Oh this looks fun! I never did get around to trying the first version, but I’d love to give this a go.
This product will be better than the original in basically every way. I promise! For one, it will contain a higher concentration of the primary active ingredient (kratom alkaloids). It also contains ingredients which work synergistically with kratom and/or reduce tolerance/dependence. For example, thymoquinone, which is standardized at a 10% concentration in the accompanying nigella sativa extract, acts as a calcium channel blocker. This has been proven to reduce tolerance and dependence with any substance which binds to the opioid receptors. Anecdotal feedback mirrors this sentiment. Many users also claim it increases the potency of kratom, as well as other opioid agonists. Here is one of many PubMed publications:
Thymoquinone: From Nigella sativa to a protective pharmacological compound in managing opioid dependence and amphetamine type stimulant issues
Abstract
Opioids, amphetamines, and other types of substances have been widely abused around the world. Opioid dependence and tolerance are two distinct phenomena that have been associated with substance abuse issues. The management of its adverse consequences is becoming more challenging. More and more people are treated in Methadone Maintenance Therapy (MMT) program yet the issues are still unresolved. Researchers are continuing to study the best formulation in treating opioid dependent people starting with modern and alternative drug therapies. Since 2008 , thymoquinone (TQ) has been extensively studied by researchers around the world and has emerged to be a new potential drug candidate in managing substance abuse issues. Thus, the aim of this article is to review the effects that TQ may have on opioid dependent subjects and other abused substances such as amphetamine may have been studied. All of the articles from 2008 until 2019 involving the effects of TQ on substance abuse from Google Scholar®, Scopus®, and Pubmed® databases have been searched and reviewed. The keywords used were thymoquinone, opioid dependence, amphetamine, and Nigella sativa. The research results also have been discussed in this article. Based on the research conducted, TQ was effective in reducing the adverse health consequences associated with substance abuse such as withdrawal symptoms, tolerance, and cell damages. It is concluded that TQ could be a potential drug that can be complemented with the currently available drugs in substance abuse therapies.
Agmatine acts similarly in that it prevents tolerance build-up at both the D-opioid and K-opioid receptors, while also increasing potency. See below:
Modulation of opioid analgesia by agmatine
Abstract
Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.
DL-phenylalanine is also a very cool compound, particularly the D-isomer. Most bodybuilders, when they think of phenylalanine, think about the essential amino acid L-phenylalanine, but D-phenylalanine is a very different substance. D-phenylalanine, which comprises 50% of DL-phenylalanine molecule, acts not as a building block for protein synthesis, but as an enkephalinase inhibitor. Enkephalinase inhibitors directly improve mood by inhibiting the breakdown on natural opioid ligands, such as enkephalin, while simultaneously increasing the potency of opioid agonists, such as kratom etc. See below:
DL-phenylalanine markedly potentiates opiate analgesia - an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system
Abstract
In the author's clinical experience, concurrent treatment with DL-phenylalanine (DLPA) often appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain. An analysis of this phenomenon suggests that it may be mediated, at least in part, by up-regulation of the 'endogenous analgesia system' (EAS), a neural pathway that projects caudally from medullary nuclei to the dorsal horn of the spinal column; when stimulated by chronic pain or therapeutic measures such as opiates or acupuncture, the EAS suppresses activation of second-order pain-receptive neurons in the dorsal horn, and thereby alleviates pain. Since serotonin and enkephalins are key neurotransmitters in the EAS, it is reasonable to predict that measures which promote serotonin activity (such as 5-hydroxytryptophan and serotonin-reuptake inhibitors) as well as enkephalin activity (such as D-phenylalanine, an enkephalinase inhibitor) should potentiate EAS-mediated analgesia - a view consistent with much previous medical research. Comprehensive support of the EAS with well-tolerated nutrients and pharmaceuticals may amplify the analgesic efficacy of chronic opiate therapy, while enabling dosage reductions that minimize opiate side-effects. Analogously, this approach may complement the efficacy of acupuncture and other analgesic measures that activate the EAS.
And for those of you who experienced nausea from the original Mitradopa, that is doubtful to occur with the new version. This is because the original Mitradopa included a substantial amount of plain powdered leaf, along with the extract. Unfortunately, plain leaf is comprised primarily of indigestible plant fiber, which, for many, causes nausea when consumed. I have removed ALL plain leaf from this new version, so for those of you who are sensitive to the potential nausea promoting effects of plain leaf, you don't have to worry about that anymore.
Furthermore, if anyone is concerned that the removal of plain leaf will reduce the overall potency of the product, don't worry. I have not only increased the dose of extract enough to off-set the removal of plain leaf, but have increased it even further! So, you can expect an increase in overall potency, not a decrease.
Of course, I will be selecting loggers shortly before or right around the time of its release.
