Abstract. – OBJECTIVE: The use of herbal medicinal products in the management of pain has been increasing steadily in recent years, often in combination with conventional analgesics, which can induce significant interactions. In tradi- tional medicine, rosemary was used as mild anal- gesic, for relieving renal colic pain and dysmenor- rhea. The aim of our study was to examine anal- gesic effects of rosemary essential oil and its pharmacodynamic interactions with codeine and paracetamol in mice. MATERIALS AND METHODS: The identifica- tion and quantification of chemical constituents of the essential oil isolated from air-dried aerial parts of rosemary were carried out by GC/FID and GC/MS. The hot plate test was performed on NMRI mice by placing them individually on hot plate and assessing their response to the ther- mal stimulus. RESULTS: In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8- cineole, camphor, and α-pinene. Administration of investigated essential oil increased signifi- cantly the latency time of animal response to heat-induced pain between 20 th and 50 th minute of the test, when compared to saline-treated group. Rosemary essential oil in the dose of 20 mg/kg was shown to be more efficient than in the dose of 10 mg/kg, in combinations with both codeine and paracetamol. CONCLUSIONS: Our findings support the use of rosemary in the management of pain and indi- cate a therapeutic potential of rosemary essen- tial oil in combination with analgesic drugs. The mechanisms involved in analgesic effects of rosemary essential oil and the potential influ- ence on cytochromes and drug metabolism should be more in-depth investigated. Key Words: Rosmarinus officinalis, Essential oil, Antinociceptive, Hot plate, Interaction. European Review for Medical and Pharmacological Sciences Analgesic effects of rosemary essential oil and its interactions with codeine and paracetamol in mice A. RASKOVIC, I. MILANOVIC 1 , N. PAVLOVIC, B. MILIJASEVIC, M. UBAVIC 2 , M. MIKOV Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia 1 High Medical School of Professional Skills, Zemun, Serbia 2 Health Care Institution for Laboratory Diagnostics ’Medlab’, Novi Sad, Serbia Corresponding Author: Nebojsa Pavlovic, MPharm; e-mail: nebojsa.pavlovic@gmail.com 165 Introduction The use of herbal medicinal products to re- lieve pain has been increasing steadily in recent years because they are often perceived as being natural and therefore harmless 1,2 . Herbal medi- cines are often taken in combination with con- ventional drug therapies and some of their pharmacologically active ingredients might in- teract with synthetic drugs 3 . Drugs that are sub- strates for metabolism mediated by cytochrome P450 (CYP) enzymes are particularly subject to herb-drug interactions, which can be attributed to a large extent to CYP polymorphism and ability of many herbal compounds to induce or inhibit these enzymes 4 . Rosemary (Rosmarinus officinalis L., Lami- aceae) is widely cultivated all over the world as an ornamental and aromatic plant, and has been commonly used for flavoring food, but also for different medicinal purposes. In traditional medicine, rosemary was used as mild analgesic, for relieving renal colic pain, dysmenorrhea, respiratory disorders, due to its antispasmodic properties 5,6 . Recently, essential oil isolated from rosemary and monoterpenes as its main active compounds have been of great interest due to their various health benefits and thera- peutic effects. According to the recommenda- tion of European Medicines Agency (EMA) from 2010, rosemary essential oil (REO) can be used for treating dyspepsia and mild spasmodic disorders of the gastrointestinal tract, as well as an adjuvant in the relief of minor muscular and articular pain and in minor peripheral circulato- ry disorders 7 . Besides, the experiments con- ducted with REO have demonstrated its several notable pharmacological effects, such as an- 2015; 19: 165-172