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Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series 1 Rocky Vista University, Osteopathic Medical Student IV, Parker, CO. Scott Shannon 2 Department of Psychiatry, Your access to this site has been limited by the site owner If you think you have been blocked in error, contact the owner of this site for assistance. If you are a WordPress user with

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series

1 Rocky Vista University, Osteopathic Medical Student IV, Parker, CO.

Scott Shannon

2 Department of Psychiatry, University of Colorado Denver, Denver, CO.

Shannon Hughes

3 School of Social Work, Colorado State University College of Health and Human Sciences, Fort Collins, CO.

Nicole Lewis

4 Department of Naturopathic Medicine, Wholeness Center, Fort Collins, CO.

3 School of Social Work, Colorado State University College of Health and Human Sciences, Fort Collins, CO.

Address correspondence to: Scott Shannon, MD, FAACAP, 2620 East Prospect Road, #190, Fort Collins, CO 80525 [email protected]

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

Abstract

Objectives: Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.

Methods: This retrospective case series examines the effect of oral CBD administration on symptoms of PTSD in a series of 11 adult patients at an outpatient psychiatry clinic. CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional. Patients also received routine psychiatric care, including concurrent treatment with psychiatric medications and psychotherapy. The length of the study was 8 weeks. PTSD symptom severity was assessed every 4 weeks by patient-completed PTSD Checklist for the DSM-5 (PCL-5) questionnaires.

Results: From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.

Conclusions: Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.

Introduction

P ost-traumatic stress disorder (PTSD) is a relatively common psychiatric condition with a lifetime prevalence of 6.1% in the United States. 1 PTSD often presents in clusters of symptoms, including the re-experiencing of traumatic events through intrusive memories and nightmares, avoidance of certain distressing factors, and alterations in mood, level of arousal, and cognition. Psychotherapy is the established first-line treatment for PTSD, and various psychiatric medications are also typically employed. The development of additional treatment agents is important because current medications, including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, antiadrenergic agents, and second-generation antipsychotics, have questionable efficacy and often carry significant undesirable side-effect profiles.

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Although the pathophysiology of PTSD has not yet been definitively described, a number of factors are suspected to contribute to the development of this disorder. One hypothesis relates PTSD to dysregulated memory retrieval through the process of reconsolidation and impaired extinction of aversive memories. 2 The endogenous cannabinoid system has been shown to play an important role in the process of aversive memory extinction through the activity of central CB1 receptors. 3 Two cannabinoid receptors are known to exist in the human body: CB1 and CB2 receptors. CB1 receptors are located mainly in the brain and modulate neurotransmitter release in a manner that prevents excessive neuronal activity, thus calming and decreasing anxiety. CB1 receptors also have a role in reducing pain, inflammation, regulating movement and posture control, and regulating sensory perception, memory, and cognitive function.

Cannabidiol (CBD) is known to have multiple physiologic mechanisms of action, including 5-HT1A serotonergic agonism, adenosine and opioid receptor modulation, activation of the endogenous endocannabinoid system, antagonism at GPR55 receptors, and activation of transient receptor potential channels. 4,5 CBD’s activity at 5-HT1A receptors may drive its neuroprotective, antidepressive, and anxiolytic benefits, although the mechanism of action by which CBD decreases anxiety is still unclear. 6 CBD was shown to be helpful for decreasing anxiety through a simulated public speaking test at doses of 300–600 mg in single-dose studies. 7–9 Other studies suggest that lower doses of 10 mg/kg have a more anxiolytic effect than higher doses of 100 mg/kg in rats. 10

Of particular interest to this study is the effect of CBD on the endogenous cannabinoid system. CBD has minimal affinity for CB1 and CB2 receptors, 11 but it does indirectly cause activation of CB1 receptors by increasing the availability of endogenous endocannabinoids. Anandamide is an endogenous cannabinoid that acts as a partial agonist at CB1 receptors. It is metabolically deactivated by the enzyme fatty acid amide hydrolase (FAAH). CBD has been shown in some studies to inhibit FAAH, thus increasing the availability of anandamide and causing activation of the endocannabinoid system. 12 Studies in rodent models have shown that pharmacologic activation of the endocannabinoid system through CB1-receptor agonist agents leads to decreased behavioral response to aversive memories in rodent models through the inhibition of memory reconsolidation and enhanced extinction. 13–15 This early research suggests that agents such as CBD that cause indirect activation of the endocannabinoid system may have utility in the treatment of PTSD.

Current evidence regarding the use of CBD for PTSD in humans is minimal. One case report showed that administration of 12–37 mg of oral CBD daily was associated with a reduction in anxiety symptoms and sleep disturbances in a 10-year-old patient with PTSD due to sexual trauma. 16 Another study showed that 32 mg of inhaled CBD resulted in consolidation of aversive memory extinction and attenuation of explicit fearful responding in healthy human subjects. 17 See Bittencourt and Takahashi 18 for a recent comprehensive review of pre-clinical and clinical studies regarding the relationship of CBD to PTSD. To date, no clinical trial evaluating the effectiveness of CBD in reducing symptoms of PTSD in humans has been completed.

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The hypothesis of this study was that patients with DSM-5-diagnosed PTSD who were administered CBD along with routine psychiatric care would show a decrease in PTSD-specific symptomatology. This hypothesis was based on prior rodent and limited human studies that suggest that (1) CBD may cause decreased response to and increased extinction of aversive memories, and that (2) CBD may have an anxiolytic effect, which, in turn, would have therapeutic value in patients with PTSD. To this end, we conducted a retrospective file review of adult patients with PTSD who were treated with CBD as part of standard psychiatric care in an outpatient clinic. The goal of this review was to examine the tolerability of CBD and its effectiveness in PTSD symptom reduction.

Materials and Methods

Design and procedures

This article describes a retrospective chart review of adult psychiatric patients with a diagnosis of PTSD who consented to treatment with CBD as augmentation to routine psychiatric treatment at an outpatient psychiatric clinic. All current patients with a diagnosis of PTSD were considered for treatment with CBD between February 2016 and May 2018. Patients were not excluded based on the presence of other psychiatric comorbidities (aside from an active thought disorder) or concurrent use of cannabis. The diagnosis of PTSD was established through clinical evaluation by a mental health professional (psychiatrist, psychiatric nurse practitioner, or physician assistant). Inclusion criteria for the present analysis required a cut-off score of 33 on the Post-Traumatic Stress Disorder Checklist for the DSM-5 (PCL-5) 19 and a minimum of two consecutive follow-up appointments after the initial intake appointment. The final sample consisted of 11 adult patients with a diagnosis of PTSD and who met inclusion criteria.

After the initial baseline assessment, PCL-5 assessments were completed by patients every 4 weeks to monitor changes in the severity of PTSD symptoms. In addition to CBD, patients also received routine treatment in the form of psychiatric medications, various psychotherapy modalities, and standard integrative treatments, as indicated for their diagnoses of PTSD and other psychiatric comorbidities. These integrative treatments often included dietary changes, herbal supplementation, neurofeedback, and intravenous infusions of vitamins and minerals.

Four patients received CBD as an oral capsule only. One patient only received CBD in the form of an oral liquid spray. Fifty-five percent (n = 6) of patients received both forms of CBD either concurrently or sequentially over the course of the study. The form of CBD (capsule vs. liquid spray) was determined by provider and patient preference. The CBD products used in this study were supplied by CV Sciences. Capsules were demonstrated by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) to contain 22–28 mg of CBD per capsule. Patients were instructed to take whole capsules, which were assumed to contain 25 mg of CBD for dosing purposes. Patients were instructed to take liquid CBD as a specified number of sprays from a spray bottle. The liquid product used in this article was demonstrated by HPLC-UV to contain between 425 and 575 mg of CBD in total per bottle, equating to about 1.5 mg of CBD per spray.

Patients were instructed to take CBD once or twice per day based on severity of symptoms. The median starting oral capsular dose was 25 mg per day (range: 25–100). The median dose of liquid CBD given throughout the study was 9 mg per day (range: 1–16). The mean total starting dose of CBD (liquid or capsular or both) was 33.18 mg (standard deviation [SD] = 23.34). The mean total dose of CBD prescribed at the 8-week follow-up appointment at the conclusion of the study period was 48.64 mg (range: 2–100). The dose of CBD was adjusted at each 4-week appointment based on the patient’s presentation and experience. Most patients received an increase in the dose of CBD because treatment was provided to maximize PTSD symptom reduction, which seemed to be directly correlated with dose. These doses are much lower than the doses used in the previous clinical literature for multiple reasons. The first is that lower doses appear to elicit an adequate clinical response in our experience. Second, the current retail cost of CBD would make the use of 600 mg per day cost-prohibitive. Finally, doses for the liquid spray route of administration are typically lower than that of capsules and are usually measured as single milligrams of CBD per spray, thus rendering higher doses impractical for patients relying on liquid CBD.

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Informed consent was obtained for each patient at their intake appointment. Appointments every 4 weeks included clinical evaluation and documentation of patients’ PTSD symptomatology through PCL-5 questionnaires. Concurrent psychiatric medications were held constant or changed according to routine clinical practice, whereas CBD was often intentionally used as a method of decreasing or avoiding the use of psychiatric medications. CBD was added to care, dropped from care, or refused as per individual patient and practitioner preference. The Western Institutional Review Board approved a retrospective analysis of the charts of patients with a diagnosis of PTSD who received CBD as part of their treatment program.

Setting

Wholeness Center is a large mental health clinic with a focus on integrative medicine and psychiatry. Practitioners from a range of disciplines (psychiatry, naturopathy, acupuncture, neurofeedback, yoga, etc.) work together in a collaborative and cross-disciplinary environment. Based on existing research and patient experience, CBD had been widely incorporated into clinical care a few years before this study.

Sample

Characteristics of the study sample are presented in Table 1 . The average age of the population in this study was 39.91 (range: 22–69, n = 11). The majority (73%, n = 8) of patients were female. On average, patients were concurrently taking three psychiatric medications, including antidepressants, mood stabilizers, anxiolytics, and stimulants. One patient used cannabis daily throughout the study. Overall, 73% (n = 8) of patients were concurrently receiving psychotherapy as part of their overall care. Patients had on average 1.8 comorbid psychiatric conditions in addition to their PTSD diagnosis, including anxiety, mood, personality, and sleep disorders.

Table 1.

Characteristics of the Patient Population and Concurrent Treatments Received

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