Kava Kava (Piper methysticum)

The kava plant was frst discovered by Captain Cook who appropriately
named it the intoxicating pepper. Obeyeskere, an acclaimed biographer of Cook,
wrote that dring his second voyage to the !oth "acifc, Cook happened pon the
kava plant when he was invited by the Tongan monarch to partake in a celebratory
party. #vidently, Cook was disgsted by the way in which the Tongan people
concocted an extraction from the herb bt $ickly looked beyond his misgivings
after he had experienced the soothing and convivial e%ects it prodced. Cook was
reported to have en&oyed these e%ects so mch that by the end of his &orney, he
was drinking almost an endless amont of kava.
'

Today, (ava is probably best known as having a mild anxiolytic e%ect and is often
sed in ntracetical combinations for transient stress)insomnia. *owever, the
clinical tility of the kava plant has far greater applications than of a simple sleep
aid. !pecifcally, empirical research has pointed the to the se of kava as a
treatment for +or ad&vant in,- anxiety disorder+s,
.
, insomnia, acte stress, painfl
conditions +specifcally those of the rinary tbles and bladder,
/
, mscle
spasticity
0
, some symptoms of premenstral syndrome 1 menopase
2
,
fbromyalgia
0
, restless leg syndrome
0
, and others.
Use in Anxiety & Sleep
(ava is considered one of the most poplar and empirically spported botanicals in
the complementary armamentarim for anxiety. The ma&ority of pblished evidence
sbstantiates the clinical tility of kava extracts +standardi3ed to /45 kavalactones,
for the treatment of anxiety and insomnia in randomi3ed, doble blind, placebo6
controlled trials.
7,8
!pecifcally, kava has been shown to increase patients report of
sleep $ality. 9oreover, ob&ective research involving polysomnographic
examination demonstrated that kava increased the amont of time patients
remained in deep sleep.
:

;nlike most stdies involving either prescription medications or botanical extracts <
the e=cacy of kava +in anxiety, has been established in placebo6controlled trials as
well as direct comparisons with commonly prescribed medications. >eslts of two
head6to6head trials between kava and low6dose ben3odia3epines +oxa3epam
8
and
dia3epam
?
, demonstrated that active treatments conferred signifcant redctions in
anxiety symptoms +as measred by the *amilton @nxiety !cale
'4
6 an ob&ective
psychometric tool sed to evalate the varios domains of anxiety
'
Aeaglehole, B.C. +'?80, The Life of Captain James Cook. Condon- The *aklyt !ociety.
.
#rnst, #. +.447, *erbal >emedies < @ !ystematic >eview of Controlled Clinical Trials. Phytomedicine '/- .426.4:.
/
Physicians !esk "eference for #er$al %edicines& +0th #dition,. +.448,. 9ontvale, DB- Thompson "E>
0
Bellin B, Fregory ". +eds., +.44?, (@G@ < a fll monograph H#lectronic GersionI. 'atural %edicines Comprehensi(e
!ata$ase& >etrieved @gst '2, .44? from http-))www.natraldatabase.com
2
Jarnecke F. +'??', "sychosomatic dysfnctions in the female climacteric- Clinical e%ectiveness and tolerance of
(ava extract. H@rticle in FermanI )ortschr %ed& '4?- '... Kn Bellin, B. 9. +.44?, !ept. 40,. (@G@- @ Lll 9onograph.
'atural %edicines Comprehensi(e !ata$ase . !tockton, C@- Therapetic >esearch Laclty. H#lectronic GersionI.
7
Gol3 *", (ieser 9. +'??8,. (ava6kava extract J! '0?4 verss placebo in anxiety disorders < a randomi3ed
placebo6controlled .26weeks otpatient trial. Pharmacopsychiatry /4- '62.
8
"ittler 9*, #rnst #. +.444, #=cacy of kava extract for treating anxiety- systematic review and meta6analysis. J&
Clin& Psychopharmacolo*y. .4-:06:?.
:
Aeabrn F, Fray F#. +.444,. @ >eview of *erbal 9edicine for "sychiatric Eisorders. Psychiatric Ser(ices& 2'+?,-
''/46''/0.
?
Fessner A, Cnota ", !teinbach T. +'??0, #stract of the kava kava rhibo3ome in comparison to dia3epam and
placebo. + Phytotherapy, '2, /46/8.
'4
*amltion 9. +'?74,. @ >ating scale for depression. Journal of 'eurolo*y and 'eurosur*ical Psychiatry& .2-2767.
Kava Kava (Piper methysticum)
symptomatology, when compared with placebo. JhatMs more, both trials were
powered to assess comparative e=cacy between active treatment grops +i.e., kava
vs. dia3epam and kava vs. oxa3epam,N the reslts of this analysis revealed no
statistical di%erences between any active treatment grop. The demonstration of
e,ui(ocal e-cacy +particlarly when compared to a gold standard treatment sch
as a ben3odia3epine, is impressive, as patients treated with kava +nlike those in
the ben3odia3epine treatment grop, showed no changes in cognition or
neropsychological fnction
'','.
, rebond anxiety once treatment was halted, or
daytime somnolence.
'/,'0
@dditional research pblications also compared the e%ects
of kava with bspirone
'2
+a serotonin '@ H26*T'@I agonist with mixed dopaminergic
e%ects
'7
, and opipramol +an anxiolytic drg strctrally similar to imipramine
'8
,.
':

@s was seen previosly, these pharmacological agents also demonstrated e$ivocal
e=cacy to kava. Kn two additional randomi3ed, doble blind, placebo6controlled
trials, kava demonstrated a rapid redction of generali3ed anxiety symptoms as
early as week one and throghot the dration of the trial. @ long6term stdy of
similar design also demonstrated a statistically signifcant e%ect with kava
treatment on generali3ed anxiety symptoms. Kn this trial, the anxiolytic e%ect of
kava also began early in treatment and was signifcant throghot every follow6p
assessment inclding the stdy endpoint +.2 weeks,. Kt shold be noted, however,
that becase kava does not directly act on F@A@@ system < the clinical e%ect of
kava is not as immediate as is seen with ben3odia3epines.
'?

#rnst +et. al., presented their fndings regarding kavaMs se for the treatment of
anxiety in a meta6analysis of seven clinical trials.
7
Kn this review, #rnst presented
compelling evidence spporting the se of kava as an anxiolytic. @dditionally, in his
review of other botanical treatments that were proposed for the management of
anxiety, he specifcally noted that only kava demonstrated fndings that have been
reprodced with similar reslts.
7
The conclsions that were drawn +initially, by #rnst
were later confrmed by a similar meta6analytic review by "ittler +et. al., as part of a
Cochrane review pblication.
'.
Of particlar interest, the "ittler analysis inclded
+only, data from doble blind, randomi3ed, placebo controlled trials that tili3ed a
standardi3ed and highly validated primary endpoint +changes in total score from the
*amilton @nxiety !cale,. The reslts of this analysis +nO /:4, were statistically
''
9nte TL, *eni3e *B, 9at3ke 9, et. al. +'??/,. #%ects of oxa3epam and an extract of kava root +"iper
methysticm, on event6related potentials in a word recognition task. 'europsycho$iolo*y& .8- 0762/
'.
Kn fact, pblished evidence has shown kava to increase cognitive fnction. Lor more information, see- "rescott, B.,
Bamieson, E., #mdr, D., 1 E=eld, ". +'??/,. @cte e%ects of kava on measres of cognitive performance,
physiological fnction, and mood. !ru* and Alcohol "e(ie. / 01 +' H'0726//7.I,, 0?628.
'/
Bellin B, Fregory ". +eds., +.44?, (@G@ < a fll monograph H#lectronic GersionI. 'atural %edicines Comprehensi(e
!ata$ase& >etrieved @gst '2, .44? from http-))www.natraldatabase.com
'0
Choinard F. +.440,. Ksses in the clinical se of ben3odia3epines- "otency, withdrawal, and rebond. J Clin
Psychiatry/72+spp 2,,86'.
'2
#ison @!, Temple EC. +'?:7,. Aspirone- >eview of its pharmacology and crrent perspectives on its mechanism
of action. Am J %ed :4+sppl. /A,- '6?.
'7
!chatberg, @. L., Cole, B. O., 1 EeAattista, C. +.448,. American Psychiatric Association2 %anual of Clinical
Psychopharmacolo*y +7th #dition,. @rlington, G@- @merican "sychiatric "blishing, Knc.
'8
Fabbard, F. O. +.448,. 3a$$ard4s Treatments for Psychiatric !isorders +0th #dition,. Jashington, EC- @merican
"sychiatric "blishing.
':
Aoerner >B, !ommer *, Aerger J, et al. +.44/, (ava6kava extract CK '24 is as e%ective as opipramol and
bspirone in generali3ed anxiety disorder- @n :6week, randomi3ed, doble6blind, mlti6centre clinical trial in '.?
otpatients. Phytomedicine/ '4+spp 0,, /:60?.
'?
!arris B, (avanagh E. +.44?,. (ava and !t. BohnMs Jort- #vidence for ;se in 9ood and @nxiety Eisorders. The
Journal of Complementary & Alternati(e %edicine/ 05+:,- :.86:/7.
Kava Kava (Piper methysticum)
signifcant +mean redction on *@96@ O 6?.8 at stdy endpoint, favoring kava.
?,.4

@lthogh it appears $ite clear that kava extracts have a demonstrable anxiolytic
e%ect < research contines to emerge as to the specifc diagnoses or symptomatic
presentation+s, in which kava cold best be deployed to e%ectively treat patients
who s%er from generali3ed anxiety.
Use in Painful Conditions2
(ava has been researched in a variety of contexts involving patients experiencing
pain. >esearch has emerged that point to a therapetic se for kava in the
treatment of postherpetic neralgia
.'
, intersistial cystitis, or other disorders of the
bladder and rinary tract.
..,./
Chavallier and colleages demonstrated that kavaMs
analgesic action, specifc to the rinary tract and bladder, might be de to a strong
binding a=nity of kava to these particlar areas of the body.
2
Lrthermore, in animal
models, Cpasso demonstrated that kava $ieted amphetamine6indced
hypermotility.
.'

Jhile kava has been shown to not directly interact with the opiate pathways +as
naloxone is ine%ective in reversing kavaMs antinociceptive activity,, 9eyer and
others have written on the possible mechanisms of action +via non6opiate pathways,
that may explain kavaMs analgesic e%ect. !pecifcally, kava has demonstrated an
ability to inhibit voltage6dependant sodim ion channels. This interaction consists
of fast and specifc inhibition of voltage6dependent sodim channels and redction
of crrents throgh voltage6activated sodim and calcim channels. Kn animal
models, the paralysis e%ect of kava on neromsclar transmission and mscle
contractility is similar to that of local anesthetics.
.0
@s sch, it is theoretically
possible that the antispasmodic and anticonvlsant e%ects seen throgh these
mechanisms of action may explain some of kavaMs analgesic activity. Lrther, kava
+particlarly the yangonin and dihydrokawain isolate componds extracted from the
root, has been shown to increase serotonin +26*T'@,, sppress the e%ects of
gltamate, and have strong inhibitory e%ects on both COP6' and COP6. +in a dose6
dependant manner,.
.2,.7,.8,.:

!ue to ka(as uni,ue pharmacolo*ical acti(ity/ compara$le e-cacy to prescription
medications (in anxiety)/ and lon* history of safe use 6 research is on*oin* to
.4
@s a frame of reference only: Kn pivotal trials for LE@ @pproval in the treatment of Fenerali3ed @nxiety Eisorder 6
Cexapro

+escitalopram oxylate, demonstrated a redction of 67.? points on the *@96@ at the stdy endpoint.
HLrom- >oseboom L*, (alin D* +.44?, Citalopram and !6Citalopram. Kn !chat3berg @, Demero% CA +#ds., The
American Psychiatric Pu$lishin* Text$ook of Psychopharmacolo*y& +0
th
ed., .?'6/4.,.
.'
Qarnell, #., @bascal, (., 1 *ooper, C. +.44/,. Clinical 7otanical %edicine +.nd #dition,. Carchmont, DQ- 9ary @nn
Ciebert "blications, Knc.
..
Cpasso @, !orrentine C. +.442,. "harmacological stdies on the seditive and hypnotic e%ects of kava kava and
passionRower. Phytomedicine/ '., /?602.
./
ArSggemann GL, 9eyer *L. +'?7/, !tdies on the analgesic e=cacy of kava constitents dihydrokavain +E*(,
and dihydromethysticin +E*9,. @r3neim Lorsch, '/, 048<04? Hin FermanI. 8n Qarnell, #., @bascal, (., 1 *ooper, C.
+.44/,. Clinical 7otanical %edicine +.nd #dition,. Carchmont, DQ- 9ary @nn Ciebert "blications, Knc.
.0
Bamieson EE, E=eld "*. +'??4,. The antinociceptive actions of kava components in mice. Clin 9xp Pharmacol
Physiol BlyN'8+8, 0?2624:.
.2
Cake, B. *., 1 !piegel, E. +.448,. Complementary and Alternati(e Treatments in %ental #ealth Care& Jashington,
EC- @merican "sychiatric "blishing, Knc.
.7
9eyer, *. +'?78,. "harmacology of (ava. Psychopharmacolo*y 7ulletin, :-'46''.
.8
;ebelhack, >., Lranke, C., 1 !chewe, *. +'??:,. Knhibition of platelet 9@O6A by kava pyrone6enriched extract from
"iper methysticm. Pharmacopsychiatry/ ;0- ':86'?..
.:
!pinella, 9. +.44.,. The Kmportance of "harmalogical !ynergy in "sychoactive *erbal 9edicines. Alternati(e
%edicine "e(ie./ < +.,, '/46'/8.
Kava Kava (Piper methysticum)
elucidate .hich disease processes .ould $e most appropriate for supplementation
.ith ka(a
.
2Kn my clinical experience, this approach to pain treatment has
particlarly benefcial for patients whose symptomatic presentation warrants a more
mlti6modal treatment sch as those s%ering from fbromyalgia, complex regional
pain syndrome, migraine headache, and possibly postherpetic neralgia.
Pharmacology:
"eak plasma levels of kava occr approximately '.: hors after an oral dose of kava
and the elimination half6life of kavalactones is ? hors.
.?
;nchanged kavalactones
and their metabolites ndergo renal and fecal elimination. "harmacokinetic data
sggests that kava easily passes the blood6brain barrier and has the theoretical
possibility of e%ecting CQ"/@0, CQ".C'?, CQ"'@., and CQ".E7 en3yme +reslting in
higher drg concentrations,.
2
*owever, sch interactions are only theoretical at this
point, and little data has been pblished to sbstantiate this hypothesis.
/4

@s with almost every pharmacological therapy today +especially those that act on
the central nervos system,, the mechanism+s, of action for kava are not
completely nderstood. Devertheless, research does indicate that there are $ite a
few actions +via varied nerotransmitters)systems, that may accont for
kavalactoneMs +the pharmacologically active ingredient of the kava plant, e=cacy in
the treatment of certain conditions.
@s discssed previosly, the reported analgesic e%ect+s, of kava have been not
shown to be a reslt of direct interaction with the opioid pathway+s, as one might
assme.
0
>ather Fleit3 +et. al., reported that the kava pyrone +T,6(avain, once
isolated from the parent kava plant, inhibited arachidonic acid +@@,6indced hman
platelet aggregation in a dose6dependent manner +in vitro,. Their research
conclded that this mechanism thereby inhibits the cyclooxygenase +COP, en3yme
in a non6specifc manner. J +et. al., fond that kavaMs root isolates +particlarly
dihydrokawain and yangonin componds, showed the strongest inhibitory e%ects on
the cyclooxygenase system.
0,/'

Kn two separate pblications, kavapyrones prodced actions involving the inhibition
of voltage6dependent sodim ion channels, increasing F@A@@ receptor densities,
/.,//

blocking norepinephrine reptake, competitively inhibiting monoamine oxidase A
+9@O6A,,
':
preventing the ptake of dopamine, and sppressing the release of
gltamate.
:

Possible Adverse Events:
.?
*me, @. +.44?,. @ppendix KC 6 Datral "rodcts and Erg Knteractions. Kn L. Lerri, )erri4s Clinical Ad(isor (1==>
9dition) ? 8nstant !ia*nosis and Treatment +pp. '0026'024,. "hiladelphia, "@- 9osby6#lsevier.
/4
@ng6Cee 9., Chn6! Q., 1 9oss B. +.44?,. Complementary and @lternative Therapies. Kn >. 9iller, C. #riksson, C.
Lleisher, B. Jiener6(ronish, 1 J. Qong, %iller4s Anesthesia +8th #dition ed., pp. ?286?77,. "hiladelphia, "@- Chrchill
Civingstone, @n Kmprint of #lsevier.
/'
J E, Q C, Dair 9F et al. +.44.a, Cyclooxygenase en3yme inhibitory componds with antioxidant activities from
Piper methysticum +kava kava, roots. Phytomedicine& ?'+',- 0'608.
/.
Eavies C", Erew C@, E=eld ", et. al. +'??., (ava pyrones and resin- stdies on F@A@@, F@A@A and
ben3odia3epine binding sites in the rodent brain. Pharmacolo*ical Toxicolo*y& 8'- '.46'.7.
//
CaLrance JC, Caterbach #C, Co%ey C#, !aloway !, (afer E, et. al. +.444, The ;se of *erbal @lternative
9edicines in Deropsychiatry- @ >eport of the @D"@ Committee on >esearch. Journal of 'europsychiatry and
Clinical 'eurosciences. '.- '886'?..
Kava Kava (Piper methysticum)
Kn general, most patients taking kava do not experience any adverse
events H>#9#9A#> 6 kava has been sed for ceremonial and social beverages in the
!oth "acifc islands for over a centryUI. That said, most C@9 practitioners wold
agree that in a small minority of patients kava cold case- gastrointestinal pset,
headache, drowsiness, and)or dry moth. *eavy kava drinkers ac$ire a reversible
ichthyosiform erption that has been called, kava dermopathy.
/0
The case is
nknown bt may relate to interference with cholesterol metabolism.
/2
@dditionally, as noted previosly, in vitro stdies have indicated that one of kavaMs
pharmacodynamic e%ects is to antagoni3e dopamine +E.,. Therefore practitioners
shold se their clinical &dgment when tili3ing kava for patients- diagnosed with
"arkinsonVs disease, severe mental illness, or those who are taking dopamine
agonist medications +e.g., Cevo6Eopa, bpropion,.
Cast, given the broad array of benefts that kava has to o%er < it is nfortnate that
its reptation was sllied after reports of hepatotoxicity were pblished in the
academic literatre. The proposed evidentiary spport for this claim is based
largely on case reportsN where kavaMs connection to hepatotoxicity cold not
properly be discerned de to varios confonding factors +sch as other
medications,.
?,'.,/7

/0

/2
Dorton, !., 1 >3e, ". +'??0,. (ava Eermopathy. Journal of the American Academy of !ermatolo*y / ;0 +',, :?6?8.
/7
Ceak (. +'???, *erbal 9edicine- Ks it an alternative or an ;nknownW @ Arief >eview of "oplar *erbals ;sed by
"atients in "ain and !ymptom 9anagement "ractice !etting. Current "e(ie. of Pain. /- ..76./7