Psychopharmacology
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Drug abuse can be conceptualized as choice between drug and nondrug reinforcers in which drug choice is excessive; factors impacting drug taking can be examined using procedures in which subjects choose between drug and an alternative reinforcer. ⋯ These results provide evidence that delaying the delivery of a mu-opioid receptor agonist reduces its potency as a positive reinforcer; more importantly, delaying the delivery of an alternative nondrug reinforcer (e.g., food) enhances the reinforcing potency of the agonist. Thus, understanding the factors that control substance abuse requires examination of contingencies for both drug and nondrug reinforcers.
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Dopamine transporter (DAT) conformation plays a role in the effectiveness of cocaine-like and other DAT inhibitors. Cocaine-like stimulants are intolerant to DAT conformation changes having decreased potency in cells transfected with DAT constructs that face the cytosol compared to wild-type DAT. In contrast, analogs of benztropine (BZT) are among compounds that are less affected by DAT conformational change. ⋯ The present results extend previous findings suggesting that cocaine-like actions are dependent on a binding equilibrium that favors the outward conformational state of the DAT. In contrast, BZT analogs with reduced dependence on DAT conformation have reduced cocaine-like behavioral effects and may prove useful in development of medications for stimulant abuse.
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Review Case Reports
Risperidone, QTc interval prolongation, and torsade de pointes: a systematic review of case reports.
A recent publication asserted that even low-dose risperidone may induce corrected QT (QTc) interval prolongation up to 500 ms without drug-induced IKr blockade. We seek to better understand the complexity of any link between risperidone-induced/associated QTc interval prolongation and torsade de pointes (TdP). ⋯ Risperidone (when properly prescribed in patients free of other risk factors for QTc interval prolongation and TdP) is a relatively safe drug. Conventional statistics can neither predict the individual patient who will experience TdP nor determine the relationship of drug dose to QTc interval prolongation and TdP. Narrative medicine using a case report format appears to be an alternative and valuable additional approach to advance our understanding of this relationship and to reduce risks.
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Randomized Controlled Trial
A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia.
A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia. ⋯ Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.
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Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. ⋯ There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug detection tests for synthetic cannabinoids need to become clinically available.