Have you ever wondered why some people always seem to be in pain? Or why someone can receive a prescription for a minor procedure and immediately feel drawn to drug use?

Scientists may have recently figured out one of the reasons for these behaviors, and they may start early in life. The developing neuron is remarkably similar to a tree. The branches are the dendrites that receive electrochemical signals from the axons of other neurons, the trunk is the cell body where summation takes place, and the roots are like the axons, extending out to influence other neurons or activate muscles and glands. Just like a tree, small changes in a sapling’s environment can cause dramatic changes in the final structure.

Have you ever seen a tree that looks like the letter “S”? It turns out that if a young tree is bent without breaking and restrained from straightening out for a critical period, perhaps by a dead tree falling against it or persistent wind, it can permanently adopt a new and unique shape. Native Americans knew this and would purposefully craft these unique trees to mark travel routes.

Similar to these trees, nutritional deficits and toxic exposures can cause permanent changes in brain development. While this has been well-documented in vitamin deficiencies, especially Vitamin D, and other nutrients like Iodine (linked to a loss of 12 IQ points on average), we must also be concerned about toxins. Lead exposure during the leaded gasoline phase in America lowered half the country’s IQ by an average of 2.6 points, according to some studies. Lead is a well-known neurotoxin, and so is alcohol.

Fetal alcohol syndrome, also known as fetal alcohol spectrum disorder, occurs when a pregnant woman drinks while pregnant, exposing the developing fetus. This results in small head size, short height, low body weight, behavioral problems, and sometimes vision and hearing issues. These children are much more likely to experience difficulties in school and with the legal system than the average population. We have known for decades that the developing brain is sensitive to alcohol, and most societies limit exposure to those over a certain age—twenty-one in the United States (except for the Virgin Islands and Puerto Rico, where it’s 18), nineteen in most Canadian provinces, and eighteen in all Mexican states. The legal drinking age is approximately eighteen in most other countries.

Despite these age restrictions, many of us in America are exposed to alcohol at a much younger age. It is not unusual for a patient to tell me they had their first drink at age twelve or thirteen. What effect does this early exposure have on brain development and the future risk of substance abuse and addiction?

As physicians, we know that the human brain does not finish the myelination process until the late teens for girls and early twenties for boys, although many studies show that the process does not peak until ages 30 to 50. The frontal lobes are the last to myelinate and, as fate would have it, are the most important for decision-making and impulse control.

Studies have also shown that ethanol leads to the activation of innate immune receptors, such as toll-like receptor four signaling in glial cells. It also triggers cytokines and inflammatory mediators, which damage myelin structure. These changes would almost certainly impair reasoning and impulse control.

What we did not know, or at least I didn’t, was that alcohol consumption in adolescence can disrupt neural development and may influence pain perception through ethanol-mediated changes in the nucleus accumbens. The nucleus accumbens is a key component of the ventral striatum, which is the part of the brain crucial for motivational targeting and reward acquisition. This is the area of the brain triggered by dopamine-mediated endorphin release and is critical for both motivational behavior and addiction through stimulus learning and action selection associated with rewards.

By monitoring changes in the accumbal dopamine kinetics during protracted withdrawal from ethanol in adolescent mice, the study found greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared with controls. They also found mechanical allodynia, an increased sensitivity to pain, in both male and female mice who had received adolescent chronic intermittent ethanol exposure. This study shows that adolescent brain exposure to alcohol increases dopamine release in the nucleus accumbens, making the person more responsive to the reward signal of opiates and other dopamine-mediated drugs of abuse, and possibly high-risk behaviors. The exposure also creates hypersensitivity to pain, hyperalgesia, and allodynia, where usually non-painful stimuli cause pain. This could result in an adult who feels much more pain after an injury than others and even feels pain when there is no actual injury, possibly causing them to seek pain relief more often or ardently than the general population. These patients would also have a much stronger response to the reward activation aspects of opiate medications or illicit drugs, putting them at a higher risk of substance abuse and addiction. Some of these changes may be epigenetic and could possibly be amenable to future therapies to alter gene expression. It might also be possible to test for this condition in patients to avoid or reduce exposure to dopamine agonists like opioids. But more importantly, working very hard to reduce adolescent exposure to alcohol could decrease the prevalence of this predisposition and reduce the patient’s lifetime risk.

L. Joseph Parker is a distinguished professional with a diverse and accomplished career spanning the fields of science, military service, and medical practice. He currently serves as the chief science officer and operations officer, Advanced Research Concepts LLC, a pioneering company dedicated to propelling humanity into the realms of space exploration. At Advanced Research Concepts LLC, Dr. Parker leads a team of experts committed to developing innovative solutions for the complex challenges of space travel, including space transportation, energy storage, radiation shielding, artificial gravity, and space-related medical issues. 

He can be reached on LinkedIn and YouTube.