Codeine brain, effects

Codeine (morphine methyl ether) resembles morphine in its general effect, but is less toxic and its depressant action less marked and less prolonged, whilst its stimulating action involves not only the spinal cord, but also the lower parts of the brain. In small doses in man it induces sleep, which is not so deep as that caused by morphine, and in large doses it causes restlessness and increased reflex excitability rather than sleep. The respiration is slowed less than by morphine (cf. table, p. 261). Cases of addiction for codeine can occur but according to Wolff they are rare. The best known ethers of morphine are ethylmorphine and benzyl-morphine [cf., table, p. 261), both used to replace morphine or codeine for special purposes. 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

The effects of morphine, codeine, and heroin in the brain are dose-related. Small doses produce drowsiness, decreased anxiety and inhibition, reduced concentration, muscle relaxation, pain relief, depressed respiration, constricted pupils, nausea, and a decreased cough reflex, which is why codeine found its way into cough suppressants. At slightly higher doses, morphine and heroin can produce a state of intense elation or euphoria. 

Opioid agonists also have an antitussive effect attributed to the depression of the cough reflex. Thus some opioids, typically codeine or one of its derivatives, are used for their antitussive activity, predominantly in combination products. The antitussive effect is in part the result of the interaction with opioid receptors at the cough center in the brain (23). The dose required for antitussive activity, however, is lower than that required for analgesia the opioid receptors involved in blocking the cough reflex are less sensitive to naloxone than those responsible for analgesia (23). 

Codeine and dihydocodeine are opioid analgesics that act directly on opiate receptors in the brain, producing analgesia, respiratory depression, euphoria and sedation. They are weak narcotic analgesics, useful for the treatment of mild to moderate pain. Their major side-effect at non-prescription dosages is constipation. 

Morphine is a strong agonist that crosses easily into the CNS. It is highly potent with regard to CNS effects, such as euphoria and medullary respiratory depression. Codeine is also a strong to moderate agonist, but does not cross the blood-brain barrier well. Thus, higher doses are needed to achieve CNS effects. Loperamide has little ability to cross into the CNS and is unlikely to produce CNS effects at any dose. It is thus sold over-the-counter. 

Thus, additive serotonergic effects on the brain are likeiy with SSRis that i reuptake of serotonin. Codeine and pentazocine causes the reiease of stored serotonin, and codeine is also a substrate of CYP2D6... 

Bolser DC, DeGennaro FC (1994) Effect of codeine on the inspiratory and expiratory burst pattern during Active cough in cats. Brain Res 662 25-30... 

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