Treatment of acute opioid withdrawal with ibogaine.

Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting.

The EEG and cocaine sensitization: a hypothesis.

The author presents the hypothesis that reduced delta EEG power observed in cocaine withdrawal is related to changes in dopamine (DA) transmission related to cocaine sensitization. Evidence for this hypothesis includes the topographic anatomical correspondence between the putative site of delta generation and the cortical terminal field of the mesotelencephalic DA system, as well as the laminar distribution and ultrastructural features of DA terminals in frontal cortex that appear to be adapted to the modulation of the delta rhythm, a global forebrain EEG mode. The effect of DA on membrane conductances of individual pyramidal neurons also suggests that DA exerts a significant influence on delta power by modulating the transition between global and local EEG modes. Access to a neural correlate of sensitization via noninvasive EEG methodology could be useful in investigating the relationship of stimulant sensitization to the clinical syndrome of cocaine dependence.

Prediction of treatment outcome in cocaine dependent males using quantitative EEG.

This study investigates the existence of outcome related neurophysiological subtypes within a population of abstinent cocaine dependent adults. We have previously reported and replicated the existence of a distinctive quantitative EEG (QEEG) profile in such a population, and demonstrated the persistence of this pattern at one and six month follow-up evaluations. This profile is characterized by significant deficits of absolute and relative delta and theta power, and excess of relative alpha power, as compared with age expected normal values. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In the current study, 35 adult males with DSM-III-R cocaine dependence, were evaluated while residents of a drug-free residential therapeutic community, 5-15 days after last use of crack cocaine. Using multivariate cluster analysis, two neurophysiological subtypes were identified from the baseline QEEGs; Cluster 1 characterized by significant deficits of delta and theta activity, significant excess of alpha activity and more normal amounts of beta activity (alpha CLUS) and Cluster 2 characterized by deficits of delta, more normal amounts of theta and anterior excess of alpha and beta activity beta CLUS). No significant relationships were found between QEEG subtype membership and length of exposure to cocaine, time since last use of cocaine or any demographic characteristics. Further, no significant relationships were found between the commonly reported comorbid clinical features of depression and anxiety and subtype membership. However, a significant relationship was found between QEEG subtype membership and length of stay in treatment, with members of the alpha CLUS retained in treatment significantly longer than members of the beta CLUS.

Persistent QEEG abnormality in crack cocaine users at 6 months of drug abstinence.

The major objective of this study was to examine the persistence of abnormal quantitative EEG (qEEG) measures over a six month time interval in subjects in strictly supervised drug free residential treatment for crack cocaine dependence. Seventeen subjects were assessed with qEEG at five to 10 days, one month and six months following their last use of cocaine. No significant changes were noted over time in abnormal qEEG measures, which included deficits of absolute and relative power in the delta band and increased relative alpha power. The persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent neurobiologic alteration resulting from chronic cocaine exposure. The specificity of the qEEG findings is discussed, and an interpretation is suggested with reference to the hypothesis of neural sensitization in cocaine dependence.

Functional EEG mapping and SPECT in detoxified male alcoholics.

Fifteen alcoholics diagnosed according to DSM-III-R, who were detoxified for at least 2 weeks and showed no clinical withdrawal signs, were investigated with 16 channel EEG mapping during resting, manumotor and music perception conditions, and were compared with 13 control persons. Single photon emission computed tomography (SPECT) using hexa-methyl-propilene-amine-oxime (HMPAO) labeled with 99m-technetium (99mTc) as tracer was performed separately (in patients only) and submitted to semiquantitative region of interest (ROI) analysis in 2 slices, 6 and 10 cm above canthomeatal line, respectively. Resting EEG showed increased power values in fast beta frequency band for the detoxified alcoholics. On cortical stimulation, patients showed signs of pathological EEG reactivity. Correlations of EEG parameters to cerebral blood flow (CBF) values (patients only) yielded coefficients around zero for all frequency bands (signs of uncoupling). All findings point to organic brain dysfunctions in these patients which extend beyond the period of withdrawal.

Quantitative electroencephalographic characteristics of crack cocaine dependence.

This study replicates preliminary findings reporting a quantitative electroencephalographic (QEEG) profile of crack cocaine dependence in abstinence. All subjects (n = 52) met criteria for DMS-III-R cocaine dependence (in the form of crack), and were residing in a drug-free therapeutic community. Baseline QEEG evaluations were conducted at intake (5-10 days after last use of crack, and at follow-up (1 month after last reported use). Previous findings of significant excess of relative alpha power and deficit of absolute and relative delta and theta power were replicated in this expanded group. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. Further, QEEG showed little change in the interval between the first and second evaluations. This QEEG profile may reflect persistent alterations in neurotransmission as a possible consequence of chronic cocaine exposure.

Quantitative electrophysiological characteristics and subtyping of schizophrenia.

Quantitative descriptors of resting electroencephalogram (EEG) (QEEG) and event-related potentials (QERP) to visual and auditory stimuli were obtained from normal subjects and 94 chronic schizophrenic patients on medication, 25 chronic schizophrenics off medication, and 15 schizophrenics with no history of medication. These schizophrenic groups showed a high incidence of neurometric features that were significantly deviant from normative values. Multivariate discriminant analysis using these features successfully separated the schizophrenic patients from normals with high accuracy in independent replication. The data from the medicated group were subjected to cluster analysis. Newly developed algorithms were used for objective selection of the most effective set of variables for clustering and the optimum number of clusters to be sought. Five clusters were obtained, containing roughly equivalent proportions of the sample with markedly different QEEG profiles. The whole sample was then classified into these clusters. Each cluster contained patients both on and off medication, but patients who had never been medicated were classified into only three of these clusters. No significant clinical or demographic differences were found between members of the five clusters; however, clear differences in QERP profiles were seen. These results are described in detail and possible physiological and pharmacological implications are discussed.

Quantitative EEG correlates of crack cocaine dependence.

Evidence for a distinctive syndrome of neuroadaptation in cocaine dependence has accumulated from behavioral, neurophysiological, and preclinical and clinical pharmacological studies. The authors report on the results of a preliminary investigation of the quantitative electroencephalographic (QEEG) correlates of severe DSM-III-R crack cocaine dependence in seven patients abstinent from cocaine for 1 to 68 days. The major QEEG finding was increased absolute and relative alpha power. Increased alpha power has also been reported in multiple previous studies of depressed patients. This series of crack-dependent patients showed significant depressive morbidity; four patients attempted suicide subsequent to initiating their use of crack and the group mean (+/- SD) Beck Depression Scale score was 18.9 (+/- 6.5). These results complement other studies that support the concept of neuroadaptation to chronic cocaine exposure. Prospective studies correlating QEEG measures with subsequent response to pharmacological interventions for cocaine dependence should be considered.