Panic attacks are the primary symptom of Panic disorder (PD). Panic Disorder is chronic and can greatly reduce quality of life for individuals suffering from it. It is usually manifests as recurrent panic attacks of varying severity. According to a recent report, approximately 3% of the world’s population suffers from PD. These percentages are dependent on socioeconomic and demographic factors, with certain races and wealth brackets carrying more of the burden.
As with all anxiety-related conditions, Panic Disorder is a psychological condition with neurological roots. Specifically, two regions of the brain – known as the hypothalamus and the amygdala – control our negative emotional responses to external stimuli. Their job is to alert us when we are in danger. Evolutionarily, this was tied to predators and things like heights and fire: things that are obviously detrimental to our physical health.
However, over recent years, as society has evolved and progressed, so has our brains’ way of responding to it. When day-to-day stimuli like school, work, bills, debt, health, life goals, and other important pieces of our life don’t go as well as we hoped, it can result in anxiety just like our ancestors 10,000 years ago would have anxiety after being attacked by a bear or mountain lion.
When the amygdala and hypothalamus don’t work properly, it can result in the presence of a fear response to a stimulus that is not dangerous or threatening: this is called anxiety disorder. Panic disorder is a severe type of general anxiety.
Current Treatment Options and Best Practices for PD
As of now, selective serotonin reuptake inhibitors (SSRIs) are the go-to drugs for the treatment of PD; these are the most-prescribed medications for general anxiety and clinical depression as well. Other drugs, including tricyclic antidepressants and benzodiazepines, are commonly used to manage PD. However, all of these drugs are highly potent and none are without many unwanted side effects. Specifically, benzodiazepines have strong sedative effects and are widely addictive.
Why CBD Improves Cases of Panic Disorder
In the last two decades, cannabinoids have been of particular interest to healthcare providers and researchers focusing on inflammatory or psychiatric disorders. However, the psycho-activity of these compounds deters healthcare providers from indicating them to patients in the first place. Fortunately, one cannabinoid stands out amongst the rest for its lack of psychoactive effects and conserved therapeutic properties.
Cannabidiol (CBD) is a major component of the cannabis sativa plant. Unlike cannabinoids such as THC, CBD is known to lack psychoactive effects while conserving those anti-inflammatory/neuroprotective properties other cannabinoids have.
Unlike other cannabinoids and endocannabinoids, CBD has a low affinity for CB1 and CB2 receptors. That is, CBD does not bind well with either of these receptors. Nonetheless, CBD promotes endocannabinoid signalling by reducing endocannabinoid uptake into the cell and hydrolysis (breakdown) of endocannabinoids.
CBD and its effect on panic attacks
Multiple studies, both clinical and preclinical, have been performed to evaluate the relationship between CBD and panic attacks. For example, various preclinical studies using animal models have demonstrated that chronic administration of CBD induces anti-anxiety/anti-panic effects. This has been further corroborated through human studies, as well as anecdotal findings, that suggest use of CBD decreases generalized panic symptoms.
When it comes to drugs, doses and administration routes (oral, intravenous, etc) could make a difference on whether the compounds exerts its intended effects or not. In the case of CBD, the oral route has been preferred over other routes such as inhalation or intravenous. For example, in a study done by Zuardi and coworkers, one 300 mg oral dose of CBD decreased panic and anxiety in healthy volunteers before a public speech.
In another case, one oral dose of 600 mg of CBD was seen to significantly decrease panic/anxiety related measures. This increase in dosage is mainly because individuals suffering from PD suffer from higher levels of social anxiety, cognitive impairment, alertness and discomfort as compared to their healthy counterparts.
As mentioned before, these same anti-panic/anti-anxiety effects have been seen in animal studies as well. In a research report looking at the reaction of a mouse to the encounter with a wild snake, acute administration of CBD (0.3-0.30 mg/Kg) decreased panic associated behaviors like sudden escape or immobility.
Neural-structural basis of CBD effects in PD patients
So you may be asking yourself, what structures does CBD act on to reduce symptoms of PD?
Previously, differences in brain structures such as the amygdala, hippocampus, hypothalamus, cingulate cortex and parahippocampal gyrus have been noted in PD patients as compared to healthy patients. This makes sense because many of the structures mentioned above are responsible for modulating emotional and physiological responses associated with fear.
CBD administered in single oral doses has been correlated with reduction in anxiety produced by an injection and scanning procedure. During this same study, CBD was also seen to alter activity in the limbic and paralimbic areas of the brain.
Other studies using imaging procedures such as functional MRIs (fMRIs) have shown that CBD can reduce activity in brain areas including the medial and temporal lobes, as well as the prefrontal cortex and insula. In terms of fMRI, a reduction in activity means less blood flow to that particular area. If there is less blood flow, then the area is less engaged and the behaviors associated with that area are less pronounced or likely to happen.
Molecular mechanisms by which CBD attenuates symptoms of PD
The mechanisms that link CBD and panic attacks are not quite understood yet. However, it has been proposed that type 1-A serotonergic receptors may interact with CBD and play a role in the reduction of panic associated symptoms.
Another receptor that has been deemed relatively important in the treatment of PD is the 5-HT1A receptor. CBD has been shown to activate these receptors in different areas of the brain including the basal ganglia, prelimbic prefrontal cortex and the dorsal raphe nucleus. Abnormal activity in some of these structures has also been associated with abnormal production of serotonin in the brain in PD patients. This may mean that CBD helps to regulate serotonin levels which in turn reduces PD symptoms.
Another interesting possible mechanism by which CBD and panic attacks are related is through the increase in levels of certain endocannabinoids like anandamide. For example, in a recent study, chronic treatment with CBD increased the concentration of anandamide in the hippocampus, which is another structure that is thought to have abnormal activity in PD patients.
How to use CBD for panic disorder
As of now, CBD has been shown to have no psychoactive effects, to reduce panic as well as anxiety symptoms in patients with PD and to be safe and tolerated by patients via the oral route. In fact some studies have suggested that patients can tolerate up to 1500 mg/day of CBD with little to no adverse side effects.
Additionally, researchers say that CBD, unlike THC, has not been shown to cause tolerance, dependence or withdrawal symptoms. This is particularly important because CBD could potentially be used as a replacement for commonly used anti-panic drugs such as benzodiazepines and antidepressants. Either way, the U.S is still some time away from approving treatment with CBD and these are just the first steps to what could possibly be a good alternative to more toxic treatments.
The good news is that many clinical trials are currently going on to test the efficacy of using CBD alone or with other drugs/cannabinoids in other conditions. Specifically, a drug known as Epidiolex, which contains CBD in its formula, is going through phase 3 trials for the treatment of pediatric epilepsy. More importantly, phase 2 and phase 3 clinical trials testing CBD on PD patients are necessary to establish any credible evidence for recommending CBD for this purpose.