Low Dose Naltrexone: websites en referenties

[greta]

Nederlandse uitleg over LDN'
http://mens-en-gezondheid.infonu.nl/aan ... icijn.html

[marlène]

Een te laag aantal mu-opioide receptoren in de hersenen onderbreekt normaal beloningsgevoel na een doelgerichte inspanning (en dus leereffect).

Disruption of endogenous opioid activity during instrumental learning enhances habit acquisition

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

Indeed, there is dense mu opioid receptor localization in the dorsomedial striatum and nucleus accumbens core (Daunais et al., 2001), regions which are implicated in the learning and performance of goal-directed actions, respectively (Balleine and Dickinson, 1998, Corbit and Balleine, 2003, Ostlund and Balleine, 2005, Yin et al., 2005). Moreover, the opioid peptides, beta-endorphin and enkephalin, have been shown to positively contribute to the motivation for rewards (Hayward et al., 2002). More recently, opioid receptors in the basolateral amygdala have been shown to be critical in encoding changes in the incentive value of an instrumental outcome (Wassum et al., 2008, Wassum et al., In Press).

...
Likewise, disruption (with Naloxone) of the basolateral amygdala has been found to alter reward-value related processing and to render instrumental performance insensitive to changes in outcome value (Balleine et al., 2003, Wang et al., 2005, Wellman et al., 2005, Ostlund and Balleine, 2008). It appears, therefore, that disrupting the specific circuitry governing either action-outcome or reward learning processes can significantly compromise the ability of animals to exert goal-directed executive control over instrumental actions.

=> door naloxone te geven, simuleren ze artificieel een te laag aantal mu opioide receptoren MOR omdat ze deze volledig blokkeren.
Als je low dose naltrexone gebruikt, stimuleer je net de aanmaak van deze MOR. Je verbetert dan het leereffect door het aantal MOR te normaliseren.

[marlène]

Naloxone en Naltrexone verhogen het aantal mu opioide receptoren (MOR) alsook de functionele hypersensitiviteit.

μ-Opioid Receptor Up-Regulation and Functional Supersensitivity Are Independent of Antagonist Efficacy

These data suggest that μ-opioid receptor up-regulation and functional supersensitivity require only receptor blockade and are independent of antagonist efficacy.

=> als je een opiaat-antagonist neemt zoals low dose naltrexone, verhoog je het aantal MOR en heb je minder pijnstillers nodig omdat je sneller reageert op pijnmedicatie.

[JannekeB]

=> als je een opiaat-antagonist neemt zoals low dose naltrexone, verhoog je het aantal MOR en heb je minder pijnstillers nodig omdat je sneller reageert op pijnmedicatie.

Dat merk ik met de migraine medicatie ook inderdaad. Soms is zelfs een Advil genoeg, geen triptaan nodig.

[marlène]

Naloxone geeft signaal om geen cytokines (stof die wordt afgegeven tijdens een immuunrespons) meer te producereren in de hersenen

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

Data show that while morphine-induced decreases in TNF release were reversed in part by naloxone (Fig 4A), naloxone treatment alone was rather effective at suppressing Tat-induced cytokine release (Fig. 4A, 4B, and 4C). One possible explanation for this unexpected finding is that endogenous opioid peptides released from microglia might act through autocrine feedback mechanisms to affect cytokine release over a 24-hr application of Tat.

=> dit onderzoek werd gedaan bij patienten met HIV die leden aan neuroAIDS ( includes sensory neuropathies, myelopathies, behavioral/cognitive perturbations, and overt HIV dementia)

=> de cascade die cytokines in werking zetten, kan leiden tot chronische en neurodegeneratieve ziekten met name als deze zich in de hersenen afspelen

[marlène]

Naltrexone geeft geen depressieve gevoelens als nevenwerking zoals algemeen wordt verkondigd.

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence.

... Within this context, depressive symptoms need not be considered a contraindication for naltrexone treatment.

... These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms.

[aquamarijn]

het wordt interessanter en interessanter, bedank voor alle info marlene, echt super!!

[marlène]

dank je wel aquamarijn. Low dose naltrexone (LDN) heeft veel toepassingsmogelijkheden want het moduleert de opioide receptoren. Deze laatste zijn rechtstreeks verantwoordelijk voor het immuunsysteem, cognitief functioneren en ons emotioneel welzijn.

[marlène]

Naloxone reguleert de blaascontrole

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

The inhibitory pudendal-to-bladder reflex that promotes bladder storage is likely mediated by inhibitory neurotransmitters including glycine, GABA (gamma-aminobutyric acid), and enkephalins (i.e. opioid peptides) which have been shown to suppress bladder preganglionic neuron firing and reflex micturition in animals. ...

These results raise the possibility that the inhibitory pudendal-to-bladder reflex is: (1) dependent in part on release of enkephalins and activation of opioid receptors, (2) facilitated by tonic activation of opioid receptors or (3) suppressed by the bladder hyperreflexia induced by naloxone.

In summary, this study revealed the involvement of opioid receptors in modulating the inhibitory pudendal-to-bladder reflex.

=> De zenuwprikkel van de blaas wordt wellicht aangestuurd door o.a. opioide peptiden. Door deze te reguleren m.b.v. low dose naltrexone kan men normale blaascontrole verkrijgen.

=> interesante toepassing voor mensen met interstitiële cystitis (overmatig plassen), onvrijwillig urineverlies, ...

[marlène]

Naloxone verbetert de opname van calcium in de botten

http://www.ncbi.nlm.nih.gov/pmc/article ... =pmcentrez

Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

Osteocalcin induces hypocalcemia and its effect on bone is enhancing mineralization and growth [11].

Naloxone is a pure opioid antagonist and blocks each of the opioid receptor types [9]. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated concurrently with naloxone [10].

It was shown that naloxone restores the functional activity of cells and tissue by removing β-endorphins from specific receptors. However, these functions are possible only if the circulating Ca concentration is adequate [12].

It also was concluded that a low-dose parenteral regimen with naloxone can relieve pain by a central pathway mechanism [13]. Naloxone reportedly produces either an increase in clinical pain or a dose-dependent biphasic change: pain intensity increases at high doses and decreases at low doses. Doses of naloxone lower than 1 mg/kg produced a significant decrease in pain intensity in humans and animal models [14-17]. Since analgesia occurs only with low doses, the effect appears to be very specific.

This study shows that a low-dose parenteral regimen of naloxone, especially if associated with calcium gluconate, aids mineralization and enhances earlier remodelling of the cortical bone in a 4 mm drill hole model system.

=> Naloxone + calcium versnelt het botherstel na een operatie. Een betere densiteit van het bot werd opgemeten.

=> interessant als toepassing bij osteoporose?

[marlène]

Zinktekort ontregelt de opioide receptoren en leidt tot ontregeling van hongergevoel (anorexia)

http://www.mendeley.com/research/the-ro ... -anorexia/

3H-naloxone binding was significantly increased to isolated brain membranes from zinc deficient animals using 1 nM unlabeled naloxone when compared to ad lib fed controls with the weight restricted animals again having intermediate values.

These data suggest that abnormalities in endogenous opiate regulation of appetite may well play a role in the anorexia of zinc deficiency. The effects of zinc deficiency on endogenous opiate action appear to include alterations in receptor affinity, a post-receptor defect and alterations in the synthesis and/or release of dynorphin.

=> zinktekort heeft een invloed op de werking van endogene opiaten in het lichaam, m.a.w. het verstoort de werking van receptoren op de cellen (= verminderde immuniteit) en verandert de synthese en/of vrijgave van dynorphin.
Deze laatste heeft ook niet-opioide werking, nl. een invloed op de NMDA-receptoren. Deze glutamaat-receptor speelt een cruciale rol in de vorming van het geheugen en de plasticiteit van het brein.

[marlène]

http://www.ncbi.nlm.nih.gov/pubmed/19799935

Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords.

[marlène]

Naltrexone maakt een einde aan neuropatische pijnen

http://www.ncbi.nlm.nih.gov/pubmed/18662331

Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4).

Thus, these data suggest that (+)-opioid antagonists such as (+)-naloxone may be useful clinically to suppress glial activation, yet (-)-opioid agonists suppress pain.

=> Naltrexone onderdrukt activatie van gliacellen. Dat zijn cellen die o.a. in de hersenen voorkomen. In het centraal zenuwstelsel (hersenen + ruggemerg) onderdrukken ze reparatie.

[marlène]

LDN efficient voor 60% van fibromyalgie-patienten

http://curetogether.com/blog/2011/10/05 ... etogether/

This finding is confirmed at CureTogether, where 26 out of 44 fibromyalgia patients report a major improvement in their symptoms after taking LDN. In fact, LDN is ranked as the #1 most effective treatment for fibromyalgia at CureTogether (see the screenshot below.)

Larger studies still need to be done, but it is remarkable that the CureTogether ratio of improvement on LDN is 59% (26/44), and the Stanford ratio of improvement on LDN is 60% (6/10). The same result!

[marlène]

De Stanford studie ivm fibromyalgie: "Low-Dose Naltrexone Reduces the Symptoms of Fibromyalgia"

http://snapl.stanford.edu/research/ldn.html