Current State of Tolerance: The Holy Grail

Opioid Tolerance–In Search of the Holy Grail

Tolerance, one of several behavioral adaptations to prolonged opioid treatment, has long been explained by desensitization of opioid receptor signaling and loss of surface receptors. However, recent evidence presents an alternative hypothesis, suggesting that receptor internalization could in fact reduce tolerance in vivo.

Pursuing the "Holy Grail".

Over the past decade, several large, randomized trials have allowed us to better define the appropriate population for primary prevention implantable cardioverterdefibrillator (ICD) placement, saving thousands of lives every year. MADIT II (Multicenter Automatic Defibrillator Implantation Trial II) and SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) have demonstrated a survival benefit o...

The Holy Grail of Psychiatry

"Holy Grail" is a well-known metaphor for the eternal spiritual pursuit for truth and wisdom. It suggests that in order for us to find what no one has found, we must search where few have looked. In 2013, a group led by Helen Mayberg published a groundbreaking paper that sought an answer to one of the most discussed conundrums in psychiatry and neuroscience: Can specific patterns of brain activ...

Spinal anesthesia: the Holy Grail?

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Searching for the Holy Grail?