The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy (CBD1) The investigators propose to study the effects of cannabidiol (CBD) on Cannabidiol (CBD) can exert neuroprotective effects without being intoxicating, and in combination with Δ<sup>9</sup>-tetrahydrocannabinol (THC) CBD has shown to protect against THC psychosis. Acute concussion and post-concussion syndrome (PCS) can result in autonomic dysfunction in heart rate varia … Dysautonomia includes POTS, neurocardiogenic syncope, and other disorders affecting the autonomic nervous system. Symptoms can be completely debilitating restricting patients from many day to day activities. Cannabis can be a helpful tool for managing symptoms of dysautonomia and POTS, but there are some things to be aware of.
The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy (CBD1)
The investigators propose to study the effects of cannabidiol (CBD) on cardiac electrical function and the autonomic nervous system in children with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), when the CBD is administered as an artisanal oil obtained through state dispensaries or other sources. The intent is to begin to assess potential risks and benefits of this therapy in a vulnerable patient population by characterizing the effects of CBD on EKG findings, heart rate variability and the occurrence of seizures.
|Condition or disease||Intervention/treatment||Phase|
|Lennox-Gastaut Syndrome Dravet Syndrome||Procedure: 12-Lead ECG Drug: Cannabidiol||Phase 1 Phase 2|
Specific Aims/Study Objectives
This is a pilot study to explore the effects of cannabidiol (CBD) on autonomic cardiac function in children with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) when the CBD is administered as an artisanal oil. This will be achieved by addressing the following specific aims.
Aim #1: To determine the effects of CBD on cardiac function in 30 children with DS and LGS. This is the primary aim of the study: The effects of CBD on the cardiac function of 30 children with DS or LGS will be assessed using a 15-lead electrocardiogram (EKG) and a 24-hour Holter monitor. Investigators hypothesize that there will be no alterations in ventricular repolarization and heart rate variability on the EKG and Holter monitoring, respectively, after taking CBD for 4-8 weeks, compared to when participants were not taking CBD.
Note: The following aims are secondary to the primary outcome and goal of assessing the effects of CBD on cardiac function.
Aim #2: To assess signs and symptoms of dysautonomia in the presence and absence of CBD. Signs and symptoms of dysautonomia include parental perception of body temperature, skin color in hands and feet, sweating, pupil size, flushing, feeding issues, heart rate, strong emotions, constipation, urination or bowel movement issues, and irritability. These signs and symptoms will be collected using a previously-established dysautonomia survey. Investigators hypothesize there will be no change in qualitative assessments of signs and symptoms of dysautonomia after taking CBD for 4-8 weeks, compared to when participants were not taking CBD.
Aim #3: To determine the effects of CBD on the occurrence of seizures. The number of seizures in children who obtain CBD will be assessed using a 7-day seizure diary (Seizure tracker). Caregivers will record the number of seizures for a 7-day period prior to CBD administration, and repeat the seizure tracking after having received CBD for 4-8 weeks. Change in seizure numbers will be compared pre- and post-CBD administration. Investigators hypothesize that study participants will have lower seizure counts after being on CBD compared to when weren’t taking CBD.
Study Design and Methodology
Study Design: Thirty patients with DS or LGS who are going to register to take medical cannabis (cannabidiol, or CBD) in the state of Minnesota will be offered the opportunity to participate in this study. If consent is obtained, the patient or guardian will be asked to complete a questionnaire developed for this study that documents observable signs and symptoms of dysautonomia, and to complete a seizure diary for 7 days prior to initially receiving the CBD. Each participant will also have a 15-lead electrocardiogram (EKG) and wear a 24-hour Holter monitor, both non-invasive measures of cardiac function, prior to being administered the CBD. The EKG and 24-hour Holter monitor will be interpreted by a cardiac electrophysiologist and will be reviewed for heart rate variability parameters. The dysautonomia questionnaire, seizure diary and cardiac measurements will be repeated 4-8 weeks after the subject has been on a stable regimen of CBD. This time-frame is based on availability of subjects schedules and clinic visits, and it is also greater than 5 half-lives previously reported for CBD (apparent half-life, 21 hours, (15)). Steady-state levels are achieved after 5 half-lives of drug dosing, thus we expect to be at steady-state concentrations.
Subjects who are already on a stable regimen of CBD, yet plan to stop taking CBD at some point for some reason, are also eligible to participate. The parent or guardian will complete the dysautonomia questionnaire and seizure diary (and research staff will be available to help with questions), and the patient will have the 15-lead EKG and 24-hour Holter monitor while still on the CBD. The subjects will then come back 4-8 weeks after their last dose of CBD to have these assessments repeated while off of the CBD. This time frame is based on availability of subjects schedules and clinic visits as well as being substantially greater than 5 half-lives of CBD, the standard wash-out period for pharmacological studies.
Effects of phytocannabinoids on heart rate variability and blood pressure variability in female post-concussion syndrome patients: case series
Cannabidiol (CBD) can exert neuroprotective effects without being intoxicating, and in combination with Δ 9 -tetrahydrocannabinol (THC) CBD has shown to protect against THC psychosis. Acute concussion and post-concussion syndrome (PCS) can result in autonomic dysfunction in heart rate variability (HRV), but less information is available on blood pressure variability (BPV). Furthermore, the effects of phytocannabinoids on HRV and BPV in PCS are unknown. The purpose of this study was to observe the influence of daily administration of CBD or a combination of CBD and THC on HRV and BPV parameters in four female PCS participants. Participants completed a seated 5-min rest followed by six breaths-per-minute paced breathing protocol. Data was collected prior to phytocannabinoid intake and continued over 54 to 70 days. High frequency systolic BPV parameter increased every assessment period, unless altered due to external circumstances and symptoms. HRV parameters showed less consistent and varying responses. These results suggest that CBD can help to improve the altered autonomic dysfunction in those with PCS, and that responses to the drug administration was individualized. Double blinded, randomized controlled trials with greater sample sizes are required to better understand the influences of the varying dosages on human physiology and in PCS.
Keywords: blood pressure variability; cannabidiol; commotion cérébrale; concussion; post-concussion syndrome; syndrome post-commotion cérébrale; variabilité de la tension artérielle.
Singh J, Neary JP. Singh J, et al. Can J Neurol Sci. 2020 May;47(3):289-300. doi: 10.1017/cjn.2020.23. Can J Neurol Sci. 2020. PMID: 32029015 Review.
Solowij N, Broyd S, Greenwood LM, van Hell H, Martelozzo D, Rueb K, Todd J, Liu Z, Galettis P, Martin J, Murray R, Jones A, Michie PT, Croft R. Solowij N, et al. Eur Arch Psychiatry Clin Neurosci. 2019 Feb;269(1):17-35. doi: 10.1007/s00406-019-00978-2. Epub 2019 Jan 19. Eur Arch Psychiatry Clin Neurosci. 2019. PMID: 30661105 Clinical Trial.
Fernández-Trapero M, Pérez-Díaz C, Espejo-Porras F, de Lago E, Fernández-Ruiz J. Fernández-Trapero M, et al. Biomolecules. 2020 Feb 11;10(2):279. doi: 10.3390/biom10020279. Biomolecules. 2020. PMID: 32054131 Free PMC article.
Tian G, Xiong L, Leung H, Soo Y, Leung T, Wong LK. Tian G, et al. J Clin Neurosci. 2019 Jun;64:187-193. doi: 10.1016/j.jocn.2019.03.003. Epub 2019 Mar 12. J Clin Neurosci. 2019. PMID: 30876936
Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, Katz R, Di Marzo V, Jutras-Aswad D, Notcutt WG, Martinez-Orgado J, Robson PJ, Rohrback BG, Thiele E, Whalley B, Friedman D. Devinsky O, et al. Epilepsia. 2014 Jun;55(6):791-802. doi: 10.1111/epi.12631. Epub 2014 May 22. Epilepsia. 2014. PMID: 24854329 Free PMC article. Review.
Ellingson CJ, Singh J, Ellingson CA, Dech R, Piskorski J, Neary JP. Ellingson CJ, et al. Curr Res Physiol. 2022 Jun 14;5:240-245. doi: 10.1016/j.crphys.2022.06.003. eCollection 2022. Curr Res Physiol. 2022. PMID: 35756694 Free PMC article.
POTS, Dysautonomia, and Medical Cannabis
When I tell people that I have a condition called POTS they often laugh and crack a joke about how it’s the perfectly named condition for me given my line of work and passion. I can’t help but chuckle and agree, but the reality of living with a condition like POTS is far from a laughing matter.
Before I was dealing with the symptoms myself I had no understanding of or awareness of the disorder or it’s umbrella category – dysautonomia. This was a bit of surprise to me considering I’d devoted my entire career to helping people with chronic illness. So how did I learn about it? By passing out cold in the bathroom and slicing my head open on a cabinet and toilet roll holder – more than once. What can I say, I like to learn things the hard way.
POTS stands for Postural Orthostatic Tachycardia Syndrome, a form of dysautonomia.
Let’s break those two down.
Dysautonomia refers to any disorder of the autonomic nervous system (ANS). The ANS controls important parts of our body that we don’t have to think about like blood vessels, stomach, intestines, liver, kidneys, heart, etc. Common forms of dysautonomia include POTS, neurocardiogenic syncope, multiple system atrophy, and diabetic autonomic neuropathy. While dysautonomia can develop for a range of reasons, conditions such as diabetes, MS, rheumatoid arthritis, Parkinson’s disease, and celiac disease can contribute to its onset.
Postural Orthostatic Tachycardia Syndrome is a form of orthostatic intolerance, meaning symptoms surface when standing from a reclining position and may be relieved upon lying back down. By definition POTS is a rapid increase in heart beat when standing (over 30bpm), but other symptoms can include dizziness, light headiness, fatigue/exhaustion, chest pain, brain fog, temperature deregulation, nausea, and other similar symptoms.
People with POTS have difficulty regulating blood flow and volume, meaning blood pressure and heart rate become unstable. For me this leads to episodes of Neurocardiogenic Syncope (NCS) in which I faint and loose consciousness. When I come to I experience extreme nausea, vomiting, exhaustion, and a general feeling of unwellness. Many individuals with dysautonomia have other related conditions like Ehlers-Danlos syndrome, gastroparesis, and Mast Cell Activation Syndrome (MCAS) that include symptoms of severe pain, stomach discomfort, difficulty with appetite, and allergic reactions. Many of these symptoms can be managed with cannabis, but there are also some things to be aware of.
Using Medical Cannabis for Dysautonomia – Things to Know
Every single person will respond to cannabis differently. Patients with dysautonomia find that cannabis helps them immensely for some symptoms, but can exacerbate others. Being aware of these potential side effects is important to getting the most out of your cannabis routine.
THC can raise heart rate.
Individuals with POTS by definition have difficulty with tachycardia, or an elevated heart rate. THC can raise heart rate for the short-term, while lowering it over the long term. Some patients with POTS have difficulty bringing their heart rate back into a normal range – even requiring IV fluids and medications to do so. Some cannabis users are particularly sensitive to this increase in heart rate and finds it worsens these POTS symptoms. Other dysautonomia patients, like myself, actually benefit from this action – I medicate with THC prior to showering as my heart rate and BP tends to bottom out during and after showers. I can use it mindfully to help regulate my heart rate and BP when needed.
Cannabis can trigger orthostatic hypotension.
Cannabis contributes to vasodilation, which for many people with chronic illness is an added benefit (reduces blood pressure). Patients already prone to orthostatic hypotension (a severe drop in blood pressure when changing from sitting/laying to standing) may find these symptoms exacerbated with cannabis, especially with high doses. As orthostatic dysfunction is a hallmark feature of dysautonomia, patients should be mindful of this potential exacerbation when using cannabis and take necessary precautions.
Everyone responds differently.
I do well with THC – I can use it mindfully to raise my heart rate in situations where my dysautonomia causes it to drop, but products and strains dominant in CBD seem to exacerbate my symptoms and propensity towards syncope (more on this below). It’s important that dysautonomia patients are aware of both the positive and potential negative effects of cannabis so they can effectively monitor their symptoms and results.
Benefits are varied and affect multiple systems.
Cannabis has neuroprotective and anti-oxidant properties. There is some suggestion that cannabis may be healing for dysautonomia patients by addressing the underlying nerve damage. However, this is a theoretical assumption and beyond our current understanding of the plant. Most dysautonomia cannabis patients use it to manage day to day symptoms including nausea, fatigue, and pain. Cannabis may also be effective in managing inflammation and other symptoms associated with commonly co-morbid conditions. For example, patients with related MCAS my find cannabis topicals helpful for localized reactions and those with gastroparesis may find it helpful for appetite.
My Personal Experience
Cannabis has been life changing for me in so many ways, but when I started experiencing symptoms of dysautonomia, primarily fainting episodes, my world was thrown upside down. My cannabis physician and friend Dr. Scott Gebhardt suggested to me that my CBD intake could be contributing to my episodes and recommended I take it out of my routine to test if it could be contributing. I was less than willing to take on this experiment, so I initially stopped my oral doses for only a week. My dysautonomia symptoms weren’t improving and my pain was increasing so I called the ‘experiment’ a loss and started taking my oral CBD again.
Months went by and my dysautonomia symptoms were continuing to worsen. I had continued to up my CBD intake over this time – both orally and via inhalation. Dr. Gebhardt was still in my ear about my CBD use dropping my blood pressure and contributing to my orthostatic episodes. I really really didn’t want to hear him.
Every time I faint or have a near fainting episode I feel a little piece of my independence slip away. Not wanting this anymore, I finally gave in and stopped my CBD intake all together – no oral and no CBD dominant strains or 1:1 via inhalation. I had to make adjustments to my overall routine to better manage my pain without the CBD, but to my surprise I went THREE MONTHS without having a fainting episode, something that was happening far more regularly prior to stopping. The first syncope episode I had after cutting out my CBD was when my air conditioner broke (heat is a major trigger). I’ve experienced a drastic reduction in orthostatic intolerance with almost no pre-syncopal episodes.
While I can’t deny that CBD was contributing to my dysautonomia symptoms, my endometriosis symptoms have really ramped up without it. I recently tried to add inhaled CBD dominant products back into my routine to work on this pain. Unfortunately, I was met with the full array of my dysautonomia symptoms – including fainting. Now that I have a better understanding of how cannabis affects my blood pressure and symptoms, I’m better able to manage both my dysautonomia and medical cannabis use.
I Have Dysautonomia and Want to Try Medical Cannabis – What Does This Mean for Me?
Choose a quality cannabis physician (who knows a thing or two about dysautonomia).
Despite all of my knowledge and experience with cannabis, I would have NEVER stopped taking my CBD and identified it as a trigger if it wasn’t for the outside perspective and guidance from my cannabis physician, Dr. Scott Gebhardt. Choose a physician who understands the plant and body, looks at the bigger picture, and is not just there to issue a certification. This will pay you back in ways you never imagined.
EVERY single patient is different. Journal your cannabis use and symptoms to figure out your personal patterns, reactions, and best products.
Take your BP and HR.
As patients with dysautonomia can have difficulty regulating blood pressure and heart rate, be mindful to take regular readings when starting a new cannabis routine.
Keep a positive mindset.
Cannabis is psychoactive and sensitive to set and setting. If you go into a situation expecting a negative reaction, you are more prone to have one. Try to be calm and collected before medicating.