Endogenous (naturally occurring in the body) opioids include endorphins, enkephalins and dynorphins.  Morphine appears to mimic and amplify the action of endorphins, which act to reduce physical pain, causing sleepiness, and provoke feelings of pleasure. They can be released in response to pain and external stimuli, such as sex and exercise. It crosses the blood-brain barrier less efficiently than heroin, which is synthesised from morphine, See: Heroin section.

It interacts predominantly with the μ-opioid receptor. These μ-binding sites are discretely distributed in the human brain, gut and spinal cord.

Morphine is an opioid receptor agonist – its main effect is binding to and activating the μ-opioid receptors in the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Activation of the μ-opioid receptors is associated with analgesia, sedation, euphoria, physical dependence, and respiratory depression. It also has a complex relationship with the way humans process and respond to emotional affect. The drug is a very potent modulating agent for psychic pain and trauma, and it is widely believed that this explains its huge appeal to people who have been victims of abuse and neglect, particularly in early life.

Morphine is also a κ-opioid and δ-opioid receptor agonist, κ-opioid's action is associated with analgesia, miosis (pinpoint pupils) and psychotomimetic (alteration of behaviour and personality ) effects. δ-opioid is thought to play a general role in analgesia.

Sigma (σ) receptors were once considered to be opioid receptors due to the alleviating or suppressing coughing actions of many opioid drugs being mediated via σ receptors, however they are now not usually classified with the opioid receptors. Although morphine does not bind to the σ-receptor, it has been shown that σ-agonists, antagonize morphine analgesia, and σ-antagonists enhance morphine analgesia, suggesting some interaction between morphine and the σ-opioid receptor.

More recently scientists have suggested that another receptor, now known as the nociceptin receptor or OLR-1 (opiate-like receptor) is more important to our understanding of how these drugs work.