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Cbd oil for ptsd research

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.

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.

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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.

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

New Research Reveals Why Cannabis Helps PTSD Sufferers

Amy Rising, an Air Force veteran, smokes medical marijuana. Rising has been working on legislation . [+] for veterans’ freedom to treat PTSD with medical cannabis. (Photo by Kevin Cook for The Washington Post via Getty Images)

The Washington Post via Getty Images

PTSD patients have been saying for years that cannabis helps with their PTSD. This debilitating condition causes chronic problems like nightmares, panic attacks, hypervigilance, detachment from others, overwhelming emotions, and self-destructive behavior. In some cases, these overwhelming symptoms can even lead to suicide. And while research on the topic has been somewhat inconclusive, many PTSD patients continue to report that cannabis does help.

Now, new research suggests the biological mechanisms behind this therapeutic effect.

Two recent studies point to the way that cannabinoids may help treat PTSD. One shows how cannabis can reduce activity in the amygdala – a part of the brain associated with fear responses to threats. Meanwhile, another suggests that the plant’s cannabinoids could play a role in extinguishing traumatic memories. Both effects could be therapeutic for those suffering from PTSD – according to recent studies.

One study, from researchers at Wayne State University in Detroit, MI, looked at how cannabis use impacts the amygdala response of those dealing with trauma related anxiety, such as PTSD. Previous research has shown that cannabis has the potential to reduce anxiety, or even prevent heightened anxiety in threatening situations. But up to this point, no studies had investigated this response in adults dealing with trauma – such as those with PTSD.

The Wayne State University study took on this challenge, and studied the amygdala responses in three groups of participants – healthy controls who had not been exposed to trauma, trauma exposed adults without PTSD and trauma exposed adults with PTSD. Using a randomized, double-blind procedure, the 71 participants were either given a low dose of THC or a placebo. Then they were exposed to threatening stimuli and their amygdala responses were recorded.

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Those exposed to THC had lowered threat-related amygdala reactivity.

This means that those who took low doses of THC showed measurable signs of reduced fear and anxiety in situations designed to trigger fear. Since these results were found in all three groups, it suggests that even those with PTSD were able to experience less fear with THC in their system.

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DENVER, CO – JULY 15: The Colorado Board of Health had a rule making hearing about people with . [+] PTSD qualifying for medical marijuana at the Colorado Department of Public Health and Environment offices in Denver. Christopher Latona, center, and his dad Mike Latona, left, both testified in support of approving medical marijuana for PTSD which Christopher has suffered from since returning from his US. Army service in Afghanistan. They were photographed on Wednesday July 15, 2015. The board voted 6-2 not to approve the change. (Photo by Cyrus McCrimmon/The Denver Post via Getty Images )

Denver Post via Getty Images

The authors conclude that the research suggests “that THC modulates threat-related processing in trauma-exposed individuals with PTSD” and add that the drug “may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

A second study, from researchers at Brazil’s Federal University of Parana, explored another potential way that cannabis could help those with PTSD – extinguishing the intensity associated with memories of their trauma. This mode of treating PTSD was first hypothesized by Yale associate professor of psychiatry R. Andrew Sewell who suggested that cannabis may be able to help PTSD patients “overwrite” traumatic memories with new memories in a process called ‘extinction learning’.

In an interview with East Bay Express, Sewell explained that the extinction learning process usually helps trauma resolve on its own. He gave the example of an Iraq War Veteran who gets PTSD symptoms while driving under bridges – after dodging explosives thrown down from bridges during the war. “Suppose some part of your reptile brain thinks if you walk under a bridge you’re going to die,” Sewell explained “life becomes very hard.”

Army veteran Kevin Grimsinger 42 and other vet’s and supporters from Sensible Colorado submit a . [+] petition to add PTSD to the list of conditions approved for the use of medical marijuana to Mark Salley the communications director for the Colorado Department of Public Health and Environment Wednesday July 7th, 2010. Joe Amon, The Denver Post (Photo By Joe Amon/The Denver Post via Getty Images)

Denver Post via Getty Images

For most who experience traumatic incidents, these fears subside after 6 months or so because of the extinction learning process. New memories of the traumatic trigger form and override the old. Someone with a traumatic experience of explosives being dropped from bridges, may at first feel terrified as they approach any bridge – with traumatic memories flooding their mind. But after months of nothing bad happening around bridges, most will begin to feel bridges are less dangerous, as many memories of driving under bridges safely accumulate. The old memories still linger, but they don’t cause the increase in fear when the trigger (like the bridge) is present. So while most with trauma remember the traumatic incidents, those memories no longer trigger intense fear.

But for those with PTSD, extinction learning doesn’t happen. The trauma attached to the old memories continues to cause problems.

Still, Sewell believed that cannabis could help. Cannabis stimulates CB1 – a receptor in the endocannabinoid system that Sewell says has improved extinction learning in animal studies. Interestingly, those with PTSD show impaired functioning of the endocannabinoid system – which may be why they are unable to go through the normal extinction learning process.

Sewell theorized that cannabis might be able to jump start this process – allowing those with PTSD to access extinction learning like their healthy counterparts, and curing the PTSD by helping them to move on from their trauma. Unfortunately, he was unable to complete his research before he unexpectedly passed away in 2013.

study from Brazil’s Federal University of Parana looks deeper into the question. These researchers conducted a thorough review of the cannabis literature from 1974-2020 looking for evidence from controlled human trials to support or refute the theory that cannabis helps with ‘extinction’ of traumatic memories.

The researchers found that cannabis could help. Low doses of the cannabinoid THC or THC combined with another cannabinoid CBD were both able to enhance the extinction rate for challenging memories – and reduce overall anxiety responses. From their study, it seems that THC drives the extinction rate improvements, while CBD can help alleviate potential side effects from higher doses of THC.

The authors conclude that the current evidence from both healthy humans and PTSD patients suggests that these forms of cannabis “suppress anxiety and aversive memory expression without producing significant adverse effects.”

These studies provide some answers about why cannabis is helping PTSD patients feel better – both immediately and in the long run. Still, future studies may help clarify a range of questions about how and when to use cannabis effectively for PTSD, and whether there are risk factors associated with using the drug for this condition.