Emotional and Physical Distress Relief Using a Novel Endorphinergic Formulation

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.

Endorphinergic Attenuation of Distress by Concomitantly Enhancing Endogenous Opioid Release and Switching Opioid Receptor Signaling from an Excessively Excitatory to a Normal Inhibitory Mode

“…caffeine, forskolin) and Opioid Receptor Switchers (e.g. NAC, magnesium sulfate), using a "cold pressor" pain tolerance assay [41,42]. Prior cold pressor tests carried out by LaVincente et al [43] demonstrated that cotreatment of healthy human subjects with the exogenous opioid, buprenorphine, together with ultra-low-dose naloxone or ultra-low-dose naltrexone markedly enhanced opioid analgesia, confirming earlier mouse tail-flick assays by Crain and Shen (Section 3).…”

“…Prior cold pressor tests carried out by LaVincente et al [43] demonstrated that cotreatment of healthy human subjects with the exogenous opioid, buprenorphine, together with ultra-low-dose naloxone or ultra-low-dose naltrexone markedly enhanced opioid analgesia, confirming earlier mouse tail-flick assays by Crain and Shen (Section 3). In Crain et al's "cold pressor" studies [42], each nutraceutical-Endorphin Enhancer and Opioid Receptor Switcher was administered to subjects separately as well in combination. Pain tolerance was not increased more than placebo by the separate administration of each agent; in fact, the Endorphin Enhancers alone generally produced a decrease in pain tolerance.…”

“…Pain tolerance was not increased more than placebo by the separate administration of each agent; in fact, the Endorphin Enhancers alone generally produced a decrease in pain tolerance. Remarkably, the combination of an Endorphin Enhancer with an Opioid Receptor Switcher produced a dramatic increase in pain tolerance for most subjects, It is important to note that these endorphinergic formulations effectively and safely increased pain tolerance even though they contained no conventional analgesics [41,42,44].…”

“…Clinical observations of the emotional state of the subjects in these "cold pressor" studies revealed unexpected, dramatic, and meaningful changes in the emotional distress they experienced when facing this stress-inducing situation [41,42]. When subjects were administered a combination of an Endorphin Enhancer (e.g., caffeine, forskolin) and an Opioid Receptor Switcher (e.g., NAC, magnesium sulfate), a remarkable reduction in emotional and physical distress, including anxiety and agitation as well as anger and irritability, was evident in the majority of subjects.…”

“…In order to evaluate the potential clinical benefits of this novel nutraceutical formulation, a 26-month clinical research project was conducted consisting of 203 case studies [41,42]. Combinations of one or more Endorphin Enhancers (e.g., caffeine, forskolin) and Opioid Receptor Switchers (e.g., NAC, magnesium sulfate), with and without synergizing agents (e.g., l-theanine, white willow bark), were administered to patients suffering from a wide variety of emotional and physical distress dysfunction disorders including chronic anxiety and agitation, anger and irritability, cravings and addictions, aches and pains, as well as affective, autism spectrum, and attention-deficit, and dementia disorders.…”