Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of hormones . The first example of such work being done was in 1962 by Earl Sutherland . Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied norepinephrine , which acts on the liver to convert glycogen into glucose via the activation of the phosphorylase enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrine's target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP ( cAMP ) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology. 
Chills or cold flashes with goose bumps (" cold turkey ") alternating with flushing (hot flashes), kicking movements of the legs ("kicking the habit"  ) and excessive sweating are also characteristic symptoms.  Severe pains in the bones and muscles of the back and extremities occur, as do muscle spasms. At any point during this process, a suitable narcotic can be administered that will dramatically reverse the withdrawal symptoms. Major withdrawal symptoms peak between 48 h and 96 h after the last dose and subside after about 8 to 12 days. Sudden withdrawal by heavily dependent users who are in poor health is very rarely fatal. Morphine withdrawal is considered less dangerous than alcohol, barbiturate, or benzodiazepine withdrawal.