Abstract:
Drug abuse in general and cocaine addiction in particular, poses a serious and growing health risk. In the withdrawal phase from cocaine use, the addict's craving level for the drug rises. This phenomenon is called "incubation of craving" and the addict is in danger of returning to drug use even after a prollonged period of time. To date, there no effective drugs to treat cocaine addiction. Opioid receptors also play an important role in cocaine addiction and Beta-endorphin binds to opioid receptors of type Delta and Mu. In previous studies that use a self administration rat model of drug addiction, there was a direct relationship between beta-endorphin, Delta opioid receptor and attenuation of cocaine craving. The main problem is to translate these results into the clinic because beta-endorphin does not pass blood - brain barrier (BBB) and therefore can only be given by direct injection to the brain. This is impractical as a therapeutic stratergy. we used phage display technology, that allows expression of recombinant peptides at the amino terminus of Phage proteins (In phage library we used contains about 1013 phages, which includes about 109 different phage clones, each expressing 12mer linear peptides of different sequence). From isolated plaques were collected randomly. Two phages showed a significant decrease in their binding to C6 cells in the presence of a specific agonist to delta opioid receptor, DSLET, whereas a specific agonist to mu opioid receptor ,DAMGO, did not change the binding of the two phages to the cells. The two new peptides reported here show potential to attenuate cocaine craving when tested in vivo in the self administration rat model. The findings of this study can provide a breakthrough in the treatment of cocaine craving.
Current status:
complete preclinical studies.
Granted patent.
Novel addiction pain treatment.
Summary Project 3:
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Sucrose self administration indicate that PEP1 does not disrupt the natural reward system.
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CPP assay shows non addictive-like properties of PEP1, therefore its use will not mimic a replacement therapy, but rather will allow rehabilitation.
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PEP1 was proved to attenuate craving in two valid animal models for addiction.
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High efficacy accessible to the brain.
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Safe. No side effects.
Intranasal administration is a safe and effective approach for addiction and may offer an efficient rehabilitation rather than a mimetic effect as other available clinically-used pharmacological agents do.
