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.



Epilepsy, pain

Cannabidiol: Is there any scientific evidence? Review of some of the novel mechanisms of action in analgesic, anti-epileptic, anti-inflammatory, anti-tumorigenic and anxiolytic effects 

Virginia Thornley, M.D., General Neurologist and Epileptologist


February 16, 2018


Cannabidiol (CBD) is the little known medical component without the euphoria used for medical indications such as analgesic, anti-inflammatory, anti-epileptic and anxiolytic effects. In the pathway for endocannabinoids, cannabinoid exerts its therapeutic effects by binding to the CBD1 receptor found in the brains and the nerves exerting their analgesic effects. CBD does not have the same euphoriant effect as THC its counterpart which is better known to the public with much stigma. CBD will need to be 100 times more potent to have the same euphoria as THC making it relatively safe to give without the intoxicating effects. THC or delta-tetrahydrocannabidiol is the main psychoactive component in the marijuana plant, the one finds in the street drugs which has caused such a stigma shadowing the beneficial effects of the plant. Cannabidiol is also thought to work on the 5HT1 receptor giving its anxiolytic properties. This review seeks to understand some of the laboratory research that study the underlying mechanisms for its beneficial actions.

Cannabidiol works on CBD1 receptor and is thought to have an analgesic and anti-inflammatory role in diseases. In many states, it still outlawed to have in possession but growing clinical evidence shows that it can be used in pain syndromes. In the state of Florida there are 10 conditions recognized that can be treated with CBD. It is most commonly used in pain from stage IV metastatic cancer. Cannabidiol has been found to have anti-inflammatory, anti-tumorigenic, analgesic, anti-epileptic and anxiolytic properties.

Analgesic effects

CB1 receptors are found to be expressed in anterior horn cells. The CB2 receptors possibly reduce pain by acting on the neutrophil accumulation and mast cell degranulation which can reduce pain both of these processes increase inflammatory algesia(1).Analgesia has been demonstrated with cannabinoids in visceral inflammation and pain due to peripheral neuropathies, important areas of therapeutic considerations.

Anti-seizure effects

Some of the vast scientific research for cannabinoid is found in the animal models for epilepsy. Cannabinoids exert effects on CB1 and CB2 receptors in the hippocampus where it has a weak affinity(5). CBD1 receptors affect transmission in the synapses through the voltage-gated calcium and potassium channels. There are studies on the effects of CBD in refractory types of epilepsy such as Dravet’s syndrome one of the SCN1a genetic disorders affecting the sodium channel manifesting as severe myoclonic epilepsy. Mechanisms of CBD include increasing excitation of the inhibitory effect of the hippocampus where seizures are propagated.  At low doses, it helps with autism and impaired cognition.  It may exert its effect by working against GPR55(7), TRPV1 in addition to voltage-gated voltage-gated potassium and sodium channels. Another study supports the role that cannabinoids may play in shifting the inhibition of glutamatergic effects and GABAergic effects in the hippocampus mediated by CB1 receptors. In the rat model, it was suggested that seizures can upset the balance of these glutamate and GABA systems (4). 15 minutes after an induced seizure, there is increased 2-arachidonylycerol which is a CB1 agonist suggesting cannabinoids act as a negative feedback loop for seizures(4). In addition, it was found there are more CB1 receptors in the hippocampi with induced seizures compared to control suggesting plasticity of the brain with a compensatory increase in CB1 receptors in response to increased seizures(4). CB2 receptors are related to the immune system and are limited in the CNS. Cannabinoids affect calcium homeostasis and may provide its neuroprotective effects. Growing evidence shows case series, case reports and anecdotal reports on patients having fewer seizures on cannabidiol. Large case-controlled clinical randomized trials are needed.

Anti-tumor effects

There appears to be increased cancel cell death, reduced viability and reduced numbers of metastatic cells. In one study, it is found to reduce epidermal growth factor-induced multiplication and chemotaxis of cells in breast cancer. In mouse models, it inhibits macrophage recruitment in tumor-related cells.n It can potentially inhibit metastasis and proliferation and may provide a novel therapeutic option in breast cancer(2).

Anxiolytic effects

It works on the 5HT1 receptor by altering effects on this receptor the exact mechanism is unknown accounting for anxiolytic properties(6).


Anti-psychotic effects

CBD may alter the effects of THC and reduce its psychoactive properties (6).


Alternative treatment in opioid use

CBD might also work in place of opioids with the growing epidemic of chronic pain and overuse of opioids, CBD may be an alternative analgesic for chronic pain without the effect of tolerance or sedating properties. CBD was found to reduce the reward effects of morphine and does not have the same properties of tolerance. CBD does not have the same euphoria and THC and works on pain(6).

In summary, it is an exciting time for research in the use of cannabinoids. There are innumerable basic science research studies demonstrating the therapeutic effects at the cellular level. Large randomized clinical trials are still needed to gain information in using cannabinoids in humans.




1. Rice, AS, et al, “Endocannabinoids and pain: peripheral and spinal analgesia in inflammation and neuropathy, ” Prostaglandins, Leukotrienes and Essential Fatty Acids, 2002, Feb., 66(2-3)246-256.

2. Elbaz, E. et al, ” Modulation of tumor microenvironment and inhibition of EGF/EGFR pathway: novel mechanisms of Cannabidiol on breast cancer,”Molecular Oncology, 2015, Apr., 9(4):906-919.

3. Welty, W.E., et al, “Cannabinoids: the promises and pitfalls,” Epilepsy Currents, 2014, Sep.-Oct., 14(5):250-252.

4. Wallace, MJ, et al, ” The endogenous Cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy, ” The Journal of Pharmacology and Experimental Therapeutics, 2003, Oct., 307(1):129-137.

5. Gaston, T. et. al, “Pharmacology of cannabinoids in the treatment of epilepsy, ” Epilepsy Behavior, 2017, May, 70:313-318.

6. Volkow, Nora, “The biology and potential therapeutic effects of cannabidiol,” National Institute on Drug Abuse Senate Caucus on International Narcotics Control, 2015, June.

7. Kaplan,, “Cannabidiol attenuates seizures and social deficits in a mouse model in Dravet syndrome, “Proceedings of the National Academy of Science, 2017, Oct.