Zofran-The New Wonder Drug for Addiction

Use in Opiod Withdrawal States

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The newest drug that I have begun to use to aid in opiod withdrawal is ondansetron.  This is the Generic name for Zofran, a medication long used for the treatment of chemotherapy related nausea.  It accomplishes this task by blocking the activity of a certain subtype of seratonin receptors, the 5HT3 receptor.

Elsewhere on this site, Zofran is discussed in regard to its ability to reduce food, alcohol and other drug cravings.  The dosages of Zofran for opiod withdrawal are at a significant higher level than those used for cravings.  It is almost as if the two dosages were separate drugs.

The development of this idea is recent and really demonstrates how modern science helps us realize the unexpected benefits of commonly used medication.  Dr. Chu et. al., out of Stanford University, did a rather elegant set of experiments that were published in 2009.  They were able measure the intensity of withdrawal in 18 different breeds of lab rats and than rank order those breeds from those that became more ill to those that became less ill.  They wanted to determine if there were any genetic determinants that predicted their withdrawal.

After the genetic studies were done, they determined that there was a correlation; those breeds that experienced more withdrawal had a lot of similarity in their 5HT3 receptors which differed from those breeds with less withdrawal.  Ondansetron, a know blocker of these receptors was than given to these rats.  It was found that withdrawal was significantly lessened.  the rats were less agitated.  Their sensitivity to pain was reduced.  The medication reduced withdrawal separate and apart from nausea. It may also have reduced nausea but this could not be assessed in rats.

They then examined what happened to these receptors when the mice were exposed to opioids.  Multiple area of the brain were examined including the Amygdala which modulates stress.    Another location of these receptors is on the dopamine neurons that go the the Nucleus Accumbens, the pleasure center of the brain.  It turns out that one effect of opiod use is to reduce the number of seratonin receptors in these areas. 

This suggests that during opiod withdrawal, the seratonin receptors will increase in number.  Therefore, it is reasonable to assume that some of the symptoms of opiod withdrawal may be due to increasing activity of this recaptor.  Blockade of this receptor with with ondansetron will block this effect.  This underlies its' benefit in reducing symtoms of withdrawal.

As a final experiment, Chu subjected human volunteers to an opiod withdrawal protocol.  These subjects were not opiod addicted.  They were given about 20 mgs of morphine followed by Narcan a few hours later.  This was done while they were given either ondansetron or placebo.  There was a 75% reduction in the intensity of withdrawal when they were using ondansetron.

I have been using this medication for the past 5 months.  I use it for patients who are weaning down on Suboxone.  It has easily become the the most valuable adjunctive medication for relieving withdrawal. 

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Stuart Wasser
11/20/10