This week, our class focused on an article that discussed the role of glutamate (an important neurotransmitter) in drug addiction. It emphasized opioid addiction and its effects on the brain. Abused opioid drugs include morphine, heroin, oxycodone, hydromorphone, and more. It is thought that 9% of the population may abuse opiates sometime during their life. The drugs can create physical dependence, tolerance, and withdrawal once the drug is removed. People who were given opioids in the hospital even exhibit withdrawal. Early symptoms of withdrawal include agitation, anxiety, muscle aches, insomnia, and sweating. Later symptoms include abdominal cramping, diarrhea, nausea, and vomiting. The symptoms are not life-threatening, but are uncomfortable and may encourage return to drug usage.
Withdrawal Treatments
Withdrawal treatments involve both support and medications. Some of the medications are used to treat symptoms individually. Clondidine, one of the most common medication, reduces anxiety, agitation, muscle aches, sweating, runny nose and cramping. Buprenorphine is an efficient medication that can also decease detox time. Methadone is another one that is used. However, methadone requires long-term administration with a decrease in dosage over time. Check out this website for more information and links to other aspects of drug addiction:
http://www.nlm.nih.gov/medlineplus/ency/article/000949.htm.
MK-801 and Naloxone
MK-801 and naloxone are common drugs used during opioid research. On one hand, MK-801 blocks withdrawal symptoms. On the other, naloxone is used to induce withdrawal. Both of these drugs were used in various studies cited in the paper. You might think that MK-801 has potential as a withdrawal treatment as it blocks the withdrawal symptoms. But its mechanism of action brings in some interesting side-effects. The molecule binds to the glutamate receptor NMDA, blocking it. The receptor cannot let ions through to continue a signal. This is good, right? It stops the glutamate signalling so it cannot start dopamine release. Thus there is no reward system encouraged by the opioid drugs. There is more to the story. The site to which MK-801 binds is the same as PCP and ketamine. It exhibits some of the same side-effects as these drugs, mainly schizophrenic-like symptoms. If that wasn’t bad enough, there are also cardiovascular side-effects and formation of brain lesions. And that, ladies and gentlemen, is why an effective withdrawal symptom-blocker is not used as a treatment.
Withdrawal will stop eventually, but the desire to return to the drug will remain. The reward system driven by dopamine release is strong. Opioids have been used for centuries, first in the form as poppy seeds then morphine, then heroin. Pain relief is important, so it is just as important to understand the addictive properties of the current forms we use.
Opioid Withdrawal. . . Not a Fun Process.
