cluster headache

Mechanism and novel approaches to treatment of cluster headache

Virginia Thornley, M.D., Neurologist
January 2, 2019
Cluster headache is a debilitating neurological condition which may be difficult to control. Novel approaches to treatment have been explored because of its refractory response to treatment.
Mechanisms involved in cluster headache
The pathophysiology involves the trigeminovascular pathway. This involves innervation to the  cerebral blood vessels and trigeminal complex including the nerves and ganglion. The ganglion has connections with the blood vessels of the cerebrum, the trigeminocervical complex and the dorsal horns of the C1 and C2 levels. In cluster headaches, certain chemicals are found to be increased during an attack  including calcitonin gene-related peptide and neurokinins which are neuropeptide vasodilators (1).
Calcitonin gene-related peptide antibody therapies
Some of the new anti-CGRP (calcitonin gene-related peptide antibody) therapies recently introduced to migraine patients have been applied to patients with cluster headache, including fremazunab and galcanezumab (2). it has been found that CGRP is released from the trigeminal ganglion and its transcription is increased when there are conditions that mimic those of migraine which includes an neurogenic inflammatory state (3).
There has been some success in its treatment although its application is not yet indicated for these drugs (2).
Botulinum toxin injection
Injection of onabotulinum toxin into the sphenopalatine ganglion was studied in 7 patients with chronic cluster headache. Of these, 3 dropped out. The patients were followed 24 months. There was a 50% reduction in occurrence of pain, after repeated injections. Due to the small size results should be interpreted with caution, however, because of repeated injections, its effectiveness may be significantly underestimated. This is a small pilot observational study. Larger studies are needed (4).
 
Vagal nerve stimulation
Vagal nerve stimulation was employed in 30 patients and a mean reduction of 26 attacks/week to 9.5 over a 3-6 month period was seen. Mean attack duration was 51.9 to 29.5 minutes. Larger studies are needed (5).
In summary 
Several new novel approaches include vagal nerve stimulation and botulinum toxin injections. Anti-CGRP antibodies are another novel treatment but have not yet been submitted for an indication. Larger studies are needed.
@VThornley_MD
Reference
  1. Goadsby, P.J., Edvinson, L., Human in vivo evidence for trigeminovascular activation in cluster headache.Neuropeptude chanes and effects of acute attackes therapies. Brain. 1994 Jun; 117 (Pt 3):427-34
  2. Ashehoug, I., Bratbak, D.F., Tronvik, E.A. Long-term outcome of patients with intractable chronic cluster headache treated with injection of onabotulinumtoxin A toward the sphenopalatine ganglion – an observational study. Headache, 2018, Nov; 58(10):1519-1529
  3. P.L. Durham, Calcitonin gene-related peptide and migraine. 2006, Jun. 46 (Suppl 1):S3-S8
  4. Tepper, S.J. Anti-calcitonin gene-related peptide (CGRP) therapies: update on a previous review after the American Headache Society 60th Scientific Meeting, San Francisco, June 2018
  5. Marin, J., Giffin, N., Consiglio, E., mcClure, C., Liebler, E., Davies, B. Non-invasive vagus nerve stimulation for treatment of cluster headache: early UK clinical experience. J. Headache Pain. 2018, Nov. 23; 19

Disclaimer: This is for informational purposes only and is not medical advice. Please see your physician. Reading this does not constitute a physician-patient relationship.

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Parkinson's disaese

Parkinson’s disease: a look at a novel biomarker, immunogenetic & mitochondrial studies

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Virginia Thornley, M.D., Neurologist, Epileptologist
December 17, 2018
Introduction
Parkinson’s disease is typically diagnosed through clinical evaluation. At times, it may be difficult to differentiate from other disorders if all cardinal features are not present. This looks at the literature to review biomarkers that may be helpful in evaluation of the diagnosis of Parkinson’s disease.
 
Novel serum marker LAG-3
One study correlates the serum marker LAG-3 lymphocyte activation gene 3  (LAG-3). It is thought to be related to the transmission of alpha-synuclein which could be connected to the degenerative process in Parkinson’s disease. Serum LAG-3 was found to be higher in the serum levels compared to patients with essential tremors and a control group that was sex and age matched. LAG-3 can potentially serve as a biomarker when the diagnosis is in question (1).
 
Immunogenicity
As the population ages, there is a proliferation of neurodegenerative disorders. Familial disorders account for a small portion of these about 5-10%. It is thought that there are genetic and environmental component to the familial types of neurodegenerative diseases. Gene variants are found on HLA (human leukocyte antigen) which code for MHL II (major histocompatibility complex class II) which is found in microglia which has an immunologic component. Microglia phagocytizes unnecessary proteins but also produces an inflammatory response. How the immune system responds to environmental factors resulting in neurodegenerative disease is a subject of research and needs to be elucidated further (2). 
 
The role of the mitochondrial dysfunction in Parkinson’s disease
Mitochondrial dysfunction and oxidative damage is found in the cells of patients with Parkinson’s disease. Mitochondrial abnormalities have been hypothesized to correlate with the pathophysiology of Parkinsons disease. Recent research has shown a tying of both genetic and environmental factors in relation to the pathophysiology of Parkinson’s disease. The PINK1 and Parkin gene are related to mitochondrial function and are present in Parkinson’s disease and the pathways involved with the  quality control in the mitochondrion. When oxidative stress is present and the cells cannot detoxify this can affect mitochondrial functioning which is the powerhouse of cells producing ATP or the energy source (3).
Reference
  1. Cui, S., Du, J.J., Liu, S.H., Meng, J., Lin, Y.Q., Li, G., He, Y.X., Zhang, P.C., Chen, S., Wang, G., Serm soluble lymphocyte activation gene-3 as a diagnostic biomarker in Parkinson’s disease: a pilot multicenter study,” Mov Disord 2018, Nov. doi:10.1002/mds.27569 (epub ahead of print)
  2. Aliseychik, M.P., Andreeva, T.V., Rogaev, E.I., “Immunogenetic factors of neurodegenerative diseases: the role of HLA Class II,” Biochemistry, 2018, Sep. 83(9):1104-1116
  3. Sato, S., Hattori, N., “Genetic mutations and mitochondrial toxins shed new light on the pathogenesis of Parkinson’s disease.” Parkinsons Dis. 2011; 2011:979231
 
 
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multiple sclerosis

Review of literature:  stem cell therapy in multiple sclerosis

Virginia Thornley, M.D., Neurologist, Epileptologist
October 8, 2018
 
Introduction
Stem cell therapy is explored for certain types of cancer such as bone marrow cancer. Its therapeutic options have been experimentally being expanded to other disease such as multiple sclerosis. This seeks to review some of the literature on current research for stem cell therapy in multiple sclerosis. As yet, there are still ongoing research and experiments and is not yet  approved by the FDA as treatment for multiple sclerosis. This seeks to review mechanisms, small studies and experimental studies in multiple sclerosis.
Some mechanisms through which stem cell therapy may help
Natural killer cells are thought to attenuate Th17 cells which are pro-inflammatory after autologous hematopoietic stem cell treatment. It may not have effect on the Th1 cell but it seems to reduce the number of Th17 cells (1).
Comparing Wharton Jelly mesenchymal cell with bone marrow mesenchymal stem cell
One study shows that Wharton Jelly mesenchymal stem cell may be comparable to the gold standard bone marrow stem cell and may be more easily extracted. There is a different gene phenotype and are found to overexpress genes that impact neurotrophic support making it a great candidate for stem cell source in neurodegenerative diseases such as amyotrophic lateral sclerosis or Parkinson’s disease. It was found to cause greater neuronal maturation in neuroblastoma cells compared to bone marrow mesenchymal cells. Genes that influenced adhesion, proliferation and the immune system were found to be greater expressed in Wharton jelly mesenchymal stem cell (2).
 
aHSCT in fatigue
In one small study in 23 patients the use of autologous human stem cell treatment helped with symptoms of fatigue using the FIS or the fatigue impact scale (1). The median score in FIS was reduced by 36% with 4 patients with a complete reduction. Some even had gainful employment and returned to driving, measured with the EDSS or expanded disability status scale(3).
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A pilot study shows mesenchymal stem cell injection slows progression
In a pilot study of 4 patients, 3 had secondary progressive type while 1 was in the relapsing-remitting stage. Autologous bone marrow stem cells were injected and patients were followed for 2 years. Those with secondary progressive type stabilized with no further deterioration while the patient with relapsing remitting type had an attack. None of the MRI tests showed any new plaques or abnormalities(4).
Mesenchymal stem cell treatment is thought to be helpful as a neuroprogenitor and slows the neurodegeneration where standard medications may be ineffective (5).
Hematopoietic cell transplant  for relapsing-remitting multiple sclerosis
In one study of 25 patients looking at high dose immunotherapy and autologous hematopoietic stem cell therapy, peripheral blood stem cell grafts were CD34+ chosen. Immunosuppression was given beforehand. It was found to reduce relapses over a course of 3 years in patients with relapsing-remitting multiple sclerosis without serious adverse effects(6).
In summary
There is growing interest in stem cell therapy as a novel treatment in multiple sclerosis.  Research has shown that Wharton’s jelly from the umbilical cord may have features making it a better therapeutic alternative compared to bone marrow mesenchymal stem cells. So far, small studies have shown promise. Larger human trials are needed.
Reference
    1. Darlington, P.J., Stopnicki, B., Touil, T., Doucet, J.S., Fawaz L.,  Roberts, M.E., Boivin, M.N., Arbour, N., Freedman, M.S., Atkins, H.L., Bar-Or, A., Canadian MS/BST Study Group. Natural killer cells regulate Th17 cells after autologous hematopoietic stem cell transplantation for relapsing remitting Multiple Sclerosis. Front Immunol. 2018, 9:834
    2. Donders, R., Bogie, J.F.J., Ravanidis, S., Gervois, P., Vanheusden, M., Maree, R., Schrynemackers, M., Smeets, H.J.M., Pinxteren, J., Gijbels, K., Walbers, S., Mays, R.W., Deans, R., Van Den Bosch, L., Stinnissen, P., Lambrichts, I., Gyselaers, W., Hellings, N. Human Wharton’s jelly-derived stem cells display a distinct immunomodulatory and preregenerative transcriptional signature compared to bone marrow-derived stem cells. Stem Cells Dev. 2018, Jan. 27(2):65-84
    3. Bose G., Atkins, H.L., Bowman, M., Freedman, M.S. Autologous hematopoietic stem cell transplantation improves fatigue in multiple sclerosis. Mult. Scler. 2018, Sep: 1352458518802544 (epub: ahead of print)
    4. Sahraian, M.A., Mohyeddin Bonab, M., Baghbanian, S.M., Naser Moghadasi, A. Therapeutic use of intrathecal mesenchymal stem cells in patients with Multiple Sclerosis: a pilot study with booster injection. Immunol Invest 2018, Aug. 29:1-9
    5. Holloman, J.P., Ho, C.C., Huntley, J.L., Gallicano, G.I. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am. J. Stem Cells. 2013, Jun. 30, 2(2):95-107
    6. Nash, R.A., Hutton, G.J., Racke, M.K., Popat, U., Devine, S.M., Griffith, L.M., Muraro, P.A., openshaw, H., Savre, P.H., Stuve, O., Arnold, D.L., Spychala, M.E., McConville, K.C., Harris, K.M., Phippard, D., Georges, G.E., Wundes, A., Kraft, G.H., Bowen, J.D., High-dose immunosuppressive therapy and autologous hematopoeitic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3 year interim report. JAMA Neurol 2015, Feb. 72(2):159-69

This is for informational purposes only not medical advice see your physician.

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multiple sclerosis

Ketogenic diet: can it play a role in treating symptoms of Multiple sclerosis?

Virginia Thornley, M.D., Neurologist, Epileptologist
September 19, 2018
@VThornleyMD
Introduction
Multiple sclerosis has no cure at this current moment. It is unclear what is the exact etiology otherwise there would be a cure. Based on research, genetic and environmental factors play a role. Based on MRI observations, there are inflammatory and degenerative components to the pathogenesis.
 
What is the ketogenic diet and how does it pertain the brain
The ketogenic diet was initially found to be effective in treatment of medically refractory seizures. But the underlying concept might be applied to other diseases as well.
Instead glucose as the energy substrate, ketones are utilized, If the supply of glucose is reduced, the energy source is shifted towards the beta-oxidation of fatty acids into ketone bodies. These ketones become the new source of energy and allows increased ATP formation which is the source of energy in the mitochondria, which is the powerhouse of the cell where energy is formed.
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Different lines of thinking regarding pathogenesis of Multiple Sclerosis
There are lines of thought that Multiple sclerosis can be inflammatory versus neurodegenerative. Because of this many agents are directed towards the autoimmune component of the disease process. It is commonly thought that the autoimmune process results in the neurodegeneration seen on MRI.
As evidenced by the “black holes” seen on MRI after acute attacks, there is evidence there is a neurodegenerative aspect. This other line of thinking suggests that it is a degenerative process that triggers the inflammatory response.
It’s been found  that degenerating axons have abnormal mitochondria.
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Ketogenic diet and inflammation
In one animal study, it was found that the ketogenic diet reduced inflammatory cytokines after 14 days in animals (2).
 
Ketogenic diet and increased ATP
In one animal model with a control group and a group on ketogenic diet, after 3 weeks it was found that those on the ketogenic diet had a higher ATP/ADP ratio which is speculated to contribute towards neuronal stability.

How can the ketogenic diet help with Multiple Sclerosis?
The ketogenic diet reduces the formation of reactive oxygen species. It preserves ATP production when the mitochondria fails. The thought is that the axons start to degenerate once the mitochondria are dysfunctional (1).
In summary
There are no human clinical studies on ketogenic diet and the improvement of multiple sclerosis. Based on pre-clinical studies, there is indication that ketogenic diet may help improve the ATP stores when the mitochondria becomes dysfunctional which may potentially slow neurodegeneration of axons.
The ketogenic diet might reduce inflammation which is thought to be triggered by a neurodegenerative process in Multiple Sclerosis. However, more studies are needed especially human clinical trials. Currently there is not enough evidence to support this based on the available studies as pre-clinical studies do not always correlate in human trials. More studies are needed.

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Reference
  1. Storoni, M., Plant, G. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis. Mult. Scler. Int. 2015. doi 10.1155/2015/681289
  2. Dupuis, N., Curatolo, N., Benoist, J.F., Auvin, S., Ketogenic diet exhibits anti-inflammatory properties. Epilepsia, 2015. 56(7):e95-98
  3. DeVivo, D.C., Leckie, M.P., Ferrendell, J.S., McDougal, D.B., Jr. Chronic ketosis and cerebral metabolism. Ann Neurol. 1978, Apr. 394):331-337
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multiple sclerosis

Review of literature: can the Wahls diet (modified Paleolithic diet) and low saturated fat Swank diet have any effect on multiple sclerosis?

Virginia Thornley, M.D., Neurologist, Epileptologist

September 17, 2018

@VThornleyMD

Introduction

Patients are seeking complementary treatments aside from conventional agents. Agree with it or not, if doctors do not listen to their patients they will seek it elsewhere so it is good to be up to date on the review of literature. While alternative treatments are commonly lacking in evidence based medicine it does not necessarily have to work in opposition with conventional agents. There are studies by Mauskop, (1) a headache specialist who found that 50% of migraineurs are magnesium deficient and magnesium can be a effective preventative agent in selected patients. Instead of being instantly dismissive, review of the literature should be sought to have an evidence-based understanding from a scientific level.

What is the modified Paleolithic diet?

In the modified Paleolithic diet, there is stress on meat, fruit and vegetables, excluding legumes, dairy and grains (2). Night shade vegetables such as tomatoes and eggplants are excluded.

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What is the Swank diet?

Dr. Roy Swank from Norway hypothesized that a diet rich in saturated fat likely caused a faster progression of the disease state in multiple sclerosis relapsing-remitting type. He followed 144 patients for 34 years. The patients consumed less than 20g of saturated fat in their diet and followed. It was observed that the relapses and progression correlated with the amount of saturated fat that was consumed. The greatest benefits were seen in those with mild symptoms at the start of the study. The patients were followed 50 years, however, there were no case controls patients for comparision (3).

Review of literature of the Wahl’s diet on Multiple sclerosis

One study focusing mainly on the dietary component seeks to understand an effect using the randomized controlled clinical trial method. The study is ongoing (2). It seeks to study the anecdotal information that diet low in saturated fat may lessen  the debilitating symptom of fatigue in patients with multiple sclerosis. While there have been anecdotal data, many patients have been found to drop out of the control group because of poor tolerability making results unreliable (2). In addition, the studies available provide a multi-prong approach including factors of stress reduction, exercise and muscle stimulation.

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Multimodal approach: exercise, stress reduction, meditation, massage and diet

One small study of 20 patients demonstrated some benefits of modifying diet, reducing stress and stimulating muscles in relation to multiple sclerosis symptoms.  They found that patients who presented with mild symptoms of progressive multiple sclerosis received some benefit to a multi-prong approach with regard to gait improvement compared to those who were more advanced in their disorder (4).

In summary

To summarize, at present there is insufficient data to support the Wahl’s diet as an effective treatment option based on the available current studies.  However, having said that there has been some anecdotal and very small studies indicating benefits in multiple sclerosis. Randomized controlled clinical trials which are the gold standard in research are ongoing which will be shed more light on its effectiveness.

In the meantime, while there are no completed large randomized controlled clinical trials, these types of diets and modalities are complementary with the current treatment and would do no harm. However, until large randomized controlled clinical trials are completed, it is difficult to ascertain if they are indeed effective and recommend it advocating it as effective.

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Reference

  1. Mauskop, et al, All migraine patients should be treated with magnesium. Journ. Neural Trans. 2012, May, 119(5):575-579
  2. Wahls, T., Scott, M.O., Alshare, Z., Rubenstein, L. Darling, W., Carr, L., Smith, Chenard, C.A., LaRocca, N., Snetselaar. Dietary appraoches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: a study protocol for randomized controlled trial. Trial. 2018, Jun. 4, 19(1):309
  3. Swank, R.L., Duggan, B.B., Effect of low saturated fat diet in early and late cases of multiple ssclerosis. Lancet, 1990, Jul., 7, 336 (8706)
  4. Bisht, B., Darling, W., White, E.C., White, K.A., Shivapour, E.T., Zimmerman, M.B., Wahls, T. Effects of a multimodal intervention on gait and balance of subjects with multiple sclerosis: a prospective longitudinal pilot study. Degen. Neurol. Neuromuscul Dis. 2017, Jun. 26, 7:79-93

 

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Medical Practice

Understanding the practical aspects of cannabidiol (CBD) and tetrahydrocannabinol (THC)

 

Virginia Thornley, M.D., Board-certified Neurologist, Epileptologist

@VThornleyMD

July 15, 2018

Introduction 

This serves as medical information for educational purposes only not medical advice. Please consult with your treating  physician.

In contrast to the rest of the blog which is more scientific, this gives more practical information in the day to day workings of recommending medical cannabis. It gives the behind the scenes processes that happens before a patient can even begin to start their medical product. It is not a magic pill but because it is unlawful in Florida, a physician cannot even write it on a prescription pad. It takes one hour or more to evaluate, counsel and go over the registration process when presenting for the first time to a doctor.

For more detailed information and scientific references for specific indications please refer to
https://neurologybuzz.com/

Medical cannabis is one of the most misunderstood and controversial medications in the world. Long suppressed for over a century, it is one of the most misunderstood medications known to mankind despite being used for thousands of years with medical intent.

This is to give a brief basic background of mechanisms, rationale for ratios, combinations, pitfalls of isolates and synthetics and legal implications.

Background

The endocannabinoid system is found naturally in our body. It is responsible for the runner’s high people get. It gives a sense of wellbeing, not endorphins like most people think, those molecules are too large to pass the blood-brain-barrier. There are 2 receptors:(1) the CB1 receptor found mostly in the nervous system and (2) the CB2 receptor which is more abundantly found in the immune system. Anandamide works on the CB1 receptor, tetrahydrocannabinol (THC) is similar to this and works on the CB1 receptor. CBD or cannabidiol is from the cannabis sativa plant and is also a phytocannabinoid. One needs 100 times the CBD to get the euphoria as THC. CBD is not intoxicating, legal and works on a wide variety of symptoms including pain, seizures and anxiety. CBD is similar to 2-arachidonoyl glycerol which is a natural cannabinoid. When the 2 are combined together, CBD will offset side effects of THC including paranoia, hyperactivity and agitation. This is a not known fact to those who self-medicate with pure THC.   Because of this THC is medically recommended in conjunction with CBD. Smoking is illegal and not medically recommended as most people think. https://neurologybuzz.com/2018/04/02/medical-marijuana-vlog-series-part-i-mechanisms-medical-benefits-of-non-intoxicating-cannabidiol-and-tetrahydrocannabinol/

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Pitfalls of self-medication

Sometimes patients self-medicate and smoke pure THC from dubious sources to alleviate symptoms, which is illegal and not medically recommended in Florida.  However, the intoxicating effects are not seen when recommended medically using oral forms, cream or patch. At low doses, as is done when recommended medically, THC is non-euphoric. When THC is combined with CBD the side effects of THC are offset. The dangers of patients who self-medicate is that they do not know where the products are coming from and it can be mixed with potentially dangerous substances that can be potentially fatal. In addition, there are highly potent synthetic illegal cannabinoids known as K2 and spice which at high doses can cause cardiotoxicity and fatalities. Self-medicating with THC from an unknown source is highly discouraged as there may be mold involved with the processing. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

Why is a CBD and THC combination important?

In regulated licensed dispensaries, CBD is combined to offset the side effects of THC allowing better tolerance. THC is not recommended by itself because of side effects including paranoia, agitation and hyperactivity.

CBD by itself

With pure CBD, there are certain medical symptoms that are alleviated.

It is legal. There are many companies with CBD products but it is difficult to know how pure these products are, even if you have a small amount of hemp it can be marketed as CBD hence, its ineffectiveness. Some of the most effective CBD products can be found from Colorado and California, anecdotally. Everything else is hit or miss.

In the state of Florida, there are very few medically beneficial CBD products, it’s trial and error. The purer the form such as full spectrum CBD oil the more expensive it will be because processing organic products are costly. A cheap product will likely not be as pure just because of the huge amount of work that goes into extracting the cannabidiol. In addition, some may have flavors, cutting agents and other agents to dilute it but because it’s unregulated.

Ratios

CBD alone has no psychoactivity but medical value. CBD is combined with THC in order to offset its side effects of paranoia, agitation and hyperactivity.

Time of onset and duration

There are different ways of trying it: vaporizer lasts 1 hour and takes about 10 minutes to get into your system. Because the vaporizer is inhaled into the lungs the onset is the fastest because of the rich supply of blood vessels in the lungs. It is advisable to try the vaporizer at home or at night before setting out to see how it affects you. Oral forms last 6 to 7 hours and takes about 1/2 hour to get into your system. Oral form comes in oil concentrate and tincture. Cream and patch last about 12 hours or longer depending on the preparation. Medical marijuana is NOT recommended by physicians to be smoked. Recreational marijuana by smoking is prohibited and unlawful in Florida. This law varies by state. When different parts of the plant are taken together including the terpenes it gives an entourage effect which is more medically valuable than when components are isolated for its use.https://youtu.be/Ir4rwgF2iNc

Are there any edibles in Florida?

As of July 2018, there are no edibles in the state of Florida. It will take an enormous amount of submitting documentation and providing capital before edibles will be implemented in Florida. The dispensaries are working on this.

Registration process: what to expect in Florida

The process includes an evaluation by a qualified licensed physician. https://neurologybuzz.com/2018/07/12/legalities-and-application-process-in-the-state-of-florida/A qualified physician undergoes a 2-hour course and holds a full medical license in the state of Florida. One is evaluated and if patient meets the stringent criteria, they obtain a registry number. The patient undergoes registration which takes between 2-4 weeks. An e-mail arrives before the card then one is instructed to call the office so that recommendations are placed in the system. Oftentimes, if you don’t hear back in 4 weeks it is advisable to give the registry a call. It may be a misentering of an e-mail causing a delay.

Regulated dispensaries in the Florida

In Florida, there are 13 medical marijuana treatment centers and 43 retail dispensaries as of July 2018. In the state of Florida, patients can only obtain the Cannabis products recommended from their treating physicians from these dispensaries. It is illegal to smoke. There are 4 ways of taking it: oral, vaporizer, cream and patch. It is advisable to visit one of the licensed dispensaries in person so that the exact instructions can be given. Physicians recommend orders which are entered into the system. So long as the product is within the number of mg dispensed and the way it is recommended (oral, vaporizer, cream or patch) patients are at the liberty to change the ratio or dosage so long as it is within the orders.

Once you are registered

An e-mail with the marijuana card number comes before the physical card. It is advisable to call the physician office so the orders are placed then physically visit the dispensary of your choice so specific instructions can be taken. Because this is not a pharmacy, doctors do not have immediate access to the dispensary. One should be aware of which product they are taking before their next checkup. This can be easily accessed through the website of the dispensary.

The orders will expire after 70 days after which there is a processing fee of renewal at the office. The certification for medical marijuana expires after 1 year. One must be re-evaluated by their physician before then.

CBD is purely cannabidiol, it is non-psychoactive and legal. THC at low doses is non-intoxicating. Dispensaries combine CBD and THC to offset side effects.  It is federally illegal. It is advisable to be registered under a medical doctor who is qualified to determine if one meets criteria. Medical cannabis products can only be dispensed from a regulated licensed dispensary. Medical marijuana products outside of the jurisdiction of Florida regulates licensed dispensaries cannot be advocated.

Legal implications of THC

In some states, such as Florida, medical use of cannabis is recognized. THC is still considered federally illegal. Recreational use of cannabis is illegal. Smoking THC is illegal. Physicians cannot prescribe it since it is a schedule 1 drug but can recommend it. Schedule 1 drugs are considered illicit and labeled as having no medical use. A statement before the qualifying course on medical cannabis states that the physician can be questioned at any time by the FBI and authorities.

In other states, medical and recreational use is allowed.

In other states, medical and recreational use is completely banned.

The law also varies regarding cultivation of the cannabis sativa plant.

Countries will vary in their marijuana laws.

The laws change very rapidly. Regulations are changed nearly every month with more documentation required from physician offices including consent, doctors’ notes, patient information with indication. As each month goes by another new document is required for submission from the physician office. There is increasing bureaucracy likely signifying resistance at some upper levels against its use related to economic and political reasons. Dispensaries have an equally challenging time. Even worse are small farms applying for licenses huge amounts of capital and documents are required.

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Legal implications of CBD

CBD is legal throughout the US. Countries may vary in their laws since they both come from the cannabis sativa plant.

FDA approved medications and products approved in Europe with CBD and THC

A medication called Epidiolex for seizures with CBD has recently been approved for seizures. Because it comes from a strain from the cannabis sativa plant, cannabis will need to be deregulated from the schedule I category before Epidiolex can be marketed to the public.

Dronabinol has long been approved for nausea and can only prescribed for patients with cancer with chemotherapy induced nausea. It is a synthetic THC and is FDA approved.

In Europe, the medication Sativex which is a combination of CBD:THC has long been used for spasms in multiple sclerosis. This is not available in the US.

In summary

For patients, it is beneficial to have a working understanding of the different strains, different forms that are available in order to obtain the best benefit.  Dispensaries have a huge breadth of products. It is easier to understand as much as possible before facing the overwhelming number of options. Patients must understand all the legal implications in your state as they change rapidly. It is not only a medication it is affected by state and federal laws that change in a blink of an eye which can affect the patient if they are not aware.  One must be mindful that there are different types of practices recommending medical cannabis. The best practices are those that are an already established practice which added medical marijuana to their repertory. Practices that are solely for medical marijuana may be of dubious quality. There are already horror stories of patients never getting a card after several months and phone calls not being advisef on what to do, being examined in a conference hall. As with any new innovative service, there will be legitimate practices and there will be those who meet the minimum requirement of care and service. http://www.tampabay.com/investigations/2018/05/04/floridas-medical-marijuana-program-is-attracting-troubled-doctors-its-like-the-wild-wild-west/

For doctors recommending, one must be well-versed in understanding the potential side effects, drug interactions, the latest scientific research since these are the only guidelines that are guiding us from a scientific level. Pre-clinical studies cannot be ignored nor studies on synthetics to have a better grasp of understanding how it works. One must have a basic understanding in the effects of the phytocannabinoids which is best taken in combination and not in isolation. Patients come with complex medical problems it is always prudent to do due diligence in understanding as much as possible before recommending a product that was never studied for medical purposes in medical school. Patients will ask tough questions, physicians should understand as much as possible and do their due diligence being up to date on legislations as well as the most recent research. The hard questions will come.

One must also follow the legal implications, current regulations which are frequently updated. It is the physician’s responsibility to understand the mechanisms, be current on the literature because this is a pioneering science. Those recommending right now are trailblazing and should still be mindful of the great role you play in understanding what literature is available and to read voraciously.

Last thoughts

While much is still unknown about CBD, THC and mechanisms, there is great anecdotal data from history and clinical anecdotal experience supporting its benefits. While many traditionally trained physicians scoff at the prospect of introducing alternative treatments, one must bear in mind cannabis was not an alternative medication before it was banned in 1830.

While scientists are working overtime in elucidating the mechanisms to combat diseases such as cancer, one must bear in mind that medical cannabis is beneficial when taken in combination with other terpenes found in the plant and the components are not isolated from each other. THC works best in combination with CBD and with other components from the cannabis sativa plant.

When components are isolated from each other and products become synthetic and manufactured much of the benefits are lost and significant side effects result. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

Once it becomes synthetic and components are isolated, the benefits will be substantially altered.

Now is a optimal time to try the benefits of medical cannabis while it is still all organic and being produced on farms and regulated for its use, unsullied by synthetic forms where the risk of side effects are greater.

While much is still to be learned, for a medicine that can easily cover 5 symptoms in one setting, it is an extraordinary time to be recommending and benefiting from medical cannabis while it is still organically natural and pure.

 

Introduction/Disclaimer

About

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fibromyalgia

Medical marijuana in fibromyalgia: molecular mechanisms and small randomized controlled trials

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

June 17, 2018

Introduction

Fibromyalgia used to be  a condition denoting excessive pain and was previously questionable as there was no testing that could prove or disprove it. Now, the current thought is that it is attributed to hypersensitivity of the nervous system to pain impulses resulting in multiple points of pain in the body.

Endocannabinoid system in pain modulation

The endocannabinoid system is a major chemical neurotransmitter system that has only come to light as to physiology in the last 20 years. The CB1 receptor is found predominantly in the nervous system on which the endogenous endocannabinoid anandamide exerts its effects. The CB2 receptor is found mostly in the immune system on which 2-Arachidonoylglycerol acts. In the nervous system, cannabinoid receptors are seen in the periaqueductal gray area, ventromedial medulla and dorsal horn of the spinal cord which are areas where pain transmission takes place. This suggests that endocannabinoids play a major role in modulation of pain and can impact pain control through manipulation of this system.

Anandamide and and 2-Arachidonoylglycerol are synthesized on demand. It is released immediately after production. 2-AG is formed from a 2 step process. Anandamide has a low affinity to the TPRV1 receptor (2).

1,2-diacylglycerol (DAG) is  a precursor or 2-AG which is formed by hydrolysis of membrane phosphoinositides. DAG is hydrolyzed by 2-AG hydrolase to form 2-AG. 2-AG may be stimulated by activation of G protein receptor such as glutamate receptors. It activates both CB1 and CB2 receptors. Cannabidiol which is found in the cannabis sativa plant is a natural mimetic of 2-AG. Endogenous 2-AG is found 170 times more than Anandamide in the brain. Exogenous 2-AG suppresses nociceptive stimulus (2). 2-AG activity is potentiated with natural 2-acylglycerols which enhances the effects which does not happen when used alone. This is an entourage effect found in the brain where the combination of substances give a combined resulting effect which does not occur if used alone (2).

Mechanisms in pain modulation

Cannabinoids were found to reduce nociceptive transmission at the level of the pain c-fiber responses in the spinal dorsal horn.

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Randomized controlled trial in fibromyalgia

In one study of 40 patients in a randomized controlled clinical trial, nabilone which is a synthetic cannabinoid was given over a 4 week period. Measures that were evaluated included the visual analog scale for primary outcome and for secondary outcome measure, tender points, secondary outcome measure, Fibromyalgia Impact Questionnaire (FIQ) at weeks 2 and 4 were used. There was statistical difference in treated vs. control groups for pain (P value< 0.02), anxiety (P<0.02 and FIQ (P<0.02). There were more side effects for the treated cohort compared tot he placebo controlled group. This study demonstrates that cannabinoids may be an effective treatment for fibromyalgia (1).

In one paper that reviewed 18 randomized controlled clinical trials of cannabinoids in chronic pain syndromes including fibromyalgia, cannabinoids were found to be an effective type of treatment. Despite the short duration of the trials, pain relief was effective and mild to moderate adverse effects were noted. Larger clinical trials are needed (2).

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Introduction/Disclaimer

https://neurologybuzz.com/

  1. Skrabek, et al, “Nabilone for the treatment of pain in fibromyalgia,” J. Pain, 2008, Feb., (9)2:164:173
  2. Lynch, et al, “Cannabinoids for treatment of chronic non-cancer pain: a systemic review of randomized trials,” Br. J. Pharmacology, 2011, Nov., 72(5):735-744
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