The War on Drugs

The Ethics & Rationale Behind the Federal Government’s ‘Other’ War

The War on Drugs

Robert PortleyIsuru KumarasingheBrooke LaFlammeJohn WidenArvind Vijayasarathi

Scientific and Ethical Aspects of Behavior Modification

Dr. Victor Hruby

18 April 2006

Presentation Overview

Introduction: History and Controversial Features

The Chemistry of Illicit Drugs: Physiological Effects/Mechanisms

Treatment Options: The Anti Drug

The Global Drug Trade: Supply Issues

Conclusion: Summary & Ethical Aspects

Introduction

The History and Controversy

War on Drugs Policy

The Modern War on Drugs began in 1971 when Nixon identified abuse of illicit substances as "America's public enemy number one."

In 1988 the Anti-Drug Abuse Act created the Office of National Drug Control Policy (ONDCP)

This branch of the executive office was created to centrally coordinate the political aspects of the war on drugs under direction of the Drug Czar.

Objectives of the War on Drugs

Reducing drug related crime and drug caused health problems by reducing drug use

Drug addiction was moved from being a personal problem to a public problem

“It is the declared policy of the United States Government to create a Drug-Free America by 1995” – Anti-Drug Abuse Act 1988

What constitutes abuse?

A drug is a substance to affect mood or behavior

For U.S. public policy purposes, drug abuse is any personal use of a drug contrary to law.

ONDCP

John P. Walters current Drug Czar since 2001

2006 National Drug Control Strategy

Goals:

Stopping drug use before it starts

Healing drug users

Disrupting the market for illicit drugs.

Drug War Expenditures

FY 2002 funding for the war on drugs was 18.8 billion according to ONDCP

http://www.drugsense.org/wodclock.htm

History

Harrison Narcotics Tax Act 1914

Tax on opium and cocaine

Marihuana (sic) Tax Act 1937

Imposed a tax on commercial distribution and lead to eventual ban

Controlled Substance Act 1970

5 Schedules (classes) determined by DEA and HHS

History (Cont.)

Drug Prohibitions targeted racial groups:

Opium as a way to target Chinese Immigration

Cocaine due to racist fears about African Americans

Marijuana during the depression targeted Mexicans

Despite popular belief to the contrary, there was never evidence that the laws were necessary, or even beneficial, to public health and safety

Constitutionality

The Controlled Substances Act stresses the impact of intrastate drug offences on "interstate commerce" and the "general welfare" of the American people.

Therefore circumventing any constitutional objections regarding states rights

Medicinal Marijuana usage was initially approved by the ninth circuit but lost in the Supreme Court in 2005

Schedule 1 Drugs(A) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has no currently accepted medical use in treatment in the United States.

(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

These include:GHB, LSD, Marijuana, Heroin, Ecstasy, Peyote

Schedule 2 DrugsA) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.

(C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

These include: CocaineRitalinOpium, morphine, oxycodonAmphetamines

Schedule 3 Drugs

(A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Includes Anabolic Steroids

Schedule 4 Drugs

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

Includes Xanax and Valium

Schedule 5 Drugs

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

Includes codeine containing cough suppressants

How big is the drug problem?

We don’t know

Unable to accurately determine number of drug users or money spent on illegal drugs due to the nature of the subject

34.8 million Americans ages 12 or over (14.5% of the US population ages 12 and over) used an illicit drug during the previous year.

Drug Mortality Statistics (per year)

Tobacco kills about 390,000.

Alcohol kills about 80,000.

Second hand smoke from tobacco kills about 50,000.

Cocaine kills about 2,200.

Heroin kills about 2,000.

Aspirin kills about 2,000.

Drug Mortality Statistics (cont’d)

Marijuana kills 0.

There has never been a recorded death due to marijuana at any time in US history.

All illegal drugs combined kill about 4,500 people per year, or about one percent of the number killed by alcohol and tobacco. Tobacco kills more people each year than all of the people killed by all of the illegal drugs in the last century.

Non-Drug Related Deaths in U.S.

Air pollution - 50,000 - 100,000

Diabetes - 73,000

Alzheimer’s - 60,000

Automobile - 30,000

HIV – 23,000

Suicide – 13,000

Still almost 100,000 less than tobacco related deaths

Health Impact

Rockefeller University concluded that "Tobacco is unquestionably more hazardous to the health than heroin."

Forty percent of all hospital care in the United States is for conditions related to alcohol.

As a medical hazard, few drugs can compete with alcohol or tobacco on any scale.

Do Drugs Cause Crime?

Alcohol is the only drug whose consumption has been shown to increase aggression

Alcohol Prohibition gave rise to a violent criminal organization. Violent crime dropped 65 percent in the year Prohibition was repealed.

Policy Causes Crime

Policy Causes Crime (cont’d)

In 1933 the homicide rate peaked at 9.7 per 100,000 people, which was the year that alcohol prohibition was finally repealed.

In 1980, the homicide rate peaked again at 10 per 100,000, coinciding with the escalation of the “War on Drugs.”

Crime & Societal Impact

The vast majority of drug-related violent crime is caused by the prohibition against drugs, rather than the drugs themselves

Illegal drugs and violence are linked primarily through drug marketing

“Drug-related” crime is a direct result of drug prohibition'sdistortion of immutable laws ofsupply and demand.

Mandatory Minimum Sentencing

Low level drug offenders are often imprisoned longer than rapists, child molesters, bank robbers, and those convicted of manslaughter

Since the enactment of mandatory minimum sentencing for drug users, the Federal Bureau of Prisons budget has increased by 1,954%. Its budget has jumped from $220 million in 1986 to more than $4.3 billion in 2001

Drug courts and drug treatment programs are seen as money saving alternatives to imprisonment

Average Federal Sentences

Drug offenses-6.5 years

Sex offenses-5.8 years

Manslaughter-3.6 years

Assault-3.2 years

Racketeering-5 years

Extortion-5 years

Costs to Society

The cost to put the average drug offender in jail is about $450,000

1.5 million people in prisons across the United States

Drug Offenses 59.6%

Of the 1,745,712 arrests for drug law violations in 2004, 81.7% (1,426,247) were for possession of a controlled substance. Only 18.3% (319,465) were for the sale or manufacture of a drug.

Federal Prisoners (By Offense)

Common Myths Influencing Drug Policy

Myth #1: Experimentation with drugs is not a common part of teenage culture

Myth #2: Drug use is the same as drug abuse

Myth #3: Marijuana is the gateway to drugs such as heroin and cocaine

Myth #4: Exaggerating risks will deter young people from experimentation.

Drug War Programs

National Youth Anti Drug Media Campaign

DARE

The High-Intensity Drug Trafficking Area Program

Drug Endangered Children

Inefficacy of Anti-Drug Campaigns

The National Youth Anti-Drug Media Campaign is a multi-dimensional effort to educate and empower youth to reject illicit drugs. Congressional Appropriations committee “deeply disturbed by the lack of evidence that the National Youth Anti-Drug Media Campaign has had any appreciable impact on youth drug use” in 2002.

DARE

Drug Abuse Resistance Education (K-12)

National Youth Program that teaches kids to “just say no” to drugs

Zero Tolerance - one of the creators at a 1990 testimony before the U.S. Senate said that the “casual user ought to be taken out and shot, because he or she has no reason for using drugs.” When asked about this outrageous testimony, he stressed that he was not “being facetious” and asserted that marijuana users were guilty of treason.

DARE Ineffectiveness

Glamorizes drugs

Mixed message

Self fulfilling prophecy

Hidden agenda

The High-Intensity Drug Trafficking Area Program

Areas within the United States which exhibit serious drug trafficking problems and harmfully impact other areas of the country

Provides additional federal resources to those areas to help eliminate or reduce drug trafficking and its harmful consequences. Law enforcement organizations within HIDTAs assess drug trafficking problems and design specific initiatives

HIDTA-designated counties comprise approximately 13 percent of U.S. counties, they are present in 43 states, Puerto Rico, the U.S. Virgin Islands and the District of Columbia.

Drug Endangered Children

Programs have been developed to coordinate the efforts of law enforcement, medical services, and child welfare workers to ensure that children found in environment where illegal substances are produced receive appropriate attention and care.Risks children face in these environments include: inhalation or ingestion of chemicals, fires, neglect, and generally hazardous living conditions.There were 1,660 children affected by or injured or killed at methamphetamine labs during calendar year 2005.

 

2002 2003 2004 2005

Child injured 11 25 13 11

Child killed 2 1 3 2

Children affected 3,660 3,682 3,088 1,647

Total injured/killed/affected

3,673 3,708 3,104 1,660

Possible Solution

The overwhelming weight of the scholarly evidence on drug policy supports decriminalization. Every major study of drug policy in history has recommended a non-criminal approach.

The best analysis done to date by any Federal official shows that "legalization" of the now illegal drugs would result in a net $37 Billion annual savings. This estimate is considered conservative.

Alternative Policies Harm reduction: diminishing individual and social risks associated with potentially dangerous behaviors.

Decriminalization: without legalizing the currently banned substances decriminalizing them would relieve the burden from law enforcement and society

Non incarceration: deterring offenders to treatment and rehabilitation rather than imprisonment

Benefits of Decriminalization

Decriminalization would increase the use of the previously criminalized drug, but would decrease violence associated with attempts to control illicit markets and as resolutions to disputes between buyers and sellers.

Moreover, because the perception of violence associated with the drug market can lead people who are not directly involved to be prepared for violent self-defense, there could be additional reductions in peripheral settings when disputes arise.

Non-Incarceration

Drug courts and local policies which favor treatment:

In 1996, Arizona Proposition 200, the Drug Medicalization Prevention and Control Act which sends first and second time non-violent drug offenders to treatment rather than incarceration.

Saved Arizona taxpayers $6.7 million in 1999.

In addition, 62% of probationers successfully completed the drug treatment ordered by the court.

California Non-incarceration

In November 2000, 61 percent of California voters passed Proposition 36, the Substance Abuse and Crime Prevention Act (SACPA), an initiative aimed at rehabilitating rather than incarcerating non-violent drug possession offenders. Under SACPA, certain persons convicted of non-violent drug possession offenses are given an opportunity to receive community-based drug treatment in lieu of incarceration.By treating rather than incarcerating low level drug offenders, SACPA would save California taxpayers approximately $1.5 billion over the next five years and prevent the need for a new prison slated for construction, avoiding an expenditure of approximately $500 million. 36,000 would be diverted to alternative treatment programs

Admission of Defeat

A report released in December 2005 by the Government Accountability Office showed that, despite U.S. law to the contrary, the more than 50 plus agencies working on the National Drug problem have little effect on the overall production and consumption of illegal drugs

The War on Drugs Could be Won If…

We could stop drug production in other countries.

We could stop drugs at the border.

We could stop the sale of drugs within the United States.

However, these are unattainable goals, so why do we continue?

References

Eddy, Mark. War on Drugs: Legislation in the 108th Congress and Related Developments. 4 April 2003.

Rosenbaum, Marsha. Safety First A reality based approach to teens drugs and drug education. Drug Policy Alliance 2004.

US Department of Justice, Bureau of Justice Statistics, Sourcebook of Criminal Justice Statistics 1996 (Washington DC: US Dept. of Justice,1997), p.20;

Executive Office of the President, Budget of the United States Government, FY 2002 (Washington DC: US Government Printing Office,2001), p.134.

U.S. National Center for Health Statistics, Health, United States, 2004.

Negro Cocaine Fiends: New Southern Menace, New York Times, February 8, 1914

Controlled Substances Act - U.S. Drug Enforcement Administration 1970

www.druglibrary.org

www.drugwarfacts.org

www.drugpolicy.org

www.Dea.gov

http://www.whitehousedrugpolicy.gov/

The Chemistry of Illicit Drugs

Physiological Effects and Mechanisms

Drugs classification

Drugs mechanism of action

Illegal drugs and their mechanism of action

Section Overview

Receptor

Any target molecule with which a drug molecule has to combine in order to elicit its specific effect.

When drug molecule binds to receptor molecule, there will be cascade of reactions– adrenaline

Agonist and Antagonist

Agonist binds to the receptor and activates the receptor, but antagonist binds to the receptor and does not activate the receptor and it prevents binding agonist to the receptor.

Receptors, Agonists & Antagonists

Drug Specificity

Drugs specificity

Drug must act selectively on particular cells or tissue. It must show high degree of binding specificity. Remove or substitute an amino acid from a peptide drug lose it selectivity for the target molecule. No drug acts complete specificity. Side effects are due to non specificity.

Lower the potency of the drug, higher the dose needed. Binding and activation are two distinct steps

Tendency of drug molecule to bind to the receptor called affinity and tendency for it once bound activate the receptor is denoted by its efficacy.

Drug with high potency generally have high affinity for the receptor thus occupy significant proportion of receptor even at low concentrations.

Agonist has high efficacy

Antagonist has zero efficacy

Drug with intermediate levels of efficacy such that even when 100 % of the receptor are occupied the tissue response is sub maximal are called partial agonist.

Drug ( agonist) (A)

Receptor (R)

AR

K1

K-1

+ AR* Response

Β

α

Drug ( agonist) (A)

Receptor (R)

AR

K1

K-1

+

No Response

Agonists & Antagonists

Receptor Binding

The binding of a drug to a receptor can often be measured directly by the use of radio active drug molecule. Radio active ligand should bind with high affinity and high specificity.

Method is incubate the sample of tissue with various concentrations of radio active drug until equilibrium is reached. Tissue is then removed or isolate and radio activity amount will be quantitated.

Concentration (nmol /l)

Specifically bound (Fmol /mg)

This is the relationship between concentration and amount of drug bound

Biological response

Rise in blood pressure

Activation of enzyme

Contraction or relaxation of strip

of smooth muscle

[E max] maximal response that the drug can produce [Emax]

[EC50] or [ED50] Concentration or dose needed to produce a 50% maximal response

Biological response (%max)

Concentration (mol /l)

10-11 10 -10 10-9 10-8 10-7 10-6 10-5 10-4

E max[EC50]

Dose response curve

Binding curves

[EC50] or [ED50] values used to comparison of potencies of different drugs that produce qualitatively the similar effect

Dose response curve can not be used to measure the affinity of agonist drugs for their receptor

Biological response (%max)

Concentration (mol /l)

10-11 10 -10 10-9 10-8 10-7 10-6 10-5 10-4

E max[EC50]

In the presence of antagonist

Agonist occupancy decreases in the presence of antagonist in competitive antagonism

10 20 30

Biological response (%max)

occupancy

In the presence of agonist

50% 100%

Partial agonist50%

100%

Inverse agonist

(Negative efficacy)

(100% efficacy)

Inverse agonist - Ligand that reduces level of constitutive activation

(Sub maximal response)

Targets for the drug action

Enzymes

Carrier molecules

Ion channels ( voltage sensitive sodium channel for local anesthetics)

Receptors

Exceptions some drugs binds to plasma protein, site of action of some drugs is still unknown. Antimicrobial drug and antitumor drugs, mutagenic and carcinogenic agents interact directly with DNA

• Receptors are the sensing elements in the system of chemical communication that coordinates the function of all the different cells in the body

• Drugs act as agonist or antagonist on receptor

Agonist molcule

Receptor

Ion channel opening and closing

Enzyme activation and inhibition

Ion channel modulation

DNA transcription

Receptor

Antagonist molcule

Receptor

Direct

Transduction mechanism

No effect endogenous mediators blocked

Types of receptors

N

C

Ligand gated ion channel

N

C

G protein coupled receptor

N

C

Kinase linked receptor

N

C

Nuclear receptor

Binding domain

Catalytic domainG protein

coupling domain

Channel DNA Binding domain

Fast response (milliseconds).These are for

neurotransmitter

E.G.Nicotonic acetylcholine receptor,

GABA receptor, gluatmate receptor

Response in seconds. These are for hormones and slow neurotransmitter

E.g Adrenoreceptor, acetylcholine, dopamine and opiate receptors.

Response in hours. Features

Receptors for insulin, cytokines and growth factors

Response in hours

regulate the gene expression. Receptors for steroid hormones or thyroid hormones.

G protein coupled receptor families

Family Receptors Structural features

Rhodopsin family The largest group. Receptors for most amine neurotransmitters, purines, prostanoids, cannabinoids

Short extra cellular ( N terminal) tail ligand binds to transmembrane helices or to extra celllar loops

Secretin / glucogen receptor family

Receptor for peptide hormones, including secretin, glucogon, calcitonin

Intermediate extra cellular tail, incorporating ligand binding tail

Metabotropic glutamate receptor/ calcium sensor family

Small group, metabotropic glutamate receptor, GABA receptor, calcium sensing receptor

Long extra celluar tail including ligand binding domain

Shares same heptahelical structure but differ in length of N terminus and location of agonist binding domain.

What is importance of having cytoplasmic loop? How it relates to response?

Rhodopsin is activated by light induced cis-trans isomerization

For thrombin, protease activate the receptor by cutting first N terimnal tail (41 residue), then the liberated N terminal binds to the receptor domains in the extra cellular loops and function as agonist (tethered)

Inactivation is by phosphorylation.

Due to the mutation in the receptor, it can be constitutively active. Several human diseases associate with this.

Mechanism of receptor activation

Signal transduction is by GPCR

First stage of signal transduction is through G proteins

Target 1 βγ

GDPα Target

2

Receptor

Target 1 βγ

GDPα

Target 2

Receptor

Target 1 βγ

Target 2

Receptor

GTPα

Target proteins activated

Target 1 βγ

Target 2

Receptor

GDPα

Target proteins activated

GTP

1 2

3 4

Resting state

G proteins is made of 3 subunits α,β, γ. There three types Gi, Gs, or Gq

G proteins are able to diffuse in plane of membrane

Agonist binds to the receptor. GDP/GTP exchange happens. Dissociation of complex occurs. α-GTP and βγ are active form of G protein. They can activate/or inactivate enzymes and ion channels (effectors). Process is terminated when GTP hydrolyze to GDP. Then α subunit dissociate from the effector and reforms complex with β and γ

These enzymes produce products and they act as second messengers

80 % of Drugs in the market target for G proteins. Since GPCR controls different cell function through followings

1. Adenylate cyclase – enzyme responsible for cAMP formation (it regulates magnitude of cAMP Formation) cAMP controls energy metabolism, cell division, ion transport, ion channels and contractile protein in smooth muscle. cAMP ultimately activates of protein kinase in turn activate or deactivate enzymes or ion channels

2. Phospholipase C – The enzyme responsible for inositol phosphate and diacylglycerol formation

3. Ion channels – Calcium and pottasium channels

βγ

GD

Pα

ACProtein kinase(inactive)

Protein kinase (active)

ATP

cAMP

Lipase inactive

Lipase active

Glycogen synthase (active)

Glycogen synthase (inactive)

Phosphorylase kinase (inactive)

Phosphorylase kinase (active)

Increased lipolysis

Reduced glycogen synthesis lipolysis

Increased glycogen synthesisPhosphorylase b inactive

Phosphorylase b

active

Second messenger

cAMP

phosphodiesterase

Hydrolysed products of cAMP

Methylxanthine,

Theophylline, Caffeine

Slidenfil(viagra)

Ion channels

BlockersPermeation blocked

modulatorsIncreased or decreased opening probability

Ion channels known as ligand gated ion channels. These open only when agonist molecule occupies the receptor. Other has different mechanism.

Interaction of the agonist molecule is direct or indirect. Direct is drug binds to it and change is fuction. Indirect mechanism happens through G protein coupled receptor

E.g. voltage gated sodium channel

Enzymes

inhibitor Normal reaction inhibited

False substrate Abnormal metabolite

produced

Active drug produced

Agonist /normal substrate

prodrug

Many drugs target the enzymes. Often the drug molecule is substrate analogue that act as competitive inhibitor of the enzyme reversibly or irrevesibly.

Drugs also act as false substrate, where drug molecule undergoes chemical transformation to form an abnormal product that subverts from normal metabolic pathway e.g. Flourouracil

Drug toxicity can happen when enzymes converts the drug molecules to reactive intermediates

Drugs require the enzymetic degradatation activty converts from inactive prodrug to active drug molecule

Phospholipids

Arachidonic acid

PGG2

PGE2PGD2

PGF2a

PGH2

PGI2TXA2

Phospholipase A2

Cyclooxygenease reaction

Cyclcoxygenase peroxidase reaction

ProstacyclinsyntheaseThromboxan synthase

Develops inflammation

Dialate small blood vessel

Vascular permeability (causes swelling)

Sensitize the peripheral nerve ending nociceptors to transmit pain signal to brain

Isomerase

reductase

Block by NSAIDS

e.g. naproxen, ketoprofen, ibuprofen

Promotes plattlet aggregation

Leukotriene

Lipoxygenase pathway

Biosynthesis of PGs

Cytoprotective propoeties in GI track

Control the renal function since PGs act as a vasodilator

Plattlet aggregation (TXA2)

Bronchodialation (PGE2)

Agonist /normal substrate

False substrate

Normal transport

inhibitor

Abnormal compound accumulated

Transport of ions or organic molecule through the lipid membrane requires the carrier protein because permeating molecules are always too polar. (glucose , amino acids, Na, K , Cl

Carrier protein molcules or transport molecules always has a special site for recognize the permeating ions. These recognition sites are always targets for drugs that block the transport system

Transporters

It is extracted from cannabis sativa

In 300, AD people found that the cannabis increases hunger and appetite particularly for sweet and palatable food

∆9 Tetrahydrocannabinol (THC) is the active component

∆9 Tetrahydrocannabinol (THC) contains 1-10 % of weight of marijuvana and hashish.

Marijuvana is name given to dried leaves and flower heads prepared as smoking mixture.

Until 20 th century due to antimarijuana attitude research in this area was neglected

O

O

OH

C5H11

OH

C5H11

Cannabis

∆9 Tetrahydrocannabinol

Active component

Cannabinol

inactive

Cannabis interacts with two types of receptors CB1 and CB2

Cannabinoid receptor belongs to G protein coupled receptor superfamily

Cannabis activates the receptor by modulating adenylate cyclase, activating potassium and inhibition of calcium channels.

CB1 mainly found in CNS. So we called this one as brain type cannabinoid receptor where as CB2 mainly expressed in immune cells it considered as peripheral part.

This classification is wrong since some CB1 express in periphery and someCB2 express in brain

In brain, CB1 modulates the release of neurotransmitter including gaba aminobutyric acid, dopamine, noradrenaline, glutamate and serotonin

Receptor for Cannabis

•This acts mainly on CNS and producing the mixture of psychotomimetic and depressant effect

•Gives a feeling of relaxation and well being similar to the effect of ethanol.

•Gives feeling of sharpened sensory awareness

•Central effect that can be directly measured by human and animal studies. Those are impairment of motor coordination and increased appetite and analgesia

•Regulates the feeding behavior

•Peripheral effect

•Vasodilatation, reduction of intraocular pressure, bronchodilation

Pharmacological Effect

1 These are substance extract from plants and several synthetic compound. (3 ring)

2 Analogues of ∆9 Tetrahydrocannabinol (THC)

3 Third is used for experimental models

4 Mimic the effects of plant derived ∆9 Tetrahydrocannabinol (THC). But structure is not similar.

Antagonist this use for therapy for obesity and eating disorders

Dronabinol – treat for chemotherapy induced nausea

Tolerance

Tolerance to cannabis occurs in minor degree and mainly in heavy users. Withdrawal effect is as same as withdrawal effect of opiate and ethanol e.g. nausea, agitation, irritability, confusion.

Overall it can not be classified as addictive

Smoking marijuana is better tolerated than the oral administration of the principle component

Tolerance of Marijuana

Adverse Effects of Marijuana

THC is relatively safe in overdose proving drowsiness and confusion.

It is safer than most abused substance e.g. opiate and ethanol.

Cannabis lowers the plasma testosterone and a reduction of sperm count

Smoking cannabis may be officious in no of conditions. It provide relief of pain relief of other types of chronic neuropathic pain.

Improvement of appetite

Also gives relief from chemotherapy induced nausea

Heroin

Heroin (Cont’d)

Diamorphine- is the diacetyl derivative of morphine. This rapidly deacyletate to morphine in the body

Because of the lipophilicity, it will pass blood barrier more rapidly than morphine

It can be used as an analgesic

Half life is 2 hours because its very rapid action, Causes dependence

Agent produces euphoria, analgesia, respiratory depression and sleep. Nausea and vomitting, constipation. Overdose causes the coma

Heroin (Cont’d)

Mechanism of action is through G protein coupled receptors. It inhibit the adenylate cyclase. So it reduces the intracellular cAMP amount. Also it effect to the ion channel. It opens k channel.(causes the hypoploarization) and closes the Ca channel (inhibiting transmitter release). Three different receptors. Alpha, beta and mu( mostly reside in brain). Analgesia effect is from mu receptor

For heroin abuse, patients are treated with naloxone.

Cocaine

Cocaine (Cont’d)

This is potent stimulant of the central nervous system. Exact mechanism of action is unclear

Cocaine acts by inhibiting catecholamine uptake (especially dopamine) by nerve terminals. It blocks the noradrenaline and dopamine transporters. This causes dopamine overaccumilation in certain regions of brain.

Cocaine also interact with GABA and opioid receptor

Cocaine (Cont’d)

Produces euphoria, increases motor activity

Duration of action is shorter

Behavioral effects of cocaine are similar to those of amphetamines

Causes the strong psychological dependence

Still this uses as a local anesthetics

Treatment for the cocaine abuse has to be multitarget.

Amphetamines and Methamphetamines

HN

NH2

Methamphetamine

Amphetamine

Locomotor stimulation

Euphoria and excitement

Stereotyped behavior

anorexia

Releases the monoamines from nerve terminals in the brain

Effects mainly from release of catecholamines such as noradrenaline and dopamine.

5 Hydroxytryptamine (5-HT) release also occurs

Stimulant effect lasts for few hours, after then depression and anxiety

Amphetamine psychosis can develop due to prolong use

Pharmacological effect

References

Endogenous cannabinoid system as a modulator of food intake, International journal of obesity (2003),27,289-301

Molecular approaches to treatment for cocaine abuse, Journal of molecular structure (2003), 259-267

Pharmacology, fifth edition, H.P Rang, M. M Dale, J.M Ritter, P.K Moore, 2003,pp 7-45

Treatment Options

The Anti-Drugs

National Policy on Drug use—3 parts

Stopping Drug use before it starts through education

Healing America’s drug users through treatment and intervention

Disrupting the market

Chapter 2: Healing America’s Drug Users

Even though drug use is ‘down’, because of increased education, “the Administration has made intervention and treatment a top priority”

The ONDCP states that 19.1 million Americans have used an illicit substance in the ‘past month’.

The government’s goal is to decrease the use of illegal drugs while providing help to addicts

Healing America’s Drug Users--Strategies

Support: Many non-medical support systems exist for recovering addicts. Examples include AA, Oxford House, and other faith-based groups.

Medical treatment: Using drugs to combat drug use

The Anti-Drugs: Marijuana

Marijuana is the most commonly used illicit substance (ONDCP)

In 2001, 14.7% (about 255,394) of drug treatment admissions in the U.S. were for marijuana use

~56.8% of those were referred through the criminal justice system

We may have a drug to cure your marijuana addiction! Marijuana is a schedule 1

substance in the U.S. (eg: heroin, LSD) There are NO legal uses of marijuana under federal law

Rimonabant (SR141716A)

SR141716A was first introduced in 1994 as an antagonist of the brain cannabinoid receptor, CB1 (Rinaldi-Carmona, et al. 1994)

The drug will be sold by Sanofi-Aventis as “Acompila” for the treatment of obesity starting this year. The FDA is requiring further information before it can be sold in the U.S.

Studies are being conducted on the effectiveness of Rimonabant in treating addiction to tobacco, alcohol, and marijuana

Rimonabant—What does it do?

SR141716A binds to the central cannabinoid receptor (CB1), but not to the peripheral receptor CB2, with nanomolar affinity

CB1 is a G-protein coupled receptor found in the brain and some peripheral tissues. Natural ligands include anandamide and 2-AG. This receptor system is thought to play a role in regulating blood pressure, etc.

Acute administration of SR141716A decreased glucose intake of rats, especially in those tolerant to THC (Freedland, et al. 2002)

A study in humans showed this drug prevents symptomatic hypotension in marijuana smokers (dizziness, lightheadedness

Rimonabant produces withdrawal symptoms in lab animals addicted to cannibinoids (eg: Beardsley & Martin, 2000)

The highest density of CB1 receptors is in the basal ganglia

Other anti-marijuana drugs

Rimonabant blocks the receptor for Δ9-THC, but it does not help withdrawal symptoms.

The following drugs have been tested in animals for their use in treating withdrawal symptoms associated with cannabinoid abstinence (reviewed in Hart, 2005):

Clonidine (Lichtman, et al. 2001): reversed some withdrawal-related symptoms (paw tremors, head shakes) in miceProstoglandin E2 (Anggadiredja, et al. 2003): alleviated withdrawal symptomsLithium (Cui, et al. 2001): blocked withdrawal symptoms

If you want to learn more…

Rinaldi-Carmoni, M., et al. (1994) “SR141716A, a potent and selective antagonist of the brain cannabinoid receptor.” FEBS Letters 350: 240-244.

Marx, J. (20 Jan 2006) “Drugs Inspired by a Drug.” Science 311: 322-325.

Gorelick, D.A., et al. (2006) “The Cannabinoid CB1 Receptor Antagonist Rimonabant Attenuates the Hypotensive Effect of Smoked Marijuana in Male Smokers.” Am Heart J 151: 754e1-e5.

Cohen, C., et al. (2005) “CB1 Receptor Antagonists for the treatment of Nicotine Addiction.” Pham Biochem Beh 81: 387-395.

Hart, C. (2005) “Increasing Treatment Options for Cannabis Dependence: A Review of Potential Pharmacotherapies.” Drug and Alcohol Dependence 80: 147-159

The Anti-Drugs: Opiates

ONDCP: heroin is highly addictive and considered one of the most abused opiates. It is a Schedule I drug.

“A rough estimate of the hardcore addict population in the United States…between 750,000 and 1,000,000”

Many drugs exist to treat heroin addiction

The anti-drugs: Opiates

Buprenorphine

Methadone

Naltrexone

RF9

Opioid Agonists

Buprenorphine: μ agonist/κ antagonist

Also shown to be an effective antidepressant (Bodkin, et al. 1995)

May be more effective at reducing heroin use in depressed addicts (Gerra, et al. 2005)

Methadone: Chemically, the simplest opiate. Methadone is a Schedule II drug (eg: cocaine, Ritalin)

Can be administered orally or by injection

Almost always, methadone must be taken indefinitely

buprenorphine Heroin (diamorphine)methadone

Opioid Antagonists

Naltrexone: Competitive antagonist at opioid receptors, completely blocks action of opioid agonists (Comer, et al. 2006), except buprenorphine

Used in “rapid detox” regimens

Can cause increased sensitivity to opioids after use.

Shown to be more effective at treating cravings than methadone (Grusser, et al. 2006)

naltrexone

Opioid Antagonists

RF-9: Antagonist of a different receptor (NPFF receptor) involved in pain modulation and tolerance to opiates (Simonin, et al. 2006)

Prevents tolerance to opiates by decreasing hyper-analgesic effects

Only tested so far in rats; not currently under consideration for treatiment of heroin addiction

If you want to learn more…

Comer, S.D., et al. (2006) “Injectable, Sustained-Release Naltrexone for the Treatment of Opioid Dependence.” Arch Gen Psychiatry 63: 210-217

Coffin, P.O., et al. (2006) “Support for Buprenorphine and Methadone Prescription to Heroin-Dependent Patients among New York City Physicians.” The American Journal of Drug and Alcohol Abuse 32: 1-6

Grussser, S.M., et al. (2005) “A New Approach to Preventing Relapse in Opiate Addicts: A Psychometric Evaluation.” Biological Psychology 71: 231-235

Gerra, G., et al. (2005) “Buprenorphine Treatment Outcome in Dually Diagnosed Heroin Dependent Patients: A Retrospective Study.” PNPBP 30: 265-272

Simonin, F., et al. (2006) “RF9, a Potent and Selective Neuropeptide FF Receptor Antagonist, Prevents Opioid-Induced Tolerance Associated with Hyperalgesia.” PNAS 103(2): 466-471

The Anti-Drugs: Cocaine

In 2000, chronic users were estimated at 2,707,000 (ONDCP)

Occasional users were estimated at 3,035,000

No drugs are currently approved to treat cocaine dependence, but many are being tested

Drugs for Cocaine Dependence

Disulfiram: Currently prescribed for alcohol dependence. Studies suggest effectiveness against cocaine dependence

This drug acts by inhibiting sulfylhydryl-containing enzymes (eg: acetylaldehyde dehydrogenase)

Baclofen: GABA agonist. Reduced cravings for cocaine in studies with humans

Modafinil: Subjects reported reduced cravings for cocaine and amphetamines. Increases alertness in narcoleptic patients and has been tested for treatment of ADHD.

For a review, see: Vocci, F.J., et al. (2005) “Medication Development for Addictive Disorders: The State of the Science.” Am J Psychiatry 162: 1432-1440

The Anti-Drugs: Methamphetamine

Available in pure form as a prescription (Desoxyn) for ADHD, obesity, and narcolepsy

It is a Class II substanceSocial stigma attached

Can be made from household products (don’t try this at home!)

597,000 people in U.S. over 12 report “past month usage” (ONDCP)

Combat Methamphetamine Epidemic Act of 2005 passed this March

The anti-drugs - MethamphetamineSelegiline: Used in the treatment of Parkinson’s and Alzheimer’s diseases

Potential in treating ADHD, cocaine, and methamphetamine abuse

Studies on the safety of selegiline in combination with methamphetamine have been conducted (eg: Schindler, et al. 2003)

Prometa: Clinical trials (phase II and III) have been registered, but not yet started as of Dec. 2005

Preliminary studies show decrease in cravings and minimal withdrawal symptoms (Alcoholism and Drug Abuse Weekly 24 Oct 2005)

Also being marketed for alcohol and cocaine dependence (Hythiam, Inc.)

Selegiline

Meth

Does Treatment Work?

For marijuana:

“To date, no medication has been shown to alter cannibis self-administration by humans” (Hart, 2005)

Side effects of Rimonabant include depression and anxiety

We don’t know the effects of messing with the endocannabinoid pathway

For heroin:

Methadone treatment works for certain individuals, but almost no one ever gets off methadone completelyIn one study, 2/3 of participants could not complete a methadone taper. 13% successfully switched to bupe/naltrex (Calsyn, et al 2005)

Does Treatment Work?

Buprenorphine works for some people, best for those with major depression

Gerra, et al. 2006

•MD: major depression

•GAD: generalized anxiety disorder

•PD: personality disorder

•SC: schizophrenia

•SUD: substance abuse disorder

Does Treatment Work?

Treatment for heroin, continued

Naltrexone completely blocks the effects of opiates. It would work great, except that people generally just stop taking it

Sustained release injectable naltrexone as well as implants may help compliance, but not entirely fix the problem

Naltrexone can cause rapid and severe withdrawal symptoms

Comer, et al 2006

Does Treatment Work?

Treatment for cocaine dependence:

Disulfiram

SIDE EFFECTS

(See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS.) O.T.(C) NEURITIS, PERIPHERAL NEURITIS, POLYNEURITIS, AND PERIPHERAL NEUROPATHY MAY OCCUR FOLLOWING ADMINISTRATION OF DISULFIRAM.

Multiple cases of hepatitis, including both cholestatic and fulminant hepatitis, have been reported to be associated with administration of disulfiram.

Occasional skin eruptions are, as a rule, readily controlled by concomitant administration of an antihistaminic drug.

Disulfiram (cont’d)

In a small number of patients, a transient mild drowsiness, fatigability, impotence, headache, acneform eruptions, allergic dermatitis, or a metallic or garlic-like aftertaste may be experienced during the first two weeks of therapy. These complaints usually disappear spontaneously with the continuation of therapy, or with reduced dosage.

Psychotic reactions have been noted, attributable in most cases to high dosage, combined toxicity (with metronidazole or isoniazid), or to the unmasking of underlying psychoses in patients stressed by the withdrawal of alcohol.

http://www.rxlist.com/cgi/generic/disulfiram_ad.htm

Does Treatment Work?

Baclofen – side effects

an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);     Seizurean irregular heartbeat. Other, less serious side effects are more likely to occur: drowsiness, dizziness, weakness, or unusual fatigue;     a headache;     ·constipation;     ·stuffy nose;     ·blurred vision;     Rashfrequent urination.

For more information see http://baclofen.drugs.com/

Does Treatment Work?Modafinil

Side effects: headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia

http://www.rxlist.com/cgi/generic2/modafinil_ad.htm

For methamphetamine dependence:

Selegiline

Side effects: This medication may cause stomach upset, loss of appetite, nausea, heartburn or dry mouth.

http://www.medicinenet.com/selegiline-oral/article.htm

may increase dopaminergic activity by interfering with dopamine re-uptake at the synapse (http://www.rxcarecanada.com/Eldepryl.asp?prodid=662)

Selegiline irreversibly inhibits the enzyme MAO-B. The mechanism of action is uknknown

Law of Unintended Consequences?General points of interest

The mechanisms of action of many of these drugs are unknown for any of their uses

In some cases, such as methadone, treatment may lead to addiction to the medication, though it may be safer than addiction to the illicit substance

The biggest concern is noncompliance. Doctors are therefore interested in taking the decision-making out of the patients hands. An example is naltrexone implants (not yet proven 100% effective).

What might be some of the unintended consequences of taking the problem of addiction out of the addicts’ hands?

The Drug Trade

Where Drugs are Being Produced, and How Much are Coming into the United States

Global Economics of the Drug Trade

Total trade in illicit drugs is $400 billion annually

The Drug Trade accounts for Slightly more commerce than the textile industry

US Drug Policy – Foreign Focus

US drug policy emphasizes source control, including interdiction and eradication

Targeting the source of drugs is often ineffective as new suppliers fill the demand

A new set of suppliers quickly emerged after the fall of the Medellin Drug Cartel in Columbia

Cocaine Supply

75 - 90% of cocaine comes form Columbia

50% world wide and 60% in US is controlled by FARC (Revolutionary Armed Forces of Colombia)

FARC has used the money to wage a 41-year war

Is Interdiction the Answer?

Successful interdiction can lead to a decentralization of the illicit industry

On the other hand, it could also lead to an increase in the concentration of the product

Examples of the latter include the concentration of alcohol during Prohibition, and the concentration of Marijuana in the 1960’s

International Implications of the US Drug War

When considering the ethics of legalized drugs should we be concerned with its effect on foreign society?

It is important to keep in mind that the US War on Drugs is part of a larger international effort, and thus has a number of wide-ranging international implications

Conclusion

Connecting the Issues & Ethical Analysis

Connecting the Issues

Historical & Statistical Analysis of the War on Drugs and the surrounding controversy.

Physiological and neurobiological effects of drug abuse: Marijuana, Cocaine, Methamphetamines, & Heroin.

Treating Drug abusers: the Anti Drug

Global Implications of the War on Drugs – Combating the Supply

Case Studies

Analysis of the Drug War

The War on Drugs, in its modern form, began in 1971.

Overarching Goal of the War on Drugs: To create a Drug free America

Method of choice: Arrest & Incarceration of drug users/sellers

Implications of the War on Drugs:

Financial - $ 18.8 Billion per yr. of taxpayers’ money

Workforce – Over 50 government agencies involved with the War on Drugs

Prison system – Drug related criminals account for the largest demographic of prisoners in the United States

Criticisms of the Drug War

Drug laws have been oftentimes selectively enforced, arguably as a way to target racial minorities.

Tobacco & Alcohol account for 100 times more deaths than illicit drugs.

The majority of drug-related crime stems from the laws that prohibit drug use/possession, not the effects of the drugs themselves.

Imprisonment of drug-offenders is a severe drain on the nation’s economy.

Some minor drug offenders face sterner punishment than rapists, child molesters, and bank robbers.

Failed Federal Initiatives & Policies

The National Youth Anti-Drug Media Campaign has produced no observable results, despite receiving millions of dollars in federal funding.

Drug Abuse Resistance Education (DARE) has been found to send mixed messages and may actually serve to glamorize drugs

The plethora of government agencies that aim to combat drugs have been for the most part ineffective.

Is it time for a national overhaul on drug policy?

The Chemistry of Illicit Drugs

Marijuana – Schedule 1 Drug – CNS Depressant

Heroin – Schedule 1 Drug – Analgesic that causes Euphoria

Cocaine – Schedule 2 Drug – CNS Stimulant

Methamphetamine – Schedule 2 Drug – Stimulant & Depressant

Treatment Options

Are non-invasive measures such as drug treatment and rehabilitation therapy effective?

Is it safe to use ethical drugs to treat illicit drug addiction?

In the case of heroin, methadone is used as a way to treat addicts. However, methadone treatment leads to methadone addiction, rather than Heroin addiction, because methadone stops your body from going through Heroin withdrawal symptoms.

Essentially, methadone treatment requires lifelong use to be effective, at what point does the treatment become worse than the problem?

The Global Drug Trade

The Illicit Drug Business is responsible for upwards of 400 billion US dollars in trade annually.

Though international interdiction efforts stop about 10-15 % of illicit drugs, UN estimates show that at least 75 % of the international drug shipments would need to be intercepted in order to have any major effect on the industry.

It is very difficult to reduce drug supply because suppliers produce excess amounts in anticipation of government seizures

According to Rydell & Everingham, in order to reduce US cocaine consumption by 1 %...

34 million dollars is needed in drug treatment programs (or)

783 million dollars towards supply reduction

Case Study # 1O’Shea Jackson, a young African-American man is pulled over on a routine traffic stop. The police officers conduct a basic search of his car and uncover a minimal amount of marijuana in the ash tray. Mr. Jackson is immediately arrested for Marijuana possession, and is subsequently taken to the local jail. After about 5 hours, Mr. Jackson is brought in front of a local night court judge. He and his public defender are presented with two basic options. The first option is to plead not guilty to felony possession of marijuana (perhaps the Marijuana was not his, but was left by another driver). By pleading not guilty, Mr. Jackson would spend upwards of 4 months in jail while awaiting trial…

Case Study # 1 (Cont’d)On the other hand, Mr. Jackson’s second option is to simply to plead guilty, and go home in a day or two on Probation. Option two seems to be a lot more practical and preferable, as no one wants to spend 4 months in jail. However, by pleading guilty, Mr. Jackson now has a criminal record, and if he subsequently commits even the most minor of infractions he can be imprisoned for a number of years without a trial, for violating his Probation. In a three strikes state, Mr. Jackson is now only two minor felonies away from a life sentence.

Ethical Issues

Mr. Jackson’s situation is all too common given the current legal policy on Drug possession

The people most likely to be suspected of and searched for illegal drugs are racial minorities with low socioeconomic status.

Examples like Mr. Jackson’s situation illustrate the way in which anti drug laws can be selectively used by law enforcement to target groups that they want to incarcerate.

Ethical Issues (Cont’d)

This was especially prominent in the 1960’s and 70’s as Black Panthers, War Protestors, and revolutionary students were the target of intense anti-drug law enforcement.

How would Mr. Jackson’s situation be different if he was an elite Hollywood celebrity, or an upper middle class white male?

Do Drug Laws & Law Enforcement that discount equity in favor of selective implementation constitute a just/ethical response to the nation’s drug problem?

Case Study # 2

Gross disparities in resource allocation exist between the ever growing US Prison Budget and the majority of other government expenditures. In 1998, the US Prison system warehoused over 1 million non-violent / low risk prisoners, the vast majority of whom were incarcerated due to drug related offenses. The taxpayer cost necessary to house these 1 million inmates was approximately 24 billion US dollars. When compared with the 16.6 Billion dollars the government spent on Welfare for 8.5 million people, and the 4 billion dollars the government spent on childcare for 1.25 million children, these drug related criminals are disproportionately draining our economy & tax revenue.

Case Study # 2 (Cont’d)

Meanwhile, as the US Prison Budget balloons to never before seen heights, states are cutting funding for universities and K-12 programs nationwide. In addition, since these non-violent offenders (mostly drug offenders) are being housed with the worst that society has to offer, the majority of them will leave the prison system in worse shape than they entered. Unable to get back on their feet and with the added burden of a prior prison stint on their record, almost all undoubtedly be back.

Ethical Issues

Why do the Federal and State governments essentially have carte blanche in regards to drug-related spending?

The 24 Billion Dollars per year (1998) spent on imprisoning the more than one million non-violent criminals in the US represents only a moderate portion of the entire expenditure related to the War on Drugs.

The money spent on the Drug War each year could easily serve to insure the nearly 50 million Americans who lack basic healthcare.

If even 10 % of the money allocated to the War on Drugs was redirected to K-12 education, the public school system could enjoy vast improvements, perhaps truly leaving NO child behind.

Are we essentially tossing billions of dollars at an unsolvable problem, in hopes of winning an impossible war?

Overarching Ethical Questions

Are the motives behind the War on Drugs just?

Does the War on Drugs constitute a necessary and effective use of public/federal resources?

Can a clear line be drawn between legal drugs and illicit drugs?

By what criteria does the government (FDA) decide which drugs are legal or illegal?

Is there a better approach?

Motives behind the War on DrugsFrom the ONDCP standpoint, the War on Drugs aims to reduce drug related crime and drug related health complications by eradicating illegal drug use.

From the research that we have presented/reviewed, the War on Drugs in its current form has clearly failed in its aim to eradicate illegal drug use.

Has the War on Drugs reduced drug related crime, or simply made thousands of criminals out of drug users?

Despite all of the negativity surrounding the War on Drugs, it is important to keep in mind that drugs like heroin, cocaine, and methamphetamines, are clearly unsafe and detrimental to health.

However, since the methods of the current War on Drugs are clearly not optimal, perhaps a new outlook and new tools are necessary.

Resource Allocation

How much time, effort, and money is being investing into this war?

Is this an effective use of taxpayers’ money?Intense Anti-drug advertisingPolice-work, prosecution, and court-related issues regarding drug usersImprisoning Drug-users (rather than treating them)

Do other causes deserve more federal resources?

Could this be accomplished by decreasing drug-related expenditures, and diverting the saved resources to other causes?

Why isn’t there a “War on Poverty” or a push for national Health Insurance?

Drawing the Line

Can a clear line be drawn between legal and illegal drugs?

Why are Alcohol & Tobacco legal, while marijuana and steroids are illegal?

As can be seen from our previous slides, illicit drugs account for less than 1 % of the deaths that alcohol and tobacco cause.

By what criteria does the government (FDA) decide which drugs are legal or illegal?

Does alcohol and tobacco lobbying have anything to do with the FDA’s stance?

Is there a better solution?

Decriminalization would certainly save billions of dollars in taxpayer money.

At the same time, Non-incarceration (drug treatment therapy) would certainly be more beneficial to the drug addicts/users than prison sentences.

However, if decriminalization, which amounts to the partial legalization of illicit drugs, was enacted, drug use would rise.

This rise in drug use would undoubtedly lead to more health problems.

On the other hand, by staying on the current course, it is clear that billions of taxpayers’ dollars will be wasted in vain

Perhaps the solution lies in the proverbial grey area of moderation, ultimately leading to a de-emphasis of the War on Drugs in its current form.

References

Associated Press, "U.N. Estimates Drug Business Equal to 8 Percent of World Trade," (1997, June 26).

Baum, D. (1997). Smoke and mirrors: The war on drugs and the politics of failure. Boston: Little, Brown/Back Bay.

Coffin, P.O., et al. (2006) “Support for Buprenorphine and Methadone Prescription to Heroin-Dependent Patients among New York City Physicians.” The American Journal of Drug and Alcohol Abuse 32: 1-6

Caulkins, Jonathan P. & Peter Reuter. “Setting goals for drug policy: harm reduction or use reduction?” Journal of Addiction (1997) 92 (9), 1143± 1150.

References (Cont’d)

Cohen, C., et al. (2005) “CB1 Receptor Antagonists for the treatment of Nicotine Addiction.” Pham Biochem Beh 81: 387-395

Comer, S.D., et al. (2006) “Injectable, Sustained-Release Naltrexone for the Treatment of Opioid Dependence.” Arch Gen Psychiatry 63: 210-217

Drugs.com “Balcofen.” http://baclofen.drugs.com/ Accessed on April 3rd, 2006.

Drug War Facts. www.drugwarfacts.org. Accessed on March 11th, 2006.

Dupont, R & Voth, E. “Drug Legalization, Harm Reduction, & Drug Policy.” Annals of Internal Medicine. 12.3, 1995; 461-465

References (Cont’d)

Eddy, Mark. War on Drugs: Legislation in the 108th Congress and Related Developments. 4 April 2003.

Endogenous cannabinoid system as a modulator of food intake, International journal of obesity (2003),27,289-301

Executive Office of the President, Budget of the United States Government, FY 2002 (Washington DC: US Government Printing Office,2001), p.134.

Gerra, G., et al. (2005) “Buprenorphine Treatment Outcome in Dually Diagnosed Heroin Dependent Patients: A Retrospective Study.” PNPBP 30: 265-272

References (Cont’d)

Gorelick, D.A., et al. (2006) “The Cannabinoid CB1 Receptor Antagonist Rimonabant Attenuates the Hypotensive Effect of Smoked Marijuana in Male Smokers.” Am Heart J 151: 754e1-e5.

Grussser, S.M., et al. (2005) “A New Approach to Preventing Relapse in Opiate Addicts: A Psychometric Evaluation.” Biological Psychology 71: 231-235.

Hart, C. (2005) “Increasing Treatment Options for Cannabis Dependence: A Review of Potential Pharmacotherapies.

Irwin, John, Vincent Schiraldi, & Jason Ziedenberg. America's One Million Nonviolent Prisoners. Social Justice Summer 2000 v27 i2 p135.

References (Cont’d)Marx, J. (20 Jan 2006) “Drugs Inspired by a Drug.” Science 311: 322-325.

Molecular approaches to treatment for cocaine abuse, Journal of molecular structure (2003), 259-267

Musings About the War on Drugs George Melloan. Wall Street Journal. (Eastern edition). New York, N.Y.: Feb 21, 2006. pg. A.19

Pharmacology, fifth edition, H.P Rang, M. M Dale, J.M Ritter, P.K Moore, 2003,pp 7-45

Prescription List. http://www.rxlist.com/cgi/generic/disulfiram_ad.htm. Accessed on April 2nd, 2006.

Prescription List. http://www.rxlist.com/cgi/generic2/modafinil_ad.htm Accessed on April 2nd, 2006.

References (Cont’d)

Rinaldi-Carmoni, M., et al. (1994) “SR141716A, a potent and selective antagonist of the brain cannabinoid receptor.” FEBS Letters 350: 240-244.

Rosenbaum, Marsha. Safety First A reality based approach to teens drugs and drug education. Drug Policy Alliance 2004.

Rydell, C.P. & Everingham, S.S., Controlling Cocaine, Prepared for the Office of National Drug Control Policy and the United States Army (Santa Monica, CA: Drug Policy Research Center, RAND, 1994), p. 6.

Simonin, F., et al. (2006) “RF9, a Potent and Selective Neuropeptide FF Receptor Antagonist, Prevents Opioid-Induced Tolerance Associated with Hyperalgesia.” PNAS 103(2): 466-471

References (Cont’d)

The Drug Enforcement Agency www.Dea.gov. Accessed on March 23rd, 2006.

The Drug Library. www.druglibrary.org Accessed on March 23rd, 2006.

The Drug Policy Organization. www.drugpolicy.org Accessed on March 18th, 2006

The White House Drug Policy. http://www.whitehousedrugpolicy.gov/. Accessed on April 1st, 2006.

Trading Classrooms for Cellblocks: Destructive Policies Eroding D.C.'s Communities. Ambrosio, Tara Jen and Vincent Schiraldi. Washington, D.C. Justice Policy Institute.

References (Cont’d)

United Nations Office for Drug Control and Crime Prevention, Economic and Social Consequences of Drug Abuse and Illicit Trafficking (New York, NY: UNODCCP, 1998), p. 3.

United Nations Office on Drugs and Crime, "Global Illicit Drug Trends 2003" (United Nations: New York, NY, 2003), p. 15.

"U.N. Estimates Drug Business Equal to 8 Percent of World Trade," (1997, June 26).

US Department of Justice, Bureau of Justice Statistics, Sourcebook of Criminal Justice Statistics 1996 (Washington DC: US Dept. of Justice,1997), p.20.

References (Cont’d)

U.S. Department of Justice (1992), Drugs, Crime and the Justice System, NCJ-133752,Washington, D.C.: USGPO.

U.S. National Center for Health Statistics, Health, United States, 2004.

US General Accounting Office, Drug Control: Narcotics Threat from Colombia Continues to Grow (Washington, DC: USGPO, 1999), pp. 2-7.

Walters, John (2002), “Don’t Legalize Drugs,” Wall Street Journal, July 19.

Wisotsky, Steven (1992), “A Society of Suspects: The War on Drugs and Civil Liberties,” Cato Policy Analysis No. 180.