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Cellular Mechanisms Cause Opiate Tolerance and Dependence

Tolerance and dependence to opioids are very common side-effects of long-term opiate use.  While the mechanisms of tolerance and dependence are not fully understood, it is known that receptor down-regulation causes desensitization and plays a role in a user’s tolerance of opiates.  Additionally, activation of other receptors in the nervous system may also play a role in a users tolerance to opiates.  As a result, patients may need more medication to reach the same levels of pain relief.

Down-regulation is a mechanical process for cells to cope with the increase of an external variable.  If there is an increase of intake of a specific molecule, there will be a cellular decrease in the number of receptors to molecules.  For instance, over time the number of opiate receptors will decrease on a cell’s surface for long-term prescription painkiller users.  As an individual continues to take their regular dose of painkillers, like Oxycontin, Vicodin and hydrocodone, there will be fewer opiate receptors for the compounds to bind to, causing less of an effect of the drug.  When this occurs, the body starts becoming desensitized to the drug, which usually causes users to increase their dosage.  Down-regulation is an example of a cell’s negative feedback mechanism, which is a self-regulating response to changes in the body, usually due to external influences like chemicals or hormones.Opioid-Induced Tolerance

Up-regulation is another cellular mechanism that takes part in the body’s tolerance and dependence to opiates.  Up-regulation occurs when an external variable, which has been provided to the body for a long period of time, is removed and the cell increases the number of receptors.  For example, when an opiate dependency patient seeks treatment and stops using opiates, the opiate receptors in their brain will increase to try to receive more opiates.  This often leads to withdrawal symptoms and cravings because the body does not have enough opiates to fill the opiate receptors.  Receptor up-regulation and down-regulation can vary in time from minutes to weeks, and the reversal process of these two mechanisms can take months.

If you or a loved one is struggling with dependency to prescription painkillers, we urge you to contact your medical physicians.  For more information on choosing an opiate detox program for yourself or a loved one, please feel free to contact our office directly.  The Waismann Method is a safe and proven treatment for opiate dependency that utilizes the most advanced medical techniques available.  The rapid opiate detoxification procedure is carried out in a full-service hospital in Southern California by board-certified anesthesiologists while patients remain under deep sedation, so they experience minimal conscious withdrawal or suffering.

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