Abuse and Effects of Salvia divinorum in a Sample of Patients Hospitalized for Substance Dependence.

The study goal is to document the prevalence of salvia use among patients admitted for detoxification of other illicit drug use and to determine its effect. This cross-sectional study included 47 heavy drug users who were admitted for detoxification of other illicit drug abuse at a psychiatric hospital in Lebanon. The prevalence of salvia use was 66%. The salvia effect started and dissipated rapidly (15 min). No significant difference was found between salvia and non-salvia users in terms of affect, cognition and somaesthesia subscales of the Hallucinogen Rating Scale. Ratings of intensity and volition subscales were higher in non-salvia users than salvia users, while perception score was higher in users. Salvia use was correlated with perceptual alteration and hallucinogenic effects.

Quinoxaline 1,4-dioxides: hypoxia-selective therapeutic agents.

A problem that confronts clinicians in the treatment of cancer is the resistance of hypoxic tumors to chemotherapy and radiation therapy. Thus, the development of new drugs that are toxic to hypoxic cells found in solid tumors is an important objective for effective anticancer chemotherapy. We recently showed that the heterocyclic aromatic N-oxides, quinoxaline 1,4-dioxides (QdNOs), are cytotoxic to tumor cells cultured under hypoxia. In this study, we evaluated the hypoxia-selective toxicity of four diversely substituted QdNOs and determined their effect on the expression of hypoxia inducible factor (HIF) 1alpha in the human colon cancer cell line T-84. The various QdNOs were found to possess a 50- to 100-fold greater cytotoxicity to T-84 cells cultured under hypoxia compared with oxia. Interestingly, the hypoxia cytotoxicity ratio (HCR), the ratio of equitoxic concentrations of the drug under aerobic/anoxic conditions, was highly structure related and depended on the nature of the substituents on the QdNO heterocycle. The most cytotoxic 2-benzoyl-3-phenyl-6,7-dichloro derivative of QdNO (DCQ) was potent at a dose of 1 microM with an HCR of 100 and significantly reduced the levels of HIF-1alpha transcript and protein. The 2-benzoyl-3-phenyl derivative (BPQ) had a hypoxia potency of 20 microM and an HCR of 40. By contrast, the 2-aceto-3-methyl and the 2,3-tetramethylene (TMQ) derivatives of QdNO were much less cytotoxic under hypoxia (HCRs of 8.5 and 6.5, respectively) and reduced the expression of HIF-1alpha mRNA to a much lesser extent. Because the nonchlorinated analogue BPQ did not demonstrate behavior similar to that of DCQ, we hypothesize that the C-6, C-7-chlorine of DCQ might play a significant role in the selective hypoxic cytotoxicity of the drug.