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The Effects of Cannabis Use: And Overview

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jrieders's picture

Introduction:

According to the International Narcotics Control Board’s Annual Report 2007, cannabis is the most commonly used illicit drug. In the US cannabis is most frequently used by people ages 18-25, with 47% in the past year reporting use and 20% of 20* year olds in the past month reporting use (*peak age for use). Marijuana use typically declines after the age of 34; in contrast, medical marijuana use typically begins after the age of 35. According to the Office of National Drug Control Policy Americans spent $10.5 billion on marijuana in 2000, about the same as heroin and less than 1/3 as much as cocaine. Marijuana use begins at an average age of 17.4 years with 2 million new users in 2006.  Common effects of low doses of cannabis include sedation, reduced coordination, altered sense of space and time, hunger, thirst, and impaired short term memory . High doses are associated increased psychoative effects such as hallucinations and paranoia. The primary psychoactive component in cannabis is delta-9 tetrahydrocannabinol (THC), but 60 other active cannabiniod forms found in cannabis are known with various observed affects.  

Abuse and Dependence:
Based on the DSM-IV there are more than 4 million Americans ages 12 and up that are dependent on or abuse marijuana. Abuse is defined as:

A pattern of substance use leading to significant impairment in functioning. One of the following must be present within a 12 month period: (1) recurrent use resulting in a failure to fulfill major obligations at work, school, or home; (2) recurrent use in situations which are physically hazardous (e.g., driving while intoxicated); (3) legal problems resulting from recurrent use; or (4) continued use despite significant social or interpersonal problems caused by the substance use. The symptoms do not meet the criteria for substance dependence as abuse is a part of this disorder.


It is interesting to note that all four of the symptoms of substance abuse as they relate to marijuana could be fulfilled in result of its illegality. For example, (1)  a cannabis user would not pass a drug test administered in their school or workplace, (2) cannabis use has not been directly related to hazardous driving, but because the relationship is unknown it is considered hazardous, and finally examples for (3) and (4) are relatively straightforward.  This is not to say that cannabis use does not lead to dependence, but rather that measures for abuse and dependence should be more rigorous.  Understanding of tolerance and withdrawal provide more standard measures for cannabis abuse and dependence. Cannabis has many effects (and effecters), and tolerance to these effects has been demonstrated to develop at different rates. Typically, tolerance to the majority of these effects develops after only a few doses, but also disappears in after a short period of abstinence. In one study conducted by the Institute of Medicine two groups of regular marijuana smokers were administered roughly the same doses of THC in the form of marijuana cigarettes and in the form of oral THC pills. After four days both groups developed tolerance to feelings of euphoria, while no tolerance to the stimulatory affects on appetite developed. Tolerance to performance impairment also develops despite the increase in blood plasma THC levels.  The oral pill’s affect took longer to peak and also lasted longer. Withdrawal has been noted in some cases but is considered mild compared to withdrawal experienced after cessation of alcohol or nicotine and lasts only about 2-4 days. Symptoms include restlessness, irritability, insomnia and nausea. These studies involved administering oral THC pills to adult patients for 10-20 days in doses roughly equivalent to smoking 9-10 2% THC joints per day, an amount far exceeding a user’s average daily consumption. Another factor that influences dependency is the length of time it takes for the drug’s effects to set in, the faster the effects set in the more likely the drug will be abused. Drugs that are injected or inhaled through the lungs enter the blood stream immediately and travel to the brain more quickly than drugs that are ingested, and therefore their effects are felt within minutes. Ingested drugs must be broken down through digestion and then enter the blood stream, so their effects typically take at least a half hour before setting in.   Other factors such as genetics and environment, are not considered specific to cannabis abuse, but rather predispose abuse to whatever is most readily available. The different rates of tolerance to different effects, the severity and length of withdrawal, and the abusability of THC in pill form versus inhalation are all important factors when considering its use for medical purposes.
Physiological Effects of Cannabis:
Recent studies have found that cannabiniods induce a variety of curative and palliative effects for nervous system disorders such as Alzheimer’s, Gliomas, Tourette’s syndrome, Amyotrophic lateral sclerosis (ALS), Fibromyalgia, and Multiple Sclerosis.   Cannabis consumption results in the binding of cannabaniods to cannabiniod receptors in the brain, which are most highly concentrated in the cerebellum, basal ganglia, and hippocampus. Cannabiniods also trigger the brain to release dopamine, which is why users feel “high”. The question arises, why do such receptors exist in the brain? Studies aimed at determining the effects of cannabis use have to lead to the discovery of the endocannabiniod system. Thus far two cannabinoid receptors, CB1 receptors (found in brain cells, immune cells, and other peripheral cells) and CB2 receptors (found primarily in immune cells), and endogenous cannabiniods, such as anandamide (AEA) and 2-aracidonylglycerol (2-AG) have been identified.  Extensive studies had previously documented the affects of cannabiniods on the immune system, but since the discovery of the endocannabiniod system the conclusions are being re-thought, for the purposes of this paper I will concentrate on the physiology as it relates to the CNS. CB1 and CB2 receptors are G-protein-coupled receptors and when activated result in complex cellular and genetic modulation, including activation and de-activation of adenylyl cyclase, calcium and potassium currents, and activation of transcription factors. Stimulation of CB1 receptors also results in the inhibition of the neurotransmitter GABA.  GABA is the main inhibitory neurotransmitter in the adult mammalian brain and is also associated with muscle tone in humans (malfunctioning in GABA signaling is associated with movement disorders as well as anxiety, schizophrenia, and addiction). This inhibition of GABA may be the reason cannabis consumption affects memory and movement and is therapeutic in cases such as Fibromyalgia. While smoking marijuana is correlated to an increased risk in head and neck cancer, various studies have found stimulation of CB1 receptors with AEA and non-endogenous cannabiniods to have anticarcinogenic properties. Treatment with cannabiniods, specifically THC, induced cell death in cultured human glioma cells (cancer cell arising from glial cells) and in establish gliomas in rats. Cannabiniods also appear to inhibit glioma cell proliferation, as well as suppress other mechanisms that allow for unchecked cell growth. On the other hand CB2 receptors, which are not found in nervous tissue, have been linked to pathways that enhance cancer cell growth.  Clearly the affects of cannabiniods, both from smoking marijuana and by other forms of administration, are complex and work on multiple physiological systems. Understanding of the endocannabiniod system is growing in leaps and bounds, and one hopes that research will soon provide clear understanding of how to exploit the positive medical effects of cannabis.
Extension:
To continue with this research, I would like to expand on the tumor suppressing and enhancing effects of cannabiniods. I will also delve into the marijuana use as it applies to depression, anxiety, and temporary psychosis and the problems with the increasing potency of marijuana.




Bibliography:

1) TANDA G., PONTIERI F.E., DI CHIARA G.. (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common l opioid receptor mechanism. Science 276: 2048–2050.
2) http://health.rutgers.edu/brochures/marijuana.htm 09/19/2006
3) Carter, Weydt, “Cannabis: Old medicine with new promise for neurological disorders.” Department of Rehabilitation and Department of Neurology, University of Washington School of Medicine, Seattle, WA 2002.
related link: http://www.cannabismd.net/endocannabinoids/

4) http://www.cannabis.net/reefer.html

5) 2008 Marijuana Sourcebook
MARIJUANA: THE GREATEST CAUSE OF ILLEGAL DRUG ABUSE. Office of National Drug Control Policy Executive Office of the President Washington, DC 20503 July 2008
http://www.whitehousedrugpolicy.gov/news/press08/Marijuana_2008.pdf

6)Gray. Tolerability and effects of oral Delta super(9)-tetrahydrocannabinol in older adolescents with marijuana use disorders. Pharmacology, biochemistry and behavior [0091-3057] yr:2008 vol:91 iss:1 pg:67 -70

7) http://allpsych.com/disorders/substance/substanceabuse.html

8) Janet E. Joy, Stanley J. Watson, Jr., and
John A. Benson, Jr., Editors. MARIJUANA AND MEDICINE:  Assessing the Science Base. Division of Neuroscience and Behavioral Health
INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C: 1999.  http://www.nap.edu/openbook.php?record_id=6376&page=R1

9)Emerging Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2008 http://www.norml.org//index.cfm?Group_ID=7002

10)Thomas W. Klein1, Cathy Newton, Kellie Larsen, Lily Lu, Izabella Perkins, Liang Nong and Herman Friedman. The cannabinoid system and immune modulation. University of South Florida, Department of Medical Microbiology & Immunology, Tampa.  Published Online: July 1, 2003.  http://www.jleukbio.org/cgi/content/full/74/4/486

Comments

Serendip Visitor's picture

possitive effects

I have glaucoma and MJ works for me! It also makes me relax and sleep better.

Paul Grobstein's picture

cannabis: positive effects?

"one hopes that research will soon provide clear understanding of how to exploit the positive medical effects of cannabis"

Do you mean to distinguish between positive "medical" effects, and positive effects of other kinds? Presumably the widespread use indicates there are "positive" effects other than "medical" for many people? Can one account for/evaluate those?

jrieders's picture

perhaps positive effects of

perhaps positive effects of other kinds are subjective, some find the psychological effects of marijuana calming and europhic, others feel paraniod and find the effects disturbing, i think these effects are less uniform and therefore harder to evaluate. Then again, I think it is arguable that the later, essentially "feeling high" could be considered a positive medical effect in terms of decreasing stress, the question becomes do medical risks associated with marijuana use outweight possible gains for medical and non medical use.

While I might distinguish some effect as havng a medical use, I do not mean to exclude other effects, but rather there I have not found research on this subject. 

This is essentially a paper considering the physioloy and medical application of marijuana, perhaps with implications to recreational use, but I do not intend (as of yet) to make applications for recreational use.