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NIDA. Marijuana. NATIONAL INSTITUTE ON DRUG ABUSE. Prepared by Dr. Linda Thomas. What Have We Learned Through Research?. 83 million Americans have tried it at least once. An estimated 2.4 million Americans used it for the first time in 2001. Extent of the Problem….

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Marijuana

NIDA

Marijuana

NATIONAL INSTITUTE ON DRUG ABUSE

Prepared by Dr. Linda Thomas

What Have We Learned

Through Research?


Marijuana

83 million Americans have tried it

at least once

An estimated 2.4 million Americans

used it for the first time in 2001

Extent of the Problem…

Marijuana is the Most Commonly

Used Illicit Drug In the U.S.

Source: 2001 National Household Survey on Drug Abuse, SAMHSA


Marijuana

Types of Drugs Used By Past Month

Illicit Drug Users Aged 12 and Older: 2001

Marijuana Only

Drug Other

than Marijuana

24%

56%

20%

Marijuana and

Some Other Drug

Source: 2001 National Household Survey on Drug Abuse, SAMHSA


Percent of students reporting any illicit drug use in past year by grade

Percent of Students Reporting Any Illicit Drug Use in Past Year, by Grade

Source: Monitoring the Future Study 2002


Percent of students reporting use of marijuana in past year by grade

Percent of Students Reporting Use of Marijuana in Past Year, by Grade

Source: Monitoring the Future Study 2002


Marijuana

Research on Marijuana

Has Taught Us A Lot About:

Marijuana, specifically

Drug abuse/addiction, in general


Marijuana

Neuroscience of

Marijuana Use and Abuse


Marijuana

-

Tetrahydrocannabinol

9`

(THC)


Marijuana

Cannabinoid

Receptor


Marijuana

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Cannabinoid

Receptors


Marijuana

CB1 Cannabinoid Receptors in Rodent Brain

Gifford, A.N. et al., Chemistry and Physics of Lipids, 21(1-2), pp. 65-72, December 2002.


Marijuana

Nucleus accumbens

Dopamine pathways

(reward, eurphoria)


Marijuana

Effects of Drugs on Dopamine Levels

COCAINE

AMPHETAMINE

Accumbens

1100

Accumbens

400

1000

900

DA

800

DA

300

DOPAC

700

DOPAC

% of Basal Release

HVA

HVA

600

% of Basal Release

500

200

400

300

100

200

100

0

0

0

1

2

3

4

5 hr

Time After Amphetamine

Time After Cocaine

MORPHINE

NICOTINE

250

Accumbens

250

Dose (mg/kg)

200

Accumbens

0.5

200

Caudate

1.0

2.5

% of Basal Release

150

% of Basal Release

10

150

100

0

1

2

3 hr

100

0

1

2

3

4

5 hr

0

0

0

1

2

3

4

5hr

Time After Nicotine

Time After Morphine

Source: Di Chiara and Imperato


Marijuana

Acquisition of THC

Self-Administration

Behavior In

Squirrel Monkeys

Effects of Injection

Dose on

Self-Administration

Behavior

Tanda, G. et al., Nature Neuroscience, 3(11), November 2000.

Recently, Self-Administration of THC

Has Been Demonstrated in

A Variety of Animal Models


Marijuana

AND…

A Cannabinoid Antagonist

Can Block THC Self-Administration

Tanda, G. et al., Nature Neuroscience, 3(11), November 2000.


Marijuana

Why Do Some People Use

and Others Don’t?


Marijuana

Genetics

Gene/EnvironmentInteraction

Environment


Marijuana

Heritabilities Derived From Twin Studies

DRUG

Males

Females

Heroin (opiates)

Sedatives

Marijuana

Cocaine

Hallucinogens

Nicotine

54%(Tsuang et al., 1996)

87%(Kendler, et al., 2000)

33%(Tsuang et al., 1996)

58%(Kendler, et al., 2000)

44%(Tsuang et al., 1996)

79%(Kendler et al., 2000)

79% (Kendler, et al., 2000)

53%(Carmelli et al., 1990)

79%(Kendler & Prescott, 1998)

81%(Kendler et al., 1999)

72%(Kendler et al., 1999)


Marijuana

A Gene Has Recently Been Identified

That May Play A Role

in Drug Addiction…

This Gene Controls An Enzyme

Responsible for the Breakdown of

Endocannabinoids, the Brain’s

Own Cannabis-Like Compounds

Source: Sipe, J.C. et al., PNAS, 99(12), pp 8394-8399, June 11, 2002.


Marijuana

Consequences of

Marijuana Abuse


Marijuana

Acute Effects of Marijuana

Initial Euphoria or "High" Followed by SedationSense of Time AlteredHearing Less DiscriminateVisual DistortionsDepersonalizationConcentration ImpairedDream-like States Prominent


Marijuana

Other Acute Effects

Heart Rate IncreasedBlood Pressure UnchangedOrthostatic Hypotension (At High Doses)Conjunctival ReddeningMuscle Strength DecreasedAppetite Increased (Variable)Food Intake Increased (Variable)


Marijuana

What are the More Persistent

Effects of Marijuana?


Marijuana

PET Scans Examining Glucose Metabolism

4 Days After Last Use

Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.


Marijuana

Deficits In Cognitive Function in

Heavy Cannabis Users Have Been

Shown to Persist For At Least 7 Days

After Discontinuing the Drug

Source: Pope, H.G. et al., Arch Gen Psychiatry, 58, October 2001.


Marijuana

Verbal and visual memory

Executive functioning

Visuoperception

Psychomotor speed

Manual Dexterity

In Very Heavy Marijuana Users,

Persistent, Negative Dose-Related Effects

Have Been Shown on Tests Measuring…

Bolla, K.I. et al., Neurology, 59, pp. 1337-1343, 2002.


Marijuana

Relationship Between Amount of

Marijuana Smoked and Task Performance

In 28-Day Abstinent Heavy Marijuana Users

Note: high IQs are less likely to

be affected on tests that require

suppression of habit---frontal

cortex function

High Shipley IQ Group Low Shipley IQ Group

Bolla, K.I. et al., Neurology, 59, pp. 1337-1343, 2002.


Marijuana

Can Marijuana Cause

Permanent Changes?

Long-term, Yes; Permanent, Probably

No


Marijuana

Recent Research Suggests That

In-Utero Cannabis Exposure Can

Negatively Impact Certain Aspects

of Executive Functioning

Note: impact on

attention/impulsivity and

problem solving after 3

years of age--considerable

equivocation

Fried, P.A. and Smith, A.M., Neurotoxicology and Teratology, 23, pp. 1-11, 2001.


Marijuana

Chronic Marijuana Use Has Been

Shown to Be Associated With

Poorer Academic Performanceand

Higher Dropout Rates

Lynsky, M. and Hall, W. Addiction, 95(11), pp. 1621-1630, 2000.


Marijuana

Chronic Marijuana Use Has Been

Shown to Be Linked To

Poor Job Performanceand

Increased Absences From Work

Lehman, W.E.K. and Simpson, D.D. Journal of Applied Psychology, 77(3), pp. 309-321, 1992.


Marijuana

Percentage Arrestees Detected As

Marijuana Users

Arrestee Drug Abuse Monitoring (ADAM) Program, NIJ

AND…

In the Last Decade, Marijuana Use

Has Been On the Rise Among Arrestees

Especially Youthful Ones


Marijuana

Recent Research Has Validated the

Reliability and Clinical Significance of

Marijuana Withdrawal Effects

Source: Budney, A. J. et al., Arch Gen Psychiatry, 58, October 2001.


Marijuana

Budney, A.J., et al., Archives of General Psychiatry, 58(10), pp. 917-924, 2001.


Marijuana

Marijuana Smokers Show Increased

Aggressive Behavior During Withdrawal

Days of Abstinence

Kouri, E.M. et al., Psychopharmacology, 143, pp. 302-308, 1999.


Marijuana

We Are Beginning to Better

Understand What Makes Marijuana

Addictive…

And How These Mechanisms

Are Affected by Other Drugs of Abuse


Marijuana

For Example…

Research Shows that the Central

Mechanism Involved in Cocaine

Relapse Is Closely Linked to the Sites

Where Marijuana Has Its Effect

Source: DeVries, T.J., et al., Nature Medicine, 7(10) October 2001.


Marijuana

(antagonist)

(agonist)

(note: hole pokes for cocaine and for no reward)

Source: DeVries, T.J., et al., Nature Medicine, 7(10) October 2001.

And So…cannabinoid agonist

reinstates cocaine-seeking

Cannabinoid Receptor Antagonists

May Prove To Be Useful

Anti-Craving Agents


Marijuana

In Addition to It’s Effects on the Brain…

We Have Learned A Lot About

Marijuana’s Potential to Affect

Other Organ Systems


Marijuana

Lung Toxicity

Heavy Hashish Use: Chronic Bronchitis Chronic CoughHeavy Marijuana Use (5 Times a Day for 59 Days): Produces Airway Obstruction Marijuana Smoke Contains More "Tar" Than Tobacco Smoke Contains Carcinogenic Materials


Marijuana

Endocrine Effects

Male Sex Hormones: - Controversial Decrease in Testosterone - Usually Within Normal Range Decreased Sperm Production - No Evidence of InfertilityGynecomastia Has Been Implicated But Not Proven THC is Not EstrogenicFemale Sex Hormones: Suppressed LH Surge and Ovulation Increased Incidence of Anovulatory Cycles (Use More Than 4 Times a Week)


Marijuana

Difficulties Associated With Establishing the Health Hazards of Marijuana

Most Animal Studies Have Been Conducted Using

High Doses of THC for Short Periods of TimeMarijuana is Used By Young Persons In the Best

of HealthIntermittent Use of Small Doses May Underestimate

HazardsUsed With Other Drugs -- Especially Tobacco and

AlcoholMarijuana Use is An Emotional Topic


Marijuana

Treatment for

Marijuana Addiction


Marijuana

Percentages of Persons Aged 12 to 25

Reporting Past Month Marijuana Use

Source: SAMHSA, 1999 and 2000 NHSDAs


Marijuana

Changes in Marijuana

Treatment Admission Rates: 1993-1999

Source: 1999 SAMHSA Treatment Episode Data Set (TEDS).


Marijuana

Number of Adolescent Marijuana

Admissions, by Referral Source

Source: 1999 SAMHSA Treatment Episode Data Set (TEDS).


Marijuana

The Adolescent Treatment System

Less than 1/10th of adolescents with substance dependence

problems receive treatment

Under 50% stay 6 weeks, 75% stay less than the 3 months

recommended by NIDA

From 1992 to 1998, admissions for treatment of primary,

secondary or tertiary marijuana use disorders increased

115% (51,081 to 109,875)

Source: Dennis, Dwaud-Noursi, Muck, & McDermeit, 2002; Hser et al., 2001; OAS, 2000


Marijuana

Behavioral Therapies


Marijuana

40

35

30

25

Percentage of Participants

20

15

10

5

0

Marijuana Abstinence at End of Treatment

Motivational enhancement

plus coping skills plus

voucher-based incentives

Motivational enhancement

plus behavioral coping

skills therapy

Motivational enhancement

therapy

Budney, A.J. et al., Journal of Consulting and Clinical Psychology, December 2000.


Marijuana

Pharmacological

Therapy


Marijuana

Cannabinoid Antagonists for

Treatment


Marijuana

MJ Only

MJ & SR141716

Cannabinoid Antagonist Reduces

Marijuana’s Effects

30

80

70

25

60

20

50

Mean Increase in Heart Rate

(beats/min)

Maximum Mean Rating of Drug Effect

15

40

30

10

20

5

10

0

0

Feeling

High

Feeling

Stoned

Strength of

Drug Effect

Heart

Rate

Huestis, M.A. Archives of General Psychiatry, 58(4), pp. 322-328, 2001.


Marijuana

25

90

80

20

70

60

15

50

40

10

30

20

5

10

0

0

0

0.3

mg/kg

1.0

mg/kg

3.0

mg/kg

0

0.3

mg/kg

1.0

mg/kg

3.0

mg/kg

SR141716 Dose

SR141716 Dose

Cannabinoid Antagonist Blocks

Major Triggers of Drug Relapse in Rats

Impact of SR141716 on Response to

Priming Dose of Cocaine

Impact of SR141716 on Response to

Cocaine-Related Cues

Cocaine-Seeking Responses

(per 30 min)

Cocaine-Seeking Responses

(per 120 min)

De Vries, T.J., and Shaham, Y. et al., Nature Medicine, 7(10), pp. 1151-1154, 2002.


Marijuana

Naloxone Reverses Brain Reward of THC

Gardner, E.L., Chemistry and Physics of Lipids, 121, pp. 267-290, 2002.


Marijuana

Naloxone Reverses THC-Induced

Increases in NAcc Dopamine

Gardner, E.L., Chemistry and Physics of Lipids, 121, pp. 267-290, 2002.


Marijuana

Does Marijuana Have

Therapeutic Utility?


Marijuana

National Institutes of Health

Workshop (1997)

National Academy of Sciences

Institute of Medicine (1999)

Comprehensive Reviews of the

Medical Utility of Marijuana

Were Undertaken By:


Marijuana

These Reviews Concluded That:

Smoking marijuana reduces intraocular

pressure in glaucoma and is claimed to

ameliorate pain, nausea, poor appetite,

and other debilitating conditions

Source: Strauss, S.E. PNAS, 97(17), August 15, 2000.


Marijuana

The Problem Is…

Large controlled trials have

not been conducted to support

the majority of such claims

Moreover…

There are better, well-defined

treatments for most

such indications

Source: Strauss, S.E. PNAS, 97(17), August 15, 2000.


Marijuana

NIDA Is Helping to Put

Science-Based Information On

Marijuana and Other Drugs of Abuse

to Work in Our Schools and Communities


Marijuana

NIDA

NATIONAL INSTITUTE ON DRUG ABUSE

Visit Our Website @

www.drugabuse.gov


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