Morphine and codeine are powerful pain-relieving medications derived from the opium poppy, Papaver somniferum. These substances, known as opiates, have been utilized in medicine for centuries due to their profound effects on pain perception. Both compounds are naturally occurring alkaloids found within the raw opium latex.
How Opioid Pain Relievers Work
Opioid pain relievers, including morphine and codeine, exert their effects by interacting with specific proteins in the body called opioid receptors. These receptors are primarily located in the brain, spinal cord, and other areas of the central nervous system, as well as in the gastrointestinal tract. There are three main types of opioid receptors: mu (μ), kappa (κ), and delta (δ).
When morphine or codeine bind to these receptors, particularly the mu-opioid receptors, they trigger a series of cellular processes. These changes reduce the excitability of nerve cells, thereby inhibiting the transmission of pain signals throughout the nervous system. This mechanism effectively blocks the perception of pain.
Medical Uses
Morphine is a potent analgesic primarily used for managing severe pain, both acute and chronic. It is frequently prescribed for pain following surgery, pain associated with cancer, and pain resulting from injuries. Extended-release formulations are available for persistent pain requiring around-the-clock treatment.
Codeine is used for the short-term relief of mild to moderate pain. It is often considered when non-opioid pain relievers have not been sufficient. Beyond pain relief, codeine is also commonly applied as a cough suppressant. It works by decreasing activity in the part of the brain responsible for the coughing reflex.
Key Differences Between Morphine and Codeine
Morphine is a considerably stronger analgesic than codeine, reflecting its higher affinity for mu-opioid receptors. This difference in strength dictates their respective clinical applications, with morphine reserved for more severe pain.
Codeine functions as a “prodrug,” meaning it must be metabolized by the liver to become active. The enzyme cytochrome P450 2D6 (CYP2D6) converts a portion of codeine into morphine, which then provides the analgesic effect. Only about 5-10% of codeine is converted to morphine in individuals with normal CYP2D6 activity.
Genetic variations in the CYP2D6 enzyme can significantly alter an individual’s response to codeine. Individuals who are “poor metabolizers” due to inactive CYP2D6 copies may experience little to no pain relief from codeine, as insufficient morphine is produced. Conversely, “ultrarapid metabolizers” with multiple active CYP2D6 gene copies convert codeine to morphine more rapidly and completely, which can lead to higher-than-expected morphine levels and an increased risk of side effects, even at standard doses.
Regarding onset and duration, morphine begins to exert its effects within about 20 minutes when administered intravenously and around 60 minutes orally, with effects lasting 3 to 7 hours. Codeine’s effects begin within 30 to 45 minutes and can last approximately 4 to 6 hours, peaking 1 to 2 hours after ingestion. These pharmacokinetic differences influence which medication is chosen based on the patient’s pain severity and desired speed and length of action.
Side Effects and Risks
Common side effects associated with both morphine and codeine include nausea, constipation, drowsiness, and dizziness. Patients may also experience itching and reduced respiratory effort.
Beyond these common effects, there are more serious risks. With prolonged use, individuals can develop tolerance, requiring higher doses to achieve the same pain-relieving effect. Physical dependence can also occur, meaning the body adapts to the presence of the drug, leading to withdrawal symptoms if the medication is stopped suddenly. These symptoms can include watery eyes, insomnia, diarrhea, muscle aches, and severe abdominal pain.
Psychological addiction, characterized by compulsive drug-seeking behavior, is another significant concern. The most severe risk is overdose, which can lead to life-threatening respiratory depression, pinpoint pupils, and loss of consciousness. In cases of overdose, naloxone can be administered as an antidote to reverse these effects by blocking opioid receptors.
Due to their potential for abuse and dependence, both morphine and codeine are classified as controlled substances. In the United States, morphine is a Schedule II controlled substance, indicating a high potential for abuse. Codeine can be classified as Schedule II, III, or V, depending on its formulation and the amount of codeine present, with formulations containing higher amounts having a higher schedule classification.