Excess Endocannabinoid Signaling: The root cause of Sudden Infant Death Syndrome?

Discussions in the medical literature have been held suggesting possible "endocannabinoid defiency states" as the underlying etiology of certain mental disorders. Less has been discussed about possible "excess endocannabinoid signaling" disorders. Perhaps Sudden Infant Death Syndrome is due to Excess Endocannabinoid Signaling? Perhaps Sudden Infant Death Syndrome (because of the adverse effects of dopamine overactivity in the infant brainstem imbalancing and overpowering serotoninergic signaling and other compensatory neurotransmitter responses) should be renamed Sudden Infant Dopamine Syndrome with dopamine excess the causative "agent of death" in SIDS?

Sudden Infant Death Syndrome (S.I.D.S.) is a multifactorial syndrome: genetic predisposition, more common in low birth weight and premature infants who have had exposure to predisposing risk factors (substance abuse or tobacco use by mothers, high ambient room temperature) and intermittent or constant stressors (prone position during sleep, airway obstruction with or without regurgitation of stomach contents, recent pulmonary infections, placenta previa, and maternal anemia during pregnancy).

Many, if not all, of the risk factors (low birth weight with low leptin levels) and stressors (endocannabinoids appear to be "neuroprotective" in infants undergoing stressor events) are associated with increased endocannabinoid signaling. Endocannabinoid signaling is linked with serotonin and dopamine signaling. Chronic endocannabinoid signaling alone, or coupled with dopamine excess, may wear down any normal compensatory serotoninergic response or other compensatory neurotransmitter responses and eventually cause secondary "deficiency" of serotonin activity. It needs to be remembered that the chronic endocannabinoid signaling may have been occurring throughout gestation as well as the early months of postpartum infant life...a long timeline for chronic endocannabinoid signaling, with or without dopaminergic excess, to "wear down" the serotoninergic centers in the brainstem. Low levels of serotonin signaling activity in the brainstem, regardless of etiology, can not balance, fine tune, antagonize or counteract overpowering excess dopamine effects in the brainstem caused by excess endocannabinoid signaling. So, using the analogy of "which came first, the chicken or the egg?", the author suspects the chronic endocannibinoid signaling and dopamine excess due to a likely increased number of dopaminergic neurons came first (even in gestation) and along the way, the serotoninergic signaling system was altered, down regulated or overwhelmed. Any subsequent stressor causing a sudden increase in dopamine in the susceptible infant during the first year of life results in a SIDS death. Dopamine excess has been associated with SIDS and endocannabinoid signaling increases dopamine levels.

Male infants, premature and low birth weight infants have a greater likelihood of dying from SIDS as well as infants who are borne to parents who have abused or continue to abuse tobacco, marijuana, cocaine, methadone, and heroin after the infant's birth. These abused substances are associated with pronounced dopaminergic neuronal activity in developing, actively remodeling infant, adolescent and adult brain reward/pleasure, appetite, arousal, and respiratory centers and systems. The number of neurons in the developing fetal and infant brain and peripheral nervous system expressing dopamine likely increases due to repetitive exposure to abused substances and other environmental factors associated with SIDS. The increased number dopaminergic neurons may arise de novo or result from a change in the type of neurotransmitter secreted by pre-existing neurons. As long ago as 1984, Canadian researchers (D.G. Perrin, M.D. Hospital for Sick Children, Toronto) discovered dopamine excess was found in two infants' carotid bodies who died of SIDS.

Excess dopamine levels and activity probably are causative of the "final" cardiorespiratory event resulting in death in S.I.D.S. So, the question may arise: Is excess endocannabinoid signaling causing a dopaminergic adverse effect surge into the infant brainstem the root cause of Sudden Infant Death Syndrome? Schematically, the catastrophic equations may be:

1. Genetic factors + Predisposing risk factors = Chronic Increased Endocannabinoid Signaling

2. Chronic Increased Endocannabinoid Signaling + Acute Stressor = Acute Excess Endocannibinoid Signaling= S.I.D.S.

In the past, it has been difficult for healthcare providers to bring together, in a common sense manner, all the factors that are in play that result in Sudden Infant Death Syndrome. Perhaps a closer look at Excess Endocannabinoid Signaling will have clarify the root cause of Sudden Infant Death Syndrome.


© Copyright, 2010. Byron L Barksdale, M.D. All rights reserved.