When our body undergoes a major physical stress such as during a major illness, it invariably leads to the release of the body's own morphine like substances, which are called endorphins. These are known to produce feelings of well being. For example it is these substances that produce feelings of well being in athletes following a period of exercise. When endorphins are released into the body it is thought that they can cause increased activity in a particular part of the brain called the limbic lobe. As regards NDE's there are a number of ways by which endorphins are thought to be involved. Firstly, endorphins are known to lead to states of happiness and peaceful feelings, and as people who come close to death are invariably in a stressful situation which causes the release of endorphins, it has been suggested that the peaceful feelings occurring during NDE may be in response to the release of endorphins. Another mechanism by which endorphins may be involved in NDE, is that the increased release of endorphins in people who are critically ill, may potentially stimulate and hence lead to over activity in the brain cells that are found in the limbic lobe of the brain. Over activity in this part of the brain may also lead to the development of hallucinations. It has therefore been proposed that NDEs may be a form of hallucination occurring in response to the extra release of endorphins which may lead to over activity in these areas.

Some other researchers have proposed that the intermediary for this process may be another brain molecule (neurotransmitter) called serotonin rather than endorphins.