Drug Addiction - Morphine

Drug addiction - Morphine is a highly potent opiate analgesic drug and is the principal active agent in opium and the prototypical opiate. Like other opiates, Morphine acts directly on the central nervous system (CNS) to relieve pain; at synapses of the nucleus accumbens in particular. Studies done on the efficacy of various opioids have indicated that, in the management of severe pain, no other narcotic analgesic is more effective or superior to Morphine. This drug is highly addictive when compared to other substances, and tolerance, physical and psychological dependences develop very rapidly.

Drug Addiction - Morphine Medical uses
Morphine is used legally:

as an analgesic in hospital settings to relieve�
pain in myocardial Infarction
pain after surgery
pain associated with trauma
in the relief of severe chronic pain, e.g.
cancer pain
pain from kidney stones
severe back pain
as an adjunct to general anesthesia
in epidural anesthesia or intrathecal analgesia
for palliative care (i.e. to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible)
as an antitussive for severe cough in nebulised form, for treatment of dyspnea, although the evidence for efficacy is slim. Evidence is better for other routes.
as an anti-diarrheal in chronic conditions (e.g., for diarrhea associated with AIDS), although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea.

Studies have shown that Morphine can alter the expression of certain genes in human DNA. A single injection of Morphine has been shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins.

Drug addiction - Morphine has long been known to act on receptors expressed on cells of the central nervous system resulting in pain relief and analgesia. In the 1970s and '80s evidence that opiate drug addicts showed increased risk of infection (such as increased pneumonia, tuberculosis, and HIV) led scientists to believe that Morphine may also affect the immune system. This possibility increased interest in the effect of chronic Morphine use on the immune system.

Interestingly, Morphine has recently been found to be endogenously produced by humans, made by cells in the heart, pancreas and brain. It has also been isolated from a range of other mammals, as well as toads and some invertebrates. What the normal endogenous role of Morphine might be is unclear.

Drug Addiction - Morphine Legal Classification

In the United States, Morphine is classified as a Schedule II drug under the Controlled Substances Act.
In the United Kingdom, Morphine is listed as a Class A drug under the Misuse of Drugs Act 1971.
In Canada, Morphine is classified as a Schedule I drug under the Controlled Drugs and Substances Act.
In Australia, Morphine is classified as a Schedule 8 drug under the variously titled State and Territory Poisons Acts.
Internationally, Morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.

Drug Addiction- Morphine History and Abuse
Morphine was first isolated in 1804 by the German pharmacist Friedrich Wilhelm Adam Sert�rner, who named it "morphium" after Morpheus, the Greek god of dreams. But it was not until the development of the hypodermic needle in 1853 that its use spread. It was used for pain relief, and as a "cure" for opium and alcohol addiction. Later it was found out that Morphine was even more addictive than either alcohol or opium, and its extensive use during the American Civil War allegedly resulted in over 400,000 sufferers from the "soldier's disease" of drug addiction - Morphine addiction. This statement has been subjected to controversy, as there have been suggestions that such a disease was in fact a hoax and soldier's disease never occurred after the Civil War.

DiaMorphine (Heroin) was derived from Morphine in 1874 and brought to market by Bayer in 1898. Heroin is approximately 1.5-2 times more potent than Morphine on a mg for mg basis. Using a variety of subjective and objective measures, the relative potency of heroin to Morphine administered intravenously to post-addicts found 1.80 mg of Morphine sulfate equals to 1 mg of diaMorphine hydrochloride (Heroin). The pharmacology of heroin and Morphine is identical except that the two acetyl groups increase the lipid solubility of the heroin molecule, and thus the molecule enters the brain a bit more rapidly. The additional groups are then detached, yielding Morphine, which is what causes the subjective effects of "heroin". Therefore, the effects of Morphine and heroin are identical except that heroin is slightly more potent and acts slightly faster. Morphine, along with heroin and cocaine were outlawed and their possession without a prescription was criminalized in the U.S. by the Harrison Narcotics Tax Act of 1914.

Morphine was the most commonly abused narcotic analgesic in the world up until heroin was synthesized and came into use. Even today, Morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce.

Drug Addiction - Morphine Addiction
Raw Morphine (Opium) is a highly addictive substance, both psychologically and physically. Its abuse potential is among the highest of all drugs known to man. Compared to other narcotic pain relievers, such as codeine, hydrocodone, and oxycodone, Morphine is considerably more liable for abuse and dependence. More potent narcotics, such as hydromorphone and fentanyl, have high abuse potential, but still less than that of Morphine.

Only heroin, which is nearly identical to Morphine, is comparable in dependence liability. Physical dependence and withdrawal symptoms can appear after only five days of administration. In a Japanese study, mice, which received Morphine (10 mg kg-1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg-1 i.p.) on the 6th day. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice.

Brown University Professor Julie Kauer and colleagues found as little as a single dose of Morphine could contribute to drug addiction - Morphine addiction. A single dose of Morphine can block a process in the brain associated with learning and memory for as long as a full day after being ingested. In a study, researchers found long-term potentiation, or LTP, is blocked in the brains of rats given as little as a single dose of Morphine. The drug's impact was very powerful, with LTP continuing to be blocked 24 hours later -- long after the drug was out of the animal's system.

In a study comparing the physiological and subjective effects of heroin and Morphine administered intravenously in post-addicts, the post-addicts showed no preference for one or the other of these drugs when administered on a single injection basis. Equipotent doses of these drugs had quite comparable action time courses when administered intravenously, and on this basis there was no difference in their ability to produce feelings of "euphoria," ambition, nervousness, relaxation, drowsiness, or sleepiness.

Although the heroin abstinence syndrome was of shorter duration than that of Morphine, the peak intensity was quite comparable for the two drugs. Data acquired during short-term addiction studies did not support the statement that tolerance develops more rapidly to heroin than to Morphine. These findings have been discussed in relation to the physiochemical properties of heroin and Morphine and the metabolism of heroin. When compared to other opioids -- hydromorphone, fentanyl, oxycodone, and meperidine, post-addicts showed a strong preference to heroin and Morphine over the others, suggesting that heroin and Morphine are more liable to abuse and addiction. Drug addiction - Morphine and heroin were also much more likely to produce feelings of "euphoria", and other subjective effects when compared to most other opioid analgesics.

Drug Addiction - Morphine Withdrawal Syndrome
The withdrawal symptoms associated with drug addiction - 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 strong drug craving, watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria, and sweating. 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. The heart rate and blood pressure are elevated. 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 occasionally fatal, although Morphine withdrawal is considered less dangerous than alcohol or barbiturate withdrawal.

The psychological dependence associated with drug addiction - 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. The psychological dependence on Morphine can, and usually does, last a lifetime. 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 the highest relapse rates among all drug users, including abusers of other opioids, cocaine, and methamphetamine.