[fgfblog]

Agençe France-Presse


SYDNEY: Addiction to morphine and heroin can be blocked, according to new research that could prove a major breakthrough in treating addicts and in pain relief treatments.

Researchers at the University of Adelaide in Australia worked with colleagues at the University of Colorado in the United States to pinpoint a key mechanism in the body's immune system that amplifies addiction to opioid drugs.

"Our studies have shown conclusively that we can block addiction via the immune system of the brain, without targeting the brain's wiring," said Mark Hutchinson from Adelaide's School of Medical Sciences.

Blocking immune response prevents cravings

"Both the central nervous system and the immune system play important roles in creating addiction, but our studies have shown we only need to block the immune response in the brain to prevent cravings for opioid drugs."

The results, to be published in the Journal of Neuroscience, reveal that laboratory studies showed that the drug known as plus-naloxone, which is not yet in clinical use, will selectively block the immune-addiction response.

The researchers said that opioid drugs such as morphine and heroin bind to immune receptors in the brain known as TLR4 which then act as amplifiers for addiction, ramping up the ‘reward’ effect of drugs of abuse to a high degree.

Reward “reduced” to food, sex and hugs

The new drug automatically shuts this effect down, Hutchinson said.

"It really reduces the reward level down to the equivalent of food, sex, and hugs," he said.

Professor Linda Watkins, from the Centre for Neuroscience at the University of Colorado, said the work fundamentally changed understanding about opioids, reward and addiction.

"We've suspected for some years that TLR4 may be the key to blocking opioid addiction, but now we have the proof," she said in a statement.

Pain relief without fear of addiction

The researchers believe the discovery could prove useful if plus-naloxone could become a co-formulated drug with morphine, to allow patients who need pain relief to take the drug without fear of addiction.

But it could have a second application.

"It can be used by itself potentially in addicted people to help their addiction," Hutchinson said.

The research team says clinical trials could be underway within 18 months.

no more...

http://www.cosmosmagazine.com/news/5...can-be-blocked

[Ndptbudd]

Apart from mental addiction, don't the opioids cause physical addiction as well? What would sudden withdrawal from the proposed cocktail do?

[voksveta]

Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement

Abstract
Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4−/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.

[Kokomoxcvcv]

Isn't this what that doctor, in Perth I think, was using naltrexone for?

[Ndptbudd]

Isn't this what that doctor, in Perth I think, was using naltrexone for?

Dr George O'Neil.

I was wondering what the difference was as well.

[voksveta]

// I was wondering what the difference was as well.

Probably /* the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances */, but I suppose scientists should focus more on the media report and less on the research article.

[fgfblog]

but I suppose scientists should focus more on the media report and less on the research article. we have both types of people here. scientists and non-scientists. i post these articles hoping they will interest both. and that both can input to their own level of expertise.

[Ndptbudd]

we have both types of people here. scientists and non-scientists. i post these articles hoping they will interest both. and that both can input to their own level of expertise.

And indeed scientists with knowledge in different fields.
I have never claimed to be a biologist.

[Vikonbarius]

> Addiction to morphine and heroin can be blocked

Doesn't methadone cure heroin addiction?

Another block for the addiction would be great. Let's see, how many decades do you think it will be before it's available?

[voksveta]

// Doesn't methadone cure heroin addiction?

Not in general, I would off thought, it's just a substitute.

I'mn't saying we all need to be the world authority on every subject, only that if we'r' going to raise the skeptical bar then perhaps we should read and take into account information that is easily accessible from more than one source! Who would ough thought!

[bmwservis]

Isn't this what that doctor, in Perth I think, was using naltrexone for?

Naltrexone blocks the Opiate receptors in a short term way. From memory the Dr in WA was blocking opiate uptake with repeated doses of Naltrexone to handle withdrawal. It wasn't a cure as the first backslide re-instated the addiction.

This sounds similar but a different mechanism.