Chapter 6

CNS Stimulants

I love coffee, I love teaI love the java jive and it loves meCoffee and tea and the jivin' and meA cup, a cup, a cup, a cup, a cup!

“Java Jive,” 1940

Drugs classified as stimulants include the two most ubiquitousdrugs on the planet, caffeine and nicotine, as well as cocaine,

the amphetamines, methylphenidate and pemoline.

General effects of the stimulantsAll stimulants cause an increase in general behavioral activity.

This response can be useful for treating depression when apathy andlack of motivation are present. These drugs can help with gettingsomeone launched on a regime of exercise and constructive activitiesthat will support the maintenance of an elevated mood. Whentaken short-term (one or two weeks) stimulant drugs cause statesof euphoria, optimism, and general feelings of well being. Initialfeelings of anorexia are frequent, a quality of stimulants that leadsto their use/abuse as diet pills. Initial insomnia is another commonadverse effect. These responses indicate that the hypothalamus, thepart of the brain which mediates these functions, is strongly affectedby stimulants. Other effects are:

• anxiety • irritability • increased talkativeness• increased blood pressure• increased thoughts and associations• decreased fatigue• decreased feelings of depression

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Tolerance to stimulantsAfter about two weeks of daily use tolerance develops to the

mood-elevating and appetite-suppressing effects. Little tolerancedevelops to the behavioral-arousal effect, which is what makes thesedrugs useful in the long-term treatment of narcolepsy.1

Stimulants for Treatment of Depression

Although not frequently prescribed to treat depression because offear of their addictive potential, the amphetamines andmethylphenidate may be appropriate for short-term use.2 Theirvirtue is that they act immediately while other antidepressants havea lag time of several weeks. Immediacy can be critical if a patientis suicidal. People who have no history of addiction usually do notbecome addicted when using these drugs for their therapeuticpurposes.3 It is the drugs’ immediacy of response which makes thesestimulants potential drugs of abuse.

Stimulants and ADHD

According the DSM-IV, the prevalence of attention deficit hyperactivitydisorder (ADHD) in the U.S. is between 8% and 16%, with boys fourtimes more likely to be diagnosed than girls.4

Amphetamines and methylphenidateThese drugs are useful in decreasing manic behavior in children

with ADHD and in hyperactive adults. In the U.S. alone about 11million prescriptions are written every year formethylphenidate/Ritalin and another six million for variousamphetamine compounds such as Adderall.5 The mechanism for theparadoxical response in these populations (i.e., why “speeding up”results in a calming “slowing down”) is not yet fully understood.6

(For mechanism of action, see Appendix D.)

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When taking methylphenidate children who were previouslyunable to concentrate and had difficulty learning were able toperform at their age-appropriate level. Tolerance and dependencedo not develop in children who are taking these medications.Slowing of growth has been observed when methylphenidate istaken for long periods. To remedy this, children are given “drugvacations” from their medication on weekends, or during thesummer when not in school. This break allows children to catch upon their growth if it had slowed due to the medication.

Methylphenidate and amphetamine both can become drugs ofabuse. They can be dissolved and injected for a more rapid effect(drug “rush”). When used in this manner they have effects likecocaine, but milder. A tolerance develops if they are used frequentlyin this way and withdrawal symptoms will occur after one hasbecome habituated.7

AtomoxetineThe drug atomoxetine/Strattera is used for the treatment of

ADHD but is not classified as a stimulant. It is not a controlledsubstance, so it is easier for a doctor to prescribe. A major advantageis that it only needs to be taken once in the morning and seems tolast until evening without causing insomnia. A 13-item parent-rateddiary was developed by E.J. Lilly to assess efficacy during eveningand early-morning periods. Symptoms evaluated included:

• inattentiveness/distractibility • an inability to concentrate on structured tasks • hyperactivity/impulsivity • oppositionality.

Atomoxetine was found to be effective in treating these symptoms.8

There are indications that a reduction in the dose of atomoxetineis necessary for patients with impaired liver functions. Additionaladverse effects may emerge now that the drug is on the market andis being used more widely.9

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BuspironeAlthough developed as an antianxiety medication (see Chapter

2) and not considered a stimulant, buspirone/BuSpar has beenfound to be as effective as methylphenidate in reducing ADHDsymptoms with minimal adverse effects. Some children takingbuspirone experienced dizziness during the first week of treatment.10

CaffeineThere is evidence that caffeine is helpful for children with

ADHD and may be valuable as an alternative to more potentstimulants (see below).11

PemolineThe stimulant pemoline/Cylert is used for the treatment of

attention-deficit disorder (ADD) and sometimes for the excessivedaytime sleepiness seen in narcolepsy.

Adverse effects of pemolinePemoline has more adverse effects than many newer drugs and

is used much less often. The most frequent of these are:

• dizziness • nervousness • insomnia • nausea • diarrhea/stomach upset • involuntary tongue and eye movements • symptoms of Tourette’s disorder, seizures or tics

may increase or become more severe

Patients with liver or kidney problems need to be closely monitoredor have their dosage adjusted if on this drug. As with all stimulantsthere is potential for abuse or dependence.7

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Withdrawal After Chronic Use

A person addicted to stimulants, or anyone who has had a longperiod of continuous use, will experience withdrawal symptoms ifstimulant use is stopped abruptly. Symptoms of withdrawal areusually feelings of depression, fatigue, and general sluggishness.These are the opposite of symptoms seen under the influence of thedrug. These symptoms are not physically dangerous but can beextremely uncomfortable.7

If a depressed person has been using stimulants on a long-termbasis, is addicted or is abusing these drugs and increasing thedosage, then a severe depression may occur when the drug iswithdrawn.7 If depression caused by withdrawal does not abate aftera week or two evaluation by a psychiatrist for antidepressantmedication is appropriate.

OndansetronThe antinausea drug ondansetron/Zofran has been found to stop

cravings in early-onset alcoholics and is now being tested as an aidfor abstinence for people addicted to methamphetamine. People areunable to get “high” while taking it. It appears to work by enhancing5-HT transmission.12

Cocaine (“coke”)Cocaine is a potent CNS stimulant which is biochemically similar

to the amphetamines (for the mechanism of action, see AppendixD) and produces similar (although shorter-lasting) mood-elevatingeffects. Cocaine in various forms (Novocaine, Lidocaine, Carbocaine)has been used as a local anesthetic agent for many years. It is alsoused medicinally in “Brompton’s cocktail” (a mixture of cocaine,methadone, and alcohol) for terminally-ill patients in extreme pain.Brompton’s cocktail is not used more generally because it has thepotential to be highly addictive due to the rapid onset of both

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stimulant and euphoric effects. Recreational use of cocaine can belethal, particularly if taken by injection. Fatality can result from heartfailure, respiratory depression, stroke, or seizures.7

The behavioral effects of cocaine are also similar to those ofamphetamines. In terms of psychological effects, cocaine use canproduce a psychosis that is indistinguishable from one seen withschizophrenia. Physical dependence has not been demonstrated,although there is evidence that a very strong psychologicaldependence can develop.7

Withdrawal from cocaineSymptoms of cocaine withdrawal are very similar to those of

amphetamine withdrawal, mainly depressed mood, apathy, andfatigue.7

Treatment of cocaine withdrawalMany treatments for cocaine withdrawal support the belief that

habitual use of stimulant drugs (the amphetamines and cocaine) isa way of self medicating a depressive disorder. This theory is basedon the idea that people suffering from depressive disorders do nothave enough endogenous NE and 5-HT, and use stimulants toincrease the amounts of neuromodulator available. In support of thistheory are the positive results seen when the antidepressantdesipramine/Norpramin (a TCA) is taken at the time of stimulantwithdrawal. Desipramine works by blocking reuptake of NE, whichresults in an increase in NE at the synapse. This leads to an increasein neuronal stimulation and increased feelings of energy. Thismakes it less likely that the patient will use a stimulant to ward offdepression.

Problems with TCA treatmentSome problems have been observed using TCAs for cocaine

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withdrawal. TCAs and cocaine both decrease the seizure threshold(i.e., make the risk of seizures more likely). The risk of seizures isgreatly increased if a person is taking desipramine (or any TCA) asa treatment for stimulant withdrawal and/or for an underlyingdepression and uses cocaine again while taking the antidepressant.This risk is particularly dangerous for a person with epilepsy.

Psychotic symptomsA treatment dilemma may occur if the cocaine user is also

having psychotic symptoms and needs to be treated with anantipsychotic drug. Craving for cocaine is increased by dopamineantagonists (including many antipsychotic drugs). The administrationof antipsychotic drugs leads to an increased craving for cocaine,which may in turn lead to the client increasing his or her use, whichin turn leads to a worsening of psychotic symptoms.7

Dopamine agonistsThe dopamine agonists bromocriptine/Parlodel and

amantadine/Symmetrel (which augment dopaminergic transmissionin the CNS) both cause a decrease in the craving for cocaine. Eitherof these agents can be helpful if taken during the first month ofcocaine withdrawal when cravings are strongest.

Problems with MAOI treatmentThere are also serious problems related to the use of MAOIs for

the depression frequently experienced during cocaine withdrawal.The combination of MAOIs and cocaine can lead to a fatalhypertensive crisis (see Chapter 4).

Amino acids for cocaine withdrawalAnother effective regimen which is much less risky if the patient

starts to use cocaine again, is treating the withdrawal with the

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amino acid tryptophan. Since tryptophan is a serotonin precursor,taking extra amounts of it will help to restore serotonin that has beendepleted by using cocaine and decrease the craving for cocaine.There is some evidence that tryptophan, by increasing the amountof serotonin, can also help to alleviate the depression that may ariseduring cocaine withdrawal.

Two other amino acids, phenylalanine and tyrosine, have beenused to alleviate symptoms of depression during cocaine withdrawal.Both are precursors to neuromodulators and can help to restore amore normal balance of the chemicals that have been depleted dueto the cocaine use.

Cocaine vaccineA vaccine is being tested that induces the formation of

anticocaine antibodies which leads to a decrease in the amount ofcocaine in the brain. The antibodies and cocaine form a largemolecular complex that has difficulty crossing the blood-brainbarrier. Because only a small amount of cocaine can get into thebrain the impact of cocaine on the pleasure centers is greatlydecreased. In animal models addiction was extinguished. Theseantibodies remain in the blood and are effective for six months toone year, after which booster shots might be required. One dangeris that very large doses of cocaine might be able to overcome theantibodies which could lead to a lethal overdose. It is expected thatthe vaccine will be a valuable adjunct when used withpsychotherapy for cocaine users who want to overcome theiraddiction.13

Relapse Prevention therapy (RP)Relapse Prevention therapy (RP) is one of the few scientifically

validated psychosocial treatments for substance abuse and has beenproven useful for treatment of cocaine abuse. No other type oftreatment is without major difficulties (see above). RP techniques

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help people recognize high-risk situations, rehearse ways to dealwith them, self-monitor substance use and learn to deal with cravingsby understanding and externalizing them. With this type of therapy“lapses” in behavior are regarded as learning tools to understandwhat happened as well as opportunities to renew the commitmentto sobriety. RP does not result in greater abstinence rates than othertreatments, but relapses are shorter and less frequent. RP may bebetter for maintaining its lower relapse rate because over timepeople improve as they practice avoiding relapse.14,15

CAFFEINE

Caffeine is the most widely-used psychoactivesubstance. Eighty-nine percent of adults in NorthAmerica use either coffee or tea daily, and theaverage coffee drinker consumes approximately1,000 cups per year, or about three cups per day.Although most people do not think of it as a drug,caffeine is a powerful stimulant, and although itsuse is legal, overdose can be fatal. Caffeine is quite addicting; atolerance and tendency to increase intake are common, andwithdrawal symptoms occur if consumption is stopped.16

Caffeine makes people feel better in general so it is frequentlyincluded as one of the ingredients in analgesics such as Anacin andExcedrin as well as in cold preparations. A dose of caffeine thatexceeds five to ten grams at one time can be fatal. Caffeine intakecan be calculated using Table 6.1. Keep in mind that caffeinecontent often varies depending on the product used and the methodof preparation.

Effects of caffeineCaffeine causes a behavioral and emotional response that is sim-

ilar to the amphetamines and cocaine, but milder. Caffeine causes

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NN

NN O

OHC3

HC3

HC3caffeine

(C8H10N4O2)

Figure 6.1

higher rates of cellularactivity in the CNS.People report thinkingmore clearly, havingmore energy, and react-ing more quickly afterconsuming caffeine.16

Increases are seen in res-piratory rate, amplitudeof reflexes, and the rateand force of the heart’scontraction. Caffeinecauses a general vasodi-latation (opening) of thesystemic blood vessels,including the coronaryarteries, resulting in an increase in blood-flow to the heart. Durationof systemic vasodilatation is brief and is accompanied by vasocon-striction (tightening) of the vessels in the brain.16 Centralvasoconstriction is the mechanism by which caffeine provides relieffrom hypertensive headaches and migraine headaches. (This isanother reason why caffeine is often used in headache remedies.)

CaffeinismChronic toxicity due to high levels of caffeine consumption is

characterized by:

• rapid changes in mood • feelings of anxiety• disruption of sleep patterns • headache• trembling • ringing in the ears • dry mouth • nausea • stomach pain • diarrhea• depression • palpitations • irregular heart beat

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C A F F E I N E C O N T E N TSOURCE

coffee (drip)coffee (perked)coffee (instant)coffee (decaffeinated)black tea (steeped 5 min.)

green tea (steeped 5 min.)hot cocoacola beveragemilk chocolatebittersweet chocolatechocolate cakeAnacin, Empirin, Midol

ExcedrinNoDozDexatrim

CAFFEINE(mg)

110–150

60–125

40–105

2–5

40–100

50

2–10

45

1–15

3–35

20–30

64

130

200

200

SERVING

5 oz.

5 oz.

5 oz.

5 oz.

5 oz.

5 oz.

5 oz.

12 oz.

1 oz.

1 oz.

1 slice

2 tablets

2 tablets

2 tablets

2 tabletsTable 6.1

Caffeine dependencePeople who are caffeine-dependent have a strong association

between caffeine consumption and general feelings of well-being.Many people enjoy the increased speed of performance and feelingsof efficiency caused by caffeine. Regular caffeine consumptioncauses both psychological dependence and physiological tolerance.16

Symptoms of withdrawal from caffeine

• headaches • lethargy • irritability • apathy• difficulty concentrating • decreased efficiency• nervousness • restlessness • mild nausea

The main symptom of caffeine withdrawal is headaches (these maycontinue for up to five days if no caffeine is consumed). Theheadaches often lead the sufferer to use of analgesic preparationswhich themselves often contain caffeine. This cures the headache,but leads to a continuance of caffeine dependence. It is possible toreduce withdrawal symptoms by gradually decreasing daily intakeof caffeine by substituting decaffeinated coffee for regular and eachday increasing the percentage of decaf.

Other effects of caffeineIt is important for women to know that caffeine crosses the

placenta and gets into the bloodstream of a developing fetus. It alsogets into breast milk of nursing mothers. In these cases, the fetusor infant is ingesting a portion of the caffeine consumed by itsmother. No significant correlation between birth defects and caffeineconsumption has been demonstrated.

Although the specifics are still unclear, there seems to be somerelationship between caffeine and fibrocystic breast disease.16 Decreasingcaffeine consumption leads to a decrease in discomfort experiencedby women with fibrocystic breast disease. Although many studieshave been done with large numbers of adults, no correlation

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between caffeine consumption and cancer has been substantiated.

One factor that reflects some change in response to caffeine isage, in that one’s sensitivity to the effects of caffeine increases withage. It has also been seen that the amount of caffeine in one’sbloodstream increases when smoking is stopped. This increase incaffeine can amplify the usual symptoms of tobacco withdrawal:irritability, nervousness, inability to concentrate, and sleeplessness.

Studies show a positive correlation between caffeine use and thepresence of anxiety disorders. People with anxiety disorders havean increased sensitivity to caffeine.17 There is marked lessening ofsymptoms of anxiety with caffeine abstention, and for some peopleantianxiety medication is not necessary when caffeine use isdiscontinued.18 The psychotherapist needs to assess caffeine intakein any patient who presents with symptoms of anxiety.

Caffeine and ADHDOpinions differ on whether caffeine use in children is harmful.

No long-term studies have been done to assess its effects on physicaland psychological function in children. Most children respond tocaffeine in the same way as adults. There is a stimulating effect,observed as nervousness, and a quicker response time.11

Caffeine has been shown to have the effect of improvingfunctioning and reducing levels of hyperactivity in children withADHD. Although the traditional treatments with methylphenidateand amphetamines outperform caffeine in improving functioning,caffeine outperforms control groups getting no treatment.Improvements are seen in relationships with parents and teachers,there are reduced levels of aggression, impulsiveness, andhyperactivity, and an improvement in executive functioning.11

Caffeine may be a tolerable option for parents who are opposedto the use of other stimulants due to fear of long-term adverse effectson their children.

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NICOTINE

The use of nicotine is widespread in our society and around theworld. Over 25% of American adults (about 50 million people) usetobacco products.19 Although nicotine is extremely addictive andharmful, its purchase and use by anyone over the age of 18 is legal.If one considers how difficult it is to stop using it, nicotine is evenmore addictive than opiates. Nicotine, particularly through smoking,is much more harmful than many other drugs in terms of numberof illnesses it causes, the costs of treating those illnesses, and thehigh fatality rates. While antismoking campaigns have loweredsmoking rates in the U.S., the percentage of people worldwide whosmoke is increasing. It is estimated there are more than 430,000smoking-related deaths every year in the U.S. alone.20

Effects of tobacco useNicotine is the addictive ingredient in tobacco whereas the

“tars” contain a large number of carcinogenic compounds. Nicotineconsumption causes the release of NE, DA, and 5-HT in the CNS.This leads to feelings of stimulation and calming. Research indicatesthat part of the calming experienced by smokers may be due to thedecrease in the unpleasant withdrawal symptoms a smokerexperiences as nicotine levels in the blood drop. When smokers arecompared with nonsmokers or former smokers indications are thatnicotine itself increases stress.21

The release of DA is probably what leads to the reinforcingexperience of pleasure associated with smoking (this is similar toother addictive drugs). Nicotine has a half-life of 30 minutes, whichleads to an urge to consume more nicotine every half hour. Smokingtwo cigarettes an hour (or consuming the equivalent from othertobacco products) will maintain a constant blood level of nicotine.

For reasons that are not yet clear, about 10% of people whosmoke do not become addicted. They are able to keep consumption

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of cigarettes to approximately five per day, as opposed to the oneor two packs a day consumed by the addict.22 People who areaddicted to nicotine have higher rates of major depression andanxiety disorders than people who smoke but do not becomeaddicted.23 More research is needed to determine the factorsresponsible for these differences. One recent study found that 90%of people who attempt suicide are smokers.24

Tars and other compounds found in tobacco productsSome known carcinogens found in tobacco tars include:

• nitrosamines • aromatic amines • pyrenes• benzopyrenes • chrysenes

Many other substances known to be harmful to humans arefrequently present in tobacco products, including:

• phenols • cresols • carboxylic acids• metallic ions • radioactive compounds• agricultural compounds (e.g., pesticides)• various additives and flavoring agents

If manufacturers removed these toxic agents the harmful effects oftobacco use would be greatly reduced.

Nicotine withdrawal symptomsPhysiological symptoms of withdrawal occur when a nicotine

addict stops consuming it. This withdrawal syndrome is commonlycalled a “nicotine fit.” Some symptoms are:

• feelings of uneasiness • anxiety • restlessness • nervousness• headache • digestive disturbances • impairment of concentration and judgement• impairment of psychomotor performance

When the body is under stress nicotine in tdepleted of faster than

90 DRUGS AND CLIENTS

usual, causing the addict to use more in order to maintain the usualblood-level of nicotine and ward off the symptoms of withdrawal.

AIDS FOR NICOTINE WITHDRAWAL

Bupropion and naltrexoneThe FDA’s Drug Abuse Advisory Council found that the

antidepressant bupropion/Wellbutrin/Zyban is safe and effective asan aid in smoking cessation.25 The drug naltrexone/ReVia, developedfor use during opiate withdrawal, has been found to decrease thecraving for nicotine. Both of these drugs are helpful as supportivemeasures to psychotherapy, especially in the early stages ofabstinence.

ClonidineAnother drug that helps with nicotine withdrawal is

clonidine/Catapres. Clonidine is an antihypertensive drug thatstimulates endorphin production, which leads to an increase inpositive feelings. If clonidine is taken during nicotine withdrawalthe craving for cigarettes is decreased.

Gamma vinyl-GABAThe antiepilepsy drug gamma vinyl-GABA/GVG is being tested

to decrease nicotine-craving during withdrawal. GVG inhibits releaseof DA and increases production of GABA. DA is believed to be thesubstance that produces the pleasurable experiences associatedwith use of addictive substances. The increased GABA would causea calming effect.

Patches and gumsThe nicotine patch and chewing gum containing nicotine are

both helpful in gradually decreasing nicotine consumption without

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the dangers and reinforcing behaviors inherent in trying to smokefewer cigarettes, cigars or pipes or “dip” less chewing tobacco orsnuff each day.

Effect of caffeine during nicotine withdrawalCaffeine is metabolized more quickly by smokers than

nonsmokers. When someone stops smoking if the amount ofcaffeine consumed remains the same, blood levels of caffeinedouble, causing an increase in nervousness that makes withdrawalfrom nicotine more difficult. It is recommended that caffeineconsumption be decreased or eliminated during withdrawal fromnicotine.18

Direct Relevance to Psychotherapy

It is very important to be aware that a paranoid psychosis may resultfrom long-term use of stimulant drugs (particularly withamphetamines or cocaine). This drug-related condition is oftenclinically indistinguishable from the psychosis seen withschizophrenia or during a manic episode. Symptoms include:

• paranoia • hostility • aggressiveness • disorganized thought patterns • delusions• hallucinations (usually auditory)

Psychotic symptoms occur most often with a sudden increase indosage or in chronic users of amphetamines who are taking morethan 100 mg/day. The treatment of choice for this drug-inducedpsychosis is to stop the stimulant use and begin a course ofantipsychotic medication. Recovery from a drug-induced psychosisis not always immediate; it may take days or weeks to clear. In some

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cases the psychosis may last for years and require antipsychoticmedication. Autopsy results show that heavy amphetamine use canproduce permanent brain damage.26

MRI and PET scans of drug abusers show that heightenedcraving is linked to increased activity in the frontal cortex. Drug userswho have shown no decision-making impairment may be least atrisk for becoming addicted and may be able to stop if they want to.This is evidence that addiction may be related to a disruption in theCNS to motivational circuits rather than only to pleasure-controlcenters.12 These findings may lead to better intervention strategiesand help to answer questions as to why some drug users becomeaddicted while others do not.

Each therapist’s family history and personal experiences withsmoking and the diseases it causes will strongly influence feelingsabout tobacco use and its associated ills. There is no denying thattobacco use is a health hazard. Consumption of nicotine, like anyother addictive drug or unhealthy habit, deserves exploration intherapy. For clients who want to stop cognitive and behavioralinterventions have proven to be most effective for changing habits.Discuss with the client whether a medication like bupropion ornaltrexone is desired in addition to psychotherapy. Studiesdemonstrate that using a nicotine patch in conjunction withbupropion while continuing therapy results in significantly higherlong-term rates of cessation than the use of either alone.25

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References for Chapter 6

1. Stahl, S. M. (1999). Awakening to the psychopharmacology of sleep andarousal: Novel neurotransmitters and wake-promoting drugs. J. ClinicalPsychiatry, 63(4), 339-402.

2. Wagner, J.G., Rabkin, J.G. & Rabkin, R. (1997). Dextroamphetamine as atreatment for depression and low energy in AIDS patients: A pilot study.Psychosomatic Research, April 42(4), 407-11.

3. Satel, S.L. & Nelson, J.C. (1989). No reports of addiction using stimulantsunder medical supervision. J. Clin. Psychiatry, July 50(7), 241-9.

4. Wender, E. H., (2002). Attention-deficit/hyperactivity disorder: Is it common?Is it overtreated? Arch. Pediatr. Adolesc. Med., 156, 209-210.

5. DEA Congressional Testimony, Caucus on International Narcotics Control,July 25, 2000, Fiano, R. A. US Dept. of Justice, Drug EnforcementAdministration.

6. Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Levin, E. D. & Jaber, M.,Caron, M. G. R. (1999). Role of serotonin in the paradoxical calming effectof psychostimulants on hyperactivity. Science, 283(5400), 397-401.

7. see p. 3 Chiang and Goldfarb ref.8. Michaelson, D., Adler, L., Spencer, T., Reimherr, F. W., West, S. A., Allen, A.

J., Wernicke, J., Dietrich, A. & Milton, D. (2003). Atomoxetine in adultswith ADHD: Two randomized, placebo-controlled studies. Biol. Psychiatry,53(2), 112-20.

9. Chalon, S.A. (2003). Hepatic impairment with atomoxetine. Clin. Pharmacol.Ther., 73, 178-91.

10. Malhotra, S. & Santosh, P.J. (1998). An open clinical trial of buspirone inchildren with attention-deficit/hyperactivity disorder. J. Am. Acad. ChildAdolesc. Psychiatry, 37, 364-71.

11. O’Connor, E. 2001. A slip into dangerous territory. Monitor on Psychology,June, 60-62.

12. Johnson, B. A. (2000). Ondansetron for reduction of dringing among bio-logically predisposed alcoholic patients. JAMA, 284(8), 36.

13. Sussman, E. (1997). Cocaine vaccine is almost ready for the market.Psychopharmacology Update, 8(2), 1, 7.

14. Foxhall, K. (2001). Preventing Relapse. Monitor on Psychology, June 46-47.15. Carpenter, S. (2001). Mixing medication and psychosocial therapy for alco-

holism. Monitor on Psychology, June, 36-37.16. Hughes, J. R., Higgins, S. T., Bickel, W. K. Hunt, W. K., Fenwick, J. W.,

Gulliver, S. B.& Mireault, G. C. (1991). Caffeine self-administration, with-drawal, and adverse effects among coffee drinkers. Archives of GeneralPsychiatry, 48, 611-617.

17. Charney, G. S.; Henninger, G. R. & Jatlow, P. I. (1985). Increased anxio-genic effects of caffeine in panic disorders. Archives of General Psychiatry, 42,233-243.

18. Bruce, M. & Lader, M. (1989). Caffeine abstention in the management of

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anxiety disorders Psychological Medicine, 19, 221-214.19. Wetter, D. E., Fiore, M. C., Gritz, E. R., Lando, H. A., Stitzer, M. L.,

Hasselblad, V. & Baker, T. B. (1998). The agency for health care policyand research, smoking cessation clinical practice guideline, findings andimplications for Psychologists. American Psychologist, 53(6), 657-669.

20. Morbidity and Mortality Weekly Report. (1997). 46(20), 444-451.21. Parrott, A. C. (1999). Does cigarette smoking cause stress? American

Psychologist, 54(10), 817-820. 22. Breslau, N., Kilbey, M. & Andreski, P. (1991). Nicotine dependence, major

depression and anxiety in young adults. Arch. Gen. Psychiatry, 48, 1069-1074.

23. Walton, R., Johnstone, E. & Munafo, M. (2001). Genetic clues to the molec-ular basis of tobacco addiction and progress towards personalized thera-py. Trends Mol. Med., 7(2), 70-76.

24. Leistikow, B.N., MD, MS, Martin, D. Jacobs, J., MD, MPH, and Sherman, C.,PHD. (1996). A meta-analysis of the prospective association betweensmoking and suicide. J. Addictive Diseases, 15, 141.

25. Jorenby, G. B. Leischow, S. J., Nides, M. A., Rennard, S. I., Johnston, J. A.,Huges, A. R., Smith, S. S., Muramoto, M. L., Daughton, D. M., Doan, K.,Fiore, M. C. & Baker, T. B. (1999). A control trial of sustained-releasebupropion, a nicotine patch, or both for smoking cessation. New EnglandJournal of Medicine, 340, 685-691.

26. Eisch, A. J., Schmued, L. C. & Marshall, J. F. (1998). Characterizing corticalneuron injury with Fluro-Jade labeling after a neurotoxic regimen ofmethamphetamine. Synapse, 3, 329.

Double-blind, placebo-controlled, dose-response trial of ondansetronfor the treatment of methamphetamine dependence. This study iscurrently recruiting patients. Sponsored by National Institute onDrug Abuse (NIDA), University of Texas study ID Number NIDA-CTO-0011-1, study start date June 2002; estimated completion dateSeptember 2003. NLM Identifier NCT00040053.

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