reviews have been limited by restrictive inclusion criteria, a narrow range of cannabinoids, inconsistent outcome assessments, and inadequate examination of new evidence. The potential health risk associated with cannabinoid use stresses the importance of a cautious, evidence-based approach. The rapidly changing legal and regulatory landscape of cannabinoids requires a revised synthesis of contemporary studies. This systematic review assesses clinical trials examining cannabis utilization in PTSD. A thorough search strategy was implemented across primary databases, followed by study selection according to established inclusion and exclusion criteria. The risk of bias and methodological quality were evaluated utilizing validated instruments. Data were meticulously gathered and synthesized across many parameters: trial design, demographic characteristics, PTSD diagnosis techniques, cannabis type and treatment duration, outcome measures, adverse events, and study constraints. This review rectifies previous deficiencies by integrating a comprehensive evidence base, encompassing both synthetic and plant-derived cannabinoids, and standardizing data assessment. It offers a contemporary, evidence-based summary to enhance clinical practice and to direct future research in the management of PTSD with cannabinoids.

References

Riaz K, Suneel S, Hamza Bin Abdul Malik M, Kashif T, Ullah I, Waris A et al. MDMA-based psychotherapy in treatment-resistant post-traumatic stress disorder (PTSD): A brief narrative overview of current evidence. Diseases. 2023;11(4):159. PubMed PMID: 37987270

Forsythe ML, Boileau AJ. Use of cannabinoids for the treatment of patients with post-traumatic stress disorder. J Basic Clin Physiol Pharmacol. 2022;33:121-32.

Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16:9-29.

Maia J, Fonseca BM, Teixeira N, Correia-da-Silva G. The endocannabinoids anandamide and 2-arachidonoylglycerol modulate the expression of angiogenic factors on HTR8/SVneo placental cells. Prostaglandins Leukot Essent Fatty Acids. 2022;180:102440. PubMed PMID: 35490598.

Zamarripa CA, Spindle TR, Surujunarain R, Weerts EM, Bansal S, Unadkat JD et al. Assessment of orally administered Δ9-tetrahydrocannabinol when coadministered with cannabidiol on Δ9-tetrahydrocannabinol pharmacokinetics and pharmacodynamics in healthy adults: A randomized clinical trial. JAMA Netw Open. 2023;6: e2254752. PubMed PMID: 36780161

Ricci V, Martinotti G, Ceci F, Chiappini S, Di Carlo F, Burkauskas J et al. Duration of untreated disorder and cannabis use: an observational study on a cohort of young Italian patients experiencing psychotic experiences and dissociative symptoms. Int J Environ Res Public Health. 2021;18(23):12632. PubMed PMID: 34886357

Rabinak CA, Blanchette A, Zabik NL, Peters C, Marusak HA, Iadipaolo A, Elrahal F. Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology (Berl). 2020; 237:1813-26.

Bonn-Miller MO, Brunstetter M, Simonian A, Loflin MJ, Vandrey R, Babson KA, Wortzel H. The long-term, prospective, therapeutic impact of cannabis on post-traumatic stress disorder. Cannabis Cannabinoid Res. 2020;7;214-23.

LaFrance EM, Glodosky NC, Bonn-Miller M, Cuttler C. Short and long-term effects of cannabis on symptoms of post-traumatic stress disorder. J Affect Disord. 2020; 274:298-304.

Colin Cameron MD, Watson D, Robinson J. Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications. J Clin Psychopharmacol. 2014;34:559-64.

Elms L, Shannon S, Hughes S, Lewis N. Cannabidiol in the treatment of post-traumatic stress disorder: a case series. J Altern Complement Med. 2019;25:392-7.