Benefits of Medical Cannabis for PTSD, Anxiety, and Pain

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Benefits of Medical Cannabis for PTSD, Anxiety, and Pain

Based on a limited number of clinical trials completed, the scientific community has determined that there is insufficient data currently available that conclusively demonstrates the benefits of medicinal cannabis for the treatment of Post-Traumatic Stress Disorder (PTSD), anxiety, and pain, as the bulk of publicly available information supporting cannabis use for these conditions is anecdotal in nature. However, there is some scientific evidence that medicinal cannabis is helpful for the reduction of anxiety, with current research targeting the effects of anxiolytic effects of medicinal cannabis on the amygdala, hippocampus, cingulate cortex, and hypothalamus. Estimates indicate that between 40 percent and 92.2 percent of medicinal cannabis users are primarily treating pain, but cannabis has been demonstrated to be effective in a limited number of trials on neuropathic pain only. It is estimated that 38.5 percent of medicinal cannabis users are primarily treating PTSD, where cannabis may positively impact hyperarousal, hypervigilance, short-term sleep quality, and intrusive thoughts. Below you will find a deep dive of our findings, as well as a discussion of the limitations of research on this topic.

METHODOLOGY

In order to identify high-quality scientific evidence regarding the use of medical cannabis in treating Post-Traumatic Stress Disorder (PTSD), anxiety, and pain, my colleagues and I first focused on research published in PubMed, which is a database sponsored by the United States National Library of Medicine National Institutes of Health, and provides access to clinical trials and review studies on this topic. We limited our focus to research conducted in the United States. At your request, we prioritized research the supports the use of cannabis to treat these conditions, so evidence regarding the potential harm of cannabis has been largely excluded. We expanded our research to include some reputable media articles, as our preliminary findings revealed there is an overall lack of tangible scientific evidence in support of cannabis treatment for PTSD, anxiety, and pain. Although we primarily limited our research to data published within the last two years, we included one article published in 2015, due to the wealth of scientific data points provided. Our findings are discussed in greater detail below, along with some explanation for the general lack of data on this topic.

CANNIBIS RESEARCH IN THE UNITED STATES

While cannabis has historically been used medicinally, prohibition laws in the United States have rendered scientific research on this topic difficult. As of August 2017, 29 American states, as well as Washington, DC, Guam, and Puerto Rico, have legalized medicinal marijuana. As marijuana remains illegal under the Federal Controlled Substances Act, research into this topic requires approval of multiple federal agencies, including the Drug Enforcement Agency (DEA), Food and Drug Administration (DEA), National Institute of Drug Abuse, and other scientific review boards, rendering clinical design difficult.

Despite legalization, research into medicinal cannabis specifically (compared with research into tetrahydrocannabinol - THC) is hampered by additional problems associated with the use of cannabis, including variations in product quality and biochemical complexity. As a result, there has been an overall lack of reputable, randomized clinical trials, and without this guidance, physicians are unable to make appropriate dosage recommendations for any of the various conditions reported to be improved by cannabis, especially in light of the current variation in cannabis administration routes, such as oral, vaporization, and inhalation. Thus, our findings indicate the pool of scientific research into the benefits of medicinal cannabis for treatment of PTSD, anxiety, and pain is limited. Below you will find a discussion of the scientific research identified as both reputable and favorable for treatment of each of these conditions.

POST-TRAUMATIC STRESS DISORDER

Post-Traumatic Stress Disorder (PTSD) is an approved condition in many states for treatment with medicinal cannabis. In 2015, it was reported that 38.5 percent of medicinal cannabis users primarily targeted PTSD. The efficacy of medicinal cannabis for treatment of PTSD appears promising. In one study, there was a 75 percent decrease in scores on the Clinician Administered Post Traumatic Scale among medicinal cannabis users. In a review of four cross-sectional observational studies of both synthetic and nonsynthetic cannabis use, three of the four studies found an overall improvement in PTSD symptoms with the use of cannabis. However, in two additional studies, while no statistically significant relationship between cannabis usage and severity of PTSD symptoms was determined, it was also not indicated that cannabis worsened PTSD symptoms.

Cannabis appears to be most helpful in reducing intrusive thoughts ("flashbacks") and hyperarousal. The use of cannabis for reducing symptoms of hyperarousal and hypervigilance typically reported by patients with PTSD appears to be related to the heavy concentration of cannabinoid receptor 1 (CB1) in the amygdala, where low doses of cannabis result in the production of an overall sense of calm. While short-term memory loss is often viewed as a negative side effect of cannabis, this symptom can be beneficial for PTSD patients; early studies in mice indicate that cannabis use reduces memories of traumatic events. Many PTSD patients report the condition interferes with their ability to sleep, and while medicinal cannabis appears to reduce sleep interference and nightmares in the short term, early evidence suggests it impairs sleep in the long term. Cannabis's anxiolotic properties may vary based on the primary cannabinoid present, rendering research difficult to replicate. Research into nabilone, a synthetic cannabinoid, is of particular interest to the scientific community, as this synthetic compound offers an opportunity to research a biochemically non-variable, stable substance.

While these early trials are promising, scientific research has consistently indicated that "the evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results." The current body of research is limited by small sample sizes, the inability to adjust clinical design to account for potential "confounders," and a lack of adequate control groups. Additionally, there is additional concern that while medicinal cannabis may be beneficial for the treatment of PTSD itself, it may increase commonly comorbid conditions, such as depression, anxiety, psychosis, and cannabis use disorder. However, with rapidly increasing rates of legalization, there are certainly new opportunities for research on the beneficial impact of medicinal cannabis on the treatment of PTSD.

As an additional note of potential interest, a significant population of Americans with PTSD include veterans, and as a result, Veteran's Affairs may prove to be instrumental in identifying innovative research on medicinal cannabis use for the treatment of PTSD. Although as a federal agency, physicians employed by Veteran's Affairs are not permitted to dispense medicinal cannabis, veterans enrolled in state-based medicinal cannabis treatment programs are not denied other health services from Veteran's Affairs. Furthermore, while Veteran's Affairs is not currently conducting any research on medicinal cannabis, the agency has expressed ongoing interest in keeping apprised of external studies, with leadership officials noting that, "We don't have enough information to confidently answer whether doctors should recommend cannabis one way or the other. We certainly need better research."

ANXIETY

Anxiety disorders are the most prevalent mental health condition in the United States, currently affecting 18.1 percent of Americans, or roughly 40 million adults. Research into the use of medicinal cannabis for treatment of anxiety may include patients suffering from a variety of conditions, including Generalized Anxiety Disorder, Panic Disorder, Social Anxiety Disorder, Post-Traumatic Stress Disorder, Obsessive-Compulsive Disorder, and/or a variety of Specific Phobias. It has been determined that the "endocannabinoid system is expressed in all brain regions that are important for the processing of anxiety, fear, and stress and has been identified as playing an important role in these responses." Of all anxiety disorders, patients suffering from Social Anxiety Disorder are the most likely to develop problematic marijuana usage habits, so trials involving patients suffering from this specific condition should proceed with caution.

It is noted, however, that anxiety is not currently identified as a condition qualifying for medicinal marijuana treatment in any of the states where it is currently legal, as of June 2017. However, in a sample of 1,746 patients from nine clinics providing medical marijuana in California, 37.8 percent of patients reported that they used medicinal marijuana to treat anxiety primarily, 16.9 percent of patients used cannabis to reduce panic attacks, and 55.1 percent used the substance to improve overall relaxation.

In one study of the effects of medicinal cannabis on Panic Disorder, which affects five percent of the global population, researchers evaluated the efficacy of cannabis in lieu of the current gold-standard treatment with selective serotonin reuptake inhibitors (SSRIs). In patients suffering from this condition, cannabis acts as an agonist for both cannabinoid receptor 1 and 2 (CB1 and CB2), and it produces an anxiolytic response. In this study, a single dose of 300 mg of cannabinoid also decreased anxiety associated with public speaking. Overall, the amygdala, hippocampus, cingulate cortex, and hypothalamus have been identified as potential targets for the impact of cannabis in treating anxiety, all of which are believed to be involved in anxiety associated with Panic Disorder. Utilizing neurological imaging, researchers in this study observed that a single dose of cannabis also reduced the anxiety associated with some medical procedures.

However, as previously noted, there is a wide spectrum of anxiety disorders, and current research has been unable to determine the effect of cannabis on the areas of the brain responsible for each of these conditions. For example, studies suggest that cannabis decreases activity in the hippocampus and left parahippocampal gyrus to improve symptoms associated with Generalized Anxiety Disorder, while modifying activity in the temporal lobe and prefrontal cortex to alleviate anxiety in patients suffering from Panic Disorder. Of particular interest to researchers is the effect of cannabis on the type 1A serotoninergic receptor, which is believed to be a key player in reducing anxiety and panic. Overall, there is insufficient yet promising evidence that cannabis may have anti-panic properties. Additionally, it has been demonstrated that unlike tetrahydrocannabinol, which increases anxiety at high doses, cannabis decreases anxiety at all doses. It has been demonstrated that 300 mg to 600 mg of oral CBD reduces anxiety in individuals who do not have anxiety disorders, and it also reduces anxiety in patients suffering from Social Anxiety Disorder.

PAIN MANAGEMENT

The most commonly cited condition targeted for treatment with medicinal cannabis is pain, reported as the primary indication for 82.6 percent to 92.2 percent of users in 2015. In 2017, another study found that between 40 percent and 80 percent of medicinal cannabis users are primarily suffering from pain, indicating that at a bare minimum, nearly half of all medicinal cannabis users primarily seek management of chronic pain.

In a review of 27 chronic pain trials, researchers found some evidence that cannabis may reduce neuropathic pain specifically, but there was insufficient evidence to address cannabis use in other populations suffering from chronic pain. Overall, low-strength evidence was found that medicinal cannabis may reduce neuropathic pain, but successful cannabis preparations exhibited a very precise tetrahydrocannabinolcannabidiol content (1:1 up to 2:1) for the treatment of neuropathic pain.

For the management of pain associated with multiple sclerosis (MS), a review of nine clinical trials indicated that there was insufficient evidence of pain relief associated with cannabis use. However, in a larger trial, patients appeared to have reduced pain at 12 weeks after using medicinal cannabis. Some research has been conducted on pain associated with cancer, but these trials have also yielded insufficient evidence of the success of intervention with medicinal cannabis, as a result of "the small number of studies and their methodological limitations, including high attrition, exclusion of patients with variable pain scores, use of some nonvalidated measures, and lack of clarity about randomization and blinding procedures." Fibromyalgia, rheumatoid arthritis, and inflammatory abdominal pain have also been targeted for additional research on the impact of medicinal cannabis on pain, but current evidence is insufficient. Some concern has been raised about the impact of combined medicinal cannabis use and long-term opioid therapy for patients with chronic pain, as medicinal cannabis users are more likely to abuse prescription opioids. Due to current medication management protocols for chronic pain in the United States, this concern may limit cannabis research.

CONCLUSION

In summary, there is some scientific evidence that medicinal cannabis is helpful for the reduction of anxiety, with current research targeting the effects of anxiolytic effects of medicinal cannabis on the amygdala, hippocampus, cingulate cortex, and hypothalamus. While up to 92.2 percent of medicinal cannabis patients are using the substance to treat pain, cannabis has been demonstrated to be effective in a limited number of trials on neuropathic pain only. It is estimated that 38.5 percent of medicinal cannabis users are primarily treating PTSD. However, despite these promising studies, it is important to note that the scientific community regards this evidence as insufficient at this time.
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