**Abstract**

Opium alkaloids, derived from crude *Papaver somniferum L.* plant, are potent analgesic drugs, but their use is limited because of dependence and withdrawal. Opium alkaloids activate the mesocorticolimbic dopaminergic system, which project from the ventral tegmental area to the nucleus accumbens and medial prefrontal cortex, and dopamine is critically important in opioid consumption and sustaining. The reward effect resulting from the activation of the dopaminergic system leads to continued opioid consumption and occurs opioid dependence. After the development of opioid dependence, consumption continues to avoid withdrawal syndrome. Opioid dependence is accompanied with tolerance, which requires the use of high doses to achieve the same effect. When tolerance develops, the chronic consumer continues to use opioid above known toxic doses to produce the same effect, which can result in death regardless of the type of opioid used. Raw *Papaver somniferum L*. has five high-density main opium alkaloids including morphine, noscapine, codeine, thebaine, and papaverine. Some of these alkaloids bind to classical opioid receptors to produce an opioid-like effect, while the other part mediates non-opioid effects. This chapter reviews the opiod history, receptors, mechanism of action, dependence, withdrawal. In addition, general information about five main opium alkaloids, their effects, uses, routes of administration, pharmacokinetics, adverse reactions, contraindications; effects on reproduction, pregnancy, and lactation were compiled.

**Keywords:** morphine, noscapine, codeine, thebaine, papaverine
