The chapter presents a study on the role of ibogaine in the treatment of heroin withdrawal. Pharmacological treatments for heroin addiction currently employ two treatment strategies: detoxification followed by drug-free abstinence or maintenance treatment with an opioid agonist. Because agonist maintenance with methadone usually has the goal of eventual detoxification to a drug-free state, the use of medications to facilitate this transition is a clinically important treatment strategy. Anecdotal reports suggest that ibogaine has promise as an alternative medication approach for making this transition. Ibogaine has an added benefit to other detoxification strategies in that the treatment experience seems to bolster the patient's own motivational resources for change. Ibogaine is a drug with complex pharmacokinetics and an uncertain mechanism of action with regards to its alleged efficacy for the treatment of opiate dependence. Ibogaine is metabolized to noribogaine, which has a pharmacological profile that is different from that of the parent drug. The chapter presents that ibogaine is effective in blocking opiate withdrawal, providing an alternative approach for opiate-dependent patients who have failed other conventional treatments. Identifying noribogaine's mechanism of action may explain the way ibogaine promotes rapid detoxification from opiates after only a single dose. Ibogaine, like most central nervous system (CNS) drugs, is highly lipophilic and is subject to extensive biotransformation. The Opiate-Symptom Checklist (OP-SCL) was developed for the present study as a subtle assessment of withdrawal symptoms.

OBJECTIVE:The objective of this study was to assess measures of psychological and neurobehavioral functioning to determine their association with unexplained symptoms in Gulf War veterans.METHODS:An epidemiological survey focusing on exposures and symptoms was mailed to a random sample of Gulf War veterans from Oregon and southwestern Washington. Volunteers were recruited from survey respondents who agreed to undergo a thorough medical examination and psychological and neurobehavioral assessment. Persistent symptoms with no medical explanation associated with service in the Persian Gulf (eg, fatigue, muscle pain, and memory deficits) that began during or after the war qualified respondents as cases. The 241 veterans with unexplained symptoms were classified as case subjects, and the 113 veterans without symptoms were classified as control subjects. All veterans completed a battery of computerized assessment tests consisting of 12 psychosocial and 6 neurobehavioral tests. Differences between case and control subjects on neurobehavioral and psychological variables were assessed with univariate and multivariate statistical comparisons.RESULTS:Case subjects differed substantially and consistently from control subjects on diverse psychological tests in the direction of increased distress and psychiatric symptoms. Case subjects had small but statistically significant deficits relative to control subjects on some neurobehavioral tests of memory, attention, and response speed. A logistic regression model consisting of four psychological variables but no neurobehavioral variables classified case and control subjects with 86% accuracy.CONCLUSIONS:Our results revealed that Gulf War veterans who report symptoms associated with that conflict differed on multiple psychological measures in the direction of increased distress and performed more poorly on neurobehavioral measures when compared with control subjects who did not report symptoms. This suggests that psychological differences have a prominent role in investigation of possible explanations of Gulf War symptoms.

Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome.

The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

Neurotoxic effects are of such breadth and complexity that functional biomarkers (behavioral tests) that integrate many areas of the nervous system predominate in human neurotoxicology research. The increasing distribution of chemical and other manufacturing throughout the world, particularly in developing nations, suggests the acute need to develop biomarkers for chemical exposures and effects that can be employed internationally. A language-free method for training performance on behavioral tests is described, which holds promise for international research that circumvents the vagaries of translation. Four behavioral tests were administered to 74-114 adult US subjects. Procedures, collectively termed shaping, produced effective performance on three tests [Symbol Digit, Vigilant Attention Test (VAT), Digit Span Forward and Backward], and produced appropriate but unacceptably slow performance in initial testing on the Simple Reaction Time test. Effective performance on the Symbol-Digit test also was produced by shaping instruction, without assistance from examiners, in small groups of residents of Taipei (Taiwan) and US children between the ages of 5 and 16.

The introduction of microcomputers in psychological research has spawned a burgeoning number of tests of psychological or behavioral function, but few computerized systems for administering questionnaires have been developed. A Health Screening System (HSS) is described that combines the benefits of the paper-and-pencil format (e.g.. convenient navigation within test questions) and the added benefits of computer-implementation (e.g., efficiency, automated scoring). The HSS features: a) appealing test appearance (e.g., text in large-size fonts, color backgrounds); b) clear wording of tests and instructions (identical wording as original tests except when clarity is served by changes): c) limiting need for Examiner-Subject interaction (e.g., continuously available on-line training, navigation within test questions, answer review capability, durable 9-button response unit); d) options (e.g., question skipping, spoken instructions, test questions, and answers on command); e) modification capabilities (e.g., color, text, test layout editing, control of test order, automated breaks, addition of tests to system); and f) extras (e.g., kernel of main instruction on each test screen, digitized video, audio message from Examiner in training, copyright notification on each screen, raw and summary data outputs in spreadsheet format). Ten HSS tests were administered to 22 US military veterans, who took slightly longer to complete them than did 10 veterans who were administered the same tests in their original paper-and-pencil format. User reaction to the computerized HSS was positive.

The development of new computer-administered neuropsychological tests has brought a renewed focus on the issue of written instructions. Designers and programmers often fail to take advantage of the display options and feedback potential available in modern computer systems to maximize the effectiveness of the instruction process. Guidelines from computer interface architecture and behavioral analysis are combined to present three principles for written instructions: precise language, attention focusing, and interactive instruction. A comparison of different instruction formats in the Symbol-Digit and Simple Reaction Time tests shows that the application of these principles can reduce training time without degrading performance.