Journey from Initial Opioid Use ???? Opioid Dependence ???? Addiction

There are 16 ounces in 1 pound; but it is true today, as it was when Benjamin Franklin stated that “an ounce of prevention is worth a pound of cure.” A little precaution to avoid/prevent an undesirable condition is preferable to developing a long-term negative situation and dealing with its potential consequences. 

If you consume an opioid tablet, you have little control of what chain of actions it triggers in your body. Hence the only way one can prevent any potential negative consequences/sequelae of initial opioid use is either avoiding opioids until when absolutely necessary, and when needed, taking the least amount possible, for a very short duration.

As mentioned in my prior articles, opioid dependence can occur very quickly. Today let’s discuss the science! Someone can go from not having taken any prior opioid to developing long-term opioid dependence, within just a few days of taking opioids. There are no warning signs before dependence sets in. 

How does this happen? Well, there is a small part of our midbrain called the Ventral Tegmental Area (VTA). The VTA produces dopamine (a neurotransmitter), which is transmitted to another part of the brain called the Nucleus Accumbens (NA). Dopamine is then transmitted from the NA to the Prefrontal cortex (PfC). This dopamine related circuitry “VTA????NA????PfC pathway” is the “Reward Pathway” responsible for making us associate specific activities with pleasure. This pathway exists as feeling pleasure motivates us to repeat behaviors that are critical to our existence. This pathway reinforces life sustaining activities like eating or having sex. Opioids and addicting substances trigger the very same pathway, but while doing so, produce pleasure 10X greater than experienced with eating or having sex; this is due to initial overproduction of dopamine. The dopamine induced pleasure experienced reinforces the opioid use behavior, as opioid use is met with the “pleasure” reward. There is then resulting continued desire to use opioids, and longer-lasting adaptations subsequently occur in our brain.  The pleasure reward provokes desire for ongoing use and dependence sets in. The “pleasure” reward also described as “euphoria” or “high” fuels the ongoing craving of the opioids initially. However, with ongoing use there are profound changes in neurons and brain circuits; the initial “high” experienced due to overproduction of dopamine, is drastically blunted as our brain tries to adjust for the overproduction of dopamine. Continued opioid use triggers a negative feedback loop which drastically turns down dopamine production. Presence of dopamine suppresses the Locus Coeruleus (LC) part of our brain. Hence with suppression of dopamine production, there is activation of the LC part of our brain. The LC part of our brain when activated produces another neurotransmitter norepinephrine (NE). When NE is released, it creates unpleasant symptoms including insomnia, anxiety, mood changes, sweating, cramping, nausea, aches and pain, diarrhea, fever, severe flu-like symptoms, and continued opioid craving. 

Another way to explain this: initially, the desire and craving for opioids is due to the experienced pleasure/high with each dose. But with additional opioid doses, the effects become less pleasurable (as dopamine overproduction is significantly blunted). Subsequently, NO further pleasure/high is experienced with each dose; instead, the desire for more opioids use is solely to allow the user to just feel “normal,” and to eliminate the unpleasant symptoms precipitated by the norepinephrine release described in the paragraph above. 


For illustration and simplicity (Numbers here are just for ease of understanding):
  • Imagine normal dopamine level to be 5.   (On a 0-10 scale)
  • With opioids dopamine level shoots up.
  • Dopamine level ≥ 9 results in “high” and “pleasure/euphoria.”
  • Dopamine level ≤ 3 results in Norepinephrine production and very unpleasant symptoms.
  • Prior to 1st opioid use: Dopamine level is = 5 (one feels like their normal self).
  • Initial few days of Opioid use: Dopamine level at 10 (overproduction).  “Increased pleasure feeling”
  • With continued Opioid use: Dopamine production is progressively blunted as the brain senses the overproduction and must counteract it. Level drops to between 1 and 2; unpleasant symptoms kick in. More opioids are then needed to allow for more dopamine release, which can now only get dopamine level to 5, as overproduction is never again experienced after the initial few days of opioid use.


Imagine craving to take a medication to remove negative symptoms including insomnia, anxiety, mood changes, aches and pain, diarrhea, fever, and flu-like symptoms? In a lot of cases, when opioid dependence sets in, a great deal of opioid intake is unrelated to the exact cause of initial pain, but more related to changes in your brain chemistry, and quest to feel normal and avoid withdrawal symptoms. 

Avoid taking opioids if there are alternatives that can help reduce your pain, remember opioids don’t eliminate pain. If you ever have to take opioids, take them sparingly, and only for a short duration of time. 

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