I have searched quite extensively about kava physical dependency, and have found no existing reports of a withdrawal syndrome. There was one very vague account on bluelight in the drug faq section about kava withdrawal being "a far lesser problem than benzodiazepine withdrawal," however that is far too ambiguous. I'll include some simple literature on some of the known pharmoacokinetics of kavalactones.
I am very interested in seeing if a true withdrawal syndrome exists for kava, because I would certainly use it extensively to treat anxiety if no gabaergic withdrawal syndrome does exist. I am worried of a gabaergic withdrawal syndrome because I have a long history of benzodiazepine and alcohol dependency issues, which I have since corrected.
This is some of the basic literature I have found:
I am inclined to think that Kava somehow is able to be exert GABAa agonist characteristics, without the possibility for down-regulation to occur at the site. Therefore, if there is a withdrawal syndrome from kava, it certainly is not GABAergic in nature. Am I correct in that assumption?Kava Uses and Pharmacology
Chewing kava causes numbness in the mouth because of the local anesthetic action of the kavalactones, which is similar to that produced by cocaine, and lasts longer than benzocaine. 43 In addition, it produces a mild euphoria characterized by feelings of contentment and fluent and lively speech. Sight, smell, and sound are also heightened. 4 Higher doses may lead to muscle weakness, especially in the legs, although some observers relate this to sitting for long periods during the “kava ceremony” rather than to kava itself. Very high doses may induce a deep sleep. CNS effects appear to be mediated by the blockage of voltage-gated sodium and calcium channels ultimately suppressing glutamate release. The kavalactones desmethoxyyangonin and methysticin are believed to block the metabolism of monoamine oxidase-B, producing psychotropic effects. 44 , 45 Sedative and antianxiety properties may result from kava's effects on facilitating gamma-aminobutyric acid (GABA)ergic transmission. 46
The molecular mechanism of action of kavalactones and kava is not entirely clear.
Kavalactones at concentrations from 0.1 to 100 mcM enhanced the binding of bicuculline to the GABA receptor by only 20% to 30%. 47 Another study found weak displacement of diazepam from rat brain membranes by kavalactones but no effect on binding of GABA or of baclofen. 48 The observation that strychnine-induced convulsions are effectively antagonized by several kavalactones supports a possible effect on the glycine receptor. 49 Kava extract and methysticin also were found to protect rats against ischemic brain damage, although several kavalactones were not active in this model. 50 This protection might operate through antagonism of the excitatory amino acids glutamate and aspartate. Inhibition of uptake of norepinephrine, but not serotonin, by kavalactones at high doses was observed. 48 No effect on dopamine or serotonin levels was found in a chronic experiment with kavalactones in rats. 51
A somewhat more persuasive mechanism involves kavalactone inhibition of various neuronal sodium channels. Patch clamp experiments with voltage-gated sodium channels of rat hippocampal neurons found that kavalactones could rapidly and reversibly lower peak amplitudes of sodium currents. 52 A noncompetitive inhibition of the binding of batrachotoxinin benzoate to voltage-gated sodium channels by kavalactones was demonstrated in saturation-binding experiments. 53 Less potently, kavalactones blocked veratridine-activated sodium channels, but had no effect on glutamate release from brain slices. 54 In rat brain synaptosomes, kavalactones appeared to interact with voltage-dependent sodium and calcium channels. 48 , 51 , 55 High concentrations of synthetic kawain relaxed evoked contractile activity in a guinea pig ileum preparation, showing that smooth muscle also is affected by kavalactones. 56 A fluorescently labeled kawain derivative was studied using fluorescence correlation spectroscopy and bound specifically and saturably to cultivated human cortical neurons. 57
Neurophysiological studies of sleep/wakefulness in cats showed decreased muscle tone and duration of wakefulness, marked changes in electroencephalogram (EEG), and increased sleep with kava. Involvement of the amygdala and other limbic structures of the brain was deduced. 58 These effects were distinct from those of tricyclic antidepressants and benzodiazepines.
The pharmacokinetics of kavalactones have been explained to some extent. In rats, dihydrokawain was completely excreted within 48 hours, primarily through urinary excretion of hydroxylated metabolites. Bile and feces did not appear to be important routes of excretion. However, lactones (eg, kawain) with poorer oral absorption than dihydrokawain were found unchanged in feces. The octanol-water partition coefficient for yangonin is 1,500; thus, these compounds are quite nonpolar and water-insoluble. This accounts in part for their poor oral absorption. 59 Because the metabolites of kavalactones are different in humans than in rats, 37 the pharmacokinetics also may differ. Kavalactones have a half-life of 9 hours and achieve peak plasma levels 1.8 hours after administration. 14 Kinetics of entry of kavalactones into mouse brains after intraperitoneal injection have been studied, and kawain and dihydrokawain were rapidly absorbed and quickly eliminated within several minutes, while yangonin and desmoethoxyyangonin were more slowly incorporated and eliminated. 38
Concerns about impaired performance under the influence of kava have motivated several studies in humans. One small study found insignificant decreases in cognitive function when using kava, with only the extent of body sway showing an increase. Subjects' rating of intoxication under kava was low to moderate, while respiration, heart rate, and blood pressure were unaffected. Kava lowered arousal rating without affecting stress rating, although the decrease was not statistically significant. 60 Another small study of 12 patients compared the effects of kava and oxazepam on behavior and event-related potentials in a word recognition task. While oxazepam produced pronounced negative effects on performance, no effects were seen with kava. 61 A study of reaction time by the same authors concluded that kava may increase attention slightly, in contrast to oxazepam, which impaired attention. 62 Kawain in EEG studies showed mild sedation at high doses (600 mg) but not at lower doses (200 mg). 63 Kava had no effect on alertness and long-term memory in a subsequent trial. 64 Minor changes in vision and balance were detected with kava in one subject. 65
Clinical studies of kava have produced evidence of substantial efficacy in mild to moderate anxiety.
Research reveals no animal data regarding the use of kava for anxiety.
In Germany, several investigations have reviewed kava in comparison with other CNS-active herbal products. 66 Kawain was compared with oxazepam in a double-blind study of 58 patients and was equally effective and safe. 67 Over 4 weeks, kava extract progressively reduced anxiety compared with placebo in 60 patients with no reported adverse reactions. 68 A longer 25-week, double-blind, placebo-controlled study of 101 patients with anxiety disorders found that Hamilton Anxiety Scale (HAMA) scores decreased faster with kava than with placebo. 69 A similar 4-week study found kava extract effective using both HAMA and Clinical Global Impression Scale scores. 70
The first US study of kava in anxiety was reported at a conference but has not been published. The study found similar therapeutic effects of kava extract under double-blind, placebo-controlled conditions. 71 A combination of kava and hormone replacement therapy for menopause symptoms was undertaken in Italy over a period of 6 months. Kava with hormone therapy accelerated the improvement in anxiety scores over single treatments alone. 72
Positive results in a sleep study involving 12 patients were found with kava extract WS 1490, as measured by EEG, electromyography, and subjective measures. No adverse effects on rapid eye movement sleep were found. 73 A clinical study of kava's ability to moderate cardiac symptoms in generalized anxiety disorder found that it improved baroreflex control (BRC) of heart rate, but not respiratory sinus arrhythmia, and improvement in BRC was associated with overall clinical improvement in kava-treated patients. 74
The effects of kava extract WS 1490 were assessed on sleep disturbances associated with anxiety disorders. After 4 weeks of double-blind treatment, the assessment of quality of sleep and recuperative effect after sleep were statistically significant in comparison with placebo. Thus, a potential role for kava in improving sleep in patients with anxiety was suggested. 75
The transition from benzodiazepines to kava extract WS 1490 in treatment of anxiety was monitored in a 5-week study involving 40 patients. While symptoms of benzodiazepine withdrawal were not controlled by kava, anxiety was reduced and symptoms decreased after kava treatment compared with during benzodiazepine therapy. 76 A meta-analysis of clinical trials of kava extracts in anxiety has been conducted. Seven trials met the acceptance criteria for inclusion and found kava superior to placebo in the treatment of anxiety as noted by a reduction in the total score of the HAMA. 77
A randomized, double-blind, placebo-controlled study was conducted to assess the effects of kava (total kavalactones 100 mg 3 times daily for 4 weeks) on anxiety. When compared with placebo, there were no statistically significant differences (+2.6 [95%, confidence interval (CI) −0.8 to +6.2]) in reductions of anxiety as measured by the State subtest of the State-Trait Anxiety Inventory. Kava also does not appear to improve measures of insomnia. 78
Additionally, data from 3 randomized, double-blind, placebo-controlled trials assessing the efficacy of kava for the treatment of generalized anxiety disorder were analyzed. From these studies, it did not appear that kava was efficacious for the treatment of generalized anxiety disorder. 79
Kavalactones are purportedly used to relieve anxiolytic effects associated with menopause through modulation of GABA-A receptors in nerve endings. 80
Research reveals no animal data regarding the use of kava for the treatment of menopausal symptoms.
Menopause-related anxiety was successfully treated with kava extract in an 8-week study of 40 women, with rapid onset of efficacy. 81 A 12-week study also found improvement in menopausal symptoms; however, poor compliance in the placebo group confounded interpretation. 82 In a randomized, prospective study, 68 perimenopausal women requiring therapy for climacteric symptoms were randomized to receive 3 months of calcium 1 g/day plus either kava 100 mg/day (kavapyrones 55 mg), 200 mg/day (kavapyrones 110 mg), or no other therapies. Perimenopause was defined as amenorrhea for 6 to 24 months in women between 47 and 53 years of age with hot flushes occurring at least 3 times daily for at least 1 week and a follicle-stimulating hormone level of greater than 30 units/L. In the control group, there were no differences with regard to anxiety, depression, or climacteric symptoms after 1 and 3 months. Patients treated with kava 100 mg/day had a significant decline in anxiety after 1 and 3 months of therapy ( P < 0.025). A similar effect was noted in patients treated with kava 200 mg/day for anxiety at 1 and 3 months ( P < 0.0003). Patients treated with both doses of kava experienced improvements in depression after 1 and 3 months of treatment as compared with baseline ( P < 0.002). Climacteric symptoms were also reduced in both kava treatment groups after 1 and 3 months ( P < 0.006). The authors concluded that kava may be an effective short-term alternative for improving mood disturbances and climacteric symptoms in women with perimenopausal symptoms. 83
In another study, the effects of hormone replacement therapy with and without kava were assessed for a total of 6 months in 40 women with menopausal anxiety. Subjects with physiological menopause were randomized to receive 50 mcg/day of estrogen with progestin plus either kava extract 100 mg/day or placebo. Subjects with surgically induced menopause were randomly assigned to receive estrogen 50 mcg/day plus either kava 100 mg/day or placebo. A reduction in anxiety scores as measured by the HAMA was noted after 3 and 6 months of treatment for all 4 treatment groups. However, the groups receiving kava extract had a larger reduction in anxiety scores compared with those who did not. Specifically, after 6 months of therapy, HAMA scores were reduced 55% compared with baseline for the patients with physiologically induced menopause receiving kava and hormone placement therapy ( P < 0.05) and reduced 23% for those receiving only hormone replacement therapy. In the surgically induced menopause group, HAMA scores were reduced 53% for those receiving hormone replacement therapy and kava, compared with baseline, and reduced 26% for those receiving only hormone replacement therapy. 72
Kavalactones, especially kawain, have modest anticonvulsant activity in electroshock and metrazol models. 84 Kawain showed an antithrombotic effect on platelets, dose-dependently blocking platelet aggregation, adenosine 5′-triphosphate release and synthesis of prostaglandins at high micromolar concentrations. 85 Despite a reputation as an antimicrobial agent in urinary tract infections, kava extracts demonstrated very minimal antifungal and no antimicrobial or antiviral activity. 86
Preliminary data collected from the Pacific Islands suggest that kava consumption is possibly associated with a lower incidence of cancer. 87
The German Commission E recommends dosages of kavalactones 60 to 120 mg daily for no longer than 3 months without medical evaluation. 88 However, clinical studies have reported that dosages of kavalactones 60 to 240 mg/day are effective. 13 Kava does not appear to be addictive at therapeutic dosages. 89 An aqueous extract can be prepared by chopping 30 g of the kava roots and extracting with 300 mL of cold water. The traditional extract was derived from 10 g of powdered crude drug and 100 mL of water to yield a product containing kavapyrones 72.6 mg, representing a daily dose of kavapyrones 210 mg when 300 mL are consumed. 12 A study using a special extract of kava containing 70% kavalactones found a dosage of 150 mg/day to be effective for the treatment of anxiety. 43 When used as a sedative, kavalactones 180 to 210 mg may be given 1 hour before bedtime. 4
Thread: The Nature of Kava "Withdrawal"
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Additionally, for those that would benefit from having the chemical structure of kavalactones readily available to aid in discussion:
Yangonin 1 R1-OCH3 R2-H R3-H R4-H
10-methoxyyangonin 1 R1-OCH3 R2-H R3-OCH3 R4-H
11-methoxyyangonin 1 R1-OCH3 R2-OCH3 R3-H R4-H
11-hydroxyyangonin 1 R1-OCH3 R2-OH R3-H R4-H
5,6-dehydrokavain 1 R1-H R2-H R3-H R4-H
11-methoxy-12-hydroxydehydrokavain 1 R1-OH R2-OCH3 R3-H R4-H
7,8-dihydroyangonin 2 R1-OCH3 R2-H R3-H R4-H
Kavain 3 R1-H R2-H R3 -H R4 -H
5-hydroxykavain 3 R1-H R2-H R3-H R4-OH
5,6-dihydroyangonin 3 R1-OCH3 R2-H R3-H R4-H
7,8-dihydrokavain 4 R1-H R2-H R3-H R4-H
5,6,7,8-tetrahydroyangonin 4 R1-OCH3 R2-H R3-H R4-H
5,6-dehydromethysticin 5 -O-CH2-O- R3-H R4-H
Methysticin 7 -O-CH2-O- R3-H R4-H
7,8-dihydromethysticin 8 -O-CH2-O- R3-H R4-H
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Maybe, I don't think benzo WD related effects are all GABA A related either. However altering GABA starts a hell of a neurotransmitter chain reaction that can involve hormones as well. Kava is certainly a more complex drug than a pharmaceutical.
Psychedelic DrugsNeuroscience and Pharmacology Discussion
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Kava is famous for being a GABA-ergic, but has a somewhat more complex pharmacological profile:
Animal studies show that kava lactones alter neuronal excitation through direct interactions with voltage-dependent ion channels,
More interesting is whether kava can inhibid BZD withdrawal-induced convulsions without merely prolonging the dependence.
Last edited by atara; 09-03-2011 at 17:36.
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- Jan 2011
Sorry, rakketakke I don't have sources (I don't keep record of stuff well) but try some wikipedia and search for a Dr. Richard Hall--he has an good article on benzos on his site.
Basically GABA is a neurontransmitter that tells nerve functions to "stop." for example, there are dopamine activated receptors that also have a site for GABA to attach to, and if a GABA attaches to it, it will prevent the dopamine neuron from firing, even if it has a dopamine at it's site too. Supposedly this is what opiates and some cannabinoids do, they increase dopamine response by blocking GABA. Heightened GABA function will also block serotonin, norepinephrine and epinephrine and possibly histamine too. It will also cause an increase in growth hormone secretion too for some reason. Wiki says that HCH, a hormone related to adrenenals and a neuropeptide Y are affected by benzos.
So essentially GABA can stop lots of neurological functions as it is an inhibitor and when GABA respnse heightening drug is removed it causes surges in almost all other neuro functions. Heightened this will affect that which will affect another thing. It seems that all these neurotransmitters and hormones are delicately interlinked and balanced. That is the best I can explain it, I'm no expert by far at this but do you see what I'm trying to say.
I am actually quite interested in this. I was given a large quantity of Kava to chew on while on vacation in the tropics. It produced an effect similar to cannabis but less strong...I cant describe it very well because I havent had it in a while, but from my experience it was a drop in the bucket compared to alcohol. It had euphoria but more of an artsy and subtle euphoria than king ethanol, which has been known to knock me on my ass.
Yes, GABA has interactions with almost every part of the body. A gaba-ergic withdrawal syndrome has a wide range of effects, due to the lack of inhibition throughout the body. This gives gabaergic withdrawal its extreme unpleasantness. Similarly, any withdrawal syndrome that results from lack of exogenic processes that have been, and still are deemed endogenic by the body will effect more than just the initial pathways that said exogenic process influences.
But, I am curious of how exactly kava can induce a gabaergic-like sedation without degrading the endogenic pathways through which sedating kavalactones work through. Or, if it is a myth after all, and kava is hardly innocuous.
Ho Chi Minh- I take it that you were chewing on kava root only, right?
artara- Thank you for your input. You present interesting information.
Last edited by Apostacious; 11-03-2011 at 04:43.
To add some anecdotal evidence, I have tried a very good batch of tongan kava root three times so far, and I have waited 48 hours between doses, from which no "flare-up" in post-acute withdrawal symptoms have occurred. To add some perspective to that, whenever I have an alcoholic drink, or anything similarly gabaergic, once it wears off, I always experience a week of heightened anxiety, muscle fasciculations, nerve pain, mood swings, and dysphoria. The last time that occurred was 3 months ago (my last alcoholic drink), and has been an ongoing problem ever since I finished tapering clonazepam on 4/08.
I've never had any withdrawal from kava, just a general feeling of lethargy the next day with occasional mild tummy pains. I have actually the published book on Kava from Wiley right next to me, I'll take a look if I get a chance.
Large doses of kava are more comparable to cannabis but with less psychedelia and more sedation. It makes me want to lay around and listen to lots of tunes.
nuke- I certainly would appreciate your effort of going through Wiley's book on Kava and reporting what you have discovered. I also notice cannabis-like effects. It seems to feel like a cannabinoid like sedation mixed with a moderate amount of adrenergic stimuation, and a small amount of empathogenic and entheogenic activity. I find that kava root works best around the 10-15 gram range when shortly boiled with water and cooking oil for one minute or less.
Nothing else was used in combination. I just mixed it with water and put in a giant lip; then I swallowed it after 30 minutes; this was repeated two times. Its strange though because the day after I felt extremely irritable a la nasty alcohol hangover and I thought alcohol offered more euphoria per unit of hangover than Kava. Perhaps I would have a different opinion now.
I remember watching the movie 'hair' and laughing openly at the joy of the musical.
It was like a less intense alcohol/cannabis fusion that left me cognitively intact.
Kava hasnt given wd to me ever. Ive had dried root in kauai, dried root by mail(probably hawaii) alcohol/glycerin & co2 extract and pills.
I remember once a friend who used ALOT of cannabis, in fact moreso than anyone I knew at the time proabably, was facing legal issues after getting jailed and said he had some addiction to it immediately, he was probably still psychologicly addicted to cannabis as well.
What I do get, is crazy tollerance builds. If this happened with benzos, or alcohol for that matter, may god have mercy on my soul.
A small amount will be effective, but suddenly thereafter I could easily drink much more. For example a bottle of alcohol extract sais 10 ml or so is a dose, and there is 70 doses in a bottle, I could soon there after, Be happy DRINKING 2 bottles. the only thing that compairs is tollerance builds with pregabalin/gabapentin.
oh yeah and aligator skin.
kava gave my bloody vomiting. no kidding. one time drugs made me go to the hospital.
How did you consume it...? It has given me abdominal pains if I don't drink enough water but nothing like that.
As a tea. I had good material. The first time I had it I had an extremely upset stomach and vomited quite a bit, an acid that no amount of Tums could cure. Cannabis didn't touch it. Second time, a year later, also good root I made into a milkshake sort of thing. bad tasting, but not terrible to get down. That time was when I ended up vomiting blood and going to the ER. they stuck a camera in my stomach but didn't find anything.
^because you aren't supposed to consume the root, just the active material
i got a bladder infection from eating the root. had to learn the hard way as well
I didn't actually eat the root. It was filtered out, of course.
I find it really implausible that eating the root could cause a bladder infection...
Eh, after a recent kava "binge," I have noticed a slight flare up in benzo p.a.w.s symptoms. Can kava create a dependency? IMO, probably, and if you don't want one, don't start one.
Nuke- Did you have a chance to read through the Kava book by Wiley?
Kava tincture on pregabalin/gabapentin with me, seem to last WAY too short, and very intense.
It will last much shorter than say a a duration of time it takes to smoke a cig of tobacco.
Does anyone have other info on duration length variances?
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- Feb 2008
I consume about 50 grams of potent root a day and have done so for a few years, and I have never felt any hint of withdrawal. I've made a few week long breaks during this time. I've never noticed any tolerance development either.
FWIW, alcohol and benzos are not remotely pleasurable for me.
^^ amen to that
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