Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.

Persistent psychotic symptoms after long-term heavy use of mephedrone: A two-case series. / Síntomas psicóticos persistentes después del uso abusivo prolongado de mefedrona: una serie de dos casos.

Mephedrone (4-methylmethcathinone) is a synthetic stimulant drug of the cathinone class. Similar effects to those of cocaine and ecstasy are reported by users, with a high addictive potential. Given its increasing rate of consumption in Europe, it is getting more and more attention from the addiction field. In spite of that, little is known about the long-term consequences of prolonged heavy use. The two following cases might depict some of them. Case 1 was a middle-age man who reported three years of intravenous use of mephedrone. He used to binge for several days in a row. Psychotic symptoms appeared after a few months, especially paranoid delusions. Sent to aftercare in a therapeutic community, delusions kept reappearing after prolonged abstinence. A good response to risperidone was observed. Case 2 was a young man who used mephedrone heavily for two years, always snorted. Upon admission to the therapeutic community, the patient reported auditory hallucinations that partially remitted with olanzapine. Both cases showed a good insight and no personality deterioration. Given its similarities to other substances that are known to induce psychotic symptoms, and the increasing consumption of mephedrone around Europe, similar cases are expected in the near future. Conventional antipsychotic treatment seems a reasonable pharmacological approach.

La mefedrona (4-methylmethcathinone) es un estimulante sintético del grupo de las catinonas. Los usuarios refieren efectos similares a los de la cocaína y el éxtasis, con un potencial adictivo elevado. Dada la creciente tasa de consumo en Europa, cada vez recibe más atención desde el campo de las adicciones. No obstante, poco se sabe sobre las consecuencias a largo plazo de su consumo abusivo. Los dos siguientes casos pueden servir para mostrar alguna de ellas. El caso 1 es un hombre de mediana edad, quien refería un consumo intravenoso de mefedrona de 3 años de duración. Su patrón de uso consistía en atracones que duraban varios días. Tras varios meses de consumo, aparecieron síntomas psicóticos, especialmente delirios paranoides. Tras ser enviado a una comunidad terapéutica, los síntomas psicóticos se continuaron produciendo pese a mantener una abstinencia prolongada. Se observó una buena respuesta a la risperidona. El caso 2 es un hombre joven, con un consume abusivo de 2 años de duración, vía nasal. A su llegada a la comunidad terapéutica, el paciente refirió alucinaciones auditivas que remitieron parcialmente con olanzapina. Ambos casos mostraron una buena conciencia de enfermedad, así como ausencia de deterioro en su personalidad. Dadas las similitudes bioquímicas con otras sustancias con potencial para inducir síntomas psicóticos, y el creciente consumo de mefedrona en Europa, casos similares son esperables en un futuro cercano. El uso de antipsicóticos convencionales parece una estrategia razonable de tratamiento.

Síntomas psicóticos persistentes después del uso abusivo prolongado de mefedrona: una serie de dos casos / Persistent psychotic symptoms after long-term heavy use of mephedrone: A two-case series

La mefedrona (4-methylmethcathinone) es un estimulante sintético del grupo de las catinonas. Los usuarios refieren efectos similares a los de la cocaína y el éxtasis, con un potencial adictivo elevado. Dada la creciente tasa de consumo en Europa, cada vez recibe más atención desde el campo de las adicciones. No obstante, poco se sabe sobre las consecuencias a largo plazo de su consumo abusivo. Los dos siguientes casos pueden servir para mostrar alguna de ellas. El caso 1 es un hombre de mediana edad, quien refería un consumo intravenoso de mefedrona de 3 años de duración. Su patrón de uso consistía en atracones que duraban varios días. Tras varios meses de consumo, aparecieron síntomas psicóticos, especialmente delirios paranoides. Tras ser enviado a una comunidad terapéutica, los síntomas psicóticos se continuaron produciendo pese a mantener una abstinencia prolongada. Se observó una buena respuesta a la risperidona. El caso 2 es un hombre joven, con un consume abusivo de 2 años de duración, vía nasal. A su llegada a la comunidad terapéutica, el paciente refirió alucinaciones auditivas que remitieron parcialmente con olanzapina. Ambos casos mostraron una buena conciencia de enfermedad, así como ausencia de deterioro en su personalidad. Dadas las similitudes bioquímicas con otras sustancias con potencial para inducir síntomas psicóticos, y el creciente consumo de mefedrona en Europa, casos similares son esperables en un futuro cercano. El uso de antipsicóticos convencionales parece una estrategia razonable de tratamiento

Mephedrone (4-methylmethcathinone) is a synthetic stimulant drug of the cathinone class. Similar effects to those of cocaine and ecstasy are reported by users, with a high addictive potential. Given its increasing rate of consumption in Europe, it is getting more and more attention from the addiction field. In spite of that, little is known about the long-term consequences of prolonged heavy use. The two following cases might depict some of them. Case 1 was a middle-age man who reported three years of intravenous use of mephedrone. He used to binge for several days in a row. Psychotic symptoms appeared after a few months, especially paranoid delusions. Sent to aftercare in a therapeutic community, delusions kept reappearing after prolonged abstinence. A good response to risperidone was observed. Case 2 was a young man who used mephedrone heavily for two years, always snorted. Upon admission to the therapeutic community, the patient reported auditory hallucinations that partially remitted with olanzapine. Both cases showed a good insight and no personality deterioration. Given its similarities to other substances that are known to induce psychotic symptoms, and the increasing consumption of mephedrone around Europe, similar cases are expected in the near future. Conventional antipsychotic treatment seems a reasonable pharmacological approach

Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users.

BACKGROUND: Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users. OBJECTIVES: Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function. METHODS: Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake. RESULTS: Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use. CONCLUSIONS: Acute ayahuasca administration impaired working memory but decreased stimulus-response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.

Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study.

Ayahuasca is an Amazonian psychoactive plant beverage containing the serotonergic 5-HT(2A) agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting alkaloids (harmine, harmaline and tetrahydroharmine) that render it orally active. Ayahuasca ingestion is a central feature in several Brazilian syncretic churches that have expanded their activities to urban Brazil, Europe and North America. Members of these groups typically ingest ayahuasca at least twice per month. Prior research has shown that acute ayahuasca increases blood flow in prefrontal and temporal brain regions and that it elicits intense modifications in thought processes, perception and emotion. However, regular ayahuasca use does not seem to induce the pattern of addiction-related problems that characterize drugs of abuse. To study the impact of repeated ayahuasca use on general psychological well-being, mental health and cognition, here we assessed personality, psychopathology, life attitudes and neuropsychological performance in regular ayahuasca users (n = 127) and controls (n = 115) at baseline and 1 year later. Controls were actively participating in non-ayahuasca religions. Users showed higher Reward Dependence and Self-Transcendence and lower Harm Avoidance and Self-Directedness. They scored significantly lower on all psychopathology measures, showed better performance on the Stroop test, the Wisconsin Card Sorting Test and the Letter-Number Sequencing task from the WAIS-III, and better scores on the Frontal Systems Behavior Scale. Analysis of life attitudes showed higher scores on the Spiritual Orientation Inventory, the Purpose in Life Test and the Psychosocial Well-Being test. Despite the lower number of participants available at follow-up, overall differences with controls were maintained one year later. In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group.

Assessment of addiction severity among ritual users of ayahuasca.

Ayahuasca is a psychoactive beverage used for magico-religious purposes in the Amazon. Recently, Brazilian syncretic churches have helped spread the ritual use of ayahuasca abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine-containing tea may lead to the medical and psychosocial problems typically associated with drugs of abuse. Here we assess potential drug abuse-related problems in regular ayahuasca users. Addiction severity was assessed using the Addiction Severity Index (ASI), and history of alcohol and illicit drug use was recorded. In Study 1, jungle-based ayahuasca users (n=56) were compared vs. rural controls (n=56). In Study 2, urban-based ayahuasca users (n=71) were compared vs. urban controls (n=59). Follow-up studies were conducted 1 year later. In both studies, ayahuasca users showed significantly lower scores than controls on the ASI Alcohol Use, and Psychiatric Status subscales. The jungle-based ayahuasca users showed a significantly higher frequency of previous illicit drug use but this had ceased at the time of examination, except for cannabis. At follow-up, abstinence from illicit drug use was maintained in both groups except for cannabis in Study 1. However, differences on ASI scores were still significant in the jungle-based group but not in the urban group. Despite continuing ayahuasca use, a time-dependent worsening was only observed in one subscale (Family/Social relationships) in Study 2. Overall, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not appear to be associated with the deleterious psychosocial effects typically caused by other drugs of abuse.