Dopamine
Today’s kava fact will be addressing dopamine, and how kava may or may not act at this specific neurotransmitter. There have been numerous papers stating that kavalactones either increase or decrease dopamine in a significant way, however this seems to boil down to only one bit of research [1] and a few adverse event case studies [2]. There really isn’t that much good evidence that would say kava, or more specifically, kavalactones seek out and directly affect dopamine receptors.
Baum et al set out to measure the levels of dopamine, it’s intermediary metabolite DOPAC, and the final ending product of the dopamine cycle, HVA (homovanillic acid) in the presence of kava extracts [1]. They found that kava extract changed the extracellular dopamine content in the nucleus accumbens area of the brain. 20mg/kg and 120mg/kg caused a slight increase in dopamine, where the highest dose (220mg/kg) caused a marked decrease followed by an increase. DOPAC was not affected by doses under 220mg/kg, and due to large interindividual differences, no statistical significance could be seen. HVA, also known as homovanillic acid is the final stage of dopamine metabolization. 20mg/kg of kava extract showed 20% increase with decreases being seen with increasing dosage and no change at the highest dose. When individual kavalactones were administered, kavain at a dose of 30mg/kg induced a decrease in dopamine and DOPEC levels for over 8 hours. Other doses had no effect. Of these results on individual kavalactones, yangonin was the only KL shown to reduce levels of dopamine sharply. If any kavalactone is directly active at blocking dopamine it would be yangonin. DMY has some dopamine increasing ability.
The results in table 1 by Baum et al. suggest that kava is not necessarily binding at dopaminergic sites and may speak more to MAO-B inhibition except for isolated yangonin. Constituents of kava were shown to have properties of MAO-B inhibition similar to that of curcumin which could speak to increased dopamine levels [4].
Case studies have presented themselves as dopaminergic in regards to kava in the past [2]. These case studies are cited over and over in kava literature as evidence towards dopamine antagonism, however there are large questions that have remained unanswered regarding this report. The patient in question had a history of genetic susceptibility by a family history of essential tremor. Quite glaringly, kava was reportedly taken for the treatment of anxiety which only developed after the first observation of symptoms of parkinsons. This does not correlate to kava causing the event.
In table two we can see where researchers sought to ascertain the binding ability of kavalactones to bind to different areas of the neuronal structure [3]. Lower numbers on this chart indicate higher ability for kavalactones to bind to the specific receptor. Based on this information we can suggest that kava has little affinity for the sites above except for GABA-A which is highlighted. Agonism in all other areas was weak, including dopamine.
Summary:
What we can take away here is that kava is an extremely dynamic pharmacologically active compound. The variability in the results found seem to underscore the fickle nature of kava when individual kavalactones are tested instead of a full spectrum extract. It’s attractive to say “This kavalactone is responsible for this action”, however there is a growing body of evidence that kavalactones exert their beneficial effects when applied in combination, with each one playing on the actions of others. The only kavalactone here that may interfere with the dopaminergic system in a meaningful way is yangonin, by possible reduction.
[1] Baum, S. S., R. Hill, and H. Rommelspacher. 1998. “Effect of Kava Extract and Individual Kavapyrones on Neurotransmitter Levels in the Nucleus Accumbens of Rats.” Progress in Neuro-Psychopharmacology & Biological Psychiatry 22 (7): 1105–20. https://doi.org/10.1016/s0278-5846(98)00062-1.
[2] Meseguer, Elena, Rocio Taboada, Vicenta Sánchez, María Angeles Mena, Victor Campos, and Justo García De Yébenes. 2002. “Life-Threatening Parkinsonism Induced by Kava-Kava.” Movement Disorders: Official Journal of the Movement Disorder Society 17 (1): 195–96. https://doi.org/10.1002/mds.1268.
[3] Dinh, L. D., U. Simmen, K. B. Bueter, B. Bueter, K. Lundstrom, and W. Schaffner. 2001. “Interaction of Various Piper Methysticum Cultivars with CNS Receptors in Vitro.” Planta Medica 67 (4): 306–11. https://doi.org/10.1055/s-2001-14334.
[4] Prinsloo, Denise, Sandra van Dyk, Anél Petzer, and Jacobus P. Petzer. 2019. “Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum).” Planta Medica 85 (14-15): 1136–42. https://doi.org/10.1055/a-1008-9491.
Today’s kava fact will be addressing dopamine, and how kava may or may not act at this specific neurotransmitter. There have been numerous papers stating that kavalactones either increase or decrease dopamine in a significant way, however this seems to boil down to only one bit of research [1] and a few adverse event case studies [2]. There really isn’t that much good evidence that would say kava, or more specifically, kavalactones seek out and directly affect dopamine receptors.
Baum et al set out to measure the levels of dopamine, it’s intermediary metabolite DOPAC, and the final ending product of the dopamine cycle, HVA (homovanillic acid) in the presence of kava extracts [1]. They found that kava extract changed the extracellular dopamine content in the nucleus accumbens area of the brain. 20mg/kg and 120mg/kg caused a slight increase in dopamine, where the highest dose (220mg/kg) caused a marked decrease followed by an increase. DOPAC was not affected by doses under 220mg/kg, and due to large interindividual differences, no statistical significance could be seen. HVA, also known as homovanillic acid is the final stage of dopamine metabolization. 20mg/kg of kava extract showed 20% increase with decreases being seen with increasing dosage and no change at the highest dose. When individual kavalactones were administered, kavain at a dose of 30mg/kg induced a decrease in dopamine and DOPEC levels for over 8 hours. Other doses had no effect. Of these results on individual kavalactones, yangonin was the only KL shown to reduce levels of dopamine sharply. If any kavalactone is directly active at blocking dopamine it would be yangonin. DMY has some dopamine increasing ability.
The results in table 1 by Baum et al. suggest that kava is not necessarily binding at dopaminergic sites and may speak more to MAO-B inhibition except for isolated yangonin. Constituents of kava were shown to have properties of MAO-B inhibition similar to that of curcumin which could speak to increased dopamine levels [4].
Case studies have presented themselves as dopaminergic in regards to kava in the past [2]. These case studies are cited over and over in kava literature as evidence towards dopamine antagonism, however there are large questions that have remained unanswered regarding this report. The patient in question had a history of genetic susceptibility by a family history of essential tremor. Quite glaringly, kava was reportedly taken for the treatment of anxiety which only developed after the first observation of symptoms of parkinsons. This does not correlate to kava causing the event.
In table two we can see where researchers sought to ascertain the binding ability of kavalactones to bind to different areas of the neuronal structure [3]. Lower numbers on this chart indicate higher ability for kavalactones to bind to the specific receptor. Based on this information we can suggest that kava has little affinity for the sites above except for GABA-A which is highlighted. Agonism in all other areas was weak, including dopamine.
Summary:
What we can take away here is that kava is an extremely dynamic pharmacologically active compound. The variability in the results found seem to underscore the fickle nature of kava when individual kavalactones are tested instead of a full spectrum extract. It’s attractive to say “This kavalactone is responsible for this action”, however there is a growing body of evidence that kavalactones exert their beneficial effects when applied in combination, with each one playing on the actions of others. The only kavalactone here that may interfere with the dopaminergic system in a meaningful way is yangonin, by possible reduction.
[1] Baum, S. S., R. Hill, and H. Rommelspacher. 1998. “Effect of Kava Extract and Individual Kavapyrones on Neurotransmitter Levels in the Nucleus Accumbens of Rats.” Progress in Neuro-Psychopharmacology & Biological Psychiatry 22 (7): 1105–20. https://doi.org/10.1016/s0278-5846(98)00062-1.
[2] Meseguer, Elena, Rocio Taboada, Vicenta Sánchez, María Angeles Mena, Victor Campos, and Justo García De Yébenes. 2002. “Life-Threatening Parkinsonism Induced by Kava-Kava.” Movement Disorders: Official Journal of the Movement Disorder Society 17 (1): 195–96. https://doi.org/10.1002/mds.1268.
[3] Dinh, L. D., U. Simmen, K. B. Bueter, B. Bueter, K. Lundstrom, and W. Schaffner. 2001. “Interaction of Various Piper Methysticum Cultivars with CNS Receptors in Vitro.” Planta Medica 67 (4): 306–11. https://doi.org/10.1055/s-2001-14334.
[4] Prinsloo, Denise, Sandra van Dyk, Anél Petzer, and Jacobus P. Petzer. 2019. “Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum).” Planta Medica 85 (14-15): 1136–42. https://doi.org/10.1055/a-1008-9491.
