Yadhu N. Singh

Kava: an overview

Since the first significant contact with Europeans in the 18th century, the Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage prepared from it, both of which are called kava, have become familiar to much of the outside world through both the written and visual media. The ceremonial preparation and consumption of the beverage are probably its most conspicuous and spectacular features. Kava continues to occupy a central place in everyday life in the islands concerned, although its role has been somewhat diminished by time and outside influences. Despite the large body of literature on kava--about 800 entries are listed in a recent bibliography by Singh (1986)--there has been no comprehensive review on the subject. Earlier contributions by Keller and Klohs (1963) and Shulgin (1973) were selective in treatment and dealt primarily with chemical and pharmacological aspects. The monograph by Steinmetz (1960) remains a standard reference but understandably some of the information in it has become dated. The attention of the reader is also drawn to two excellent additions to the recent kava literature, by Lebot and Cabalion (1988) and Brunton (1989), which are, although somewhat restricted in focus, are very significant contributions to the subject. The present review paper provides an updated and a multidisciplinary overview of the subject. It was prepared on the basis of the authors personal experience--he is a native of Fiji and lived in that country for about 30 years--as well as the relevant literature listed in the Singh (1986) bibliography and some more recent publications.

Therapeutic Potential of Kava in the Treatment of Anxiety Disorders

Anxiety disorders are among the most common psychiatric disorders that affect all age groups of the general population. Currently, the preferred treatment is with pharmacological drugs that have antidepressant or anti-anxiety properties. However, these agents have numerous and often serious adverse effects, including sedation, impaired cognition, ataxia, aggression, sexual dysfunction, tolerance and dependence. Withdrawal reactions on termination after long-term administration are also a major limiting factor in the use of these agents.Herbal remedies, including kava (Piper methysticum), have been shown to be effective as alternative treatments, at least in mild to moderate cases of anxiety. Kava is a social and ceremonial herb from the South Pacific. It is available in the west as an over-the-counter preparation. Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties.The pharmacological properties of kava are postulated to include blockade of voltage-gated sodium ion channels, enhanced ligand binding to γ-aminobutyric acid (GABA) type A receptors, diminished excitatory neurotransmitter release due to calcium ion channel blockade, reduced neuronal reuptake of noradrenaline (norepinephrine), reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A2, which antagonises GABAA receptor function.Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions.Until recently, the adverse effects attributed to kava use were considered mild or negligible, except for the occurrence of a skin lesion. This disorder, called kava dermopathy, occurs only with prolonged use of large amounts of kava and is reversible on reduced intake or cessation. Rare cases of interactions have occurred with pharmaceutical drugs that share one or more mechanisms of action with the kavalactones. In the past few years, about 35 cases of severe liver toxicity associated with kava intake have been reported in Europe and the US. However, a direct causal relationship with kava use has been difficult to establish in the majority of the cases, and there is insufficient evidence to implicate kava as the responsible agent. Nevertheless, until further research clarifies any causality, kava should be used with caution.

Psychopharmacological Intervention I Teacher Perceptions of Psychotropic Medication for Students with Serious Emotional Disturbance

A 27-item questionnaire was used to explore the perceptions, knowledge, and opinions of 146 teachers of students with serious emotional disturbance regarding medication used with their students. The results indicated that the students doctor was perceived as the leading professional responsible for taking steps to have the student on or off medication for behavior disorders. Parents, the school psychologist, and the students case committee had a moderate degree of influence on such decisions. The doctor and school psychologist were perceived to be responsible for determining the type of assessments used for evaluating drug effects. Teachers rated global impressions as the assessment procedure used most frequently for such evaluations, but suggested that informal teacher diary would be their choice. Hyperactivity and delusions/hallucinations were seen as the behavior disorders that most likely would lead to medication and, to a lesser extent, acting out and aggression. In general, the teachers desired more involvement in drug decisions and better liaison with the doctors. In addition, they uniformly suggested that their preservice and inservice training in matters related to drug treatment was inadequate, and indicated that there was a great need for further training in this area. Changes in current school policies and practices were suggested by the teachers.

Opioid antagonists. II: Clinical effects in the treatment of self-injury in individuals with developmental disabilities

Two hypotheses have been proposed linking dysfunctions of the endogenous endorphin system with the origin and maintenance of self-injury in some individuals. This has spurred interest in the use of opioid antagonists, most commonly naloxone and naltrexone, to treat self-injury. Although many of the studies have reported positive findings, these data must be interpreted wit caution because the majority of the studies were typically anecdotal case reports or were methodologically flawed. We present a clinical and methodological review of the research on the efficacy of both naloxone and naltrexone in the treatment of self-injury in individuals with developmental disabilities. Taken in their best light, seven of nine studies using naloxone showed a positive effect on self-injury and 16 of 18 studies using naltrexone showed a positive effect. The implications of these data are discussed in terms of future research.

Opioid antagonists. I: Pharmacology and rationale for use in treating self-injury

Endogenous opioid peptides have been implicated in the genesis and maintenance of self-injurious behavior. This paper presents an overview of the basic pharmacology of opioid peptides and opioid antagonists and briefly outlines the rationale for using these agents to treat self-injury in individuals with mental retardation. The basic assumption is that self-injury is related to the endogenous opioid system, with two, nonexclusive mechanisms having been postulated that may account for this behavior.

Effects of thyroxine and naloxone administration on metabolism and ventilation in hamsters.

This study examined the interaction between hyperthyroidism and opioid receptor function on control of ventilation and metabolism in male Harlan hamsters 4 and 8 weeks after implanting thyroxine (T(4)) or placebo pellets. Metabolism, but not body temperature, increased in T(4)-treated hamsters relative to placebo-treated animals. After 4 weeks, body weights were greater in the T(4)-treated hamsters, but comparable to controls after 8 weeks. At that time, body length was greater in T(4)-treated hamsters than in controls. Thyroxine did not affect ventilation in air or in response to CO(2). Naloxone, an opioid receptor antagonist, decreased metabolism in T(4)-treated, but not in placebo-treated hamsters without affecting ventilation in air in either group. In the placebo group naloxone augmented the ventilatory response to hypercapnia by increasing frequency. These results negate our hypotheses that: (1) hyperthyroid hamsters exhibit greater ventilation in air and in response to hypercapnia than controls; and (2) that naloxone augments these effects.

Calcium channel blockers and vitamin E for tardive dyskinesia in adults with mental retardation

Tardive dyskinesia (TD) is one of the major problems associated with the long-term use of neuroleptic medication in individuals with mental retardation. Although no satisfactory treatment is currently available for TD, there has been a suggestion in the research literature that, in theory, calcium channel blockers and vitamin E may be effective in reducing the symptoms of TD. We assessed the effects of verapamil, a calcium channel blocker, and vitamin E on TD in seven adults with mental retardation in a double-blind, placebo-controlled, cross-over study. Following an open baseline, each subject received placebo, verapamil (80 mg/qid), and vitamin E (400 IU/tid) in random order, with each phase lasting 8 weeks. The subjects were rated on the Abnormal Involuntary Movement Scale (AIMS) and the Dyskinesia Identification System: Condensed User Scale (DISCUS) by trained raters. The maintenance medication for all subjects was kept constant during the course of the study. Results showed that although some subjects had a reduction in their TD ratings neither verapamil nor vitamin E produced clinically or statistically significant changes when compared to placebo and baseline conditions. However, the changes associated with vitamin E were promising enough to warrant further investigation of this agent in the treatment of TD in individuals with mental retardation.

Reliability and validity of three rating scales for assessing tardive dyskinesia in individuals with developmental disabilities

The incorporation of a standardized assessment and monitoring procedure for TD into the treatment plans for all individuals prescribed antipsychotic medications has become the standard of care. There are several well-known and established rating scales designed specifically for this purpose. The AIMS and the DISCUS are two of the most commonly used instruments to detect and monitor abnormal movements associated with TD in individuals with developmental disabilities. The CLAMPS is a newly developed rating scale also designed for use in individuals with developmental disabilities to monitor for and assess abnormal movements, including those associated with TD and other disorders. In this study, we investigated the concurrent validity and interrater reliability of these three scales in a sample of seven adults with mental retardation and TD. The results indicated that, overall, the dyskinesia subscales of the CLAMPS showed the greatest level of agreement with the DISCUS subscales. Lower levels of agreement were observed between the CLAMPS and AIMS dyskinesia subscales. The degree of interrater reliability observed for the AIMS and DISCUS subscale scores was consistent with that found in previous research and, with the exception of three subscales, the CLAMPS demonstrated an interrater reliability of a magnitude comparable to the other two. There are some advantages of the CLAMPS and further research on this rating scale is warranted.

Effects of calcium channel blockers on tardive dyskinesia

Tardive dyskinesia (TD) is a serious iatrogenic disorder that is induced by long-term neuroleptic therapy. There are no well-established treatments for TD but a number of agents, such as calcium channel blockers and vitamin E, have shown some promise in decreasing the symptoms of TD. We reviewed the treatment outcome literature on the efficacy of the three prototypic calcium channel blockers, verapamil, diltiazem, and nifedipine, on TD. Although the outcome data were equivocal, when taken in their best light, they suggested that calcium channel blockers may be effective in decreasing the symptoms of TD. However, the studies were methodologically flawed in many respects and future research must ensure that the basic requirements for scientific validity are incorporated in the experimental design. Further, there is a need for dose-response studies of the three prototypic calcium channel blockers, as well as investigations of their comparative effects.

5'-Deiodinase type 1 activity in liver and brain of the thyroxine-treated dystrophic hamster.

Dystrophic hamsters (DH), as well as dystrophic patients, exhibit alveolar hypoventilation (AH) and low plasma thyroid hormone levels. Thyroxine (T4) treatment of young DH retards AH development, and improves respiratory function and contractility of skeletal muscles. However, the mechanism responsible for the hypothyroidism in DH is not known. One possible cause of the hypothyroidism is reduced activity of the 5′‐deiodinase enzyme system, which converts T4 to the more active triiodothyronine (T3). This study tested the above hypothesis by measuring the serum T3 and T4 levels and the activity of the enzyme type 1 5′‐deiodinase (D1) in the liver and brain of normal and dystrophic hamsters before, and 8 weeks after, placebo or T4 treatment. There was no significant difference in T4 level between normal and dystrophic hamsters before or after treatment. However, the T3 level was lower in DH before treatment and 8 weeks after placebo and T4 treatment. Both in the liver and brain, D1 activity in DH was depressed compared with normal hamsters. In the liver, T4 supplementation restored enzyme activity to normal level, while in the brain there was no significant difference. The data indicate that the hypothyroidism in DH may be, in part, due to reduced activity of D1 enzyme, which could be partially reversed by T4 treatment.