Physiology and Pharmacology of Psychoactive Substances

For thousands of years psychoactive substances were utilized for both intoxication and medical purposes. Research shows that ancient civilizations were located where various substances were indigenous to the land. In many cultures it was customary to use these psychoactive substances on various occasions such as for the reduction of anxiety before battle, in rituals and ceremonies, and also to relieve social phobia at a party. Some of the earlier identified civilizations like the Mayans, Incans, and Aztec hieroglyphs have depicted substance use for ritualistic reasons (Francis, Mack, & Miller, 2005).

With respect to the pharmacology of substance use, it is believed that various factors affect choice of psychoactive substance use among varying populations. Historical and cultural factors may theoretically affect the pharmacokinetics and pharmacodynamics of psychoactive substance, just as the pharmacology of these substances may affect their historical and traditional use. A case and point is the flushing reaction observed among a greater-than-expected- number of Asians and Native Americans (Francis, Mack, & Miller, 2005). This particular flushing reaction has been offered as a reason for two opposite phenomena:

1. The low rates of alcoholism among Asian peoples, who presumably find the reaction aversive and hence drink little-although rates are increasing across much of Asia. 2. The high rates of alcoholism among certain Native America groups, who presumably must “drink though” their flushing reaction to experience other alcohol effect (Francis et al, 2005). Arguably so, it was historically believed that there had been some biological causation that depicted the varying effects of psychoactive substances among different ethnic groups. 2 Physiology and Pharmacology of Psychoactive Substances.

However, when it comes to an individual’s experience with psychoactive substances use, dual roles are more than likely played by both, the pharmacodynamic factors related to culture and the pharmacokinetic factors related to biology along with environmental influences. Becoming Addicted Many populations in early history recognized ongoing use of psychoactive substances as problematic.

For others, continual use was not thought to be as troublesome as members appeared to be ‘supernatural’ in their intoxicated state enabling them to perform better in various circumstances unlike others. Today, research on the neurobiology of addiction has made many large leaps, especially in the past 15 years. An important question to be asked is why some people make the transition from recreational use to compulsive use whereas others do not?

When we examine a potential substance user’s emotional/affective state at the onset of use many postulations can be made, especially when the affect is negative. In such circumstances the negative emotional state is relieved through continued use of the substance producing a feeling of euphoria and pleasure.

The euphoria and dysphoria processes occur simultaneously and measured on a hedonic scale, and they both make up the components of the opponent-process theory. As the hedonic set point is raised, the same amount of drug results in weaker hedonic effects and stronger negative after-effects when the drug is withdrawn. The transition from the initial hedonic state to an increasing negative hedonic state draws the individual into a spiral of homeostatic dysregulation of brain reward pathways, resulting in the development of addiction and vulnerability to relapse (Cha & Nestler, 2005).

The user becomes accustomed to utilizing the psychoactive substance as 3 Physiology and Pharmacology of Psychoactive Substances a means to cope with the negative feelings, spiking the ‘dependency’ on the drug for the alleviation of the negative and increasing the likelihood of chronic use. Public Concerns and Scientific Research Concerns regarding the use of substances have become a public health issue due to the social ills related to it. Some of these social ills include high crime rates, incarceration, psychiatric hospitalization, perpetual poverty, and mortality.

Such issues have prompted leading researchers and scientist to further their knowledge of the biological processes of addiction and search for alternative methods of treating addiction. Great discoveries have been made and continue to be to this day. Brain pathways in the brains reward system demonstrate to the non- scientist how psychoactive substances alter an individual’s behavior producing undesired actions. For instance, cannabis sativa preparations have been used by humans for the last 5000 years.

But being one of the oldest recreational drugs with abuse potential, its neurobiological mechanisms remained obscure until the isolation and identification in 1964 of tetrahydrocannabinol (THC), its main psychoactive constituent. Regarding addiction, many different approaches identified how natural cannabinoids modulated reward systems and induced tolerance.

But only with the identification of the cannabinoid CB1 receptor did we come to understand why cannabinoids did so and how the endocannabinoid system participated in cannabis addiction (DeFonseca & Schneider, 2008). Neurortransmitters and Behavioral Pharmacology The human brain is comprised of a complex network of proteins and receptors that are extremely active during the use of chemical substances.

Pleasure neurochemicals such as dopamine located in the nucleus accumbens induce the good feelings when someone is getting high. The 4 Physiology and Pharmacology of Psychoactive Substances interesting phenomenon is that acute use excites the release of dopamine within the nucleus accumbens. It could be hypothesized that the drug-dependent individual may be “self- medicating” to compensate for the underactive dopaminergic system. Cocaine, methamphetamine, and alcohol all excite the release of dopamine within the nucleus accumbens.

Additionally, cocaine blocks the re-uptake of synaptic dopamine, thereby prolonging the high (Fortuna & Smelson, 2008). Since the identification of nicotine as the primary psychoactive component in tobacco smoke, a great amount of research has been undertaken to unravel the neuropharmacological, anatomical, and behavioral underpinnings of its psychoactive effects (Laviolette & van der Kooy, 2004).

Many people tend to look at tobacco in a euphemistic fashion suggesting that it is not as hard a substance as the others therefore not worthy of as much attention. However, when youanaly ze the activity in the brain pathways, you can begin to understand why it is the most addictive and deadly substance.

Nicotine acts on endogenous nAChRs that are found ubiquitously throughout the central (CNS) and peripheral nervous systems in almost all vertebrate and invertebrate species. We tend to think about drugs in terms of their ability to produce feelings of pleasure. Indeed, nicotine is known to induce feelings of pleasure and reward in humans and other species. But like many other addictive drugs, nicotine also potent, aversive, unpleasant effects.

Nicotine can produce powerful anxiogenic effects systemically and centrally through activation of nAChR that contains subunits (Laviolette et al, 2004). Withdrawal One of the most serious complications with withdrawal is early depression and the potential for suicide. There are numerous withdrawal complications based on the particular psychoactive substance being used.

Patients must be watched when manifesting depression and 5 Physiology and Pharmacology of Psychoactive Substances agitation. If symptoms of depression do not remit within 10 days to 2 weeks, despite relative normalization of sleep patterns, underlying major depression requiring psychiatric intervention is suggested.

In addition, repeated exposure to cocaine followed by withdrawal leads to an activation of the neuroendocrine stress response, which may increase susceptibility (Frances et al, 2005). Overdose and Medical Complications With intoxication, cocaine blocks monoamine neuronal reuptake, initially leading to increased dopamine serotonin norepinephrine availability at receptor sites. 6 Physiology and Pharmacology of Psychoactive Substances This stimulation of the endogenous pleasure center results in euphoria, increased energy and libido, decreased appetite, hyperalertness, and increased self-confidence when small initial doses of cocaine are taken.

Higher doses of cocaine are accompanied by increasing toxicity. Not only is there intensification of the “high”, but anxiety, agitation, irritability, confusion, paranoia, and hallucinations may also occur. More than any other stimulant, acute intoxication with cocaine is characterized by convulsions and cardiac arrhythmias. Death may be caused by peripheral autonomic toxicity and/or paralysis of the medullary cardiorespiratory centers (Frances et al, 2005).

Other difficulties associated with chronic cocaine use include weight loss, dehydration, nutritional deficiencies, and endocrine abnormalities. Treatment Options and Future Implications For the addicted individual, treatment options are plentiful.

The rate of effectiveness is measured on the ability to sustain long-term sobriety and periods of abstinence. Relapse prevention strives to teach the addict how to recognize high-risk situations and deal with these cognitive strategies that have been well rehearsed. Techniques such as cognitive behavioral therapy teach the chemical dependent how to retrain their thinking and recognize its connection with emotions and behaviors.

When treating these individual’s it is crucial that the counselor is able to discuss some of the basics of neuroscience as it relates to addiction. Discussing these topics is crucial when providing relapse prevention or cognitive behavioral therapy. The topic of neuroscience as it pertains to addiction has come a long way. There are implications that with greater understanding of the human brain, methods of combatting addiction can be developed in a more effective methodology. Traditional ways of addressing addiction may not only be the way to combat it in the near future.

With medications like subutex, methadone, and other opiate agonist we have already began to take treatment for 7 Physiology and Pharmacology of Psychoactive Substances addiction to an entirely different level. Neurobiology along with psychopharmacology remain sciences that are at the forefront of the development of treatment therapies for addiction that can potentially put the twelve step tradition in a historical state. 8 Physiology and Pharmacology of Psychoactive Substances References Chao, J. , & Nestler, E. J. (2004). Molecular neurobiology of drug addiction. Annual Review Of Medicine, 55113-132.

doi:10. 1146/annurev. med. 55. 091902. 103730 De Fonseca, F. , & Schneider, M. (2008). The endogenous cannabinoid system and drug addiction: 20 years after the discovery of the CB1 receptor. Addiction Biology, 13(2), 143-146. doi:10. 1111/j. 1369-1600. 2008. 00116. x Fortuna, J. L. , & Smelson, D. A. (2008). The phenomenon of drug craving. Journal Of Psychoactive Drugs, 40(3), 255-261. doi:10. 1080/02791072. 2008. 10400640 Kalivas, P. W. (2007). Neurobiology of cocaine addiction: Implications for new pharmacotherapy. The American Journal On Addictions, 16(2), 71-78. doi:10.

1080/10550490601184142 Kozlowski, L. T. , & Edwards, B. (2004). Breaking Up With Your Drug Can Be Hard to Do, But is it Mainly Because Compulsive Behavior Involves Specific Brain Regions?. Addiction, 99(12), doi:10. 1111/j. 1360-0443. 2004. 00896. Laviolette, S. R. , & van der Kooy, D. (2004). The neurobiology of nicotine addiction: Bridging the gap from molecules to behaviour. Nature Reviews Neuroscience, 5(1), 55-65. doi:10. 1038/nrn1298 Frances, J. R. , Mack, H. A, Miller, I. S. , &. (2005). Clinical textbook of addictive disorders. New York, NY: The Guilford Press. DOI: www. guilford. com.

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