Cannabis to treat anxiety and post-traumatic stress disorder
As physicians, it is of utmost importance to know the proper management of stress and anxiety, as well as the neuropsychiatric disorders that result from them. In addition, the COVID-19 pandemic situation has resulted in anxiety and stress disorders in the world's population. Cannabis is an excellent option to mitigate and treat these conditions, learn how in this article.
This article was created to guide health professionals and requires medical knowledge to read and understand.
Fear and anxiety are normal adaptive responses to cope with threats and survive, but when they become excessive or persistent they can lead to disability. Symptoms arising from excessive fear and anxiety occur in several neuropsychiatric disorders, including generalized anxiety disorder (GAD), panic disorder, anxiety disorder or social phobia, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). The latter two are no longer classified as anxiety disorders, but excessive anxiety is central to the development of the symptomatology of both disorders. [3]
Anxiety
Anxiety is an emotional state characterized by an excessive emotional response to potentially dangerous circumstances. It is a normal reaction to stress and can alert us to dangers, help us prepare for them, and help us pay more attention to our surroundings. Anxiety is associated with muscle tension and avoidance behaviors. [8]
When anxiety occurs pathologically, it can lead to chronic emotional disturbances and constant apprehension about the future. [8] Anxiety disorders differ from normal feelings of nervousness or anxiety and involve excessive fear or anxiety in the face of stimuli that should not trigger them. [1]
Anxiety disorders are the most common mental disorders and affect almost 30% of adults at some point in their lives. These disorders are treatable and require proper stress and anxiety management; there are several effective methods available whose main goal is to help the patient lead a productive and normal life. [1]
Post-traumatic Stress Disorder (PTSD)
According to the American Psychiatric Association, post-traumatic stress disorder (PTSD) is a psychiatric disorder that can occur in people who have experienced or witnessed a traumatic event, or who have been victims of violence or crime. [2,6]
People with post-traumatic stress disorder may have intense and disturbing thoughts and feelings related to the traumatic experience, and these remain long after the traumatic event has passed.
Patients with this condition may relive the event through flashbacks or nightmares; they may feel anxiety, sadness, fear or anger; they may even feel distanced from other people, and may avoid situations or people that remind them of the traumatic event, and may have strong negative reactions to something as common as a loud noise or accidental physical contact. [2,6] Without adequate management of stress symptoms, the condition becomes chronic and can become more complex.
Anxiety and stress disorders in Mexico
Studies conducted by the Ministry of Health at the national level reveal that anxiety cases increased by 75% between 2013 and 2018. In addition, data from the National Survey of Psychiatric Epidemiology in Mexico indicate that almost 30% of the adult population will suffer from some mental disorder in their lifetime. The most relevant: anxiety disorders (14.3 %), substance use disorders (9.2 %) and affective disorders (9.1 %). [5]
According to figures, in Mexico it is "extremely common" to experience traumatic events. A study published in 2014 mentions that 68.8% of the Mexican population has experienced an event that can be classified in this way. Meanwhile, another study conducted in 2013 indicates that 28.2 % of young Mexicans between the ages of 10 and 25 have lived through two or three traumatic events, and that 13 % have witnessed four or more. [4]
A study published by Norris and colleagues in 2003 mentions that PTSD is present in 11.2% of the Mexican population, and 62% of these cases became chronic, while only 42% of them received medical or professional care and treatment. [7] Therefore, it is vital to identify the symptoms and refer to a mental health professional for an adequate management of PTSD and other anxiety disorders.
Conventional pharmacological treatment
Currently available pharmacological treatments for these conditions include serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressants and 5A-hydroxytryptamine (5-HT) receptor partial agonists.
Anticonvulsants and atypical antipsychotics are also used to treat PTSD. [3]
These medications are associated with limited response rates and residual symptoms, particularly in PTSD, and adverse effects may also limit tolerance and adherence to treatment.
The substantial burden of anxiety-related disorders and the limitations of current treatments place a high priority on the development of new pharmaceutical treatments whose side effects are not disabling. [3]
Endocannabinoid system and anxiety modulation
The endocannabinoid system (ECS) is microscopic and found throughout the body. Several of the cannabinoid receptors, especially CB1 receptors are found in the limbic or "emotional" brain, where they modulate neurotransmitter release in a manner that prevents excessive neuronal activity, thereby decreasing anxiety, reducing pain and inflammation, regulating movement, sensory perception, memory and cognitive function. [10] Increased endocannabinoid signaling has anxiolytic and antidepressant effects, whereas blockade or deletion of CB1 receptors has anxiogenic properties and produces depressive phenotypes. [9]
The neural mechanisms by which endocannabinoid signaling affects anxiety are not fully understood; however, most of the available data indicate that endocannabinoid signaling has anxiolytic properties in both conditioned and unconditioned models of anxiety, and that these effects are most active during states of stress or high arousal.
Anxiolytic properties of cannabis
The use of cannabinoids in mental health research has been considered controversial and the evidence base for their therapeutic effects is poorly developed. However, in the United States, cannabinoid use is approved for people with PTSD in most states that allow medical cannabis. [12]
As a result of several studies it was suggested that cannabinoids may have a role in modulating emotional memory, fear and anxiety; in 2008 and 2013 studies it was observed that a single acute dose of THC significantly reduced amygdala reactivity to social cues of threat. THC has also been shown to enhance amygdala-prefrontal connectivity, modulate subjective anxiety (depending on dose), and increase fear extinction. Other research suggests that THC at high doses can exacerbate anxiety, suggesting that THC has a complex effect on reactivity and anxiety. [12]
The mechanisms of action of CBD are several: [10]
It has an indirect effect by stopping the enzymatic breakdown of anandamide, allowing it to remain longer in the body and provide medical benefits.
It has a mild effect on CB2 receptors in lymphoid tissue, mediating the release of cytokines and reducing inflammation and pain.
Stimulates vanilloid pain receptors, mediators of pain perception, inflammation and body temperature.
It can exert its anxiolytic effect by activating adenosine receptors (regulating cardiovascular function and with a broad anti-inflammatory effect throughout the body).
At high concentrations, CBD directly activates the serotonin receptor, which confers an antidepressant effect.
In a study published in May 2020, marijuana was administered to patients diagnosed with PTSD, these patients indicated a 50% decrease in symptoms immediately after administration of the cannabinoid treatment. [11]
CBD and THC as promising treatments
Preliminary data suggest that THC modulates threat-related processing in individuals with PTSD exposed to trauma, which may be advantageous as a pharmacological approach to treat stress-, anxiety-, and trauma-related psychopathology. [13]
CBD, on the other hand, may be an effective compound for reducing anxiety and insomnia secondary to PTSD. A literature review suggests some benefits of CBD use due to its anxiolytic and sleep-inducing effects. Animal studies support the use of this treatment and report that CBD can block anxiety-induced sleep disturbance through anxiolytic effect in the brain. [10]
Together, these findings add to the growing body of literature suggesting that pharmacological modulation of the endocannabinoid system may be a promising approach to address corticolimbic dysfunction, which centrally characterizes PTSD and anxiety- and stress-related psychopathologies. [13] Appropriate management of stress and anxiety may find answers in cannabinoid medicine, and further research is needed to support them as legitimate and medically useful treatments.
The diagnosis, dosage and dose titration of these cannabinoids should always be carried out by a medical specialist: a psychiatrist in the case of humans or a veterinarian specializing in ethology in the case of animals.
References:
[1] American Psychiatric Association. (2017). What Are Anxiety Disorders? Recuperado de <Sitio web>, última consulta 23 junio 2020.
[2] American Psychiatric Association. (2020). What Is Posttraumatic Stress Disorder? Recuperado de <Sitio web>, última consulta 23 junio 2020.
[3] Blessing, E. M., Steenkamp, M. M., Manzanares, J., & Marmar, C. R. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 12(4), 825-836. doi:10.1007/s13311-015-0387-1.
[4] Flores, S. (2017). Traumas. Nexos. Recuperado de <Sitio web>, última consulta 23 junio 2020.
[5] Gudiño, A. (2018). Ansiedad aumenta 75% en los últimos cinco años en México. Recuperado de <Sitio web>, última consulta 23 junio 2020.
[6] National Institute of Mental Health. (2019). Post-Traumatic Stress Disorder. Recuperado de <Sitio web>, última consulta 18 junio 2020.
[7] Norris, F. H., Murphy, A.D., Baker, C.K., Perilla, J.L. (2003). Epidemiology of trauma and post-traumatic stress disorder in Mexico. Journal of Abnormal Psychology, 112(4), pp. 646-656.
[8] Tambaro, S., and Bortolato, M. (2012). Cannabinoid-related Agents in the Treatment of Anxiety Disorders: Current Knowledge and Future Perspectives. Recent Patents on CNS Drug Discovery, 7(1), 25-40.doi:10.2174/157488912798842269
[9] Kendall, Dave and Alexander, Stephen (2009). Behavioral Neurobiology of the Endocannabinoid System. 10.1007/978-3-540-88955-7.
[10] 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), 16-005. https://doi.org/10.7812/TPP/16-005.
[11] LaFrance, E. M., Glodosky, N. C., Bonn-Miller, M.,& Cuttler, C. (2020). Short- and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. Journal of affective disorders. 274, 298-304. Advance online publication. https://doi.org/10.1016/j.jad.2020.05.132
[12] Hindocha C., Cousijn, J., Rall, M., & Bloomfield, M. A. P. (2019). The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review. Journal of Dual Diagnosis, DOI: 10.1080/15504263.2019.1652380.
[13] Rabinak, C. A., Blanchette, A., Zabik, N. L., Peters, C., Marusak, H. A., Iadipaolo, A., & Elrahal, F. (2020). Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology. doi:10.1007/s00213-020-05499-8