The World's Most Addictive Drug (Essay Sample)

The World’s Most Addictive Drug
Name:
Institution:
The World’s Most Addictive Drug
Drug addiction is a serious medical and social issue in the United States and around the world. Every year, a significant number of people worldwide die from the consequences of smoking, and these deaths, principally from lung cancer, are avoidable. However, there is a formidable obstacle to the prevention of these deaths. Tobacco contains a drug, nicotine, which creates a dependence that is more severe than that generated by cocaine or heroin. An overview of nicotinic receptors, data on genetic considerations and epidemiological studies reveal that nicotine is the most addictive drug in the world
The reward-enhancing actions of nicotine are hypothesized to play a key role in the establishment and maintenance of the tobacco habit in human smokers. The reward-related actions of nicotine are thought to be related to the stimulatory effects of the drug on neuronal nicotinic acetylcholine receptors of the brain (nAChRs) containing α4 and β2 subunits, particularly those located in the Ventral Tegmental Area (VTA) (Fowler & Kenny, 2013). Indeed, nicotine-induced activation of α4β2* nAChRs in the VTA increases forebrain dopamine transmission, most prominently in the shell region of the Nucleus Accumbens (NAc), and this has been shown to contribute to the reinforcing properties of the drug in laboratory animals. Because of their central role in nicotine reinforcement, α4β2* nAChRs are considered important targets for the development of smoking cessation agents (Fowler & Kenny, 2013). α4β2* nAChRs easily enhances addiction than all other chemical agents found in other drugs, making nicotine to be the most addictive drug in the world.
Emerging data from Genome-Wide Association Studies (GWAS) are identifying polymorphisms that increase vulnerability to tobacco dependence in humans, and also support the notion that sensitivity to nicotine aversion may be influenced by genetics (Changeux, 2009). A prominent gene in which allelic variation has been associated with risk of developing tobacco dependence is CYP2A6. This gene encodes a cytochrome P450 enzyme responsible for about 80% of nicotine metabolism in the human liver (Changeux, 2009). The CYP2A6 gene is highly polymorphic, with over 60 allelic variants known. Of these, 17 alleles have been shown to exhibit reduced function, whereas two of the variants result in increased nicotine metabolism. Allelic variation that results in slower nicotine metabolism would be expected to allow for more prolonged actions of nicotine. Individuals with a slow metabolizer CYP2A6 genotype are less vulnerable to develop tobacco dependence than those with normal metabolism, potentially due to a greater sensitivity to aversive effects of nicotine at doses that do not trigger aversion in those who metabolize nicotine normally.
Long-term adaptation occurs in the expression and function of the subunits of the nicotinic receptor, and a functional reorganization of the brain circuits ensures the homeostasis of cognitive functions in the presence of nicotine (Picciotto & Mineur, 2013). However, the chronic presence of the drug becomes indispensable. Several subunits of the nicotinic receptor are involved in the establishment of this dependence. Others are involved in the appearance of withdrawal symptoms when people quit smoking. Remarkably, three independent epidemiological studies this year have highlighted the importance of three genes encoding subunits of the nicotinic recepto...