cannabinoids, Uncategorized

What are the risks of vaping medical cannabinoids in the state of Florida?

Virginia Thornley, M.D.
October 9, 2019
Given the recent rash of deaths thought to be caused by vaping e-cigarettes, patients are scrambling to ask their doctors regarding the risks of vaping medical cannabinoids.
Many of the reports reporting deaths have been with e-cigarettes which do have chemicals that can potentially cause irreversible damage to the lungs.  Some reports report that THC oils were used but do not state the source. THC oils were reported to be placed in the vaporizer device used for e-cigarettes to be vaped. In Florida, medical products used in vaping for medical purposes from regulated dispensaries are from all natural products, a very different set-up compared to the components found in e-cigarettes.
It is not clear if some of these reports are from tightly regulated medical marijuana dispensaries. In the state of Florida, there have been no reports of deaths related to vaping cannabinoids used for medical use that come from stringently regulated dispensaries. In the state of Florida, medical cannabinoids have strict regulations and there is a vertical distribution meaning the products are with the company from time they are grown as a seedling to the time of dispensing so that there are no other outside products that are added later.
At this point, October 2019, there have been no reported deaths due to vaping medical cannabinoids in Florida when taken from legal regulated dispensaries. The lung-related illnesses associated with vaping in Florida are related to vaping from e-cigarettes which may also have other substances added.  This is completely different from vaping the cannabinoid medical products which are all natural products from medical dispensaries.
We turn to research for the analysis of the potential risks involved with vaping. There is one study but it involves vaping cannabinoids using e-cigarette devices. The gas-thermal degraded products have not yet been thoroughly analyzed. In this study, there is potential exposure to benzene, methacrolein and methyl vinyl ketone. Tetrahydrocannabinol alone and mixed with terpenes can lead to elevated levels of isoprene. Terpenes may lead to higher gas products. Overall, gas-phase products are much lower compared to smoking products (1). There has been little research on vaping medical cannabinoids dispensed from the dispensaries and so far, no deaths have been reported from cannabinoids coming from regulated dispensaries in Florida.
This is information only not advice. Please consult with your physician.
Neurologybuzz.com
Reference
  1. Meehan-Atrash, J., Luo. W., McWhirter, K.J., Strongin, R.M. Aerosol gas-phase components from cannabis e-cigarettes and dabbing: mechanistic insight and quantitative risk analysis. ACS Omega. 2019, Sep. 16,;4(14):6111-16120
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migraine

Effects of barometric pressure changes in weather change in patients with migraine

Virginia Thornley, M.D.
October 9, 2019
A common question that is asked in the office setting is whether weather changes can increase migraines.
In one study of 98 patients followed 45 days, higher humidity between the warm months of April and September correlated with increase number of migraines (1).
In a 7-year study of ER patients, an increase of barometric pressure resulted in more ER visits by patients with migraine. There were less visits when it was a decrease in pressure. There was no correlation with migraine with the actual magnitude of barometric pressure change. Tropical air masses correlated with more ER visits compared to polar masses (2).
In a smaller study of 28 patients followed over 1 year, weather changes correlated with increased migraine frequency in 64%. 14 of those reported low barometric pressure to be associated with it (3).
In summary, despite some mixed results regarding reduction of barometric pressure, if a weather change affects a patient’s underlying condition, it is likely a trigger.
This is information only not advice please see your doctor.
Neurologybuzz.com
Reference
  1. Li, W., Bertisch, S.M., Motofsky, E., Buettner, C., Mittleman, M.A., Weather, ambient air pollution, and risk of migraine headache onset among patients with migraine. Environ. Int. 2019, 132:105100
  2. Elcik, C., Fuhrmann, C.M., Mercer, A.E., Davis, R.E., Relationship between air mass type and emergency department visits for migraine headaches across Triangle region of North Carolina. Int. J. Biometeor. 2017, Dec. 61(12):2245-2254
  3. Kimoto, K., Alba, S., Takashima, R., Suzuki, K., Takekawa, H., Watanabe, Y., Tatsumoto, M., Hirata, K., Influence of barometric pressure in patients with migraine headache. Intern Med. 2011. 50(18):1923-8
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neurology

Can anti-psychotic agents reduce brain volume?

Virginia Thornley, M.D.
Neurologist, Epileptologist
October 9, 2019
Can medications cause cerebral atrophy? Atrophy refers to shrinkage of the cells causing the appearance of the brain to have less volume than usual.
This question was asked last week. Anti-epileptics such as phenytoin is well-known in the literature and clinically to cause cerebellar atrophy. But what about other agents such as anti-psychotics.
Animal studies
In one animal study, exposure to anti-psychotic drugs showed a reduced volume of brain on volumetric studies. The number of cells remained the same but the volume was increased for cells in the anterior cingulate gyrus which is in the  limbic lobe. The limbic lobe subserves emotions and has influence on memory. Animal studies do not always correlate with human responses.
Human studies
One small study showed that the thalamic volume was reduced after olanzepine administration. This was a small study of 10 patients (2).
While there is some information in the literature the studies are animal studies and small human studies. More information is needed. Based on the current literature, there are not enough significant studies to correlate atrophy with use of anti-psychotics.
References
  1. Vernon, A.C., Crum, W.R., Lerch, J.P., Chege, W., Natesan, S., Modo, M., Cooper, J.D., Williams, S.C., Kapur, S. Reduced cortical volume and elevated astrocyte density in rats chronically treated with anti-psychotic drugs-linking magentic resonance imaging findings to cellular pathology. Biol Psychiatry. 2014, Jun. 15, 75(12):982-90
  2. Khorram, B., Lang, D.J., Kopala, L.C., Vandorpe, RF.A., Rui, Q., Goghari, V.M., Smith, G.N., Honer, W.G. Reduced thalamic volume in patients with chronic schizophrenia after switching from typical anti-psychotic medications to olanzepine. Am J sychiatry. 2006, Nov. 163 (11):2005-7
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dementia

Animal study demonstrating CBD’s (cannabidiol) effects on neuroplasticity and memory loss

Virginia Thornley, M.D.
Neurologist, Epileptologist
August 26, 2019
In an animal study, one group demonstrates that Cannabidiol may help with the neuroplasticity in patients with Alzheimer’s disease (1).
LTP in the hippocampus is the long-term potentiation seen that elevates the efficacy of synapses involved in memory. Beta-amyloid peptide is toxic towards this  feature. When animals were pretreated with CBD the neurotoxicity was found to be reduced against beta-amyloid peptide. The same study showed that it did not involve the 5-HT1a, CB1 or adenosine receptors (1).
There have been other previous studies showing that cannabidiol could have protective effects against the toxic effects of beta-amyloid peptide which is involved in the neurodegenerative process seen in Alzheimer’s disease.
More clinical randomized control trials are needed. Animal studies do not always translate into human studies.
Neurologybuzz.com
References
  1. Hughes, B., Herron, C.E., Cannabidiol reverses deficits in hippocampal LTP in a model of Alzheimer’s disease. Neurochem. Res. 2019, Mar. 44(3):703-713

This is medical information not medical advice. Please consult with your physician.

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multiple sclerosis, Uncategorized

The impact of immunomodulating agents used in multiple sclerosis on the risk of cancer

Virginia Thornley, M.D., Neurologist, Epileptologist
June 14, 2019
Introduction
Multiple sclerosis is already an illness where the immune system recognizes the nervous system specifically the white matter tracts as foreign and attacks it. The complex cascade of mechanisms make adequate treatment challenging. Many treatments focus on the inflammatory mechanism with little attention on the degenerative mechanism involved.
Presentation of symptoms come in a wide variety depending on the the location of the multiple sclerosis plaque in the brain.
Patients may have concomitant morbidities which may make treatment challenging.
 
Immunomodulating agents and its impact on cancer
Many of the newer treatments for multiple sclerosis work at the level of the immune system through immunosuppression, the newer ones tend to be very potent. With greater efficacy comes greater risks including the risk of cancer.
Some of the newer medications can potentially increase the risk of cancer. Higher risk of cancer was found in many reports to occur with use of cyclophosphamide, azathioprine and mitoxanthrone. Fingolimod, natalizumab and alemtuzamab  can potentially increase the risk of cancer, these agents lack long-term data and work through the immune system. Dimethyl fumarate, terifluonimide, ocrelizumab, daclizumab and cladribine merit mandatory risk management plans to detect cancer before its use.
Reference
  1. Lebrun, C., Rocher, F., Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs. CNS Drugs. 2018, Oct. 32(10):939-949 doi:10.1007/s40263-018-0564-y
Disclaimer: This is medical information only not medical advice. Please consult your physician
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cerebellar ataxia

Genetics of Hereditary Cerebellar Ataxia and Hereditary Spastic Paraplegia

Virginia Thornley, M.D.
Neurologist, Epileptologist
March 18, 2019
Introduction
Cerebellar ataxias are rare disorders, only a few types are treatable. This reviews some of the research regarding the genetics of cerebellar ataxias.
Next generation sequencing is a revolutionary way of DNA sequencing that can sequence an entire genome in one day which previously took 10 years. Clinical applications are still pending (1).
Genetics of hereditary cerebellar ataxias
In one study of 87 patients, the genetics were studies. In the probands meaning the first in a genetic line, triplet repeat testing was done. 58% were male. Genetic variants included ANO10, CACNA1A, SPG7 and DRKCG. The detection rate in probands for the trinucleotide repeat was about 13.8%. Those with variants may have a longer duration of disease and a slower progression of the disorder (2).
 
Genetic testing in hereditary spastic paraparesis
In another study where 306 were genetically tested, next generation sequence testing was performed and different genes were found. These include ATL1 (atlastin 1, SPG3),
PAST (spastin, SPG4),  ITPR1, WASHC5 (SPG8),  KIF1A (SPG30), SPG11 spastacsin), KIF5A (SPG10), CYP27A1, and SETX (3).
There are overlapping genetics and clinical symptoms with spinocerebellar ataxia and amyotrophic lateral sclerosis.
Reference
  1. Behjati, S., Tarpey, P., What is next generation sequencing? Arch Dis Child Educ Pract Ed. 2013 Dec; 98(6)236-238
  2. Kang, C., Liang, C., Ahmad, K.E., Gu, Y., Siow, S.F., Colebatch, J.G., Whyte, S., N, K., Cremer, P.D., Corbett, A.J., Davis, R.L., Roscioloi, T., Cowley, M.J., Park, S.J., Sue, C.M., Kumar, K.R. High Degree of Genetic Hetereogeneity for Hereditary Cerebellar Ataxias in Australia, Cerebellum, 2019, Feb. (1):137-146
  3. Elert-Dobkowska, E., Stepniak, I., Krysa, W., Ziora-Jakutowicz, K., Rakowicz, M., Sobanska, A., Pilch, J., Antczak-Marach, D., Zaremba, J., Sulek, A. Next-generation sequencing reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes. Neurogenetic, 2019, Feb, doi:10.1007/s10048-019-00565-6
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Sleep

Does chronic sleep deprivation affect cognition in shift workers?

Virginia Thornley, M.D.
Neurologist, Epileptologist
March 6, 2019
Introduction
What is the impact of sleep on cognition of shift workers?
 
Does circadian misalignment have impact on cognition?
Those with circadian misalignment such as night shift workers are most affected in terms of sustained attention, visual-motor performance and processing of information(1).
CAA11F12-A957-4FAF-B74D-6C7D2CE6E613
 
One study sought to clarify the relationship of circadian cycle misalignment with cognition. It found that on the first night of shift work, attention is markedly impaired which improves after the same schedule is followed. This did not hold true for areas in visual-motor or cognitive throughput. Cognitive throughput means the summation of data going through a network.
Declarative memory is stable while attention was greatly impacted. This may be because memory is not impacted by areas where the sleep-wake cycle is important.
 
Mechanism

It is thought that there is increased GABAergic tone at night which could depress cognition. The natural circadian rhythm allows for maximum cognitive abilities during the daytime. . This is when we get our peak performance. The worse time for vulnerabilities in cognition occurred in the hours between 4-6am(1).
The neurobiology is thought that lack of sleep at night affects the conduction of nerves including the local potential field which affects neuronal activity. This results in reduced reaction time and speed for visual motor performance and tasks requiring sustained attention (2).
Reference
  1. Chellappa, S.L.,Morris, C., Scheer, F.A. Effects of circadian misalignment on cognition in chronic shift workers. Sci. Rep., 2019, 9:699. published online 2019 Jan 24. doi: 10.1038/s41598-018-36762-w
  2. Nir, Y., Andrillon, T., Marmelshtein, A., Suthana, N., Cirelli, C., Tononi, G., Fried, I. Selective neuronal lapses precede human cognitive lapses following sleep deprivation. Nat Med. 2017, Dec: 23(12)1474-1480
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