Cessation of dosing with morphine creates the prototypical opioid withdrawal syndrome, which unlike that of barbiturates, benzodiazepines, alcohol, or sedative-hypnotics, is not fatal by itself in neurologically healthy patients without heart or lung problems; it is in theory self-limiting in length and overall impact in that a rapid increase in metabolism and other bodily processes takes place, including shedding and replacement of the cells of many organs.
Nonetheless, suicide, heart attacks, strokes, seizures proceeding to status epilepticus, and effects of extreme dehydration do lead to fatal outcomes in a small fraction of cases.
Acute morphine and other opioid withdrawal proceeds through a number of stages. Other opioids differ in the intensity and length of each, and weak opioids and mixed agonist-antagonists may have acute withdrawal syndromes that do not reach the highest level. As commonly cited[by whom?], they are:
Stage I: Six to fourteen hours after last dose: Drug craving, anxiety
Stage III: Sixteen to twenty-four hours after last dose: Rhinorrhea (runny nose) and increase in other of the above, dilated pupils, piloerection (gooseflesh), muscle twitches, hot flashes, cold flashes, aching bones and muscles, loss of appetite and the beginning of intestinal cramping.
Stage IV: Twenty-four to thirty-six hours after last dose: Increase in all of the above including severe cramping and involuntary leg movements ("kicking the habit"), loose stool, insomnia, elevation of blood pressure, moderate elevation in body temperature, increase in frequency of breathing and tidal volume, tachycardia (elevated pulse), restlessness, nausea
Stage V: Thirty-six to seventy-two hours after last dose: Increase in the above, fetal position, vomiting, free and frequent liquid diarrhea, which sometimes can accelerate the time of passage of food from mouth to out of system to an hour or less, involuntary ejaculation, which is often painful, saturation of bedding materials with bodily fluids, weight loss of two to five kilos per 24 hours, increased white cell count and other blood changes.
Stage VI: After completion of above: Recovery of appetite ("the chucks"), and normal bowel function, beginning of transition to post-acute and chronic symptoms that are mainly psychological but that may also include increased sensitivity to pain, hypertension, colitis or other gastrointestinal afflictions related to motility, and problems with weight control in either direction.
Some authorities[which?] give the above as grades zero to four, and others[which?] add chronic withdrawal as a seventh stage. Some separate post-acute and chronic withdrawal, others do not. For and example of the use of the above system, methadone clinics require, in the absence of a direct and documented referral from a doctor, Stage II withdrawal symptoms and/or recent needle marks and/or surrender of injecting equipment and/or unused drug at the intake appointment to begin the methadone maintenance or withdrawal process; two urine tests positive for opioids must then be collected shortly thereafter.
The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next scheduled dose, sometimes within as early as a few hours (usually between 6–12 hours) after the last administration. Early symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria, sweating and in some cases a strong drug craving. Severe headache, restlessness, irritability, loss of appetite, body aches, severe abdominal pain, nausea and vomiting, tremors, and even stronger and more intense drug craving appear as the syndrome progresses. Severe depression and vomiting are very common. During the acute withdrawal period systolic and diastolic blood pressure increase, usually beyond pre-morphine levels, and heart rate increases, which have potential to cause a heart attack, blood clot, or stroke.
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 and 96 hours 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.
The psychological dependence associated with morphine addiction is complex and protracted. Long after the physical need for morphine has passed, the addict will usually continue to think and talk about the use of morphine (or other drugs) and feel strange or overwhelmed coping with daily activities without being under the influence of morphine. Psychological withdrawal from morphine is a very long and painful process. Addicts often suffer severe depression, anxiety, insomnia, mood swings, amnesia (forgetfulness), low self-esteem, confusion, paranoia, and other psychological disorders. Without intervention, the syndrome will run its course, and most of the overt physical symptoms will disappear within 7 to 10 days including psychological dependence. There is a high probability that relapse will occur after morphine withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. Testimony to morphine’s addictive and reinforcing nature is its relapse rate. Abusers of morphine (and heroin) have one of the highest relapse rates among all drug users, ranging up to 98 per cent in the estimation of some clinicians, neuropharmacologists, mental health/AODA professionals and other medical experts.