Noradrenergic activity in anticipatory nausea.

Two studies were conducted to examine the hypothesis that noradrenergic activity is a cause of the anticipatory nausea associated with cancer chemotherapy. In the first study concentrations of plasma 3-methoxy-4-hydroxyphenyl-glycol (MHPG) on day 1 of cycle 5 of initial chemotherapy were significantly higher in patients with than without anticipatory nausea. To determine whether elevated MHPG reflected a clinically significant causative role for noradrenergic activity in anticipatory nausea, we conducted a randomized, double-blind, placebo-controlled, crossover trial of clonidine for anticipatory nausea. At a dose of clonidine that produced significant side effects and reductions of plasma MHPG, anticipatory nausea was improved only marginally. These studies do not support a causative role for noradrenergic activity in anticipatory nausea that can be reduced by clonidine with an acceptable therapeutic index

Noradrenergic activity in anticipatory nausea.

Two studies were conducted to examine the hypothesis that noradrenergic activity is a cause of the anticipatory nausea associated with cancer chemotherapy. In the first study concentrations of plasma 3-methoxy-4-hydroxyphenyl-glycol (MHPG) on day 1 of cycle 5 of initial chemotherapy were significantly higher in patients with than without anticipatory nausea. To determine whether elevated MHPG reflected a clinically significant causative role for noradrenergic activity in anticipatory nausea, we conducted a randomized, double-blind, placebo-controlled, crossover trial of clonidine for anticipatory nausea. At a dose of clonidine that produced significant side effects and reductions of plasma MHPG, anticipatory nausea was improved only marginally. These studies do not support a causative role for noradrenergic activity in anticipatory nausea that can be reduced by clonidine with an acceptable therapeutic index

Efeitos comportamentais, cognitivos e psicofisiológicos dos canabinoides: relevância para a psicose e a esquizofrenia Behavioral, cognitive and psychophysiological effects of cannabinoids: relevance to psychosis and schizophrenia

Avanços recentes no conhecimento sobre a função do receptor de canabinoide renovaram o interesse na associação entre cannabis e psicose. Linhas convergentes de evidências sugerem que os canabinoides podem produzir uma ampla gama de sintomas transitórios positivos, negativos e cognitivos assemelhados aos de esquizofrenia. Os canabinoides também produzem alguns déficits psicofisiológicos sabidamente presentes na esquizofrenia. É igualmente claro que em indivíduos com um transtorno psicótico estabelecido, os canabinoides podem exacerbar sintomas, desencadear recaídas e ter consequências negativas no curso da doença. Evidências crescentes sugerem que a exposição precoce e pesada à cannabis pode aumentar o risco de se desenvolver um transtorno psicótico como a esquizofrenia. A relação entre exposição à cannabis e esquizofrenia preenche alguns, mas não todos os critérios usuais de causalidade. Porém, a maioria das pessoas que utilizam cannabis não desenvolve esquizofrenia e muitas pessoas diagnosticadas com esquizofrenia nunca utilizaram cannabis. Portanto, é provável que a exposição à cannabis seja uma "causa componente" que interage com outros fatores para "causar" esquizofrenia ou outro transtorno psicótico, mas não é nem necessária nem suficiente para fazê-lo sozinha. No entanto, na ausência de causas conhecidas da esquizofrenia e com as implicações de políticas de saúde pública, se tal vínculo for estabelecido, as causas componentes, tais como a exposição a canabinoide, devem continuar sendo um foco de estudos futuros. Finalmente, são necessárias mais pesquisas para identificar os fatores subjacentes à vulnerabilidade à psicose relacionada a canabinoide e para elucidar os mecanismos biológicos subjacentes a esse risco.<br>Recent advances in knowledge about cannabinoid receptor function have renewed interest in the association between cannabis and psychosis. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative and cognitive symptoms. Cannabinoids also produce some psychophysiological deficits also known to be present in schizophrenia. Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Increasing evidence suggests that early and heavy cannabis exposure may increase the risk of developing a psychotic disorder such as schizophrenia. The relationship between cannabis exposure and schizophrenia fulfills some, but not all, of the usual criteria for causality. However, most people who use cannabis do not develop schizophrenia, and many people diagnosed with schizophrenia have never used cannabis. Therefore, it is likely that cannabis exposure is a "component cause" that interacts with other factors to "cause" schizophrenia or other psychotic disorder, but is neither necessary nor sufficient to do so alone. In the absence of known causes of schizophrenia, however, and the implications for public health policy should such a link be established the role of component causes such as cannabinoid exposure should remain a focus of further study. Finally, further work is necessary to identify the factors that underlie individual vulnerability to cannabinoid-related psychosis and to elucidate the biological mechanisms underlying this risk