Extreme experiences such as accidents, life-threatening illnesses, war, rape or natural disasters can result in post-traumatic stress disorder (PTSD). Flashbacks, nightmares, constant tension and other symptoms such as anxiety, sleep disorders and fatigue determine the daily life of patients. Since those affected often avoid situations and places that remind them of the trauma, many live socially withdrawn lives. Other mental illnesses such as anxiety disorders, depression and addiction can also occur.
Psychotherapies and medications such as antidepressants are often not enough to help sufferers and bring side effects. Studies show that our endocannabinoid system (ECS) is important for “forgetting” unpleasant memories. Therefore, medical cannabis can assist with PTSD. Many sufferers with PTSD use cannabinoids. The psychotropic tetrahydrocannabinol (THC) can relieve anxiety, but it can also make it worse. Therefore, cannabis is not suitable for all sufferers. In a double-blind study, the synthetic cannabinoid nabilone reduced nightmares. The non-intoxicating cannabidiol (CBD) combined with psychotherapy and other medications improved numerous PTSD symptoms in a case series: Anxiety, nightmares, concentration, sleep, and mood. The extent to which CBD reduces symptoms also depends on the cause of the trauma: a double-blind study showed that CBD significantly alleviated anxiety in nonsexual trauma experiences, while CBD was not effective in sexual trauma.
PTSD made more common by pandemic
The Covid 19 pandemic negatively impacted the lives of the entire global population. A review paper published in 2022 shows that the prevalence (incidence of illness) was over 17 percent during times of Corona. This means many more people are affected by PTSD than before the pandemic. PTSD affects not only Covid-19 infected individuals (15 percent), but also medical personnel (17 percent) and the general population (17 percent). Covid-19 ward staff (31 percent), nurses (28 percent), and Europeans (25 percent) are particularly affected .
PTSD – What is it?
Post-traumatic stress disorder (PTSD) is a mental illness that occurs as a result of extreme stress. Such traumatic experiences or traumas can be, for example, war, accidents, sexual abuse, natural disasters, or serious illness (e.g., cancer). The experience can affect PTSD sufferers for life; they relive the drama in their minds over and over again. Eyewitnesses to traumatic situations may also suffer from PTSD [2,3].
Symptoms of PTSD include [2,3,4]:
- Distressing memories (flashbacks): The horror scenario is relived over and over again in thoughts and nightmares. Typically, flashbacks are triggered by key stimuli. Affected individuals suddenly feel transported back to the trauma and relive it.
- Avoidance behavior: To prevent flashbacks, sufferers often avoid situations, places or activities related to the trauma. Sounds and smells can also awaken traumatic memories.
- Withdrawal and apathy: Many affected persons withdraw socially and no longer feel joy.
- Nervousness and tension (hyperarousal): People with PTSD are constantly on alert, even though rationally there is no threat of danger. They often suffer from sleep and anxiety disorders. Affected individuals are excessively alert (hypervigilance).
Other symptoms of PTSD include anxiety, insomnia, fatigue, anger, and aggression . Often other mental illnesses are added such as anxiety disorders, depression, addictive disorders [2,3].
Treatment of PTSD
The most important treatment method for PTSD is psychotherapy. The most effective is the so-called trauma-focused psychotherapy, which is therefore recommended for all sufferers. In addition, various medications and other procedures such as occupational therapy are used [2,3].
So far, only antidepressants from the group of selective serotonin reuptake inhibitors (e.g., sertraline or paroxetine) have been approved for PTSD. However, they do not work for some sufferers, so combinations are made with atypical antipsychotics  or antiadrenergic agents .
Cognitive behavioral therapies help to “eradicate” anxiety, but are not effective in half of the patients. Even after successful treatment, symptoms of PTSD often recur .
Therapy options for PTSD [2,3]:
- Trauma-focused psychotherapy: trauma-focused cognitive behavioral therapy (TF-KVT), eye movement desensitization and reprocessing (EMDR) method.
- Medications: sertraline, paroxetine, venlafaxine
- Additional methods: e.g., occupational, art, music, body and movement therapy
The development of additional treatment procedures is important because many psychotropic drugs used for PTSD do not work adequately and often have an unfavorable side effect profile .
Cannabis for PTSD
How PTSD develops is not completely understood. Scientists assume that many factors are involved in the pathophysiology. Among them is the endocannabinoid system (ECS), which is involved in erasing memories via cannabinoid-1 receptors (CB-1 receptors) in the brain – which is why it is believed that traumatic experiences are also “forgotten”. These receptors modulate the release of neurotransmitters to prevent excessive neuronal activity. The ECS is involved in pain relief, anti-inflammation, control of movement and posture, regulation of sensory perception, memory, and cognitive function .
Many people with PTSD use cannabis for symptom relief. Tetrahydrocannabinol (THC), the psychotropic active ingredient in the cannabis plant, has an anxiety-relieving effect via CB1 receptors. The endocannabinoid system (ECS) plays a critical role in anxiety-related learning and memory processes .
In 2013, a study using imaging techniques showed that individuals with PTSD have decreased activity of the ECS in several brain regions, most notably the amygdala, hippocampus, cerebral cortex, and striatum .
Different brain regions are active during threatening situations .
- Medial prefrontal cortex (mPFC).
- Rostral anterior cingulate cortex (rACC: adjacent rostral anterior cingulate cortex).
Patients with PTSD often exhibit dysfunction of these brain regions. This dysfunction may contribute to the persistence of acute stress reactions after traumatic situations and lead to mental illness. Scientific studies showed altered cooperation between the amygdala and cerebral cortex in processing threats in PTSD sufferers compared to healthy subjects.
Thus, the amygdala in people with PTSD reacts more strongly to traumatic triggers such as images, sounds, smells, photographs, words, and threatening faces. Decreased regulation of the amygdala by the cerebral cortex may explain this. This leads to hyperarousal (overexcitation of the autonomic nervous system). Affected individuals are also unable to suppress their attention and response to traumatic triggers.
THC (tetrahydrocannabinol) in PTSD
Anxiety-processing brain regions contain many CB-1 receptors. Imaging studies have shown that in healthy subjects, THC modulates amygdala and mPFC/rACC activity. Low-dose oral THC reduces amygdala activity, and at the same time, coupling between the amygdala and mPFC/rACC increases in response to threat. The results suggest that cannabinoids may remedy the dysfunction of these brain regions in PTSD and other stress-related disorders.
Important: other studies showed that THC – especially at high doses (over 10mg) – activates the amygdala, which can increase anxiety and arousal to threats.
How THC affects anxiety processing is very complex and depends on the dosage, scientifically referred to as the biphasic effect: Low doses of THC often have an anxiety-relieving (anxiolytic) effect, while high doses can have the opposite effect, i.e., they can have an anxiety-inducing (anxiogenic) effect .
Cannabis is not suitable for all PTSD sufferers. Patients* should start with low doses of THC and closely monitor the effects. The dosage is slowly increased until anxiety is optimally controlled. This can prevent possible panic attacks due to overdoses.
Double-blind study: Nabilone relieves nightmares in soldiers
Many PTSD patients have sleep disorders. Particularly distressing are nightmares, which can re-traumatize sufferers. A Canadian double-blind study published in 2015 examined the effect of the synthetic cannabinoid nabilone, a THC derivative, on the frequency and intensity of nightmares in soldiers with PTSD. Standard treatment failed to improve nightmares in the ten participating men. The men, who averaged 44 years of age, had a severity score of 3.3 (Global Impression of Secerity of PTSD), with 4 meaning most severe.
The study used a cross-over design, with participants taking nabilone or placebo for seven weeks. After a two-week break in therapy, participants switched to the other therapy group. The dosage was slowly increased until the nightmares subsided.
Nightmares decreased significantly in the nabilone group. Five of ten subjects reported significant improvement under nabilone compared to only one participant under placebo. Symptom reduction as measured by CAPS Recurring and Distressing Dream Scores was -3.6 with nabilone and only -1.0 with placebo. Mean global improvement was measured by Clinical Global Impression of Change (CGI-C) and showed significant improvement with nabilone (CGI-C of 1.9) and marginal improvement with placebo (CGI-C of 3.2).
This small study shows that nabilone can reduce nightmares in PTSD. Cannabinoid therapy may be a promising treatment option for patients* plagued by nightmares for whom other therapies do not help. However, studies with larger groups of people are needed. The influence of other PTSD symptoms such as insomnia, re-experiencing trauma, and hypervigilance (increased alertness) should also be investigated .
CBD (cannabidiol) for PTSD.
Non-psychotropic CBD has several physiological effects as it not only activates the ECS but also modulates other receptors such as serotonin, adenosine, and opioid receptors. The anti-anxiety, neuroprotective, and antidepressant effects of CBD could be mediated through serotonin receptors (5-HT1A receptors). In contrast to THC, CBD hardly activates CB1 receptors. However, CBD inhibits the endogenous enzyme fatty acid amide hydrolase (FAAH), making more endocannabinoids such as anandamide available, which indirectly activates CB1 receptors. Animal studies suggest that activation of CB1 receptors can cause memories to be “forgotten,” so CBD may help with PTSD. Case reports show that CBD can be anxiety-relieving and improve sleep in PTSD. However, extensive human clinical trials are still pending .
Retrospective case series: CBD alleviates various PTSD symptoms.
American researchers retrospectively analyzed medical records of 11 PTSD patients who received oral CBD extracted from commercial hemp between February 2016 and May 2018. Most of the patients, who averaged 40 years of age, received psychotherapy and integrative therapies such as dietary changes, herbal medications, neurofeedback, and vitamins. An average of three psychotropic drugs were taken, including antidepressants, mood stabilizers, anxiety relievers and stimulants. One person used cannabis daily. The subjects’ accompanying symptoms included anxiety, mood, personality, and sleep disturbances. CBD was dosed individually in capsule or spray form. The severity of symptoms was assessed before the start of the study and after four and eight weeks using standardized questionnaires (PCL-5). This consists of 20 questions, each of which is rated by the patients with values between 0 and 4, resulting in 80 points for maximum complaints.
The results of the data collection showed that almost all patients (10 out of 11) were able to relieve their PTSD symptoms with CBD. After four weeks of ingestion, questionnaire scores dropped 21 percent (decreasing from 51.82 to 40.73). After eight weeks, scores continued to decline (dropping to 37.14), a decrease of one-third (28 percent). One person, however, experienced worsened PTSD symptoms. Four sufferers took CBD for longer than nine months and benefited from long-lasting symptom relief. Results also showed subjective improvement in nightmares, less anxiety, and improvement in sleep, concentration, and mood for some sufferers. CBD was mostly well tolerated, with occasional occurrences of fatigue, tiredness, and digestive discomfort.
Retrospective data analysis indicates that oral CBD can relieve PTSD symptoms in addition to psychotherapy and medication. Double-blind studies are needed to further investigate its potential. Further research will also show whether CBD can help with nightmares .
Double-blind study: anxiety-relieving effect of CBD depends on type of trauma
In a double-blind study published in 2022, researchers from the University of Sao Paulo, Brazil, divided 31 PTSD sufferers into two groups. One received oral CBD, the other a placebo. Participants then listened to an audio recording of a pre-recorded account of their trigger event.
To examine effects on PTSD symptoms, subjective and physiological measures were taken before and after listening. The scientific team observed that when listening to the audio recording, i.e., thinking about the trauma, subjects experienced increased anxiety, alertness, discomfort, and cognitive impairment. In addition, blood pressure and heart rate increased. The researchers* investigated whether there were differences in the effects of CBD in sexual and non-sexual trauma.
Result: In the group with non-sexual trauma, significantly smaller differences were observed in measurements before and after listening with CBD than with placebo. Similarly, lower differences in anxiety and cognitive impairment were shown with CBD. Thus, CBD showed stronger effects for traumas of nonsexual origin. In contrast, for sexual trauma, neither CBD nor placebo significantly alleviated PTSD symptoms, which can be explained by the particularly severe symptomatology .
Much about PTSD is still in the dark. Psychotherapy is the most important treatment for PTSD, as there are no approved medications to date other than antidepressants. Further basic research is needed in this area. According to research, the endocannabinoid system helps to “forget” memory content, which is why medicinal cannabis can also help PTSD sufferers. Case reports and initial small studies show that THC and CBD can relieve anxiety. Other ailments such as nightmares, sleep disturbances, concentration and mood disorders may also benefit from medicinal cannabis. Since THC can also cause panic, treatment should be done under medical supervision.
Larger clinical trials are underway. A double-blind study at the University of Texas at Austin, which began in 2020, is examining the effects of CBD on 150 PTSD sufferers. Researchers* will examine the effects of treatment on PTSD symptom severity, as well as various associated symptoms such as depression, overall disability, anxiety, quality of life, and alcohol use. This study will be the first to compare a CBD isolate with a broad-spectrum CBD extract and placebo. Results are expected in May 2024 and will help improve understanding on cannabis therapy for PTSD [11,12].
 Yunitri N, Chu H, Kang XL, et al. Global prevalence and associated risk factors of posttraumatic stress disorder during COVID-19 pandemic: A meta-analysis. Int J Nurs Stud. 2022;126:104136. doi:10.1016/j.ijnurstu.2021.104136
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 Sadeghi M, McDonald AD, Sasangohar F. Posttraumatic stress disorder hyperarousal event detection using smartwatch physiological and activity data. PLoS One. 2022;17(5):e0267749. Published 2022 May 18. doi:10.1371/journal.pone.0267749
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 Lee, B., Pothula, S., Wu, M. et al. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Mol Psychiatry 27, 2580–2589 (2022). https://doi.org/10.1038/s41380-022-01498-7
 Rabinak CA, Blanchette A, Zabik NL, et al. Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology (Berl). 2020;237(6):1813-1826. doi:10.1007/s00213-020-05499-8
 Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015;51:585-588. doi:10.1016/j.psyneuen.2014.11.002
 Bolsoni LM, Crippa JAS, Hallak JEC, Guimarães FS, Zuardi AW. The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event. Braz J Psychiatry. 2022;44(3):298-307. doi:10.1590/1516-4446-2021-2317
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