Duncan CrowOpioids mimic the effects of ‘morphine-like’ substances called endorphins, which are normally produced by the body as a natural defence against pain. The endorphin release is what athletes sometimes become "addicted" to. Endorphins and narcotic pain killers (analgesics) attach themselves to specific sites on the outside of nerve cells which we have come to refer to as opioid receptors.
There are five major groups of opioid receptors: mu, kappa, sigma, delta and epsilon. Narcotic analgesic (pain killing) activity occurs at the mu, kappa and sigma receptors. Opioid agonists (stimulators) such as morphine and other drugs exert their activity mainly at the mu receptor; you might call it the main addiction receptor. These peptides are physically addictive, causing dependence, asthma, obesity, apathy, ignorance and numbness. Wheat and dairy products and beta-carbolines from prepared food also contain opioid peptides.
Where kappa-opioid receptor agonists differ from mu-opioid agonists is that they provide effective pain control without the dependence and respiratory depression that is associated with mu receptor activation. Potential applications include eating disorders, motion sickness, neuroprotection, and treatment for convulsions, ischemic brain damage, diuresis, hypertension, AIDS, arrhythmia and other physiological activities that may be mediated through kappa opioid receptors.
Moreover, kappa opioid agonists are delta opioid antagonists, so other areas of application include rheumatoid arthritis, systemic lupus erythematosis, Sjogren's Syndrome, multiple sclerosis, chronic lymphocytic leukemia, Type 1 diabetes, Epstein-Barr virus, AIDS, coronavirus infection, cytomegalovirus infection, antitussive agent, and other physiological activities.
Treatment with kappa-opioid agonists actually averts the frequent use of other drugs, not only morphine relatives, but even for cocaine and other mu-opioid addictions. The treatment can be done at home or any informal setting; research shows the ability of one kappa-opioid agonist, U69593, to attenuate cocaine self-administration and the reinstatement of drug-taking behavior, and suggests that U69593 may decrease low dose cocaine self-administration by decreasing the priming effects of cocaine. Yet another study shows that motivational effects of cannabinoids (marihuana) are mediated by mu-opioid and kappa-opioid receptors. Salvinorin A was found to be a full agonist, being significantly more efficacious than U50488 or U69593 and similar in efficacy to dynorphin A (the naturally occurring peptide ligand for kappa-opioid receptors). It may thus be possible to use Salvinorin A to treat heroin, cocaine, alcohol and amphetamine dependency, depression, and even excessive marijuana use.
Buy Salvia leaf, 5x, 10x, and 15x extract or live Salvia plants in the USA.
Salvia Divinorum References:
Easy planting instructions for salvia divinorum
Salvinorin A: the magic mint hallucinogen finds a molecular target in the kappa opioid receptor
Trends Pharmacol Sci 2003 Mar;24(3):107-9
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist (free full-text)
Proc Natl Acad Sci USA 2002 Sep 3;99(18):11934-9
Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. (free full-text article)
J Pharmacol Exp Ther. 2004 Mar;308(3):1197-203
Antidepressant Effects of the Herb Salvia Divinorum: A Case Report
Journal Of Clinical Psychopharmacology 2001;21:634-635
Effect of the kappa-opioid receptor agonist, U69593, on reinstatement of extinguished amphetamine self-administration behavior
Pharmacol Biochem Behav 2001 Apr;68(4):629-34
U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking
Psychopharmacology (Berl) 1999 Jun;144(4):339-46
Effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine in rats.
Psychopharmacology (Berl) 2002 Apr;161(1):17-22
Regulations of opioid dependence by opioid receptor types.
Pharmacol Ther 2001 Jan;89(1):1-15
Kappa-opioid receptor modulation of nicotine-induced behaviour
Neuropharmacology 2000 Oct;39(13):2848-55.
Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors (free full-text)
J Neurosci 2002 Feb 1;22(3):1146-54
Modulation of volitional ethanol intake in the rat by central delta-opioid receptors
Alcohol Clin Exp Res 1998;22(6):1185-9
Downregulation of kappa opioid receptor mRNA levels by chronic ethanol and repetitive cocaine in rat ventral tegmentum and nucleus accumbens.
Neurosci Lett1999;275(1):1-4
Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain.
Alcohol2000;22(3):165-71
Article:
The existence of mu, delta and kappa opioid receptors in the central nervous system is well documented. The present review focuses on the relationships between opioid receptor types and physical and psychic dependences. Mu and delta, but not kappa opioid receptor agonists produce physical dependence. From behavioral, biochemical and molecular biological studies, it is suggested so far that development of physical dependence on morphine results predominantly from an activation of mu 1 and mu 2 opioid receptors which causes functional changes in Gi/o, adenylate cyclase, protein kinases A and C, beta-adrenoceptor and NMDA receptor in the locus coeruleus.
Recently, there have been significant advances in studies on psychic dependence. Mu and delta opioid receptor agonists produce psychic dependence, but kappa opioid receptor agonists rather produce an aversive effect. Activation of the mesolimbic dopamine system may lead to psychic dependence on opioids. Mu and delta 1 opioid receptor agonists activate the mesolimbic dopamine system to induce a rewarding effect, whereas the rewarding effect of delta 2 opioid receptor agonists may be produced through a non-dopaminergic system.
There are complicated interactions among opioid receptor types. The activation of kappa opioid receptor suppresses physical and psychic dependences on mu and delta opioid receptor agonists, but the activation of delta opioid receptor potentiates the dependence on mu opioid receptor agonists. The clinical use of morphine in patients with cancer pain won't develop dependence probably due to the balance of the opioid system coming from these interactions.
Article:
This invention provides certain amino acid conjugates useful for selectively agonizing kappa opioid receptors in mammalian tissue. The selective activation of kappa opioid receptors can produce analgesia without the dependence and respiratory depression that is associated with mu receptor activation by morphine. In addition to analgesia, potential applications of kappa selective agonists include the areas of diuresis, eating disorders, motion sickness, and neuroprotection.
Article:
This invention provides kappa receptor agonists and delta receptor antagonists of specific formulas, as well as compositions comprising them, methods for their use, and synthetic procedures and intermediates useful for their preparation. The compounds described in this invention provide highly selective pharmacological activities both in vivo and in vitro at their respective opioid receptors. Therefore, the compounds can be used as therapeutic agents or as pharmacological tools to further investigate kappa or delta receptor binding, structure and function. Potential areas of application for the kappa agonists include analgesia, convulsions, ischemic brain damage, hypertension, AIDS, arrhythmia and other physiological activities that may be mediated through kappa opioid receptors. Potential areas of application for the delta antagonists include rheumatoid arthritis, systemic lupus erythematosis, Sjogren's Syndrome, multiple sclerosis, chronis lymphocytic leukemia, Type 1 diabetes, Epstein-Barr virus, AIDS, coronavirus infection, cytomegalovirus infection, cocaine use or addiction, antitussive agent, tolerance or physical dependence on a mu-opioid agonist and other physiological activities that may be mediated through kappa opioid receptors.
