Effect of an acute dose of crude kava root extract on problem solving in healthy young adults.
Kava is an intoxicating drink that has been used traditionally by the indigenous peoples of the South Pacific (Singh 1992). Much like alcohol in Western cultures, kava plays an important role in many South Pacific social and religious rituals and is also used as a recreational intoxicant (Singh 1992). Traditionally kava is prepared through the use of a crude water or saliva extraction of the pounded or chewed root of Piper methysticum and is consumed orally (Singh 1992). This root extraction contains a number of structurally related compounds that are bioactive and are collectively referred to as kavapyrones or kavalactones (Bilia 2002).
When consumed, kava produces several psychological effects including reductions in fatigue and anxiety and a depressive intoxication that resembles that produced by alcohol and benzodiazepines (Singh 1992). These psychological effects are thought to be the result of the non specific, complex and multifaceted effects of several kavalactones produced by Piper methysticum on the human central nervous system (Cairney 2002, Sarris 2009, Singh 1992, Singh 2002). These effects include alterations in the activity of voltage gated ion channels and the modulation of several neurotransmitter systems (Bilia 2002, Cairney 2002, Singh 2002).
Historically kava has been used in the South Pacific as an anxiolytic (Singh 1992). Interestingly traditional kava use does not seem to be associated with the negative cognitive effects or development of dependency often seen in chronic alcohol or benzodiazepine users (Singh 1992). Because of this, kava is currently viewed as a potentially clinically viable alternative to other anxiolytics such as antidepressants and benzodiazepines (Kumar 2006, Singh 2002) and several studies have been conducted to assess the efficacy of kava root extracts as a treatment for clinical anxiety that does not produce drowsiness and cognitive impairment (Ernst 2006, Malsch 2001, Singh 2002). Although these studies have collectively shown that kava root extracts are effective anxiolytics at low doses (Singh 2002, Ernst 2006), their effects on cognition are somewhat less clear.
Kava's principle clinical advantage over benzodiazepines and other accepted anxiolytics is its purported lack of cognitive, perceptual and motor side effects at anxiolytic dosages, so an understanding of such potential effects is critical in the evaluation of kava as a psychotherapeutic of merit (Singh 2002, Thompson 2004). A recent systematic review of the literature found that the effects of kava on cognition were somewhat equivocal, with acute doses producing enhancements or no statistically significant alterations in working memory, divided and sustained attention, reaction time and memory retrieval speed (LaPorte 2011). Although the reviewed works demonstrate that kava does not negatively affect (or may even enhance) several specific aspects of cognition, these studies have tended to focus on basic cognitive functions including attention, reaction time and short term memory (Bilia 2002, Cairney 2003a, Cairney 2003b, LaPorte 2011, Thompson 2004), while not examining complex cognitive processes such as executive control, which broadly encompasses several functions including planning, decision making and problem solving (Fuster 2000, Kimberg 1998).
Studies examining the effects of chronic and very high doses of kava in traditional users have shown that such elevated doses result in specific problems with coordination and visual attention but do not impair visual searching, pattern recognition or associative learning (Cairney 2003a, Cairney 2003b, LaPorte 2011).
The present study extended this corpus of work by using a randomised double blind placebo controlled design to assess if impairments in executive function (specifically the ability to solve ambiguous problems) are associated with the consumption of a single 200 mg oral dose of a standardised 30% crude kava root extract (60 mg kavalactones) in young adult humans.
Materials and methods
Participants were recruited from the undergraduate student body of a university in the south eastern United States via email and class announcements. No inducements for participation were provided and all procedures were approved by the Institutional Review Board of Elon University. Prospective participants were excluded from the study if they reported: 1) current viral or bacterial illness or antibiotic use; 2) personal history of jaundice or liver problems; 3) personal history of heavy alcohol consumption (4 drinks/day or 14 drinks/week for men, 3 drinks/day or 7 drinks/week for women); 4) current use of any prescription medication except hormonal birth control; 5) current use of any over the counter drug, herbal or nutritional supplement except daily oral multivitamins; 6) current pregnancy or breastfeeding; and 7) known adverse or allergic reactions to gelatin or kava extract. For each participant, weight (in kg) measurements were taken using a digital scale.
A randomised double blind placebo controlled design was used. Participant assignment to the kava or placebo group was random and was based on an alternating odd/ even scheme using participant ID numbers that were chronologically assigned to the participants based on their order of study enrollment. All participants were asked to abstain from the use of recreational drugs, alcohol and acetaminophen for 24 hours prior to their testing appointment, and fast (allowing for the consumption of plain water) for three hours prior to the appointment. Compliance with these requests was verbally confirmed at the appointment. Each participant was randomly provided with one clear, unmarked gelatin capsule that contained either 648 mg powdered gelatin (placebo; Bernard Jensen Products, Solana Beach CA, USA) or 200 mg of a standardised and commercially prepared kava (Piper methysticum) extract (Natrol Inc, Chatsworth CA USA). Kava extract was 30% kavalactones (60 mg containing 6-7% kavain, 5-6% dihdromethysticin) from an unreported cultivar and was obtained from ground root using an ethanol/water extraction process. This low kava dose was chosen based on the manufacturer's daily dose recommendation as well as a desire to avoid potential hepatotoxic effects in participants. This was of particular concern given the possibility that kavalactone preparations obtained via ethanol extraction may contain notable levels of flavokawain B, which has been suggested to be a cause of kava related hepatotoxicity (Zhou 2010).
The kava extract was prepared using GMP (good manufacturing practice) quality procedures. Specific kavalactone ratios in the extract were not available from the manufacturer. The capsules were visually indistinguishable and all participants ingested their assigned capsule 60 minutes before cognitive assessment. Both the placebo and kava capsules were stored in identical opaque plastic jars labeled A and B, and the identity of the capsules was known only to the study administrator (MHG) who did not interact with any of the participants. The identity of the A and B capsules was not revealed to the experimenters (AKS and DPM) until after data collection was completed.
Assessment of executive function/problem solving was conducted using a computerised adaptation of the Russell Revised Short Form of the Halstead Category Test (RCat; part of the Cat[TM] Category Test, Multi-Health Systems Inc, North Tonawanda NY USA), which is a component of the larger Reitan test battery. The RCat assesses specific aspects of executive function related to ambiguous problem solving such as cognitive flexibility, abstraction and the capacity to modify responses based on experience (Choca 2008, Spreen 1998). The RCat involves the presentation of six subtests utilising ambiguous geometric figures as stimuli, with a range of 5 to 20 figures in each subtest set. Each set is organised around a particular geometric principle and participants must deduce (without any clues) the organising rule in each subtest through the feedback they receive from correct and incorrect guessed responses they provide by pressing one of four buttons on a keyboard (Choca 2008, Spreen 1998). The primary outcomes of interest on the RCat were the number of errors committed and the average response time (in seconds) for each subtest.
RCat data was analysed using the PROC MIXED feature of SAS 9.1 for Windows (SAS Institute, Cary NC, USA) to create mixed model repeated measure ANOVAs for the number of errors committed and average response time. For each outcome measure of interest an ANOVA was created that included treatment group, body weight (median split of the participants' body weight in kg), sex, subtest, treatment/subtest interaction, treatment/sex interaction and treatment/body weight interaction. Graphical methods were used to confirm that model residuals were approximately normally distributed. Statistical significance was considered to be p < 0.05.
Fifty-four young adults (age 19.9 [+ or -] 1.3 years; height 170.8 [+ or -] 10.5 cm; weight 68.6 [+ or -] 15.6 kg) participated in this study. The sample consisted of 21 males and 33 females. Of the 54 participants, 52 self identified their ethnicity as White/Caucasian, 1 self identified as African-American, and 1 self identified as Hispanic/Latino/Latina. A total of 10 males and 16 females received the placebo and 11 males and 17 females received kava. Participants required an average of 272.4 [+ or -] 51.9 seconds to complete the six sections of the RCat.
As expected (given the difference in the number of items and varying difficulty of each subtest), subtest was significant in both the errors and average response time models (p <0.0001 for both tests). Body weight and sex were not significantly related to errors or average response time on the RCat (p > 0.25 for all tests).
The kava and placebo groups did not significantly differ in regards to the number of errors committed on the RCat (F1,54=0.58; p=0.45). Treatment did not significantly interact with subtest (F5,270=1.63; p=0.15), sex (F1,54=0.25; p=0.62) or body weight (F1,54=0.03; p=0.87) in regards to errors.
The kava and placebo groups did not significantly differ in regards to average response time on the RCat (F1,54=0.54; p=0.46). Again treatment did not significantly interact with subtest (F5,270=0.94; p=0.46), sex (F1,54=0.49; p=0.49), or body weight (F1,54=0.36; p=0.55).
Using a randomised double blind placebo controlled study design, a single oral dose of 200 mg of a standardised and commercially prepared kava extract (30%/60 mg kavalactones) had no effect on performance on the RCat in young adults. This finding is in agreement with past research demonstrating that acute oral doses of kava do not negatively impact attention, reaction time or short term memory (Bilia 2002, Cairney 2003a, Cairney 2003b, LaPorte 2011, Thompson 2004).
This research makes a notable contribution as it is one of the first studies to specifically investigate the effects of kava on problem solving, which is an important element of overall executive control. Because rapid and accurate problem solving requires fully functional attention and working memory systems (Fuster 2000, Kimberg 1998), the null result reported here replicates past studies that have documented a lack of effect of kava on these domains.
Given the complex and multifaceted nature of the components of executive function tapped by the RCat (cognitive flexibility, abstraction and the capacity to modify responses based on experience), performance on this task should be particularly sensitive to pharmacologically induced global and subtle impairments to visual perception and prefrontocortical function (Choca 2008, Fuster 2000, Kimberg 1998, Spreen 1998). The current study supports the notion that therapeutic doses of kava extract do not negatively impact executive control.
Kava may therefore possess a notable advantage over other widely used anxiolytics such as benzodiazepines, which (along with ethanol) significantly impair multiple components of executive function (Noel 2001, Schweizer 2004, Stewart 2005). However it should be noted that this advantage is tempered by continued concern regarding the hepatotoxic potential of kava preparations (potentially containing flavokawain B) derived from an ethanol extraction of ground Piper methysticum root (Kinrys 2009, Zhou 2010). Because of kava's potential hepatotoxicity, the present study utilised the daily dose recommended by the extract's manufacturer. Therefore the current finding cannot be generalised to more ecologically relevant chronic kava use that employs elevated daily doses. Additional research is required to determine if impairments in various components of executive function (including decision making, planning, problem solving and behavioural control) are produced by such patterns of kava administration.
A single oral dose of 200 mg of a standardised and commercially prepared kava extract (30%/60 mg kavalactones) had no effect on performance on the RCat in young adults. Clinically relevant doses of kava extract do not appear to induce dysfunction in ambiguous problem solving that requires cognitive flexibility, abstraction and the capacity to modify responses based on experience.
This study was funded by the Elon University Undergraduate Research Program. The authors would like to thank Olivia Kohrman for assistance with participant recruitment and data collection.
Author disclosure statement
No competing financial interests exist.
Bilia A, Gallori S, Vincieri FF. 2002. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci 70;2581-97.
Cairney S, Maruff P, Clough AR. 2002. The neurobehavioral effects of kava. Aust NZ J Psychiatry 36;657-62.
Cairney S, Clough AR, Maruff P, Collie A, Currie BJ, Currie J. 2003a. Saccade and cognitive function in chronic kava users. Neuropsychopharmacol 28;389-396.
Cairney S, Maruff P, Clough AR, Collie A, Currie J, Currie BJ. 2003b. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol 18;525-33.
Choca J, Laatsch L, Garside D, Gupta R, Fenstermacher J. 2008. Cat Category Test Technical Guide and Software Manual. North Tonawanda NY: Multi-Health Systems.
Ernst E. 2006. Herbal remedies for anxiety: A systematic review of controlled clinical trials. Phytomed 13;205-8.
Fuster JM, Bodner M, Kroger JK. 2000. Executive frontal functions. Exp Brain Res 133;66-70.
Kimberg DY, D'Esposito MD, Farah MJ. 1998. Cognitive functions in the prefrontal cortex-working memory and executive control. Curr Dir Psychol Sci 6;185-92.
Kinrys G, Coleman E, Rothstein E. 2009. Natural remedies for anxiety disorders: Potential use and clinical applications. Depress Anxiety 26;259-65.
Kumar V. 2006. Potential medicinal plants for CNS disorders: an overview. Phytother Res 20;1023-35.
LaPorte E, Sarris J, Stough C, Scholey A. 2011. Neurocognitive effects of kava (Piper methysticum): a systematic review. Hum Psychopharmacol 26;102-111.
Malsch U, Kieser M. 2001. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazapines. Psychopharmacol 157;277-83.
Noel X, Van der Linden M, Schmidt N, Sferrazza R, Hanak C, Le Bon O et al. 2001. Supervisory attentional system in nonamnesic alcoholic men. Arch Gen Psychiatry 58;1152-8.
Sarris J, Kavanagh DJ. 2009. Kava and St. John's Wort: Current evidence for use in mood and anxiety disorders. J Alt Comp Med 15;827-36.
Schweizer TA, Jolicoeur P, Vogel-Sprott M, Dixon MJ. 2004. Fast, but error-prone, responses during acute alcohol intoxication: effects of stimulus-response mapping complexity. Alcohol Clin Exp Res 28;643-649.
Singh YN. 1992. Kava: An overview. J Ethnopharm 37;13-45.
Singh YN, Singh NN. 2002. Therapeutic potential of kava in the treatment of anxiety disorders. CNS Drugs 16;731-43.
Spreen O, Strauss E. 1998. A Compendium of Neuropsychological Tests. 2nd edn. New York, NY: Oxford University Press.
Stewart SA. 2005. The effects of benzodiazepines on cognition. J Clin Psychiatry 66 Suppl 2;9-13.
Thompson R, Ruch W, Hasenohrl RU. 2004. Enhanced cognitive performance and cheerful mood by standardised extracts of Piper methysticum (kava-kava). Hum Psychopharmacol 19;243-50.
Zhou P, Gross S, Liu JH, Feng LL, Nolta J, Sharma V, Piwnica-Worms D, Qiu SX. 2010. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways. FASEB J 24;4722-4732.
MH Gendle is an Associate Professor of Psychology at Elon University.
AK Stroman and DP Mullin are both undergraduate students in Psychology at Elon University.
* Gendle MH, Stroman AK, Mullin DP
Department of Psychology, Elon University Elon NC 27244 USA * Corresponding author email: firstname.lastname@example.org
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|Author:||Gendle, M.H.; Stroman, A.K.; Mullin, D.P.|
|Publication:||Australian Journal of Medical Herbalism|
|Date:||Dec 22, 2011|
|Next Article:||Herbal medicine practice: future environmental impacts.|