Virginia Thornley, M.D., Neurologist, Epileptologist
March 27, 2018
Anxiety is a state of unease, the sense of restlessness you feel when you are out of sorts. It may be due to the simple circumstances of being late for a charity dinner to feeling scared out of your wits when your car is trembling on the highway because your wheels are not balanced. Everybody has experienced it at some point in their life. Some more chronically and severely than others. In primitive times, one must redirect their attention from the task of scavenging for food in the jungle to suddenly be alert to imminent danger from the bear prowling behind you. In modern times, one must react quickly to that bus coming at you as you try to cross the street on 51st Street and 5th Avenue. You suddenly look up startled redirecting your focus to the imminently life-threatening event. For someone with clinical anxiety, this would be akin to being fearful every time you try to walk and cross the street despite no threats just the usual fast-paced taxicabs waiting for that green light. There is a chronic response of fearfulness that is not befitting to the situation. Threats are perceived more frequently harboring frequent fearful responses.
Current approach to anxiety
The current armamentarium of a physician includes prescribing anti-anxiety agents, referring to a therapist, recommending relaxation techniques such as yoga, Tai Chi or meditation, or any physician’s all-time fallback choice which is to refer to a psychiatrist. Many medications take weeks to take effect and after all that, not all of them are effective requiring several trials of medications to get to one that may even partially work. A therapist is beneficial, however, cons include the patient not having enough time or resources. In some patients it may help in others, similar to medications, it does diddly squat. In addition, some patients must cope with anxiety through natural means due to the prohibitive nature of their occupation. Some highly sensitive occupations disallow any use of anti-anxiety agents which might be potentially sedating in a patient’s history which could cost them their jobs. Medications may be helpful in certain populations but it often takes time to find the right agent and the right dose.
The science and mechanisms behind anxiety
The mechanism of anxiety and its complexities are studied. At the chemical level, it is thought to be due to the lack of serotonin. Many anti-anxiety agents work at the level of the serotonin receptor. But the thought processes underlying anxiety are far more complex than at a single chemical level which likely is the reason why many medications do not work given the complexity of the emotional response.
Neuroimaging studies have elucidated that anxiety may be attributed to the involvement of an amygdala to prefrontal cortex circuit. Instead of the normal fear response one has to certain stimuli, the amygdala is overly responsive to the threat. This leads to an abnormal attentional and interpretive response level that is consistently fearful. For instance, your bakery might be the best in town but if the client is highly anxious, any little mistake on that wedding cake may be perceived as a personal slight giving rise to an extremely anxious response causing them to want their money back. In other words, the level of anxiety is greatly out of proportion to the situation. There is nothing that bakery could have done to ease that person’s anxiety over the cake.
Patients with anxiety are selectively attentive to threat-related situations. Anxious patients perceive neutral events with negative connotations and potentially threat-related. Stimuli with conditioned threat significance may elicit attention and lead to physiologic responses including increased heart rate, sweating, heavier breathing. This may be the reason why in dealing with an anxious person, no matter what has been said that individual has a hyperalert response and has a very low threshold for a fearful response to a threat-perceived situation when the situation is very neutral (1). For example, you could be the most highly skilled neurosurgeon in the world, if your delivery of the prognosis is a 60% chance of recovery, that could be a source of great angst. The clinically anxious person will hear how she or he will have the 40% chance of not recovering.
Cannabidiol is the non-intoxicating phytocannabinoid from the Cannabis sativa plant. It has a weak affinity for the CB1 receptor and one needs 100 times the amount to get the same euphoria as tetrahydrocannabinol. Cannabidiol is found to help with anxiety. It works at the level of the 5HT-1 receptor to exert its anxiolytic properties. A combination of cannabidiol and tetrahydrocannabinol often called Indica is often used for anxiety and insomnia. It is often used by patients with anxiety primarily at night due to its calming and sedating properties.
In one study of 24 patients with anxiety who were about to give a presentation, cannabidiol was given at 600mg. The anxiety, cognitive impairment, and alert arousal response were much lower compared to the control group who had a placebo. The placebo group had much higher anxiety, greater discomfort, and alert responses (2).
Although federally illegal in many states despite medical marijuana laws and dispensaries popping up around the nation, medical marijuana is an alternative agent that should be considered in patients who are medically refractory to medications, psychotherapy, and other techniques. It has a valuable place in the physician’s medicine bag in treating anxiety and illnesses related to anxiety-related disorders.
- Bishop, et al, “Neurocognitive mechanisms of anxiety: an integrative account,” Trends in Cognitive Behavior, article in press.
- Bergamaschi, et al, “Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients,” Neuropsychopharmacology, 2011, May, 36 (6): 1219-26.
Virginia Thornley, M.D. Neurologist, Epileptologist
The endocannabinoid system is found naturally in the brain. It is responsible for the sense of well-being one gets after running a 5-mile course. It does not work through endorphins or adrenaline, as some people may think. It works at the level of the endocannabinoid system. There is a community of CBD producers and consumers and it is in this mysterious world that it is well-known to be used in many medical conditions, still shunned by the majority of the medical community, Congress and even patients in general. The 2 most commonly known are cannabidiol and tetrahydrocannabinol. Cannabidiol has medical properties and has a weak affinity to the CB1 receptor which is predominantly found throughout the central nervous system, which is likely why it is found to work in numerous neurological conditions. Tetrahydrocannabinol (THC) is a well-known cannabinoid most notoriously known for the euphoria of kingpins seen on movies propagated by pop culture. Unfortunately, these connotations overshadow the well-known medicinal benefits. Cannabinoids have been used for centuries even in the B.C. period. It was part of the American pharmacopeia in the 1980’s until it was banned in the 1930’s. Slowly, these products are gaining popularity as a treatment for many medical conditions, primarily neurological because the CB1 receptor is so abundant in the nervous system, due to patients becoming more and more frustrated with the adverse effects and ineffectiveness of conventional treatments. In Europe, a combination of THC and CBD have been used in multiple sclerosis patients since 2010. Animal studies and cell line culture studies demonstrate many potential mechanisms in which CB1 receptors, CBD and THC may be beneficial at the cellular level in many diseases, mechanisms are still being elucidated. It is most commonly used for chronic pain and epilepsy. As with any medication, it may or not be effective for everybody.
How it works–the nitty gritty
Cannabidiol has none of the psychoactive properties as THC. One needs 100 times the amount of CBD to have the same intoxication as THC. Therefore, it works well for those who are reluctant to go this route but who have found conventional medications which do not provide effectiveness, they are simply not cutting it. Because very little is know about its titration, medical marijuana can seem like entering into the world of an apothecary, or such as that found in the medieval days when potions are concocted. Physicians who use it in their treat it similar to a medication and the guidelines are similar start low and go slowly. Tetrahydrocannabinol is more potent and at higher doses works more effectively for pain control and seizures. THC is used at relatively low concentrations in order to effect its medical properties, at higher concentrations one may run into side effects which offsets its medical value. There are different ratios of CBD:THC, different ratios correspond to different symptoms treated. CBD is required in conjunction with THC in order to offset the potential side effects of THC. Tolerance does not build in the system such as that seen with opioids, although if one is medical marijuana naive, the lowest dose possible is ideal. There are no side effects of respiratory depression such as that seen with other medications for pain such as opioids.Consult with your treating physician.
Current legal state of affairs
Currently, there are many states that recognize the medical value of medical marijuana with medical marijuana laws allowing the opening of licensed dispensaries. However, the same cannot be said for the federal law. In some states, the carrying of THC on your person can result in fines and imprisonment. Despite marijuana laws enacted, qualified physicians are at risk for being questioned by authorities, its recommendation and use is not for the faint of heart on the part of physicians and patients. Cannabidiol comes from hemp oil and is not considered illegal. However, anyone who even has 1% hemp oil in their product can still label that product as cannabidiol, which may be the reason why some patients are not getting the full medical effects when bought from the flea market or a vitamin store. Tetrahydrocannabidiol which is more well-known for its recreational use and concomitant psychoactive properties at very high doses is federally illegal in many states. Many states often have registries so patients who require this may obtain an ID and verify they are under the care of a qualified physician. It can take a few months to obtain an ID because many patients are often at the end of their ropes in terms of effectiveness of medications. Many patients wish to come off opioids or do not like the idea of needing higher and higher pain medications for their chronic illnesses. It may serve as a great antidote for the current opioid crisis that is well-documented in the news or overdocumented in the news. Many mothers order products online from other countries to counteract the illegalities of their states in order to help their child who may be using 4 potent anti-epileptic agents and is now like a zombie because of the number of medications. While physicians are leery suggesting anything that is in category 1, its medical value cannot be disputed. There is too much evidence tipping it towards the other side of the scale. As tPA was in its infancy of use and physicians were hesitant using it due to its hemorrhagic adverse effect and is now the standard of care for stroke protocols, medical marijuana will likely find its way back into the pharmacopeia, the amount of medical evidence is far too compelling to ignore.
In short, when used wisely, cannabidiol is a non-intoxicating effective treatment for many medical conditions especially neurologic, as evidenced by thousands of years of history of its use and current animal models, clinical trials and wider clinical experience in Europe. When cannabidiol is combined with low concentrations of THC, the medical effect is even greater with the entourage effect without the stigmatized psychoactive effects that are usually associated with THC.