There are several different types of seizures, and some different physiology between them. Some seizure types are caused by overactive neurons. Other seizure types can be caused from extreme vasodilation, not allowing proper blood flow to the brain. In this section, we will go over:

 

Cannabinoids for Seizure Control: Reviewing how different cannabis compounds may influence seizure thresholds.

 

Potential Cannabinoid and Terpene Combinations: Exploring theoretical mixes that may warrant further research.

 

Terpenes and Their Influence on Seizures: Examining how these aromatic plant compounds can modulate neuronal and vascular processes, how they affect different seizure types, and possible interactions with a vagus nerve stimulator.

 

Adenosine A2A receptor: Seizure reduction with Humulene and its role as an adenosine A2A modulator, and the possible roles with seizure control with adenosine A2A agonists, antagonists, and modulators.

 

Medications Commonly Prescribed for Debilitating Seizures: An overview of established pharmaceutical approaches to help us understand pharmacological targets.

 

Febrile Seizure Caution: Considering the roles of TRPV3 and TRPM8 activation, and why they may matter in fever-related seizure types.

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Cannabinoids for seizure control

 

     CBD, CBC, and CBN are effective at reducing seizures at low doses. (13F)  THC and THCA has shown to reduce some types of seizures. A mouse with Dravet did show an increase in seizures with THC and THCA. THCA has a hard time entering brain cells, unlike THC. (14F) Using THC or THCA is going to be an individual response, with some people getting less seizures, while other types might have their seizures worsened.

 

     CBDV has anti-seizure properties, and was used in a Phase 2a placebo-controlled study for focal seizure but did not reach the primary endpoints back in February 2018. There is not much more known about the mechanism of action. (81B)

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Possible Cannabinoid and Terpene Combinations Worth

Researching for Seizure Control

 

1. Seizure Types Caused by Vasodilation Worsened by THC

 

Possible Cannabinoid Combination: Cannabidiol (CBD), cannabichromene (CBC), and cannabinol (CBN). Each of these cannabinoids has shown some seizure-reducing effects in various models. (13F)

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Possible Helpful Terpenes: Humulene, Terpineol and Eucalyptol

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Humulene: May help maintain blood flow to the brain by modulating the adenosine A2A receptor, which is involved with vascular tone regulation. (6D,17F)

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Terpineol: Could help reduce excessive brain activity and increase blood pressure due to its anticholinergic properties. (11D,47F,48F)

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Eucalyptol: TRPM8 agonist which could increase blood flow to the brain by causing peripheral vasoconstriction. (33D,19F,49F)

 

Avoid: excessive TRPV3 activation which will cause vasodilation. (42A,43A)

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2. Seizure Types Caused by Vasodilation Lessened by THC

 

Possible Cannabinoid Combination: THC, THCA, CBD, CBC, and CBN. (13F,51F) A wider range of cannabinoids could reduce the side effects of only taking large doses of one, and help reduce seizures through their anti-inflammatory or other effects.

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Possible Helpful Terpenes: Humulene, Terpineol and Eucalyptol

 

Humulene: May help maintain blood flow to the brain by modulating the adenosine A2A receptor, which is involved with vascular tone regulation.(6D,17F)

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Terpineol: Could help reduce excessive brain activity and increase blood pressure due to its anticholinergic properties. (11D,47F,48F)

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Eucalyptol: TRPM8 agonist which could increase blood flow to the brain by causing peripheral vasoconstriction. (33D,19F,49F)

 

Avoid: excessive TRPV3 activation which will cause vasodilation. (42A,43A)

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Personal Example

 

Lemon Walker (THC) Infused Chocolate: Dominant terpenes are limonene and terpineol. Strain side effects include dry mouth and eyes.

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White Walker (THC) in MCT Oil: Dominant terpenes are humulene and terpineol. Strain side effects include dry mouth and eyes, as well as a hungry and shaky feeling.

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Water-Cured CBD Lemon Skunk in MCT oil: Terpenes largely removed, some CBN present due to trichome oxidation. Strain side effects are minimal for water-cured, but original lemon skunk terpenes can be nauseating.

 

     I do use about twice as much THC as CBD. Individual responses will vary, and each person would need to try out different combinations to see what works for them. The strains I have are what I have available to me, and what grows well taking a clone from a clone year after year. Another combination I would like to try is the original White Widow, or CBD White Widow along with Lemon Walker. The original White Widow has humulene, caryophyllene, a-pinene, terpineol, and myrcene; which might be a little less sedating than White Walker.

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3. Seizures Caused by Brain Overactivity

 

Possible Cannabinoid Combination: Non-Psychoactive CBD, CBC, CBN — Each may help reduce excessive neuronal firing. (13F) CBN has sedative properties, potentially calming overactive brain activity. THC tends to heighten excitatory activity. THCA is relatively unstable, possibly converting into THC over time.

 

Potentially Helpful Terpenes: Terpineol and linalool - Both are often regarded as sedative or relaxing terpenes; they may reduce excitatory signaling.

 

Avoid: Acetylcholinesterase inhibitors (e.g., α-pinene in high doses) if overactivity is a concern, as they may increase brain excitability.

 

Terpenes that are acetylcholinesterase inhibitors are: limonene, a-pinene, beta-caryophyllene, beta-caryophyllene oxide, humulene, and delta 3 carene. (37E,52C)

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Notes and Considerations

 

Individual Responses: The effect of specific cannabinoids and terpenes can vary dramatically among individuals. Some may experience reduced seizure frequency, while others see no improvement or even a worsening of symptoms.

 

Research Gaps: Much of the discussion around cannabinoid-terpene synergy (entourage effect) in seizures remains preclinical or anecdotal. Rigorous clinical trials are needed.

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Strain Variability: Cannabis strains labeled with the same name can still differ in terpene/cannabinoid profiles, known as chemotypes. Lab testing is ideal for knowing exact chemical compositions.

 

Medical Oversight: Anyone considering these combinations for seizure management should consult a licensed medical professional.

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How terpenes could influence seizures

 

     Research on how specific terpenes influence various seizure disorders is extremely limited. Much of what is here is theoretical and should not replace professional medical advice. Always consult a licensed medical professional before attempting to treat medical problems with terpenes or any other supplements.

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Alpha-Pinene

 

 

Acetylcholinesterase Inhibition: α-Pinene is reported to inhibit acetylcholinesterase (AChE).(5C) Inhibiting AChE raises acetylcholine (ACh) levels, which can enhance parasympathetic (vagal) activity, potentially lowering heart rate. (10C)

 

Effects on the Brain: Because AChE inhibitors are used in certain forms of dementia to boost cholinergic signaling, (10C) α-pinene may similarly increase central cholinergic activity. This could, in theory, heighten excitatory processes in certain brain regions.

 

Cerebral Blood Flow: Chronic AChE inhibition can lead to increased cerebral blood flow, (15F) which might help conditions triggered or exacerbated by reduced perfusion to the brain.

 

Possible Interaction with Vagus nerve stimulators (VNS): May enhance parasympathetic tone and can cause bradycardia or, in rare cases, cardiac standstill.(16F) Combining VNS with any additional parasympathetic stimulation (such as α-pinene) could possibly worsen the cardiovascular risks. 

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Potential Seizure-Related Implications with a-pinene

 

Vasodilation-Induced Seizures: If a person’s seizures are linked to reduced blood flow (due to excessive vasodilation elsewhere in the body), α-pinene’s boost in parasympathetic tone and improved cerebral circulation might be beneficial.

 

Hyperexcitable Seizure Types: Elevated ACh in the brain could worsen seizure disorders characterized by neuronal overactivity.

 

Cardiovascular Caution: Using α-pinene alongside a vagus nerve stimulator may carry serious cardiovascular implications, such as profound bradycardia. Individuals with cardiac concerns or those who already use VNS should approach α-pinene (or any strong AChE inhibitor) with extreme caution.

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Humulene

 

     Humulene is an adenosine A2A modulator, and an acetylcholinesterase inhibitor with an IC(50)=785.3 ± 66.0. (6D,37E) When Adenosine A2A is activated by an agonist, vasodilation will occur. This receptor is also involved with vascular tone regulation.(17F) Since humulene is a modulator, it could be regulating the blood pressure, maintaining the blood flow in the body. With this type of modulation, blood pressure could be less prone to changes from outside influences like heat induced vasodilation.

 

     Humulene is not researched for anti-seizure effects. I have found this terpene to be incredibly helpful for my seizures, which is characterized as non-epileptic. Some doctors say that it can be called convulsive syncope. The main problem is that blood pressure changes, and vasodilation will cause me to have that type of seizure. Hot showers, hot weather, or any type of external heat will cause an excessive vasodilatory response in me. Adrenaline and noradrenaline responses can also affect those seizures. 

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Isolated Humulene

 

     Isolated terpenes can be dangerous, even ones extracted from food. 1 sublingual drop of isolated humulene caused me to have some severe chest pain, even if it was mixed with another strain of marijuana. I did not ever experience chest pain with humulene strains, like White Widow or strains crossed with it like Skywalker X White Widow, or Blue Dream X White Widow. Diluting the humulene (1 part) with 30 parts of myrcene made it more tolerable. It did not work as well, and had more side effects compared to using a humulene strain like White Widow.

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Possible effects of Adenosine A2A agonists, antagonists, and modulators with

Sudden Unexpected Death in Epilepsy (SUDEP)

 

An A2AR agonist could worsen SUDEP risk in this model by further raising receptor activity already elevated under epileptic conditions. This can be inferred due to role of antagonists of A2A.

 

An A2AR antagonist (as shown by SCH58261) reduces SUDEP events, likely by dampening excessive or maladaptive NTS signaling.(18F)

 

An A2AR modulator might fine-tune these pathways, providing seizure- or SUDEP-preventing benefits while minimizing side effects. This needs more targeted research.

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Eucalyptol and TRPM8 activation -The cold receptor

 

Can TRPM8 activation reduce seizures?

 

     It is known that cold air blowing on the face while driving can increase cerebral perfusion.(19F) When I systemically activated TRPM8 through either a raw THCA Lemon Kush filled capsule, or tea made with the leaves of that plant; my seizures were gone. This did create a cold feeling throughout my whole body. Taking too much TRPM8 agonists can cause shivering. About 0.2-0.3 grams of Lemon Kush dried flowers worked well for about 4-6 hours. 1 large fan leaf soaked in hot water was enough to get a good cold effect. Eating the large leaf was too intense with the cold activation.

 

     Most strains do not cause a cold feeling, and the decarboxylated form of Lemon Kush also did not provide the cold feeling. This could be from more TRPM8 antagonists, and TRPV agonists from the decarboxylated cannabinoids. Eucalyptol is the only known cannabis compound known to activate TRPM8 (agonist). I don’t have a lab test to see what is all in that plant.

 

     Eucalyptol is an agonist of TRPV3 and TRPM8, and a TRPA1 antagonist,(38A,33D) which seems like they would cancel each other out. I personally feel the cold sensation from eucalyptol, but it is not known if others would feel differently with it. It is possible that the TRPM8 activation could be stronger than the TRPV3 activation, overriding the warm feeling effect of it. The antagonism of TRPA1 could also influence the vascular changes, but research is lacking on this type of information.

 

     TRPM8 activation worked well for a few years to reduce my seizures, but I had to stop taking that after developing some minor heart problems from low phosphate caused by Keppra. After this point, I had to switch to a humulene strain (White Walker). 

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Cold can increase cerebral perfusion

 

     A study about cold face stimulation (from a driving reflex) resulted in bradycardia, peripheral vasoconstriction, and an increase in blood pressure. Some cerebral vasoconstriction occurred, but there was an increase in cerebral perfusion.(19F)

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Studies on weather, temperature, and humidity affecting the heart

 

Ventricular Tachycardia in Warmer or Higher-Pressure Conditions - A study found that older adults and women experienced more episodes of ventricular tachycardia when temperature or atmospheric pressure was higher. (20F)

 

Atrial Fibrillation in Cold, Dry Air - In contrast, colder, drier weather was linked to increased atrial fibrillation in elderly individuals. (21F)

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Linalool

 

     Linalool is a NMDA receptor antagonist.12F Ketamine is also a NMDA antagonist (22F) that has been used to treat super-refractory status epilepticus, (23F) and also can induce seizures in people with no seizure history. (50F) The NMDA receptor is where the ligands like glutamate which is the brain's primary excitatory neurotransmitter. (24F)

 

Linalool would likely be helpful with seizure types that involve neuronal overactivity, but it might not help vasodilation induced seizures.  

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What will happen with inhibiting acetylcholine with linalool along with a vagus nerve stimulator?

 

     There is no research to show what happens with lowering acetylcholine while using a vagus nerve stimulator (VNS). It is possible that the VNS could be less effective, and also, parasympathetic side effects like bradycardia could also be reduced.

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Terpineol

 

Terpineol is an anticholinergic. (11D) Anticholinergics can increase blood pressure and heart rate. (25F)

 

    Side effects or toxicity of prescription anticholinergics include rapid heart rate, arrhythmias, urinary retention, blurred vision, constipation, reduced gut motility, hyperthermia, and inhibition of sweating. (35C) 

 

Anticholinergics could reduce seizure frequency and spontaneous recurrent seizures in posttraumatic epilepsy (PTE), which occur after a traumatic brain injury. (26F)  Terpineol might be helpful for seizures with increased brain activity by reducing the activity of acetylcholine. It also might help with the vasodilation type of seizures by increasing blood pressure.

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What will happen with inhibiting acetylcholine with terpineol along with a vagus nerve stimulator?

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     Terpineol combined with a vagus nerve stimulator could be less effective at seizure reduction. It can also reduce the parasympathetic side effects like bradycardia.

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Myrcene

 

     Myrcene is a mu-opioid and alpha 2-adrenoreceptor modulator. (69C) The Mu-3 opioid receptor is responsible for vasodilation. (90A)

 

     Some opioid medications like morphine and tramadol can induce seizures. Some individuals could get a seizure with low or high doses of those medications. This is an individual response, and myrcene does not act exactly the same as those medications. (27F)

 

     Myrcene also modulates the adenosine A2A receptor (69C) which is involved with vascular tone regulation.(17F) This terpene is a well known Indica terpene that has been described as contributing to a “stuck sitting on the couch” type effect, AKA Couch Lock. It is possible that myrcene could worsen some seizure types. It might be helpful for people with adrenaline type disorders that contribute to certain seizure types. The vasodilation effects of myrcene are from the Mu-opioid receptor activation, and would likely override the action of modulating the alpha 2-adrenoreceptor.

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Terpenes that could worsen vasodilatory induced seizures

 

     TRPV3 agonists can cause vasodilation through triggering the release of Adenosine Triphosphate (ATP), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and prostacyclin (PGI2). (42A,43A)

 

     Terpenes that are TRPV3 agonists include: camphor, menthol, dihydrocarveol, 1,8-cineol (eucalyptol),(38A) 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol, (+)-borneol, (39A) and eugenol. (36A)

 

     Other agonists: 2-aminoethoxydiphenyl borate (2-APB),(38A) TRPV3 is activated from temperatures 22 and 40 degrees C, and an increased response at noxious temperatures greater than 39 degrees C. (40A)

 

Whole herbs that contain terpenes that are agonists to TRPV3: oregano, savory, clove and thyme. (41A)

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Febrile Seizures Warning with TRPV3 and TRPM8 activation

 

     There is research lacking on how receptors like TRPV3 and TRPM8 can affect seizures induced by a fever. Since TRPV3 can cause vasodilation, that could possibly reduce a fever from allowing the body heat to leave the body faster. Even though TRPV3 causes a warming sensation. The vasodilation effect could worsen seizures that are caused from the lowered blood pressure.

 

TRPM8 agonists like eucalyptol and menthol can cause a cooling sensation. (55A)

 

     TRPM8 activation can cause vasoconstriction or vasodilation, depending on previous vasomotor tone. (28F) When blood vessels constrict, blood leaves the periphery and goes to central circulation. If there is peripheral vasoconstriction, it could make a fever worse by not allowing the body heat to leave effectively.

 

TRPV3 information is mentioned earlier on this page, in the previous section.

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Medications often prescribed for debilitating seizure types

 

     Lennox-Gastaut syndrome: Medications for Lennox-Gastaut syndrome can include valproate, clobazam, felbamate, lamotrigine, rufinamide, topiramate, and cannabidiol (CBD). (29F)

 

     Dravet syndrome has symptoms that include spontaneous generalized tonic-clonic seizures, susceptibility to seizures induced by elevated body temperature, and elevated risk of sudden unexpected death in epilepsy. The Cav3.1 subunit of the T-type calcium channel family is abnormal in Dravet syndrome. (30F) Treating abnormal calcium channels can be tricky since that can affect blood pressure, heart rate and rhythm.

 

     Dravet syndrome is often treated with seizure meds like oxcarbazepine, carbamazepine, phenytoin, lamotrigine, fenfluramine and cannabidiol (CBD). (31F)

 

     Stiripentol (STP; Diacomit®) is an antiepileptic drug indicated for Dravet syndrome that has been identified as a γ-aminobutyric acid (GABAergic) positive allosteric modulator. (32F)

 

     The medication valproate is generally considered a first-line therapy for various seizure types. Other anticonvulsant medications may include clobazam, felbamate, lamotrigine, rufinamide, topiramate, and cannabidiol. The U.S. Food and Drug Administration (FDA) approved cannabidiol (Epidiolex, derived from marijuana) for the treatment of seizures associated with Lennox-Gastaut syndrome in individuals ages 2 and older. The drug contains only a small amount of the psychoactive element in marijuana and does not induce euphoria associated with the drug. (36F)

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Keppra (Levetiracetam)

 

     Keppra (Levetiracetam) is used to partial, myoclonic, and tonic-clonic seizures. It reduces calcium-dependent vesicular neurotransmitter release from binding to the synaptic vesicle protein 2A (SV2A). (33F) Keppra inhibits presynaptic glutamate release in the dentate gyrus by reducing both AMPA- and NMDA-mediated excitatory postsynaptic currents (EPSCs). (34F)

 

     Side effects of Keppra include low phosphate, low calcium, elevated alkaline phosphatase,(35F) sedation, fatigue, mood swings, headache, agitation, irritability, aggression, depression, memory loss, confusion, paresthesia, a decline in cognition, and increased suicide risk. (33F)

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Valproic Acid

 

     Sodium Channel Inhibition: Valproic acid (VPA) decreases the ability of neurons to fire at high frequencies by prolonging the inactivated state of voltage-gated sodium channels. (36F)

 

     Enhancement of GABAergic Tone: VPA increases the synthesis of GABA and inhibits GABA transaminase, thereby raising GABA levels in the brain and promoting an inhibitory effect on neuronal firing. (36F)

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     Histone Deacetylase (HDAC) Inhibition: VPA, particularly against HDAC1, influences gene expression by modifying histone acetylation status—altering the accessibility of DNA for transcription. (36F)

 

     Calcium Channel Modulation: While best known for blocking T-type calcium channels (key in absence seizures), VPA can also modulate L-type and N-type channels to a lesser degree. (36F)

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Dilantin (Phenytoin)

 

     Phenytoin is a medication used in the management and treatment of epilepsy, generalized tonic-clonic seizures, complex partial seizures, and status epilepticus. (37F)

 

     Inhibition of Voltage-Gated Sodium Channels: Phenytoin binds preferentially to sodium channels in their inactivated state, slowing their return to the resting state and thus reducing repetitive neuronal firing, which stabilizes hyperexcitable neuronal membranes. (38F)

 

     Minor Modulation of Calcium Channels: Some studies suggest phenytoin has a weak effect on high-voltage–activated calcium channels (e.g., L-type). (39F)

 

     Reduces excessive glutamate release: Excessive glutamate release is associated with some seizure disorders, and glutamate is needed for normal neuronal signaling. (40F, 41F)

 

     Side effects can include: rash, sedation, peripheral neuropathy, phenytoin encephalopathy, psychosis, locomotor dysfunction, hyperkinesia, megaloblastic anemia, decreased bone mineral content, Stevens-Johnson syndrome, toxic epidermal necrolysis, immunoglobulin A deficiency, gingival hyperplasia, dress syndrome (drug reaction accompanied by eosinophilia and systemic symptoms), cardiovascular collapse, hypotension, arrhythmias, hydantoin syndrome in newborns, purple glove syndrome, and hypertrichosis. (37F)

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Other treatment options include

 

     Dietary therapy with the ketogenic diet: The keto diet can increase extracellular adenosine levels, allowing more to bind to the adenosine A1 receptor. This reduces the amount of glutamate being released in the brain. (42F)

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     Vagus nerve stimulation; Vagus nerve stimulation (VNS) modifies plasticity in key brain areas by triggering the release of neuromodulators like acetylcholine and norepinephrine. This will enhance the brain's ability to reorganize neural circuits, particularly in regions associated with motor function, sensory processing, and emotional regulation. VNS can be useful in conditions like stroke, depression, and epilepsy when paired with targeted rehabilitation or training. (43F)

 

     Complications of a VNS include: voice alteration, hoarseness, cough, tingling, dyspnea, vocal cord paralysis, implant site infection, left facial nerve paralysis, and Horner syndrome. (44F)

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     Epilepsy surgery (typically a corpus callostomy, which involves severing the band of nerve fibers that connect the two halves of the brain to prevent seizures from spreading). Complications can include: superficial hemosiderosis (anatomic hemispherectomy), progressive hydrocephalus (anatomic hemispherectomy), postoperative infarction from injury to the Sylvian vein sinus thrombosis, memory decline and anomic aphasia (temporal lobe resection), vasospasm and with contralateral superior quadrantanopia following the injury to Meyer's loop (amygdalohippocampectomy), disconnection syndrome (corpus callosotomy), hemiparesis and dysphagia (multiple subpial transections), and cough and hoarseness of voice (vagal nerve stimulation). (45F)

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Epidiolex (CBD)

 

     Epidiolex (CBD) is prescribed for children that are at least 1 year old. It is not known what happens to children under 1 that take Epidiolex. (46F) The doses are as follows (taken from the Epidiolex insert):  

 

     “The recommended starting dosage is 2.5 mg/kg by mouth twice daily (5 mg/kg/day).  After one week, the dosage can be increased to a maintenance dosage of 5 mg/kg twice daily (10 mg/kg/day). Based on individual clinical response and tolerability, EPIDIOLEX can be increased up to a maximum recommended maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day).“ 10 and 20 mg/kg/day dosages may lead to elevated liver enzymes. (46F)

 

     Possible side effects in patients with Lennox-Gastaut syndrome or Dravet syndrome are:  somnolence; decreased appetite; diarrhea; transaminase elevations; fatigue, malaise, and asthenia; rash; insomnia, sleep disorder, and poor quality sleep; and infections. (46F)

 

     Possible side effects in patients with tuberous sclerosis complex are: diarrhea; transaminase elevations; decreased appetite; somnolence; pyrexia; and vomiting. (46F)

 

     Personally, I cannot handle more than about 50mg of CBD every 4 hours. It makes me feel shaky, nauseated, and tired. Everyone will be different on how much they can take without side effects. Some of these pediatric doses can reach 10 mg/kg twice per day. A 20 kg child (44 Lbs) would be taking 200 mg twice per day. That high of a dose at a time could contribute to side effects. If the side effects are not tolerated well, then doctors should consider doing a lower dose more frequently, or try an entourage effect with CBD, CBC, CBN, and some terpenes like humulene, eucalyptol, and terpineol. Taking 3 cannabinoids and terpenes could possibly lower the amount of CBD needed, and reduce side effects. These combinations really need some targeted research.