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SummaryBuprenorphine has been described as a potent analgesic with low abuse potential. Sporadic reports in the world literature would seem to contradict this view. A retrospective study of all opiate addicts first presenting over a 12‐month period showed an increasing level of buprenorphine abuse. The implications of these findings are discussed

Purpose-Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non-small cell lung cancer (NSCLC).Patients and methods-Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: Cohort 1 received oral atovaquone at the standard clinical dose 750 mg twice-daily, whilst Cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Inter-cohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed.Results-Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction with median change −28.0% [95% confidence interval (CI), −58.2 to −4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, −6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24% to 74%) lower in Cohort 1 compared to Cohort 2 (p=0.004), adjusting for cohort, tumor volume and baseline HV. A key pharmacodynamic endpoint was reduction in hypoxia regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported.Conclusions-This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant anti-tumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.