Anxiety, cannabidiol

Anxiety: the science behind anxiety and effectiveness of cannabidiol and tetrahydrocannabinol in anxious patients

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.


  1. Bishop, et al, “Neurocognitive mechanisms of anxiety: an integrative account,” Trends in Cognitive Behavior, article in press.
  2. 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.
Autonomic system, Neuroanatomy, Spidey senses

Do your spidey senses tingle, better listen up

Virginia Thornley, M.D., Neurologist, Epileptologist

March 24, 2018

Have you ever walked down a quiet lonely corridor of a building where almost everyone has gone home for the day and your spidey senses started to tingle? Or perhaps, you were caught up at work in a facility and it is now 8pm with not a soul in sight and you have a long desolate walk to the parking lot to your car. Your spidey senses tingle as you place your first step out the door leaving the brightly fluorescent-lit building to go out in the cold darkness. Your heart races, your eyes widen checking out your surroundings in front, on the sides and behind you. That is your fight or flight response kicking in in high gear. This is a common scenario where your senses tell you instinctively that you are not in the best situation and you need to be hyperalert to survive a situation should something adverse were to occur.

How about a less straightforward situation where you waltz into a bank minding your own business, you just needed quarters to do your laundry because you live in an apartment building with no washer or dryer. As the teller is getting you a roll of coins, someone comes in from your peripheral vision. You think how rude, I was here first why is this guy cutting my line? He has sunglasses, a hat and holds up a note to the teller while telling you to be chill, be chill. Then it dawns on you that you are suddenly in the middle of a bank heist. Do you a) scream and ask for assistance from the security guard standing 2 feet away? b) run for your life because the man beside you has his hand in his pocket and you could turn into smithereens in the next few seconds c) stay frozen as your life passes through your mind thinking hmm, what should I do scream for assistance or be chill like the guy reassuringly told me to be. Your mind instinctively tells you it is prudent to do the latter. This is another situation where you are on edge, your systems are overloaded with information and your mind is racing like a marathon on what was the best case scenario to get yourself out of that situation.




Many times in our life we are faced with situations when we feel potential threat or fear of the unknown and lightning speed logic and actions are required. Our bodies are designed to react quickly to situations. The amygdala has an emotional function in our brain that directs our reactions when the unnerving situation is detected. Signals are sent to the hypothalamus in the brain that connects with the adrenal medulla which lies on top of the kidneys and from where epinephrine and norepinephrine are released  The sympathetic nervous system is the system that allows our pupils to dilate, our heart to pump quickly and our palms to sweat. It is part of the autonomic nervous system that controls and regulates the cardiac muscles, muscles, and glands. During fight or flight response to stress, there is an adrenergic rush when epinephrine is released and is available for immediate reuptake by the post-ganglionic nerve endings in order to kick our bodies into high gear to react rapidly if need be. The heart is pumping to ensure the body gets adequate blood flow. In primitive times, you will need your muscles to outrun that cougar. The blood vessels constrict within the organs to make blood flow more available to the muscles necessary for running. Blood flow is shunted to the liver to make energy stores more available. The pupils dilate so they widen allowing more light and you can see your surroundings better in dark light. The breathing becomes heavier because you will need more oxygen when you try to outrun that crouching cheetah in the jungle.

It is a primitive response so engrained in our system that we cannot ignore or control it.  The palms sweat, well, because that’s part of the sympathetic nervous system. Sweating allows you to cool off in hot temperature. If you run hard and fast you become hot, you need sweat to cool down. It is essentially a primitive response entrenched within our systems that help you react towards an untoward situation. By the same token, animals must sometimes freeze in the jungle so they are not seen and eaten by large predators. This is similar to the evolutionary freezing we feel when we are involved in a potentially dangerous situation and suddenly stop and do not know what to do.


However, everything is interrelated. It is not just the fear of the unknown or being in an unusual situation that can trigger this response. Our memories and emotions may trigger the sympathetic nervous system. Say you walk into a business deal that is supposed to be mutually beneficial. You have high hopes for a great outcome. You walk into the conference room, look your interviewer in the eye and shake his hand. This person is unusually cheerful and accommodating.  You are just happy to have someone interview you in the location of your choice. However, as you start to listen to the situation your mind is triggered by statements that harken back to a situation in a previous job from which you suffered burnout. They are way too accommodating but little statements are voiced making you wonder about the real situation and why they are being a little too nice and too happy about an overburdened schedule. This is where the hippocampal cells in the temporal lobe come in to subserve their function with learned memory.  Your amygdala is processing everything emotionally connecting the dots. While logic is saying take the job it is an ideal location, the salary is great, your amygdala is dissecting emotional content in the discourse and on facial features. It picks up on any fallacy when emotions and statements do not coincide. You detect a disconnect between the sunny disposition and the weight of the job. The intuition many people opine about is really the primitive amygdala telling you when something is not quite right. It detects the unsaid component of a situation and ultimately determines your next course of action. While you are about to start the job your amygdala is screaming out to you releasing hormones producing a milder version of the fight or flight response veering you away from a potentially stressful situation and giving you a completely different reaction from what logic would determine. You feel stressed every time you think about your first day at work. The heart beats a little more quickly, it is a milder version of the sympathetic response found in fight or flight but essentially your amygdala is activating your system to respond as you do in an adverse situation.

The same is true when encountering the threatening looking person. You have an idea they are up to no good, looking shiftily away darting their eyes back and forth. Your brain registers something adverse is about to go down. It’s not paranoia, it’s your primitive brain the amygdala picking up on suspicious activities steering you towards a reaction towards a  potentially adverse event.

Therefore, when your spidey senses tingle, it’s not intuition, it’s not a sixth sense or premonition. It is cerebrally mediated with your primitive brain steering your emotional component to wind your body up about to react to a stressful situation. At one end of the spectrum, it is the fight or flight response at the milder end of the spectrum it is the stress you feel when you are about to make a big mistake. The axiom is true, listen to your gut, to be more apt listen to your amygdala masquerading as your spidey senses.

When the hair on the back of your neck tingles, listen to those spidey senses.