ABSTRACT
While the endogenous opioid system has generally been associated with regulation of pain, it also modulates the experience of distress and may play a central role in many psychiatric and neurodevelopmental disorders. Decades of preclinical research on the analgesic effects of endogenous opioids, i.e., endorphins, suggests that opioid receptors have plastic bimodal (inhibitory/excitatory) properties that may explain conflicting findings in clinical research. An exploratory study with 60 healthy volunteer participants, using a cold pressor-induced pain paradigm, found evidence that a combination of a nutraceutical agent that enhances endorphin release (Endorphin Enhancer) with one that switches opioid receptors from an excitatory to inhibitory mode (Opioid Receptor Switcher) not only increases pain tolerance but also reduces emotional and physical distress. This discovery led to clinical application of a critically formulated endorphinergic treatment in 203 case studies over a two-year period. Findings revealed the remarkable clinical efficacy and safety of this treatment in the relief of chronic emotional and physical distress, including anxiety, anger, depression, cravings, and hyperalgesia, as well as enhancement of well-being, productivity, mental clarity, relationships, and an adaptive response to life’s stresses. These studies provide new insights into the role of endogenous opioid system imbalances in the development, treatment, and prevention of dysfunctional emotional and physical distress. We postulate that an Endorphinergic Distress Syndrome (EDS) consists of abnormal endorphin levels together with opioid receptors predominately in their excitatory mode. EDS may account for many core distress symptoms associated with chronic anxiety, addictions, pain, as well as affective personality, autism spectrum, attention-deficit, and distress-related medical problems. Our research has led to new endorphinergic formulations, combining Endorphin Enhancers, such as caffeine, with Opioid Receptor Switchers, such as n-acetylcysteine, for the relief of emotional and physical distress. Our studies also provide a novel method to reverse the anxiogenic effects of caffeine and related hyperexcitatory substances.