The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD)... more The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD). This study investigated the effects of psilocybin on voluntary ethanol consumption in adult male and female C57BL/6J mice administered saline or psilocybin intraperitoneally as a single dose of 0.1, 0.5, 1.0 or 2.0 mg/kg and provided 20% ethanol utilizing a two-bottle choice alcohol drinking paradigm. Ethanol was provided continuously for 3 days immediately following the administration of psilocybin, then withheld for 2 days, and then provided continuously for two subsequent additional days. A multilevel model (MLM) for repeated measures was used to compare ethanol consumption and preference in psilocybin-treated groups versus controls. Ethanol consumption and preference were reduced in male mice during the 3-day interval that immediately followed psilocybin administration. The effect of psilocybin on ethanol consumption was dose-related and was consistent across the 3-day interval at ...
Background: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for... more Background: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine. Objectives: To study outcomes following opioid detoxification with ibogaine. Methods: In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively. Results: SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all post-treatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month. Conclusion: Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
There is a substantive clinical literature on classical hallucinogens, most commonly lysergic aci... more There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls ( = 0.0035), as was ethanol preference ( = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administr...
Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical an... more Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5-76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine.
Objective: The iboga alkaloids are a class of small molecules defined structurally on the basis o... more Objective: The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of μ-opioid receptor (MOR)-related G proteins by iboga alkaloids. Methods: Ibogaine, its major metabolite noribogaine, and 18-methoxycoronaridine (18-MC), a synthetic congener, were evaluated by agonist-stimulated guanosine-5´-O-(γ-thio)-triphosphate ([ 35 S]GTPγS) binding in cells overexpressing the recombinant MOR, in rat thalamic membranes, and autoradiography in rat brain slices. Results And Significance: In rat thalamic membranes ibogaine, noribogaine and 18-MC were MOR antagonists with functional Ke values ranging from 3 uM (ibogaine) to 13 uM (noribogaine and 18MC). Noribogaine and 18-MC did not stimulate [ 35 S]GTPγS binding in Chinese hamster ovary cells expressing human or rat MORs, and had only limited partial agonist effects in human embryonic kidney cells expressing mouse MORs. Ibogaine did not did not stimulate [ 35 S]GTPγS binding in any MOR expressing cells. Noribogaine did not stimulate [ 35 S]GTPγS binding in brain slices using autoradiography. An MOR agonist action does not appear to account for the effect of these iboga alkaloids on opioid withdrawal. Taken together with existing evidence that their mechanism of action also differs from that of other non-opioids with clinical effects on opioid tolerance and withdrawal, these findings suggest a novel mechanism of action, and further justify the search for alternative targets of iboga alkaloids.
Journal of Neuropsychiatry and Clinical Neurosciences, 1999
The author presents the hypothesis that reduced delta EEG power observed in cocaine withdrawal is... more 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.
The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which mod... more The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC 50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 lM) or by extraction from T. iboga (3.53 ± 0.16 lM); ibogaine's principal metabolite noribogaine (2.86 ± 0.68 lM); and voacangine (2.25 ± 0.34 lM). In contrast, the IC 50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was [50 lM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (K i) for the entire set of compounds , including 18-MC, ranged from 0.71 to 3.89 lM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure–activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel. Keywords Toxicology Á hERG Á Iboga alkaloid Á Ibogaine Á Noribogaine Á 18-Methoxycoronaridine (18-MC)
Ethnopharmacological relevance: Ibogaine is a psychoactive monoterpine indole alkaloid extracted ... more Ethnopharmacological relevance: Ibogaine is a psychoactive monoterpine indole alkaloid extracted from the root bark of Tabernanthe iboga Baill. that is used globally in medical and nonmedical settings to treat drug and alcohol addiction, and is of interest as an ethnopharmacological prototype for experimental investigation and pharmaceutical development. The question of whether ibogaine inhibits acetylcholinesterase (AChE) is of pharmacological and toxicological significance. Materials and methods: AChE activity was evaluated utilizing reaction with Ellman's reagent with physostigmine as a control. Results: Ibogaine inhibited AChE with an IC 50 of 520 ± 40 M. Conclusions: Ibogaine's inhibition of AChE is physiologically negligible, and does not appear to account for observations of functional effects in animals and humans that might otherwise suggest the possible involvement of pathways linked to muscarinic acetylcholine transmission.
Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illnes... more Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psycho...
Neuroimaging methods have provided an important contribution to the search for pathophysiologic c... more Neuroimaging methods have provided an important contribution to the search for pathophysiologic correlates of schizophrenia, as outlined in this volume and emphasized by Buchsbaum and Haler (1987). Information on results of positron emission tomography (PET) is provided, e.g., by Brodie (this volume); information on findings obtained with computerized electroencephalogram (EEG) and mapping are reviewed by Duffy (this volume). Here, we report on preliminary results obtained utilizing the simultaneous application of PET and computerized EEG mapping.
Motorische Storungen bei Schizophrenen sind bereits lange vor Einfuhrung der Neuroleptika in die ... more Motorische Storungen bei Schizophrenen sind bereits lange vor Einfuhrung der Neuroleptika in die Therapie beobachtet und beschrieben worden (z.B. Kleist 1908). Eigene psychometrische Befunde (Gunther u. Gruber 1983; Gunther et al. 1986a, 1988) fuhrten zur Abgrenzung eines „psychotisch-motorischen Syndroms“. Dieses bestand aus Storungen der Lippen-, Zungen- und Mundmotorik, der komplexen Bewegungskoordination und der Feinmotorik der Finger und Hande.
The recognition of a syndrome of dependence associated with cocaine use is a relatively recent de... more The recognition of a syndrome of dependence associated with cocaine use is a relatively recent development. The statement that “Since only transitory withdrawal symptoms occur after cessation of or reduction in prolonged use, a separate category of dependence on cocaine is not included,” quoted from DSM III (American Psychiatric Association 1980), has taken on an ironic significance in view of the present epidemic of crack cocaine use. Phenomenologic evidence for a syndrome of cocaine dependence indicates the existence of a characteristic progression of abstinence symptoms in withdrawing addicts which include anhedonia persisting for weeks after the last use (Gawin 1986). Evidence for biological correlates of the anhedonia of cocaine withdrawal includes the observation of decreased cerebral blood flow in abstinent cocaine abusers (Volkow et al. 1988) and reports of efficacy of pharmacological agents such as flupenthixol (Gawin et al. 1989a), desipramine (Gawin et al. 1989b), and bromocriptine (Giannini et al. 1989) in treating the anhedonia and craving associated with cocaine withdrawal. Collectively, the available behavioral, neurophysiological, and pharmacological evidence appears to support the concept of neuroadaptation in cocaine dependence (World Health Organization 1981).
The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD)... more The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD). This study investigated the effects of psilocybin on voluntary ethanol consumption in adult male and female C57BL/6J mice administered saline or psilocybin intraperitoneally as a single dose of 0.1, 0.5, 1.0 or 2.0 mg/kg and provided 20% ethanol utilizing a two-bottle choice alcohol drinking paradigm. Ethanol was provided continuously for 3 days immediately following the administration of psilocybin, then withheld for 2 days, and then provided continuously for two subsequent additional days. A multilevel model (MLM) for repeated measures was used to compare ethanol consumption and preference in psilocybin-treated groups versus controls. Ethanol consumption and preference were reduced in male mice during the 3-day interval that immediately followed psilocybin administration. The effect of psilocybin on ethanol consumption was dose-related and was consistent across the 3-day interval at ...
Background: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for... more Background: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine. Objectives: To study outcomes following opioid detoxification with ibogaine. Methods: In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively. Results: SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all post-treatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month. Conclusion: Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
There is a substantive clinical literature on classical hallucinogens, most commonly lysergic aci... more There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls ( = 0.0035), as was ethanol preference ( = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administr...
Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical an... more Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5-76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine.
Objective: The iboga alkaloids are a class of small molecules defined structurally on the basis o... more Objective: The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of μ-opioid receptor (MOR)-related G proteins by iboga alkaloids. Methods: Ibogaine, its major metabolite noribogaine, and 18-methoxycoronaridine (18-MC), a synthetic congener, were evaluated by agonist-stimulated guanosine-5´-O-(γ-thio)-triphosphate ([ 35 S]GTPγS) binding in cells overexpressing the recombinant MOR, in rat thalamic membranes, and autoradiography in rat brain slices. Results And Significance: In rat thalamic membranes ibogaine, noribogaine and 18-MC were MOR antagonists with functional Ke values ranging from 3 uM (ibogaine) to 13 uM (noribogaine and 18MC). Noribogaine and 18-MC did not stimulate [ 35 S]GTPγS binding in Chinese hamster ovary cells expressing human or rat MORs, and had only limited partial agonist effects in human embryonic kidney cells expressing mouse MORs. Ibogaine did not did not stimulate [ 35 S]GTPγS binding in any MOR expressing cells. Noribogaine did not stimulate [ 35 S]GTPγS binding in brain slices using autoradiography. An MOR agonist action does not appear to account for the effect of these iboga alkaloids on opioid withdrawal. Taken together with existing evidence that their mechanism of action also differs from that of other non-opioids with clinical effects on opioid tolerance and withdrawal, these findings suggest a novel mechanism of action, and further justify the search for alternative targets of iboga alkaloids.
Journal of Neuropsychiatry and Clinical Neurosciences, 1999
The author presents the hypothesis that reduced delta EEG power observed in cocaine withdrawal is... more 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.
The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which mod... more The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC 50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 lM) or by extraction from T. iboga (3.53 ± 0.16 lM); ibogaine's principal metabolite noribogaine (2.86 ± 0.68 lM); and voacangine (2.25 ± 0.34 lM). In contrast, the IC 50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was [50 lM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (K i) for the entire set of compounds , including 18-MC, ranged from 0.71 to 3.89 lM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure–activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel. Keywords Toxicology Á hERG Á Iboga alkaloid Á Ibogaine Á Noribogaine Á 18-Methoxycoronaridine (18-MC)
Ethnopharmacological relevance: Ibogaine is a psychoactive monoterpine indole alkaloid extracted ... more Ethnopharmacological relevance: Ibogaine is a psychoactive monoterpine indole alkaloid extracted from the root bark of Tabernanthe iboga Baill. that is used globally in medical and nonmedical settings to treat drug and alcohol addiction, and is of interest as an ethnopharmacological prototype for experimental investigation and pharmaceutical development. The question of whether ibogaine inhibits acetylcholinesterase (AChE) is of pharmacological and toxicological significance. Materials and methods: AChE activity was evaluated utilizing reaction with Ellman's reagent with physostigmine as a control. Results: Ibogaine inhibited AChE with an IC 50 of 520 ± 40 M. Conclusions: Ibogaine's inhibition of AChE is physiologically negligible, and does not appear to account for observations of functional effects in animals and humans that might otherwise suggest the possible involvement of pathways linked to muscarinic acetylcholine transmission.
Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illnes... more Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psycho...
Neuroimaging methods have provided an important contribution to the search for pathophysiologic c... more Neuroimaging methods have provided an important contribution to the search for pathophysiologic correlates of schizophrenia, as outlined in this volume and emphasized by Buchsbaum and Haler (1987). Information on results of positron emission tomography (PET) is provided, e.g., by Brodie (this volume); information on findings obtained with computerized electroencephalogram (EEG) and mapping are reviewed by Duffy (this volume). Here, we report on preliminary results obtained utilizing the simultaneous application of PET and computerized EEG mapping.
Motorische Storungen bei Schizophrenen sind bereits lange vor Einfuhrung der Neuroleptika in die ... more Motorische Storungen bei Schizophrenen sind bereits lange vor Einfuhrung der Neuroleptika in die Therapie beobachtet und beschrieben worden (z.B. Kleist 1908). Eigene psychometrische Befunde (Gunther u. Gruber 1983; Gunther et al. 1986a, 1988) fuhrten zur Abgrenzung eines „psychotisch-motorischen Syndroms“. Dieses bestand aus Storungen der Lippen-, Zungen- und Mundmotorik, der komplexen Bewegungskoordination und der Feinmotorik der Finger und Hande.
The recognition of a syndrome of dependence associated with cocaine use is a relatively recent de... more The recognition of a syndrome of dependence associated with cocaine use is a relatively recent development. The statement that “Since only transitory withdrawal symptoms occur after cessation of or reduction in prolonged use, a separate category of dependence on cocaine is not included,” quoted from DSM III (American Psychiatric Association 1980), has taken on an ironic significance in view of the present epidemic of crack cocaine use. Phenomenologic evidence for a syndrome of cocaine dependence indicates the existence of a characteristic progression of abstinence symptoms in withdrawing addicts which include anhedonia persisting for weeks after the last use (Gawin 1986). Evidence for biological correlates of the anhedonia of cocaine withdrawal includes the observation of decreased cerebral blood flow in abstinent cocaine abusers (Volkow et al. 1988) and reports of efficacy of pharmacological agents such as flupenthixol (Gawin et al. 1989a), desipramine (Gawin et al. 1989b), and bromocriptine (Giannini et al. 1989) in treating the anhedonia and craving associated with cocaine withdrawal. Collectively, the available behavioral, neurophysiological, and pharmacological evidence appears to support the concept of neuroadaptation in cocaine dependence (World Health Organization 1981).
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