KAVA (PIPER METHYSTICUM)
With a rich history originating in the pacific islands and the native use of the plant for various medicinal and reactional reasons, there’s no doubt that kava is one of the more interesting herbs out there.
It’s complex mechanism through its layers of action through its various primary kavalactones has been said to produce different subjective effects and therapeutic benefits, depending on the type of kava used and its dose.
Kava, which is ideally used in its noble types and those which are full spectrum yet standardized, constituting of the the root extracts are often standardized to kavalactones. Its also shown to with a relatively acceptable safety margin in terms of daily recommended kavalactones highly variable based on its indication.
Despite this however, some claim it may have some hepatotoxic compounds or kavalactones, whilst others blame the types and extraction methods used for such negative effects.
Its likely, that similarly to how standardization or ratio of alkaloids (as an example) in a herb dictates it’s potency, selectivity and efficacy for a given indication, the same may apply to kava, its various kavalactones, and the ratio in which they’re formulated in.
Up to 250mg has been safely used in various trials for the treatment generalised anxiety disorder, and according to sources such as Medscape it can also be used in doses from 180–210mg of active kavalactones for insomnia.
It’s also said to be helpful at a gradually decreasing dose over several days downward to 50mg kavalactones when used for treating benzodiazepine withdrawal symptoms in dependent individuals, based on some of the limited scientific literature and research.
Upwards of several grams are sometimes taken in many traditional uses of the plant in places like Pacific islands are sometimes used, and often under-dosed when used therapeutically in western medicine in doses of as low as 50–60mg, which have a significantly less clinical effect.
It’s recommended that daily consumption be ideally limited to anywhere from 250–500mg depending on the the country and its general use of the plant. Using lower doses of kavalactones can still however be useful for certain conditions in some people, and can still benefit from what’s usually described as a “reverse tolerance” effect in regards to tolerance.
Over the years, new formulations have emerged both in concentrated forms which have the kavalactones in their pure form, ready to be dissolved either in water or sometimes milk. Micronised kava is also sometimes used when a higher potency formulation is required.
As of more recently, even sublingual forms of the extracts have become widespread and gained a market interest in the supplement world. Such formulations may have the advantage of a slightly increased onset of action, making it suitable for those who use kava for anxiety or panic attacks for example.
All primary 6 (as of what’s mainly known about now) kavalactones appear to be weak reversible inhibitors of monoamine oxidase B enzyme, with at least 2 showing some GABAergic activity, though mainly as a positive allosteric modulation rather than specific or selective agonist.
The complex mechanism of kava have made it a target in self-medication for the treatment of a range of different conditions which fall into the milder side of the spectrum, including neurological pain, muscular pain, some inflammatory diseases, anxiety, depression, ADHD, insomnia and even benzodiazepine, tobacco, cannabis and opioid withdrawal.
Yangonin which appears to exert it’s action in addition to a high binding affinity in the human brain for both cannabinoid receptors CB1 and CB2, with a slight pretence for CB1, and a higher affinity though significance due to levels present, than THC and CBN. It’s CB1 effects are likely to be reduced by high doses of THCV.
Furthermore, mechanisms of some cannabinoids including THCV and CBD isolates may also produce antidote like properties, potentially affecting the complex psychopharmacology of both cannabis/hemp as well as kava species when used in varying standardized or non-standardized forms.
As more quality research is presented, a more selective control over the standardization or specific use of the six primary kavalactones will greatly improve out understanding of its complex mechanism.
Potentially also lowering certain side effects or interaction involved with CYP450 enzyme, whilst also allowing for more specific dosing and usage of each isolated kavalactone or the ratio in which its guaranteed to be present in a given formulation or extract.
In many cultures, MAOI containing herbs have been implemented in potentiating or otherwise prolonging the effect of a primary compound throughout history. As a complex plant, whose primary constituents all have shown to at least weak-to-moderate selective, and reversible inhibitors of monoamine B, its likely that kava may have the ability to also potentiate various other sedative herbs such as lemon balm, when they’re used in a combination.
Though its typically considered safe, at least for short term use (since long term use may increase certain liver enzymes), kava like many other herbs is capable of having interactions with other herbs and medications.
There are known enzymatic and at times dangerously additive effects which must be cautioned against. This is especially the case when kava is co-administered with benzodiazepines, barbiturates or alcohol to produce additive and potentially dangerous effects.
Most of these interactions is often produced by drug-herb interactions, rather than herb/herb interactions however.(despite both being possible). Certain herbs should especially be cautioned against, with one being St John’s Wort which has shown to be dangerous when combined with most types of antidepressant medications or other serotonergic agents. In addition to this, there are also enzymatic interactions which can affect the effectiveness of both herbs when used together.
Other Herbs That May Have Additive/Synergistic/Potentiation Effects
The additive effects observed with using such herbs in combination with one or two other specific herbs may likely be due to reasons varying reasons ranging from additive effects, synergistic mechanism, potentiation or more than one such factor.
Slightly additive effect of high dose, standardized magnolia bark extract with high content of magnolol and honokiol, through positive allosteric modulation effect on GABA receptors is observed when combined with kava.
There may also likely be some synergistic effects in regards with sedation and anxiolysis with its combination with lemon balm, especially in the presence of a PAM for GABA such as passionflower.
In cases where passionflower is used, the synergistic and often potentiation effect is likely linked to the mild activity of full spectrum passionflower as an MAOI of both enzyme, with a slight preferential inhibition for the monoamine A, over B.
This effect is likely due to the presence of naturally MAOIs (most commonly preferentially for the B enzyme, with less known examples of either non-selective or MAO-A selective compounds) including the naturally occurring beta Carbolines which are also found in tobacco. It’s likely that these beta carboline compounds likely at least partially contribute in an increase in the addictive and dependence liability of nicotine.
More research is needed to establish such links which may provide more efficacious treatment options for not just the dependence on nicotine, but also psychological addiction to its effects.
Another herb, German Chamomile is also capable of binding to the gamma sub receptor site at the benzodiazepine receptors and may have additive effects with both pharmaceutical benzodiazepines, as well as the herbs discussed.
Notes To Consider In Regards With Interactions
Combining doses upward of a few grams of standardized lemon balm such as Cyracos to constituents including rosmarinic acid with other herbal sedative including high dose extracted passionflower derived organically and from full spectrum flowering buds, to potentiate the effects of lemon balm (Melissa officials L) potentially through both mild MAO Inhibiting activity, in addition to the relatively more well known GABAergic activities which may additively and synergistically pair with the mechanisms of lemon balm.
This is simply a theoretical assumption and may not be the mechanism involved in the synergistic actions. Furthermore, valerenic acid, found in varying concentrations in Valerian root has shown to act as a positive allosteric modulator for GABA, increasing GABA levels and mildly enhancing its effects which in addition to its partial agonistic activity at serotonin sub receptors especially 5HT5A receptor.
This sub-receptor has shown to partially modulate the sleep-wake cycle and may explain the increased hypnotic effects of the herb, compared to herbs which lean toward a more anxiolytic action via enhancement of GABA A activity, without the same significant hypnotic effects at therapeutic, standardized doses of the herbal extracts of the plant.
Its therefore likely, that considering the more significant actions of kava, especially on MAO B, that its combination with other herbal sedatives may produce either desired or undesired effects, depending on the combination, dose and indication of use.
Other Supplements Which Can Increase Sedative Effects Of Kava
- Hops
- Zizyphus
- High Dose Sour Cherry (which has naturally- occurring melatonin)
- Valerian Root
- Ashwagandha
- California Poppy
- Magnesium, in forms such as Glycinate or Magnesium Amino Acid Chelate amongst others
- Tryptophan
- L-Theanine
- Taurine
These supplements have been selected in no specific order.
