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BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Salvia divinorum is a plant indigenous of Oaxaca, Mexico. Traditionally, the plant is used for healing and divinatory purposes. At present, S. divinorum is also used recreationally by teenagers and young adults around the world. The main active component is salvinorin A, a unique non-nitrogenous kappa-opioid receptor agonist with hallucinogenic properties. Scientific interest is high, due to two facts: 1) salvinorin A was the first non-nitrogenous opioid-receptor ligand, 2) it elicits hallucinogenic effects without binding at serotonin receptors, as classical hallucinogens (LSD, psilocin, mescaline) do. Structural modifications of salvinorin A led to the discovery of herkinorin and other non-nitrogenous opioid receptors ligands, which are a powerful tool for elucidating the complex biological mechanisms of opioid receptors and for drug discovery of new therapeutic agents for pain treatment, drug dependence and mental disorders. The pharmacological profile of salvinorin A suggests several clinical applications related to the regulation of gastrointestinal functions, mood and drug-seeking behavior. The fast metabolism and pharmacokinetics of salvinorin A hinder clinical development, however it has been shown that some analogs have improved metabolic and pharmacokinetic profile. The first psychopharmacological studies on humans reported intense and unique psychedelic effects and positive after-effects on mood, well-being and awareness which may outweigh negative effects. Moreover, the drug exhibits low toxicity, few reported adverse effects and low abuse potential, making it suitable for further clinical studies. Taking in account the traditional use of the plant, the overall safe pharmacological profile, and the positive results on mood and general well-being obtained so far, it would be interesting and potentially beneficial to investigate further on the psychopharmacology of this unique molecule in respect of drug-assisted psychotherapy and treatment of depression

The therapeutic properties of MDMA were discovered by Alexander Shulgin in 1965, after which it was used in more than a thousand therapy sessions in the United States of America. The high potential for abuse of MDMA led to questions about illegalization of MDMA. Eventually, the neurotoxic effects and the illicit use have led to the illegalization in 1988 and from then on MDMA was classified as a schedule 1 drug by the DEA. This classification prohibits the therapeutic use of MDMA and further testing in clinical trials. Therefore it was no longer possible to study or make use of the potential medical properties of the drug. During the last decade in Switzerland and other countries, clinical trials with MDMA have been performed. This research is heavily criticized by some people who argue that even a single dose of MDMA possesses neurotoxic properties (Parrott 2012). Nevertheless, promising results have been found in a clinical trial on MDMA as a treatment for individuals suffering from post-traumatic stress disorder (PTSD). In the light of those findings, a risk assessment of MDMA is necessary (M. C. Mithoefer et al. 2013). The dose of MDMA used in PTSD therapy is around 1-2 mg/kg body weight (BW) and will be considered as the standard in the present study. The safety of this dose in the clinic will be assessed via a scientific literature review. This review will treat MDMA as if it was a new drug to enter the market. All use of ecstasy or MDMA as a party drug is beyond the scope of this risk assessment, and therefore the emotions often related to the use of illicit drugs will not influence this review. Since the ‘war on drugs’ has tried to put all drugs in a negative ambience, this research pays extra attention to the backgrounds and positions of the authors to make a well-weight risk estimation. Disclaimer: Any information given in this risk assessment cannot be used to justify the illicit use of MDMA.