Assignment 1 Psychology 486 / 686 Chapter 7: Drugs and Hormones



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Psychology 486 / 686
Chapter 7: Drugs and Hormones

Marijuana: Neurotoxin or Neuroprotective?

Considerable controversy surrounds the effects of marijuana. On one hand, studies have illustrated that marijuana harms the brain and nervous system. To learn about these effects, examine readings 1, 2. On the other hand, research has also concluded that marijuana may have valid medical applications. Examine readings 3,4 to learn about the beneficial effects of marijuana on the brain. Next, conduct your own Web search to learn more about the research and controversy. Finally, choose a side and write a two-page paper that discusses your personal viewpoint on the effects of marijuana on the brain. Make sure you include examples from the articles you read as well as information from 2 additional sources to support your opinion.


Reading 1: Website: http://www.theantidrug.com/drug_info/marijuana-hazards.asp

Marijuana: Health Hazards

Usually smoked as a cigarette or joint, or in a pipe or bong, marijuana has appeared in "blunts" in recent years. These are cigars that have been emptied of tobacco and re-filled with marijuana, sometimes in combination with another drug, such as crack. Some users also mix marijuana into foods or use it to brew tea. The main active chemical in marijuana is THC (delta-9-tetrahydrocannabinol). Short-term effects of marijuana use include problems with memory and learning; distorted perception; difficulty in thinking and problem-solving; loss of coordination; and increased heart rate, anxiety, and panic attacks.



Health Hazards

Effects of Marijuana on the Brain. Researchers have found that THC changes the way in which sensory information gets into and is acted on by the hippocampus. This is a component of the brain's limbic system that is crucial for learning, memory, and the integration of sensory experiences with emotions and motivations. Investigations have shown that THC suppresses neurons in the information-processing system of the hippocampus. In addition, researchers have discovered that learned behaviors, which depend on the hippocampus, also deteriorate. Take the virtual tour to learn more about the effects of marijuana on the brain.

Effects on the Lungs. Someone who smokes marijuana regularly may have many of the same respiratory problems that tobacco smokers have. These individuals may have daily cough and phlegm, symptoms of chronic bronchitis, and more frequent chest colds. Continuing to smoke marijuana can lead to abnormal functioning of lung tissue injured or destroyed by marijuana smoke. Regardless of the THC content, the amount of tar inhaled by marijuana smokers and the level of carbon monoxide absorbed are three to five times greater than among tobacco smokers. This may be due to marijuana users inhaling more deeply and holding the smoke in the lungs.

Effects of Heavy Marijuana Use on Learning and Social Behavior. A study of college students has shown that critical skills related to attention, memory, and learning are impaired among people who use marijuana heavily, even after discontinuing its use for at least 24 hours. Researchers compared 65 "heavy users," who had smoked marijuana a median of 29 of the past 30 days, and 64 "light users," who had smoked a median of 1 of the past 30 days. After a closely monitored 19- to 24-hour period of abstinence from marijuana and other illegal drugs and alcohol, the undergraduates were given several standard tests measuring aspects of attention, memory, and learning. Compared to the light users, heavy marijuana users made more errors and had more difficulty sustaining attention, shifting attention to meet the demands of changes in the environment, and in registering, processing, and using information. The findings suggest that the greater impairment among heavy users is likely due to an alteration of brain activity produced by marijuana. Longitudinal research on marijuana use among young people below college age indicates those who used have lower achievement than the non-users, more acceptance of deviant behavior, more delinquent behavior and aggression, greater rebelliousness, poorer relationships with parents, and more associations with delinquent and drug-using friends.

Information provided by the National Institute on Drug Abuse.

Reading 2: Website: http://www.webmd.com/mental-health/news/20050207/marijuanas-effects-linger-in-brain

Marijuana's Effects Linger in the Brain


Blood Flow to Brain Altered Weeks After Smoking Pot

By Jennifer Warner


WebMD Health News

Reviewed by Brunilda Nazario, MD

Feb. 7, 2005 - The effects of marijuana in the brain may linger long after the last joint goes out. A new study shows that blood flow to the brain in people who smoked marijuana remained altered up to a month after they last smoked pot.

Researchers say the findings may help explain the problems with memory and thinking found in previous studies of chronic marijuana users.


Marijuana's Effects on the Brain


In the study, which appears in the Feb. 8 issue of Neurology, researchers studied the blood flow in brain arteries of 54 marijuana users and 18 nonusers.The marijuana users volunteered to participate in an inpatient program and abstained from marijuana use for a month. Blood flow in the brain was analyzed at the beginning of the study and at the end of the month for the marijuana users. Researchers found blood flow was significantly higher in marijuana users than in nonusers, both at the beginning and at the end of the study. However, the marijuana users also had higher scores on the pulsatility index ( PI), which is a measure of resistance to blood flow.

Researchers say the level of resistance to blood flow among light and moderate marijuana users improved over the course of the abstinence month. But there was no improvement among heavy marijuana users. This resistance is thought to be caused by the narrowing of blood vessels that happens when the body's own ability to regulate the circulatory system becomes impaired. "The marijuana users had PI values that were somewhat higher than those of people with chronic high blood pressure and diabetes," says researcher Ronald Herning, PhD, of the National Institute on Drug Abuse in Baltimore, Md., in a news release. "However, their values were lower than those of people with dementia. This suggests that marijuana use leads to abnormalities in the small blood vessels in the brain, because similar PI values have been seen in other diseases that affect the small blood vessels." Light marijuana users smoked two to 15 joints per week, moderate users smoked 17 to 70 joints per week, and heavy users smoked 78 to 350 joints per week.



Reading 3: Website: http://www.sciencedaily.com/releases/2007/10/071014163644.htm

Science Daily

Cannabis Use, Effect And Potential Therapy For Alzheimer's, MS and Parkinson's


ScienceDaily (Oct. 15, 2007) — Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20--40% (EMCDDA 2006).

Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues. Intensive cannabis use is correlated with non-drug-specific mental problems, but the question of co-morbidity is intertwined with the questions of cause and effect (EMCDDA 2006). Prevention is of importance in adolescents, which is underlined by evidence that early-onset cannabis-users (pre- to mid-adolescence) have a significantly higher risk of developing drug problems, including dependence (Von Sydow et al., 2002; Chen et al., 2005).

The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems -- the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.

One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006).

Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.

Raphael Mechoulam will tell the discovery story of the endocannabinoid system. His research has not only helped us to advance our understanding of cannabis use and its effects, but has also made key contributions with regard to understanding "neuroprotection," and has opened the door for the development of new drugs.



Endocannabinoid system

In the 1960s the constituent of the cannabis plant was discovered -- named tetrahydrocannabinol, or THC -- which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug -- apparently cannabis users prefer the plant-based marijuana and hashish.

Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions.

In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components -- one from the brain, named anandamide (from the word ´ananda, meaning ´supreme joy´ in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).



Neuroprotection

The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli -- traumatic brain injury (TBI) for example -- enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI.

The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.

Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006).



Clinical importance

Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy.

Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.

Numerous additional endocannabinoids -- especially various fatty acid ethanolamides and glycerol esters -- are known today and regarded as members of a large ´endocannabinoid family´. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system.

The endocannabinoid system acts as a guardian against various attacks on the mammalian body.

Conclusion

The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:



  • The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.

  • The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles -- in particular in neuroprotection.

  • These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.

  • The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases.

References

Avraham Y, Israeli E, Gabbay E, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiology of Disease 2006;21:237-245

Chen CY, O´Brien MS, Anthony JC. Who becomes cannabis dependent soon after onset of use" Epidemiological evidence from the United States: 2000-2001. Drug and alcohol dependence 2005;79:11-22

Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-1949

[EMCDDA 2006] European Monitoring Centre for Drugs and Drug Addiction. The state of the drugs problem in Europe. Annual Report 2006 (http://www.emcdda.europa.eu)

Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Amer Chem Soc 1964;86:1646-1647

Journal Interview 85: Conversation with Raphael Mechoulam. Addiction 2007;102:887-893

Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50:83-90

Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury. Trends Mol Med 2002;8:58-61

Pachter P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462

Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001;413:527-531

Panikashvili D, Shein NA, Mechoulam R, et al. The endocannabinoid 2-AG protects the blood brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol Disease 2006;22:257-264

Von Sydow K, Lieb R, Pfister H, et al. What predicts incident use of cannabis and progression to abuse and dependence" A 4-year prospective examination of risk factors in a community sample of adolescents and young adults. Drug and alcohol dependence 2002;68:49-64



Adapted from materials provided by European College of Neuropsychopharmacology, via EurekAlert!, a service of AAAS.

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European College of Neuropsychopharmacology (2007, October 15). Cannabis Use, Effect And Potential Therapy For Alzheimer's, MS and Parkinson's. ScienceDaily. Retrieved August 20, 2009, from http://www.sciencedaily.com­ /releases/2007/10/071014163644.htm



Reading 4:

Website: http://norml.org/index.cfm?Group_ID=4345



Marijuana Is Neuroprotective, Journal Says

September 6, 2001 - Utrecht, Netherlands

Compounds in marijuana dramatically protect brain cells during acute head trauma, according to research findings published in this week's Journal of Neuroscience. Researchers reported that THC injected intracerebrally in rats significantly "reduce[d] neuronal injury ... compared with control animals."


Scientists concluded, "These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration."
NORML Foundation Executive Director Allen St. Pierre said that the findings should dispel myths that marijuana is toxic to the brain. "This research indicates that just the opposite is true" he said.
Former NORML Foundation Chairman Dr. Lester Grinspoon, author of Marijuana: The Forbidden Medicine, said the study confirms earlier research performed in Israel and the US showing cannabinoids to be potent anti-oxidants. He added that smoked marijuana likely also possesses the same neuroprotective properties.
In their 1999 report Marijuana as Medicine: Assessing the Science Base, authors at the Institute of Medicine noted, "One of the most prominent new applications for cannabinoids is for 'neuroprotection,' the rescue of neurons from cell death associated with trauma ... and neurological diseases."

For more information, please contact Paul Armentano or Allen St. Pierre of The NORML Foundation at (202) 483-8751.    updated: Jan 09, 2006


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