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Introduction: Recently, it has been demonstrated that olive leaf extract and its main component have calcium channel blocker, anti-inflammatory and anti-oxidative properties. However, the effects of olive leaf extract on opioid dependence have not yet been clarified. Methods: To develop morphine dependence, morphine was injected twice daily for 7 days according to an escalating dose in rats. On day 7, the animals received naloxone (3 mg/kg, i.p.) 5 h after the last injection of morphine. Withdrawal signs (weight loss, abdominal contraction, diarrhea, teeth chattering, jumping, grooming and ptosis) were evaluated during 1h after naloxone. To determine the effect of OLE and oleuropein on the development of morphine dependence, OLE was given at doses of 200, 300 and 500 mg/kg and oleuropin with 10 mg/kg (i.p.) concomitant with morphine. Results: Our results showed that rats chronically injected with morphine showed physical dependence. OLE (300 mg/kg) and oleuropin (10 mg/kg) could attenuate naloxone-induced withdrawal syndrome. Conclusion: Our data revealed that olive leaf extract had a beneficial effect on chronic morphine-induced side effects such as physical dependence and can be useful in the period of drug withdrawal and its main component, oleuropein, is responsible for such observed effects.

Keywords: Olive leaf extract, Oleuropein, Morphine, Dependency, Withdrawal syndrome, Rats

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