Mescaline: The forgotten psychedelic.

INTRODUCTION: Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited. OBJECTIVES: This article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research. FINDINGS: Mescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting. CONCLUSION: The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.

Preparing today's cardiovascular trainees to meet the challenges of tomorrow: team research and interdisciplinary training.

There is a growing focus on interdisciplinary team approaches in science and public health research, including cardiology. This trend is apparent in a large body of team publications and the strong interest from the funding agencies to support interdisciplinary research. Despite this increased emphasis on the importance and roles of teams, schools fail to better prepare their students and trainees with skills that allow them to work in or lead teams. In this article, we discuss the strengths and weaknesses of different team models and highlight the training program implemented by the Alberta Heart Failure Etiology and Analysis Research Team (HEART), which involves 24 scientists/mentors across the research and health care spectrum focused on understanding heart failure with preserved ejection fraction.

Defining the DNA mismatch repair-dependent apoptotic pathway in primary cells: evidence for p53-independence and involvement of centrosomal caspase 2.

Many studies have shown that DNA mismatch repair (MMR) has a role beyond that of repair in response to several types of DNA damage, including ultraviolet radiation (UV). We have demonstrated previously that the MMR-dependent component of UVB-induced apoptosis is integral to the suppression of UVB-induced tumorigenesis. Here we demonstrate that Msh6-dependent UVB-induced apoptotic pathway is both activated via the mitochondria and p53-independent. In addition, we have shown for the first time that caspase 2, an initiator caspase, localizes to the centrosomes in mitotic primary mouse embryonic fibroblasts, irrespective of MMR status and UVB treatment.

Non-tumor cells from an MSH2-null individual show altered cell cycle effects post-UVB.

The multi-functionality of the DNA mismatch repair (MMR) proteins has been demonstrated by their role in regulation of the cell cycle and apoptosis, as well as DNA repair. Using a unique MSH2-/- non-tumor human lymphoblastoid cell line we show that MMR facilitates G2/M arrest after UVB-induced DNA damage. Deficiency in MSH2 leads to a decrease in the induction of G2/M cell cycle checkpoint following UVB radiation in MSH2-null non-tumor cells. We also show evidence that the above-mentioned cells deficient in MSH2 have decreased levels of key cell cycle proteins such as CHK1 phosphorylated at Ser345, CDC25C phosphorylated at Ser216 and CDC2 phosphorylated at Tyr15, Thr14, compared to MSH2-proficient cells after UVB radiation. In addition, we demonstrate an altered p53 protein in the MSH2-null cell line. Our data show that the MMR protein MSH2 is involved in the regulation of normal cell cycle response after UVB-induced DNA damage.