Psychoactive PlantsStimulants - II: Nicotine

Nicotine Major alkaloid in the genus Nicotiana

Nicotiana, a large genus mainly from New World (~ 65 species) in the Solanaceae

Cultivated species: N. tabacum & N. rustica

Nicotiana tabacum

Tobacco history New World usage 1492 – Columbus Introduction to Europe British colonies

Nicotine Major alkaloid First isolated early in 19th century Synthesized in roots of tobacco plant and

translocated to the leaves One of the most toxic plant poisons In pure form, nicotine is deadly, causing death

by respiratory paralysis Nicotine is the most addictive drug in

widespread use

Nicotine

Nicotine insecticides Effective against most all types of insect

pests, but is used particularly for aphids and caterpillars - soft bodied insects

Mimics acetylcholine at the neuromuscular (nerve/muscle) junction and results in twitching, convulsions, and death

Same action is observed in all insects

Nicotine effects and mode of action Acts as a CNS stimulant and also affects peripheral

nervous system Stimulation of adrenal glands and discharge of

epinephrine (adrenaline) Nicotine also suppresses insulin output from the

pancreas, which means that smokers are always slightly hyperglycemic

In addition, nicotine indirectly causes a release of dopamine in the reward region of brain that controls pleasure and motivation

Mode of action on brain Nicotine exerts its effects in the brain by acting on a

specific type of receptor for acetylcholine, known as the nicotinic receptor

These receptors on dopamine neurons within the ventral tegmental area

Activates acetylcholine receptors (locks the channel open) - this increases the activity of these dopamine neurons, leading to an increase in dopamine release in synapse, which is thought to mediate reward

Nicotinic Receptor Researchers believe the beta 2 subunit of the

nicotinic receptor is a critical component in nicotine addiction

Mice that lack this molecule fail to self-administer nicotine, implying that without the beta 2 molecule, the mice do not experience the positive reinforcing properties of nicotine

This suggests a potential site for targeting the development of anti-nicotine addiction medications

Other Psychoactive Compounds? Research is also beginning to show that nicotine may

not be the only psychoactive ingredient in tobacco Cigarette smoking results in a marked decrease in

the levels of monoamineoxidase (MAO) in the brain MAO an important enzyme that is responsible for

breaking down dopamine.

The decrease in two forms of MAO, A and B, results in higher dopamine levels

Also a depressant?

Health Risks King James I of England in 1604 1948 JAMA

“More can be said in behalf of smoking as a form of escape from tension than against it....”

In 1964 U.S. Surgeon General’s report stated that cigarette smoking linked to lung cancer, heart disease, emphysema, and other conditions

Cigarette smoking the number one cause of preventable death

Cigarette smoking leading cause of death in US

Cigarette Smoking Most prevalent form of nicotine addiction Most cigarettes today contain 10 mg or more of

nicotine Through inhaling smoke, the average smoker takes

in 1 to 2 mg nicotine per cigarette Smoking results in rapid distribution of nicotine

throughout the body, reaching the brain in 10 sec Delivery to the brain Other forms of tobacco

Over 438,000 Annual Deaths in US Due to Cigarette Smoking

Risk of Cancer 85% to 90% of all lung cancer is due to cigarette

smoking About 1/3 of all cancer cases are due to cigarette

smoking Smoking associated with cancers of mouth, pharynx,

larynx, esophagus, stomach, pancreas, uterine cervix, kidney, ureter, bladder, colon, and leukemia

Chewing tobacco strongly linked to oral cancer - 50X increase in risk of oral cancer

Tobacco Smoke Over 4,700 chemical compounds found in tobacco

smoke Several (43) cancer causing substances Several alkaloids in addition to nicotine although

nicotine not implicated in cancer there is some evidence that it is converted to a carcinogenic cmpd in the body

Tars may be the leading carcinogens in cigarette smoke However, low tar cigarettes do not decrease incidence of

smoking related diseases

Cardiovascular Disease Smoking increase risk of cardiovascular disease

including stroke, sudden death, heart attack, peripherall vascular disease and aortic aneurism

Cigarettes caused almost 180,000 deaths from cardiovascular disease (1990)

Components of smoke also damage lining of blood vessels which can lead to atherosclerosis

Pulmonary Disease Cigarette smoking the leading cause of pulmonary

disease In 1999, there were over 82,000 deaths from

pulmonary disease in US – mainly from pneumonia, emphysema, bronchitis

In a recent study, maternal cigarette smoking the single most important risk factor in children developing asthma – way ahead of all other risk factors

Passive Smoking Smokers not the only ones affected by

cigarette smoke Much research has focused on the risks of

secondary smoking 53,000 annual deaths in US A non-smoker living with a smoker has a 30%

higher risk of death from coronary heart disease and a 30% or higher risk of lung cancer depending on exposure

Smokers 22.8% of the US population smokes cigarettes Decrease from 25% in 1998 Decrease greater among men than women Women now account for 39% of the smoking related

deaths – lung cancer has surpassed breast cancer as leading cause of cancer deaths among women

Smoking by teens continues to be a major problem but has actually decreased in the past few years

Tobacco Use in the US, 1900-2002

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1900

1905

1910

1915

1920

1925

1930

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

2000

Year

Per

Cap

ita

Cig

aret

te C

onsu

mpt

ion

0

10

20

30

40

50

60

70

80

90

100

Age

-Adj

uste

d Lu

ng C

ance

r D

eath

R

ates

*

*Age-adjusted to 2000 US standard population. Source: Death rates: US Mortality Public Use Tapes, 1960-2002, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2005. Cigarette consumption: US Department of Agriculture, 1900-2002.

Per capita cigarette consumption

Male lung cancer death rate

Female lung cancer death rate

Trends in Cigarette Smoking Prevalence* (%), by Gender, Adults 18 and Older, US, 1965-2004

*Redesign of survey in 1997 may affect trends.Source: National Health Interview Survey, 1965-2004, National Center for Health Statistics, Centers for Disease Control and Prevention, 2005.

0

10

20

30

40

50

60

1965

1974

1979

1983

1985

1990

1992

1994

1995

1997

1998

1999

2000

2001

2002

2003

2004

Year

Pre

vale

nce

(%)

Men

Women

Trends in per capita cigarette consumption for selected states and the average consumption across all states, 1980-2003

0

20

40

60

80

100

120

140

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002

Year

Per

Cap

ita S

ales

(#

of P

acks

) United States

Massachusetts

California

Data from: Orzechowski W, Walker RC. The tax burden on tobacco: historical compilation 2003: Volume 36. Arlington (VA): Orzechowski and Walker; 2003.

Trends in Smoking Among Teens

Current* Cigarette Smoking Prevalence (%), by Gender and Race/Ethnicity, High School Students, US, 1991-2003

*Smoked cigarettes on one or more of the 30 days preceding the survey.Source: Youth Risk Behavior Surveillance System, 1991, 1995, 1997, 1999, 2001, 2003, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 2004.

28

35

31

13

16

27

23

11

1918

19

3230

11

14

23

40

37

12

28

33

4040

17

32

36

28

34

39 38

22

32

18

33

2726

0

10

20

30

40

50

White, non-Hispanic Female

White, non-Hispanic Male

AfricanAmerican, non-

Hispanic Female

AfricanAmerican, non-Hispanic Male

Hispanic Female Hispanic Male

Pre

vale

nce

(%

)

1991 1995 1997 1999 2001 2003

Tobacco Industry Legal battles By end of 1998 all 50 states and DC had reached

settlements with 5 largest tobacco companies Master Tobacco Settlement which will cost the

tobacco companies over $200 billion Federal legislation