Ammonia, Methamphetamine, Cigarette Smoke and Parkinson's Disease

A number of noxious fumes and toxins are produced in the manufacturing process of the illegal drug methamphetamine and in recent months there have been a number of broadcasts on dangers associated with "meth lab homes". If you have missed these broadcasts it may interest you to know that 1 pound of meth produces 6 pounds of toxic chemicals. If you're not in the market for renting or buying a home, you might not be concerned by this now but these chemicals end up in the soil, air and water that surround the manufacturing site or are dumped along the roadside from mobile labs. Chemicals produced indoors from meth labs absorb into any porous material including carpets, clothing, blankets, food products, paint, flooring etc and get distributed onto all surfaces through air flow, ventilation and duct work and tracked into "clean" environments by contaminated shoes. Cars that house mobile labs are also a lifetime hazard because upholstery is porous and absorbs toxins.  

Most people are familiar with the fact that one of the most common chemicals associated with meth lab exposure is ammonia that can be toxic at certain amounts. Of course, the level of what determines the effects of toxicity is going to depend on the concentration, the route of exposure, the duration and metabolic characteristics of those exposed. Different people have different levels of detoxification that ultimately determines how serious the exposure to ammonia or to any chemical will be and there are a number of factors that influence this including genetics. One author explains ammonia toxicity can occur as a result of "alterations of ammonia metabolism including enzyme issues within the urea cycle, Reyes Syndrome and liver failure and the effects of these conditions may lead to brain edema and severe neurological impairment. Generally, it is now known that ammonia crosses the blood-brain barrier and interacts with a number of cellular processes including neurotransmission and brain metabolism." (Butterworth)

 For several years now, health experts have been aware that the illegal use of  methamphetamine may lead to long-lasting health consequences including dental disease and mental health problems in addition to those associated with addiction. Another consequence is an increased risk for Parkinson's disease for those who abuse methamphetamine, later in life. While there are a number of reasons for this, there are two that stand out in importance in addition to ammonia-inducing mitochondria dysfunction. The first is because of the vulnerability of certain neurons including those that regulate dopamine to the toxic effects of ammonia. There are also "lasting decrements in something called the dopamine transporter" and the elevation of oxidative stress by dopamine which damages tissues and causes neural injury. Luckily, under normal circumstances and at normal concentrations and when all things are working properly these kinds of toxic processes can be neutralized through the activities of antioxidants but meth labs are not considered normal circumstances and produce ammonia levels at much higher levels than normal.  

Unfortunately and as noted above, a number of physiological conditions influence how toxins are detoxified and levels of antioxidants may be reduced as a consequence of genetic polymorphisms, injury or the natural processes associated with aging. As far as antioxidant production in PD, the antioxidant system Nrf2 has been found to modulate the severity of toxicity associated with drugs and other toxic exposures. In experimental models, the loss of the expression of Nrf2  results in a greater loss of the dopamine transporter and much greater oxidative stress and greater neural damage.  While this process is more complex than what is explained here, the main point is expression of the Nrf2 is necessary to reduce the kinds of toxicity implicated in PD. (McCann) Nrf2 also regulates the production of certain cofactors necessary that are used in mitochondrial biogenesis which further influences neurological health. Oxidative stress at optimal levels is important for activation of different protective mechanisms including Nrf2 but too much is just too much to continue homeostasis (Widmer) and these conditions significantly complicate methods for treatment. Alterations in functions of antioxidant systems influence a number of diseases and specifically, dysfunction of the Nrf2 system has been implicated in several including cancer, respiratory diseases like COPD and autoimmune diseases.

  

Notes:

• Interestingly, it has been suggested that cigarette manufacturers add ammonia to cigarettes to make it more addictive because it enhances the effects of nicotine. This is achieved by "the addition of ammonia in the manufacturing process which helps convert bound nicotine molecules in tobacco smoke into free nicotine molecules and commonly known as "freebasing." This process is similar to that of freebasing cocaine, the end result is an enhanced effect of the drug on the user. This becomes a real problem upon cigaratte exposure for those who may have inborn errors for ammonia detoxificaton or genetic alteractions in other protective pathways such as Nrf2. (Martin)
• It takes a number of months before a baby's detoxification system is developed and so exposures to toxins in the womb and after birth can take a tremendous toll on the "little ones".
• Alterations in metabolic pathways that influence the excretion of ammonia are negatively influenced by heavy metals. One can be exposed to them from exposure to methamphatamine or meth precursors.
• Elevated levels of ammonia have been implicated in health conditions such as autism and may contribute to different types of brain injury.
• Because physical activity improves neural function and toxic exposure may negatively influence olfaction which also dictates behavior --- there is potential for increase atrophy and damage. Olfactory deficits present themselves often years before PD motor deficits appear.  
• Sleep deprivation from drug abuse has potential to speed mitochodrial dysfunction and shut off the antioxidant system. (Kresiun) Hyperammonemia alters expression of orexins which have a responsibility in control of sleep wake cycles and as a result may alter circadian rhythm and hormone function. (Ahabach) Specific dopamine signals regulate orexins and studies show the loss of orexin neurons is correlated to disease severity of PD. (Bubser, Thannickal)

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428: "McCann, U. D., Wong, D. F., Yokoi, F., Villemagne, V., Dannals, R. F., and Ricaurte, G. A. (1998). Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: Evidence from positron emission tomography studies with [11c]win-35,428. J. Neurosci., 18(20):8417-8422." http://www.citeulike.org/user/HEIRS/article/6639032
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