The brain's mistaken belief that opioid use is essential to survival is directly involved in many of the behavioral symptoms of opioid dependence.¹

The Reward Circuit
The dopamine reward circuit spans several sections of the brain.^2,3

One of the more important sections innervated by the reward circuit is the limbic system. These structures are considered primitive from an evolutionary perspective, and their functions are somewhat primitive as well: regulating survival emotions (eg, fear, anger) and survival rewards (eg, pleasure triggered by eating, sex).²

The reward circuit also runs through the cerebral cortex, which, in comparison to the limbic system, is a relatively recent evolutionary development. This area of the brain is responsible primarily for judgment, planning, problem solving, and decision making.²

Impressive though the cerebral cortex may be, during times of crisis, its higher cognitive functions are useless. This is because when the body is threatened or under stress, the modern cerebral cortex is overrun by its more primitive, survival-oriented counterparts (eg, the limbic system)—thereby ensuring that nothing competes with the survival response.¹

Overriding the cerebral cortex essentially means that the most "intelligent" part of the brain has absolutely no say regarding human behavior during a crisis.

This survival response sheds light on one of the reasons opioids are able to exert such powerful control over behavior. This control starts with opioids' ability to affect activity in the reward circuit, which, in turn, acts on the more primitive sections of the brain, such as the limbic structures. This process allows opioids a direct line to those areas of the brain most likely to control behavior in times of stress.¹

The other primary reason for opioids' influence on behavior goes back to the brain's misperception that opioids are important for survival. This particular influence is most clearly demonstrated by its effects on those who regularly use opioids.

Regular opioid use prompts the brain to modulate its sensitivity to this recurring stimulation, for example, by allowing mu receptors to gradually become less responsive to opioid molecules—one of the first signs that an individual is developing an opioid tolerance.⁴

As this tolerance continues to take hold, repeated exposure to escalating dosages of opioids further alters the brain so that it functions more or less normally when drugs are present and abnormally when they are not.⁴ In essence, an individual cannot be deprived of opioids for any extended length of time without it causing uncomfortable symptoms.

The brain, however, perceives the possibility of opioid withdrawal as a meaningful threat. For one thing, opioids are needed to ensure normal brain function. For another, opioid use has been equated to eating and other life-sustaining activities. Under these circumstances, the prospect of not having enough opioids to ward off withdrawal is no different from the prospect of not having enough food to ward off starvation.

The brain's response is to approach this threat just as it would any other. The cerebral cortex is subverted, along with the capacity for judgment and reasoning, and those areas of the brain involved with motivating and carrying out behaviors necessary for survival take over. In this way, the brain ensures that it has marshaled every resource available in order to obtain the opioids it "needs." As withdrawal symptoms emerge and worsen, the drive for opioids becomes increasingly intense, and the intensity of effort is tantamount to a basic instinct.^1,3

In a healthy brain, feedback from the prefrontal cortex helps overcome the drive to obtain pleasure when it entails actions that might be unsafe or unwise. However, this feedback is compromised in opioid-dependent individuals, in part because planning and judgment (prefrontal cortex) have both been subverted for the survival-oriented portions of the brain to focus all available resources on obtaining opioids.^1,4