Kavain and glutamate.
Back in the late 90s researchers aimed to see if kavain had any activity at glutamate.
Glutamate
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. It is used in every major excitatory function in the brain, and accounts for over 90% of all synaptic connections. This excitatory action has been known since the 1950s, however it wasn’t until the 1970s that it became widely known that glutamate was the principal neurotransmitter responsible for this [1]. Outside of biomedical science, glutamate is best known as “monosodium glutamate”. The very same “flavor enhancer” we see used culinarily [2]. Glutamate is also the precursor to the neurotransmitter GABA [3].
How does glutamate work?
For this instance glutamate receptors are ligand-gated receptors that allow for the flow in of potassium, sodium and calcium once bound to by glutamate. These cations (positive ions) are positively charged and when they enter the neuron it increases the chances of the neuron firing. Disorders in the function of glutamate can cause a number of different negative health states. This can include epilepsy, depression, ALS, and neurodegenerative diseases [4]. Overstimulation of these receptors can cause neurodegeneration and neuronal damage through a process known as excitotoxicity. This is one of the mechanisms in which stimulants can eventually cause neurotoxicity [5].
Veratridine
Veratridine is a neurotoxin derived from the plants in the family Liliaceae [6]. Veratridine attaches itself to sodium channels in the nervous system and opens them by abolishing inactivation. This causes an influx of positively charged ions to enter the neuron and can cause a state of excitotoxicity [7]. In today’s fact this chemical is used to evoke a glutamate release to compare results given the addition of kavain.
Kavain’s actions
Researchers administered vertradine to adult male rats' cortex. They observed the release of glutamate in combination with kavain. It was found that kavain, in a dose dependent manner, blocked the artificial influx of Sodium into neurons and blocked the excess release of glutamate [8].
What does this mean to the average kava drinker?
This research underscores the calming and balancing nature of kava and its constituents. Both the increase in influx of positively charged ions and the release of glutamate are excitatory actions. Kava, being shown to decrease both of these activities just speaks more to it’s relaxing and tranquil nature.
[1] Meldrum, Brian S. 2000. “Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology.” The Journal of Nutrition 130 (4): 1007S – 1015S.
https://doi.org/10.1093/jn/130.4.1007S
[2] Zhou, Y., and N. C. Danbolt. 2014. “Glutamate as a Neurotransmitter in the Healthy Brain.” Journal of Neural Transmission 121 (8): 799–817.
https://doi.org/10.1007/s00702-014-1180-8
[3] Rutten, Erica P. A., Marielle P. K. J. Engelen, Emiel F. M. Wouters, Annemie M. W. J. Schols, and Nicolaas E. P. Deutz. 2006. “Metabolic Effects of Glutamine and Glutamate Ingestion in Healthy Subjects and in Persons with Chronic Obstructive Pulmonary Disease.” The American Journal of Clinical Nutrition 83 (1): 115–23.
https://doi.org/10.1093/ajcn/83.1.115
[4] Danysz, Wojciech, and Chris G. Parsons. 2012. “Alzheimer’s Disease, β-Amyloid, Glutamate, NMDA Receptors and Memantine--Searching for the Connections.” British Journal of Pharmacology 167 (2): 324–52.
https://doi.org/10.1111/j.1476-5381.2012.02057.x
[5] Yamamoto, Bryan K., Anna Moszczynska, and Gary A. Gudelsky. 2010. “Amphetamine Toxicities: Classical and Emerging Mechanisms.” Annals of the New York Academy of Sciences 1187 (February): 101–21.
https://doi.org/10.1111/j.1749-6632.2009.05141.x
[6] Zhang, Xiao-Yu, Rui-Yun Bi, Peng Zhang, and Ye-Hua Gan. 2018. “Veratridine Modifies the Gating of Human Voltage-Gated Sodium Channel Nav1.7.” Acta Pharmacologica Sinica 39 (11): 1716–24.
https://doi.org/10.1038/s41401-018-0065-z
[7]Ulbricht, W. 1998. “Effects of Veratridine on Sodium Currents and Fluxes.” Reviews of Physiology, Biochemistry and Pharmacology 133: 1–54.
https://doi.org/10.1007/BFb0000612
[8] Gleitz, J., A. Beile, and T. Peters. 1996. “(+/-)-Kavain Inhibits the Veratridine- and KCl-Induced Increase in Intracellular Ca2+ and Glutamate-Release of Rat Cerebrocortical Synaptosomes.” Neuropharmacology 35 (2): 179–86.
https://doi.org/10.1016/0028-3908(95)00163-8
Back in the late 90s researchers aimed to see if kavain had any activity at glutamate.
Glutamate
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. It is used in every major excitatory function in the brain, and accounts for over 90% of all synaptic connections. This excitatory action has been known since the 1950s, however it wasn’t until the 1970s that it became widely known that glutamate was the principal neurotransmitter responsible for this [1]. Outside of biomedical science, glutamate is best known as “monosodium glutamate”. The very same “flavor enhancer” we see used culinarily [2]. Glutamate is also the precursor to the neurotransmitter GABA [3].
How does glutamate work?
For this instance glutamate receptors are ligand-gated receptors that allow for the flow in of potassium, sodium and calcium once bound to by glutamate. These cations (positive ions) are positively charged and when they enter the neuron it increases the chances of the neuron firing. Disorders in the function of glutamate can cause a number of different negative health states. This can include epilepsy, depression, ALS, and neurodegenerative diseases [4]. Overstimulation of these receptors can cause neurodegeneration and neuronal damage through a process known as excitotoxicity. This is one of the mechanisms in which stimulants can eventually cause neurotoxicity [5].
Veratridine
Veratridine is a neurotoxin derived from the plants in the family Liliaceae [6]. Veratridine attaches itself to sodium channels in the nervous system and opens them by abolishing inactivation. This causes an influx of positively charged ions to enter the neuron and can cause a state of excitotoxicity [7]. In today’s fact this chemical is used to evoke a glutamate release to compare results given the addition of kavain.
Kavain’s actions
Researchers administered vertradine to adult male rats' cortex. They observed the release of glutamate in combination with kavain. It was found that kavain, in a dose dependent manner, blocked the artificial influx of Sodium into neurons and blocked the excess release of glutamate [8].
What does this mean to the average kava drinker?
This research underscores the calming and balancing nature of kava and its constituents. Both the increase in influx of positively charged ions and the release of glutamate are excitatory actions. Kava, being shown to decrease both of these activities just speaks more to it’s relaxing and tranquil nature.
[1] Meldrum, Brian S. 2000. “Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology.” The Journal of Nutrition 130 (4): 1007S – 1015S.
https://doi.org/10.1093/jn/130.4.1007S
[2] Zhou, Y., and N. C. Danbolt. 2014. “Glutamate as a Neurotransmitter in the Healthy Brain.” Journal of Neural Transmission 121 (8): 799–817.
https://doi.org/10.1007/s00702-014-1180-8
[3] Rutten, Erica P. A., Marielle P. K. J. Engelen, Emiel F. M. Wouters, Annemie M. W. J. Schols, and Nicolaas E. P. Deutz. 2006. “Metabolic Effects of Glutamine and Glutamate Ingestion in Healthy Subjects and in Persons with Chronic Obstructive Pulmonary Disease.” The American Journal of Clinical Nutrition 83 (1): 115–23.
https://doi.org/10.1093/ajcn/83.1.115
[4] Danysz, Wojciech, and Chris G. Parsons. 2012. “Alzheimer’s Disease, β-Amyloid, Glutamate, NMDA Receptors and Memantine--Searching for the Connections.” British Journal of Pharmacology 167 (2): 324–52.
https://doi.org/10.1111/j.1476-5381.2012.02057.x
[5] Yamamoto, Bryan K., Anna Moszczynska, and Gary A. Gudelsky. 2010. “Amphetamine Toxicities: Classical and Emerging Mechanisms.” Annals of the New York Academy of Sciences 1187 (February): 101–21.
https://doi.org/10.1111/j.1749-6632.2009.05141.x
[6] Zhang, Xiao-Yu, Rui-Yun Bi, Peng Zhang, and Ye-Hua Gan. 2018. “Veratridine Modifies the Gating of Human Voltage-Gated Sodium Channel Nav1.7.” Acta Pharmacologica Sinica 39 (11): 1716–24.
https://doi.org/10.1038/s41401-018-0065-z
[7]Ulbricht, W. 1998. “Effects of Veratridine on Sodium Currents and Fluxes.” Reviews of Physiology, Biochemistry and Pharmacology 133: 1–54.
https://doi.org/10.1007/BFb0000612
[8] Gleitz, J., A. Beile, and T. Peters. 1996. “(+/-)-Kavain Inhibits the Veratridine- and KCl-Induced Increase in Intracellular Ca2+ and Glutamate-Release of Rat Cerebrocortical Synaptosomes.” Neuropharmacology 35 (2): 179–86.
https://doi.org/10.1016/0028-3908(95)00163-8