Opioids are drugs with major medical uses, including the treatment of pain and diarrhea, and have been used throughout human history for both the relief of human suffering and their psychotropic properties (Box 5.1).

Opioids are the most potent and effective analgesics known to man. Opiates, such as morphine and codeine, together with 20 other alkaloids were originally derived from the extracts of the juice of the opium poppy (Papaver somniferum; Figure 5.1). An opiate drug was defined as any natural or semi-synthetic derivative that has morphine-like effects. Because of the development of synthetic drugs with morphine-like actions and the discovery of morphine-like acting substances in the brain, the term opioid came into use and can be defined as all drugs, both natural and synthetic, with morphine-like actions. The term “opioids” also encompasses endogenous opioid peptides (i.e., neuropeptides found naturally in the body that have morphine-like actions), such as enkephalins, dynorphins, and endorphins, that bind to the same receptors as opioid receptor agonists and antagonists. For simplicity, this book generally uses the term “opioids.”

BOX 5.1


Opioid drugs – natural, semisynthetic, and synthetic – all have pharmacological actions similar to morphine and bind as direct agonists to the opioid receptors in the brain to produce their behavioral effects. Opioid drugs mimic the actions of endogenous opioid peptides that also bind as agonists to the opioid receptors, including β-endorphin (which has cell bodies in the hypothalamus) and enkephalins and dynorphins (which are widely distributed throughout the brain and have high concentrations in reward- and pain-related neurocircuits). The behavioral effects of opioids are transduced by three transmembrane G-protein-coupled opioid receptors – μ, δ, and κ – and subsequent second-messenger gene transcription changes. The μ opioid receptor is responsible for the pain-relieving and intoxicating effects of opioids, in addition to a wide range of other behavioral and physiological effects. The intoxicating effects of opioids are largely mediated by actions on μ opioid receptors in the origin and terminal areas of the mesocorticolimbic dopamine system, including the nucleus accumbens and extended amygdala (central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition zone in the shell of the nucleus accumbens). The addiction potential of opioids largely derives from powerful within-system neuroadaptations (signal transduction mechanisms) and between-system neuroadaptations (neurocircuitry changes) in the brain motivational and stress systems.

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