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Adverse Effects of Substance Abuse on Aging: Implication of Brain Cell Injury
Kevin K.W. Wang, Ph.D., Firas Kobeissy, Ph.D. and Mark S. Gold, M.D.


The terms "drug abuse" or "substance abuse" is defined as the use of chemical substances leading to an increased risk of problems and an inability to control substance use. Substance use disorders are chronic relapsing conditions that are prevalent throughout the world. The widespread incidence of substance abuse or club drugs among teenagers has been shown to contribute to memory decline and cellular injury in the brain as shown in animal and human studies. This worldwide spread of substance abuse has had its impact, affecting the whole of Asia, especially China. Drug abuse has spread quickly since reemerging as a national problem in China in the late 1980s. As discussed by Fang et al, the number of registered drug abusers increased from 70,000 in 1990 to more than one million by the end of 2004. Among these widely-abused substances: methamphetamine (METH), ketamine, nicotine, 3,4-methylenedioxymethamphetamine (MDMA), and ethanol have been implicated in damaging brain cells by altering cell growth and affecting normal functional aspects of these cells in the developing brain.

Impacts of Drug Abuse on Brain Cells

Club drugs set off a chain of events that injure brain cells. Animal studies as well as human studies have indicated that brain cellular injury is akin to those observed in traumatic brain injury where similar deleterious pathways are activated that ultimately lead to the death of brain cells (neurons). Methamphetamine, (also known as ice, crank, speed, and crystal meth), for example, which is among the most widely abused, illegal form of amphetamines, is estimated to be abused by 25 million people worldwide. METH is the most widely spread illicit drug since it is easy to prepare and cheap to obtain. METH can be smoked, inhaled, or injected leading to a variety of social behaviors with a feeling of euphoria and increased self-esteem. Of interest, METH abuse is associated with a number of negative consequences, which include cognitive dysfunctions and has been linked to numerous adverse neuropsychological effects involving impairment of execution of memory, motor skills, and declined cognitive functions (Gold et al., 2007; Gold et al., 2009; Kobeissy et al., 2008; Warren et al., 2006). On the molecular levels, our research group as well as others have shown that METH is able to cross the brain and activate cellular enzymes (caspases and calpains) similar to what we see in brain injury! In humans, imaging studies of patients who use METH chronically show abnormalities with significant hippocampal brain region volume reduction (7.8% decrease) compared to the control subjects which is correlated to memory deficits.

Similarly, nicotine and ethanol use and abuse have direct implications on damaging brain cells which affects the developing brain and causing apoptotic death as indicated in perinatal brain development of rodents. Many of these mechanisms that affect fetal brains can trigger similar deleterious effects on adolescent brain altering integral cellular functions including: cell differentiation, synaptic maturation and cell signaling. Accumulated evidence has indicated the co-use of tobacco and alcohol, showing that smokers consume twice as much alcohol as nonsmokers. There is a strong correlation between onset of an early age tobacco consumption and alcohol addiction. In an interesting study by Oliveira-da-Silva et al, the co-administration of nicotine and ethanol in mouse models have shown that there was reduction in neuronal and glial cells densities in the hippocampal brain region.

Drug Abuse and Dementia

Recently, these studies have triggered scientists to investigate whether substance abuse contribute to further risk of developing early onset of dementia. Current studies estimating the levels of drug abuse-related cognitive impairment as well as drug abuse-induced neuronal cell injury that might be classified as dementia is currently under- investigation (Hulse et al., 2005). Accumulating evidence from drug abuse animal models and human studies have proposed that such pattern of cellular injury occurring in the brain must contribute to the cognitive impairment observed, thus predisposing our brain to early dementia (Hulse et al., 2005). For example, several studies have reported that a large majority of 75% of detoxified alcoholics exhibit some kind of cognitive or memory disturbance coupled with impulsivity, learning, memory and verbal fluency deficits (Oscar-Berman and Marinkovic, 2007; Stavro et al., 2013; Vetreno et al., 2011). In one Neuroimaging study, the association between white matter integrity and cognitive performance in normal aging, and various neuropathological conditions (alcoholism) was assessed. Trivedi et al compared alcoholics with controls and the degree of disconnection of white matter fibers using diffusion tensor imaging was performed on 10 abstinent chronic alcoholics and 10 demographically equivalent subjects. Abstinent chronic alcoholics showed white matter deficit in these white matter fibers that was correlated to the underlying dysfunction in memory in alcoholism (Trivedi et al., 2013).

Effects on Aging

From another perspective, researchers are beginning to discover and understand the excessive use of substance abuse among people age 60 and older (Snyder and Platt, 2013). This throws focus on the intersection of drug abuse, aging, and neuropsychological alterations impacting neurochemical balance in the drug induced- aging brain and trace the relationship between substance abuse and aging. Health care providers tend to overlook substance abuse and their adverse consequences among older populations. As discussed elegantly by Dr. Norah Volkow (Volkow, 2011), it has been shown that the percentage of Americans in the 50- to 59-year age group reporting abused illicit or prescription drugs during the year 2011, increased from 2.7 percent to 6.2 percent, between 2002 and 2009 which indicates that the abuse of illicit drugs by older adults is on the rise (Samhsa, 2009). Complications that occur in old age with increasing drug use frequency, such as medical comorbidities, cognitive impairment, and neuropsychological behavior, contribute to the potential adverse interactions between substance misuse and an aging brain. Elderly pateints suffering from substance abuse often present to the emergency department with severe illness; several consequences of substance abuse include cardiovascular, GI, immune system impairment and endocrine problems (Weathermon and Crabb, 1999).

Taken together, though quite subtle at the beginning and mildly observed, substance abuse drugs increase the likelihood of neurotoxic events inflicted on the brain. Brain science tells us that neuronal cells when lost at early stages, may not have drastic effects on a young individual; however, age-related memory decline and deficits may occur at a faster rate, manifest at earlier stages and be more severe in those with pre-existing conditions related to drug abuse. Consequently, patients may develop cognitive and behavioral alteration years later when they are under stress or as part of regular aging due to lost cellular reserves. It is alarming to see the increasing patterns and frequency of club drug use by college students and even high school students whose brains are still developing and are prone to insult related injury. This bodes poorly for consequences that such abuse would have on future generations!

Photo credit: David Robert Bliwas/Flickr/CC

About the Authors

Dr. Wang obtained his Ph.D. in Pharmaceutical Sciences with Distinction from the University of British Columbia in Vancouver in 1989. He is internationally recognized for his original contributions to the fields of CNS disorders-linked proteolytic enzymes, neuroproteomics and disease biomarker discovery. He joined Parke-Davis Pharmaceutical Research (Ann Arbor, MI) in 1991, and following the company's merger with Pfizer Inc. (2000), he became Group Leader of CNS Therapeutics/CNS new targets team. In 2002, he became Associate Professor of Psychiatry at the University of Florida (Gainesville, FL), Associate Director of the Center for Traumatic Brain Injury Studies and Director of the Center of Neuroproteomics and Biomarkers Research. In 2002, he co-founded Banyan Biomarkers Inc. (Alachua, Florida) and transitioned as full-time Chief Scientific Officer and the Center Director of the Center of Innovative Research. In 2011, he rejoined the University of Florida McKnight Brain Institute as Executive Director of the Center of Neuroproteomics and Biomarkers Research (https://mbi-cnbr.sites.medinfo.ufl.edu/) / Chief - Translational Research & Associate Professor of Psychiatry and Neuroscience to rededicate himself to basic and translational research. He is also Chair Professor of the Taipei Medical University. Dr. Wang published more than 200 peer-reviewed papers, reviews and book chapters and co-authored eight US patents. He also serves on five international journal's Editorial Board. Dr. Wang was Past President and is current Council member of the National Neurotrauma Society (USA).

Dr. Firas Hosni Kobeissy, is a Research Assistant Professor at the University of Florida; Department of Psychiatry, University of Florida, Gainesville, FL, USA. He obtained his Ph.D from the University of Florida in the area of Neuroscience. His current research overlaps the fields of neuroscience and psychiatry with focus on drug abuse and traumatic brain injury neuroproteomics. Dr. Kobeissy has authored more than 45 peer-reviewed scientific papers. He holds five patents in the areas of drug abuse, and TBI biomarkers. He serves as an editorial member on several journals related to proteomics. He is also an actively participating member at the Center of Neuroproteomics and Biomarker Research .

Professor Mark S Gold, M.D is the Donald Dizney Eminent Scholar, Distinguished Professor and Chair of Psychiatry at the Departments of Psychiatry, Neuroscience, Anesthesiology, and Community Health & Family Medicine, University of Florida, Gainesville,. He is also vice chair for Education and thief, Division of Addiction Medicine. Dr. Gold has worked for 30 years to develop models for understanding the effects of tobacco and other drugs on the brain and behavior, and he has developed new treatments for addicts. Dr. Gold maybe best known for writing over 900 medical articles, chapters, and abstracts in journals for health professionals on a wide variety of psychiatric research subjects and authoring 12 professional books including practice guidelines, ASAM core competencies, and medical text books for primary care professionals. He is the author of 15 general audience books.

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