Chapter 8—Caffeine & NicotineChapter 8—Caffeine & Nicotine

Robert M. Julien

Presentation By:

Tamyra Frazier & Sarah Massamore

Differentiate CNS Stimulant Actions of Caffeine Differentiate CNS Stimulant Actions of Caffeine From Those of Amphetamine & Cocaine.From Those of Amphetamine & Cocaine.

Unlike the actions of cocaine & amphetamine, caffeine does not induce a release of dopamine in the nucleus accumbens; it leads to a release of dopamine in the prefrontal cortex, which is consistent with caffeine reinforcing properties.

It appears that although caffeine fulfills some of the criteria for drug dependence & shares with amphetamines & cocaine a certain specificity of action on the cerebral dopaminergic system, it does not act on the dopaminergic structures related to reward, motivation, & addiction.

Mechanism of Action--CaffeineMechanism of Action--Caffeine

4 different adenosine receptors (A1, A2A, A2B, A3) exist in humans, & caffeine is most potent in blocking A1 & A2A.

The positive stimulatory effects appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. Caffeine as a competitive antagonist at adenosine receptors, may produce its behavioral effects by removing the negative modulatory effects of adenosine from dopamine receptors, thus stimulating dopaminergic activity.

Panic Attacks & CaffeinePanic Attacks & Caffeine

The usually ingested doses of caffeine do not induce panic attacks in normal individuals. However, in people predisposed to panic disorders, the peripheral & the CNS effects of caffeine are exaggerated.

Effects of Caffeine in the Effects of Caffeine in the Cardiovascular SystemCardiovascular System Slight stimulant action on the heart.

Increases both cardiac contractility (workload of the heart) & cardiac output.

Raises blood pressure in adults prone to hypertension. Dilates the coronary arteries, providing more oxygen to the harder working heart.

Constricts the cerebral blood vessels, decreasing blood flow to the brain by 30% (migraines).

Evidence for & Against Caffeine Evidence for & Against Caffeine Use by Pregnant or Nursing WomenUse by Pregnant or Nursing Women Safety during pregnancy is unresolved. Caffeine in breast milk equals or exceeds level that exists

in the mother’s plasma Heavy consumption (6+ cups) is associated with an

increased risk of spontaneous abortion but moderate consumption does not further increase the risk.

Does not appear caffeine is a teratogen, & it does not appear to affect the course or normal labor & delivery.

Relatively safe in moderate doses. Higher levels=increased incidence of intrauterine growth. Later study showed low doses in 1st trimester increased risk of intrauterine growth retardation; high consumption, even in month before pregnancy, nearly doubled the risk of spontaneous abortion.

Smoking StatisticsSmoking Statistics

450,000 smokers die annually: 115K (lung cancer), 30K (cancer of other organs), 200K (heart & vascular diseases)

Life span shortened by 14 minutes for every cigarette smoked. 2 packs/day*20 years= 8 years of life lost

Smoking, the greatest public health hazard, is ironically the most preventable cause of premature death, illness, & disability

50 million+ people (1/5) alive today will die prematurely from effects of smoking

9 million suffer from cigarette-induced bronchitis & emphysema. 70% of pulmonary diseases & deaths, 57K emphysema deaths are tobacco related

Of all cancer deaths in the US, 30% (154K) would be prevented if no one smoked.

Nicotine As an AntidepressantNicotine As an Antidepressant

Several reports note an antidepressant effect of nicotine as well as the comorbidity of depression with cigarette use. Subjects with depression had odds of nicotine dependence that were more than 4.5x the odds for those w/o depression. This begins as early as age 16.

In nonsmokers, transdermal nicotine patches produced improvement in depression. Researchers think the high rate of smoking among depressed individuals may represent an attempt at self-medication to assist in dealing with symptoms.

Addictive or Habit Forming?Addictive or Habit Forming?

Nicotine clearly induces both physiological & psychological dependence in a majority of smokers.

In 1988, the surgeon general concluded that:– Cigarettes & other forms of tobacco are addicting.– Nicotine is the addictive drug in tobacco.– The pharmacological & behavioral processes that determine

tobacco addiction are similar to heroin & cocaine.

In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine, & alcohol.

Nicotine Replacement DevicesNicotine Replacement Devices

Nicotine patches, nicotine gum, inhalers, etc. Experts identified nicotine replacement therapies as

the only pharmacotherapy showed to be effective as an aid to smoking cessation.

All methods of nicotine replacement appear to be equally efficacious, approximately doubling the quitting rate of smokers attempting to quit w/o assistance.

The limitations are in health care workers who fail to recommend or monitor their use during cessation.

Nicotine Therapies & Nicotine Therapies & AntidepressantsAntidepressants

• Efficacy of Nortriptyline is reported but supra-additive effect of the drug plus cognitive-behavioral therapy.

• The antidepressant Bupropion doubled quitting rates.• Combination of Bupropion & nicotine patch only

slightly improved the results over use of only Bupropion.

• Bupropion is equally effective whether the smoker is or is not clinically depressed, suggesting that Bupropion’s efficacy is not solely due to its antidepressant effect.