Int Rev Neurobiol
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Observational studies in humans suggest that exposure to marijuana and other cannabis-derived drugs produces a wide range of subjective effects on mood tone and emotionality. These observations have their counterpart in animal studies, showing that cannabinoid agonists strongly affect emotional reactivity in directions that vary depending on dose and context. Based on these evidence, the activation of central CB(1) receptor has emerged as potential target for the development of antianxiety and antidepressant therapies. ⋯ Therefore, inhibition of AEA metabolism activity could amplify CB(1) activation mainly where AEA release is higher. Furthermore, the inhibition of FAAH causes an accumulation of AEA but not 2-AG, which, being 200-fold more abundant than AEA in the brain, might differently modulate CB(1)-mediated behavioral responses. The evidence outlined above supports the hypothesis that the EC system plays an important role in anxiety and mood disorders and suggests that modulation of FAAH activity might be a pharmacological target for novel anxiolytic and antidepressant therapies.
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Every pregnancy, even under the best of circumstances, carries risks with it. Having epilepsy and taking medications to treat seizures further increase these risks and not all patients are willing to accept risks. The issues related to pregnancy, epilepsy, and antiepileptic drugs and pregnancy are fraught with confusion and misperceptions. ⋯ In this chapter, we review the most common risk factors and divide them in two broad categories: (a) avoidable or modifiable risk factors and (b) unavoidable or non modifiable risk factors. Physicians counseling women with epilepsy who are pregnant or are planning a pregnancy should make every effort to understand the nature and magnitude of the risks associated with epilepsy and antiepileptic drugs in order to ensure the best possible outcomes in these cases. We discuss preventive measures that, when properly followed, can minimize risks and allow the vast majority of women with epilepsy to give birth to normal children.
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Most seizures during pregnancy occur in women who already have epilepsy. During pregnancy most women will continue their previous level of seizure control, although 15-30% may experience an increase in seizures. Pregnancy-induced changes in antiepileptic drug pharmacokinetics are a major factor affecting changes in seizure control during pregnancy, although compliance is also a significant factor. ⋯ Structural and metabolic changes may precipitate new-onset seizures during pregnancy. The structural causes include intracranial hemorrhage of multiple types, cerebral venous sinus thrombosis, and ischemic stroke. Metabolic causes include hyperemesis gravidarum; acute hepatitis (due to fatty liver of pregnancy or viral hepatitis); metabolic diseases, such as acute intermittent porphyria; infections, such as malaria; and eclampsia.
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Schizophrenia is a serious mental disorder that affects up to 1% of the population worldwide. As of yet, neurochemical mechanisms underlying schizophrenia remain unknown. To date, the most widely considered neurochemical hypothesis of schizophrenia is the dopamine hypothesis, which postulates that symptoms of schizophrenia may result from excess dopaminergic neurotransmission particularly in striatal brain regions, along with dopaminergic deficits in prefrontal brain regions. ⋯ As compared to dopaminergic agents, NMDA antagonists induce negative and cognitive symptoms of schizophrenia, as well as positive symptoms. Treatment studies with NMDA modulators, such as glycine, d-serine, and glycine transport inhibitors (GTIs), have yielded encouraging findings, although results remain controversial. Finally, genetic linkage and in vivo neurochemical studies in schizophrenia highlight potential etiological mechanisms giving rise to glutamatergic/NMDA dysfunction in schizophrenia.
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Recent epidemiological studies and advances in understanding of brain cannabinoid function have renewed interest in the long-recognized association between cannabinoids and psychosis. This chapter presents evidence supporting and refuting the association between cannabinoids and psychosis. Cannabinoids can induce acute transient psychotic symptoms or an acute psychosis in some individuals. ⋯ Nevertheless, in the absence of known causes of schizophrenia, the role of component causes such as cannabis exposure (exogenous hypothesis) is important and warrants further study. There is also tantalizing evidence from postmortem, neurochemical, and genetic studies suggesting CB1 receptor dysfunction (endogenous hypothesis) in schizophrenia that warrants further investigation. Further work is necessary to identify those factors that place individuals at higher risk for cannabinoid-related psychosis, to identify the biological mechanisms underlying the risks and to further study whether CB1 receptor dysfunction contributes to the pathophysiology of psychotic disorders.