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1989

Effects of Cocaine Use and Withdrawal on ClinicalMemory and New Learning.Madeline Uddo-craneLouisiana State University and Agricultural & Mechanical College

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EFFECTS OF COCAINE USE AND WITHDRAWAL

ON CLINICAL MEMORY AND NEW LEARNING

A Dissertation

Submitted to the Graduate Faculty of the Louisiana State University and

Agricultural and Mechanical College in partial fulfillment of the

requirements for the degree of Doctor of Philosophy

in

The Department of Psychology

byMadeline Uddo Crane

BA. , Loyola University of New Orleans, 1982 M.S., University of Southwestern Louisiana, 1987

August 1989

Acknowledgements

I wish to express my sincerest gratitude to Dr Wm. Drew Gouvler, the

chairman of my committee, for his guidance, cooperation, f le x ib il ity ,

insight, end unfaltering calmness I am indebted to him for making a

potentially unbearable task bearable Appreciation is also expressed to

my entire committee, Dr. Fredda Blencherd-Fields, Dr. John Junginger, Dr

Arthur Riopelle, and Dr. W illiam Waters for their cooperation and

guidance.

I am deeply grateful to Dr Patric ia Sutker for the opportunities which

she has afforded me, for her fa ith in me, and mostly, for the example

which she has set for me to follow. Without her encouragement, this goal

would not have been reached as expeditiously

I am grateful to Colonel Martinez of the Louisiana National Guerd,and

his entire s ta ff at Jackson Barracks,for the ir cooperation end courtesy

I am also indebted to Dr Jose Pena and the entire s ta ff of the Drug

Dependence Treatment Unit (DDTU) of the Veterans Administration

Medical Center - New Orleans. In addition, I would like to express my

sincerest gratitude to the DDTU residents who participated in this study

for the ir willingness end re liab ility .

ii

I am grateful to Jack Moore for his assistance, patience, and

knowledge of statis tics .

Appreciation is also expressed to Jacque Egan for the support,

encouragement, and diversion which she consistently offered

I am grateful to my entire fam ily for the ir love and support. I am

particularly thankful to my parents who so w ill ing ly provided me the

opportunity to acquire my education and for encouraging me to achieve

the goals to which I aspire Additionally, I thank them for the stab ility ,

love, and perspective which they have given me throughout my life

Lastly, this dissertation is dedicated to my husband, Stephen, who

accompanied me on this " q u e s tT h e love, help, understanding, patience,

end distraction which he unfailingly provided gave me the strength to

complete this project

iii

TABLE OF CONTENTS

Acknowledgements it

List of Tobies..............vi

Abstroct........................ vit

CHAPTER

I History of Cocoine Abuse.....................................

Phormocology............................................................

Routes of Administrotion.....................................

Neuropsychology ond Substonce Abuse ........

Effects of Specific Drugs on Memory.........

Alcohol...............................................................

Morijuono..............................................................

Opioids .....

Polydrug Abuse................................................

Cocoine...............................................................

Withdrowol E ffects...........................................

Rotionole................................ ....................................

2

10

12

16

16

16

17

17

IB

16

20

21

II Method.....................................................................................................................24

Subjects....................................................................................................... 24

M aterials............... .................................................................................. 27

Procedure..................................................................................................... 34

III Results................................................................................................................... 36

IV Discussion............................................................................................................. 40

Limitations of the S tudy.........................................................................45

CLinical Implications......................................................................... 47

Conclusion................. 49

REFERENCES ...................................................... 50

TABLES........................................................................................................................ 64

Table 1.......................................................................................................... 64

Table 2 .......................................................................................................... 66

Table 3 .......................................................................................................... 66

Table 4 ...................... 71

APPENDIX Informed consent for control subjects.......................................72

V ITA ...............................................................................................................................74

v

LIST OF TABLES

1. Mean Subject Demographic Characteristics

2 Mean Scores on Memory Tests for Each Group

3 Summary of Results from the Analyses of Variance

4 Summery of eta square values

vi

Abstract

This project was conceptualized as an exploratory examination of

the neuropsychological sequelae of cocaine abuse, specifically the drug's

effect on new learning and memory The experimental groups were

composed of 30 veterans enrolled in a drug treatment program for

cocaine abuse This group was divided equally by route of administration,

i e , group one included 15 individuals whose preferred route of

administration was intravenous injection, group two included 15

individuals whose preferred route of administration was smoking The

comparison group consisted of 15 individuals enlisted in the National

Guard The groups were essentially homogeneous, w ith a mean age of 34 6

(SD=6 6), mean education level of 13.1 (£Q= 1.7), mean IQ of 98.6 (SD=8.8)

On two separate occasions, five widely used memory assessment

instruments were administered to measure visual memory, verbal

memory, and attention/concentration (Auditory Verbal Learning Test

(AVLT), Complex Figure Test, Digit Span, Visual Memory Span, Verbal

Fluency Test) A lternate forms of these memory tests were administered

during the posttest (four weeks subsequent to the in it ia l testing). Nine

univariate analyses of variance (ANOVA) using a 3 x 2 repeated

v i i

measures design were employed to analyze the date. Controls

performed significantly better then the IV group on two measures of

new learning ab ility sum of AVLT tr ia ls 1-5 F (2 ,42 ) = 5.60, p > .006

and on the immediate memory score of the Complex Figure Test £

(2 ,42) - 3.08, p < 020 Smokers end controls performed significantly

better than the IV group on the delayed recall component to the Complex

Figure Test F (2 ,42) - 4 35, p < 019 Controls performed significantly

better than both experimental groups on tr ia l 7 (delayed recall) of the

AVLT F (2 ,42) = 6 42 p < .004 The results of this study indicate that

chronic cocaine ingestion has an adverse effect on new learning end

recall of both verbal and visually mediated tasks. Additionally, the

degree of impairment appears to be correlated w ith the route of

administration, i.e., individuals who reported intravenous injection as

their preferred route of administration demonstrated greater impairment

than those who chose smoking as their primary route of ingestion.

Because IV injection provides the most e ffic ien t delivery of the drug to

the brain, it is hypothesized that cocaine Is a neurotoxin w ith a dose

dependent effect on memory functioning.

v li i

Chapter I

Cocoine use ond Its untoward e ffec ts have Increased dram atically

since the drug's resurgence of popularity over the past tw o decades Use

of this i l l i c i t drug is now approaching epidemic proportions. The most

recent National Ins titu te on Drug Abuse (NIDA) epidemiological

investigation of cocaine use revealed that the number of Americans who

hod used the drug at least once increased from 5.4 m illion in 1974 to 22

m illion in 1985, and that 5 6 m illion were current users ( i.e., individuals

who hod used cocoine w ith in the post 30 days), a 29J5 increase from 1977

to 1985 As a correlate to increased use, the number of cocaine re lated

emergency room admissions, trea tm ent admissions, and deaths has also

risen (Adams & Kozel, 1985). Additionally, th is survey estim ated that In

1985, 3 m illion people were dependent on the drug.

A recent assessment of demographic trends in cocaine use is

provided by a survey conducted via the National Cocaine Hotline,

800-C0CAINE, which receives an average of 1400 calls per day (Herridge

& Gold, 1966) Compared to 1983, survey respondents In 1987 were

younger (average age=27), hod fe w e r years of education, low er incomes,

1

2

higher rotes of unemployment, were more likely to be mole, end

chose smoking os the preferred route of edministrotion Results of this

survey suggest thot cocoine is being used by o larger, more diverse

somple of the population

History of Cocoine Abuse

Cocoine, derived from the leaves of the Erythroxylum coca plant, is

found predominantly at high altitudes in Peru, Bolivia, and Columbia. From

0 6 -1 .8 percent of the alkaloid cocoine is contained In the small leaves

(Ritchie & Greene, 1905), which ore harvested on on overage of three

times per year It is estimated that 4 0 0 ,0 0 0 acres of South American

highlands ore utilized to cultivate cocoine and thot approximately 200

tons of i l l ic i t cocoine ore imported into the United States annually, half

of the total exports (White, 1908)

Despite its dangers, many diverse cultures have used cocaine for its

psychotropic properties fo r thousands of years. Archaeological evidence

suggests thot South American cocoine use may dote to 3,000 b.c. (Van

Dyke & Byck, 1982) However, the Incos were the f irs t to document Its use

end hence are often cited as the f i rs t to self administer cocaine for its

psychotropic effects. Coco leaf chewing is w ell described as an Integral

port of early Inca civ ilization , where i t was known os the ‘ g ift of the Sun

3

God' (Kteber, 1986), Members of this culture believed the coca plant was

the divine providence of the God Inti, who sent I t to alloy unhappiness and

satiate basic needs (Allen, 1987a) Following P lzarros conquest in the

early 1500's, coca leaf chewing was banned by the Spaniards, until I t was

found thot the Incos were more productive while under the influence of

the drug As a result of this discovery, King Philip II endorsed cocoine os

beneficial to the Indian people and the Catholic church become the major

South American supplier of coca to the indigenous Indian people

(Peterson, 1977)

In spite of In it ia l impediments, cocaine was soon introduced to

Europe Early attempts by the Spaniards to introduce the stimulant to

their homeland were fru it less because the leaves lost their potency

during the voyage from South America (Allen, 1987a) Hence, the drug did

not become known in Europe until the alkaloid cocaine was extracted from

the coco leaf. Although Friedrich Gaedecke, a German chemist, was the

f i rs t to successfully execute this procedure in 1855, the product of

extraction was not named “cocaine' until 1859 by Albert Niemann, a

professor at the University of Gottingen in West Germany (Allen, 1907a)

Niemann observed thot his discovery had an unpleasant taste and caused

4

his tongue to become numb (Ritchie & Greene, 1985) Following these

discoveries, cocoine ossimiloted into European society

Because eorly reports presented cocoine os o wonder drug, i t soon

become o popular ingredient of beverages and elixirs. In 1659 Pablo

Mentegazzo published on essoy which praised the new drug os o cure for

fatigue, weakness, and decreased libido Attendant to the publication of

Mantegazzo's research, cocoine was added to many over-the-counter

preparations (Kleber, 1908) During the mid 1860's Angelo Moriani, a

Corsican entrepreneur, developed one such mixture of cocoine and wine

called Vin Moriani Well received os a stimulant end digestive aid, i t was

endorsed (in exchange for a free case) and used by turn of the century

leaders of society, e g, Pope Leo Xlll, Robert Louis Stevenson, Henrik

Ibsen, Thomas Edison, President W illiam McKinley, Sarah Bernhardt

(Allen, 1987a, Kleber, 1988) In the sp irit of competition, John Styth

Pemberton of Georgia introduced Coca-Cola, a non-alcoholic product

containing coca syrup and caffeine, to the United States In 1886, Cocaine

remained a major ingredient of this new product, which was marketed as

"the intellectual end temperance beverage," until 1903 (Allen, 1987a)

While the general public was enjoying the stimulant e ffec ts of

cocaine in beverages, a Russian physician and professor was

5

experimenting w ith the clinical properties of the drug In 1080, Vassili

finding that his skin was numbed to a pin puncture following a cocaine

von Anrep documented the anesthetic properties of the compound a fte r

injection (Ritchie & Greene, 1905). Cocoine was the f i rs t local anesthetic

to be discovered and has since been employed in this capacity, primarily

in the fields of opthalmology, dentistry and facial surgery Currently local

anesthesia is the only medically indicated use for cocaine

Contemporaneously w ith von Anrep's discovery, other investigations

into the drug’s psychotropic qualities were being conducted by Sigmund

Freud, who became interested in the central nervous system effects of

cocaine while employed in neurology at a Vienna hospital. Following

personal experimentation, he endorsed its use in treating a vast array of

unrelated ailments, such as alcohol ond drug obuse, gastrointestinal

disorders, venereal disease, asthma, fatigue, impotence, depression,

hysteria, and altitude sickness (Kleber, 1908). As Freud extolled the

virtues of the drug in his 1804 book entitled Uber Coca, the head of the

American Medical Profession made collateral laudatory testimony Such

endorsements lead to prevalent cocaine use in both Europe and America

(Allen, 1987a). It is estimated that in 1907, 1.5 m illion pounds of cocaine

entered the United States and that Americans consumed equivalent

6

amounts of the drug tn 1906 and 1976, even though the population hod

Increased two fold by the la te r date (Allen, 1987a).

Although originally deemed safe, disillusionment and sanctions began

as the untoward effects of cocoine ( e g , addiction, death) became

evident. Cocoine was mode Illegal by the Harrison Narcotics Act of 1914

(Kleber, 1986) Such restrictions on the use, sole, and distribution of

cocoine elic ited concomitant increases In price and decreases In

availab ility and popularity. Between the end of this f irs t , turn of the

century, epidemic and the beginning of the second, cocaine was prim arily

recreation for the e lite and avant-garde

As drug experimentation increased during the late 1960*s and

early 1970’s, cocoine was rediscovered, currently, because of

greater potency and availability , the use of this drug Is

approaching epidemic proportions. The In it ia l resurgence of cocaine's

popularity may be partia lly attributable to the widespread belief that,

relative to other i l l ic i t drugs, cocoine was safe and not physically

addicting. This tenet was put forth by credible sources Including the

Comprehensive Handbook of Psuchtatru (Kaplan, Freedmen, & Sodock,

1960), the Diagnostic and S ta tis tica l Manual of Mental Dlsorders-Thlrd

Edition (DSM-111,1960), the National Commission on Marihuana and Drug

7

Abuse (Notional Commission, 1973) and the Strategy Council on Drug

(Strategy Council, 1973). Originally, cocoine was deemed psychologically,

but not physically addicting because i t did not produce tolerance or

w ithdraw al However, Gewin and Kleber (1 9 0 6 ) hove described a cocaine

w ithdraw al syndrome which is characterized by sleep end appetite

disturbances, fatigue, depression, and i r r i ta b i l i ty . While th is w ithdraw al

symptomatology is not l ife threatening or as debilita ting os syndromes

common to w ithdraw al from central nervous system depressants, i t does

represent a w e ll-de fined syndrome experienced fo llowing cessation of

prolonged cocoine use In addition, a tolerance phenomenon is described

by individuals who abuse the drug over extended periods of tim e, i. e ,

chronic users report an in ab ility to a tta in levels of intoxication

comparoule to those experienced during the early stages of cocaine use,

despite drastic increases in the quantity consumed (Jones, 1907)

Additionally, several theorists hove begun conceptualizing cocaine as

physically addicting based on the findings that chronic Ingestion of

cocoine a lte rs neurochemistry which results in cravings to continue

cocoine use.

The most compelling evidence that cocaine use can lead to dependence

is seen w ith in animal research paradigms and in the e ffec ts of the drug

0

on Individuals who abuse it. Animal studies which have examined the

reinforcing properties of cocaine provide cogent illustrations of the

unparalleled addiction potential of cocaine. These studies which have

examined the consequences of allowing rots and monkeys unlimited,

continuous access to self administered Intravenous Injections of cocaine

have consistently shown that w ith in days these animals w i l l

compulsively ingest cocoine to the point of death (A1gner& Bolster, 1976,

Bozorth & Wise, 1965, Deneou, Yanogita, Seevers, 1969; Johenson,

Bolster, Bonese, 1976) Likewise, animals w i l l go to great lengths to

obtain cocoine For example, Yanogita (1 9 7 3 ) found thot rats would bar

press over 12,000 times in order to receive a cocaine injection, studies

w ith comparable results were conducted by Bedford, Baily, & Wilson

(1976), G riffiths , Brody, &. Shell (197B), and G riffiths , Findley, Brady,

Dolan-Gutcher, & Robinson (1975) S im ilarly , i t was demonstrated thot

monkeys continued to self administer cocaine even when the infusion was

accompanied by on electric shock (Bergman & Johonson, 1961; Grove &

Schuster, 1974) Furthermore, Johonson (1 9 7 7 ) found thot monkeys

preferred infusion of a high dose of cocoine given in tandem w ith on

electric shock to half thot dose w ith no shock.

Examples of s im ila r compulsive behavior in humans, i.e., endurance of

9

severe punishment in order to obtain and use cocaine, maintenance of

cocaine use despite adverse consequences and to the exclusion of other

pleasurable ac tiv it ies and basic sustenance are replete in the cocaine

l itera ture and mass media. Additionally, there has been an escalation in

cocaine-related treatment admissions, emergency room admissions, and

deaths during recent years Although the Image of cocaine as a benign,

nonaddicting drug persisted until the beginning of the present decode, it

has become apparent thot this conceptualization was erroneous It

appears that cocoine may be psychologically addicting because of its

highly reinforcing effects , and physically addicting because of its effec t

on neurotransmitter systems The revision of the DSM ill (DSM -III-R ,

1987) has added cocaine dependence to its l is t of psychooctive substance

abuse disorders and in recent years cocaine has become regarded os a

powerful drug w ith high addiction l ia b il ity

During the early stages of its rebirth , the high price of the drug

was both a deterrent and on enticement; that is, the high cost mode it a

status symbol Although cocoine use continued to escalate Into the early

1980's, the expense and lim ited supply prevented widespread abuse

(Julien, 1988). However, new trends in cocaine use hove emerged,

part ia lly os a result of basic economic principles: new cocoine marketing

10

strategies hove effec tive ly increased the supply, therefore decreasing

price ond increasing availab ility , while higher potency has boosted the

demand As a consequence of increased potency and decreased price, abuse

l ia b il ity of the drug has greatly Increased and use has spread to a wider

range of social strata, age, ond educational level (Roehrich, Gold, &.

Lonoff, I9 6 0 )

Pharmacoloqu

Both the pharmacological properties of cocoine and the hedonistic

qualities of living organisms ore major factors In the drug's high

addiction l ia b il ity A rapid alternation between pleasant and unpleasant

states occurs in the cocoine use cycle, that Is, ingestion of cocaine

Induces euphoria of short duration followed by a state of craving to

re-experience the "high" (Woshton, Stone, & Hendrickson, 1908). This

pattern is Intensified when smoking ond injection are used os Ingestion

routes, making these routes of administration more prone to abuse.

Latency to addiction is shorter and severity of addiction Is more

profound In individuals employing these highly e ff ic ie n t methods of

administration (Verebey & Gold, I9 6 0 )

The most widely held pharmacological theory of this local anesthetic

ond central nervous system stimulant is that reinforcing properties

11

result from dopamine reuptake Inhibition ond consequent increase of

dopamine in the synoptic c le ft ( Dockis & Gold, 1980, Wise, 1984, Wyatt,

Karoum, Suddoth, & H itri, 1988) Psychological e ffects are attributed to

its sensitization of the dopomine reword pathways of the brain. Support

for the dopamine hypothesis is provided by animal research which

suggests amelioration of the reinforcing properties of cocaine w ith the

administration of dopomine antagonists (Wise, 1984) In addition,

Bromocriptine, a dopamine agonist, has been found to decrease cocaine

cravings in human subjects (Dockis & Gold, 1985) Although evidence

suggests that the m ajor actions of cocaine likely result from effects on

the dopaminergic pathways, other, less understood, neurotronsmitter

(eg , norepinephrine, serotonin) and possibly neuroendocrine effects may

contribute to its actions In fact, while acknowledging the central role of

dopamine, the most current NIDA research concludes that the

pharmacological mechanisms of cocaine are likely more complex than

previously hypothesized That is, more recent investigations suggest that

effec ts w ithin the dopaminergic system, and between dopamine, other

neurotransmitters, and peptides are likely more extensive than suggested

by earlier research (Dunwiddie,1988)

12

Routes of Administration

Routes of administration are important in determining the efficacy of

drug delivery to the brain, and hence the potential for addiction (Verebey

& Gold, 1908). Recent trends Indicate that smoking ond parenteral routes

of administration are replacing Intranasal use (Malow, 1989). A partial

explanation for the increased abuse of cocaine Is the increased popularity

of these more e ffic ient modes of ingestion. Although cited as a form of

cocaine administration in the United States fo r over a decade, s ta tis tics

indicate a drastic increase in cocaine smoking (Cohen, 1907). A survey

conducted via the Cocaine Hotline reported that 5 6 * of the callers

employed the smoking route of Ingestion in 1967, up from 2 1 * in 1963

(Roehrich, Gold, & Lonoff, 1986).

Purified cocaine Is smoked in e ither the form of "crack" ( 5 0 - 9 5 * pure)

or freebase ( 9 0 - 1 0 0 * pure), While pharmacologically slmtlor, crack and

freebase are d ifferentiated by method of preparation and presentation.

Freebase Is produced by adding a vo latile substance (e g , ether) and heat

to cocaine hydrochloride and crack is formed by treating the drug w ith an

alkaloid, e g , sodium bicartonete (baking soda) or sodium hydroxide

(Julien, 1968) The la t te r process yields a mass of pure cocoine which is

then divided into chips, or "rocks," ond smoked, most commonly, in a

w ater pipe or cigarette. These preparations have a low er melting point

than cocaine hydrochloide, and as a result, potent concentrations of the

drug are delivered to the brain when smoked (A r if , 1987). The major

distinction between crack and freebase is packaging freebase

preparation is the responsibility of the consumer, while crack is

purchased in a "ready to smoke" form (Gawin & Ellinwood, 1966)

Additionally, this marketing strategy makes it cost e ffec tive to sell

small quantities at low prices, which are affordable to adolescents and

individual of lower socio-economic status (Cohen, 1987). Smoking is an

effic ien t method of administration because very high concentrations of

pure cocaine are delivered from the lungs to the brain w ithin seconds,

however, duration of the extremely reinforcing effects is only 5 to 10

minutes (Verebeyi* Gold, 1980)

Although cocaine smoking is re la tive ly new to the United States, coca

paste smoking is an established method of use In the South American

countries which cultivate the drug (Cohen, 1987) Coca paste is an

intermediate product in the preparation of cocaine hydrochloride,

w ith 4 0 - 0 5 * purity This o f f -w h ite sem i-solid extraction is the product

of ground coco leaves and a solvent, e.g., gasoline, kerosene, or sulfuric

acid The paste is added to a tobacco or marijuana cigarette and smoked

14

Although s im ila r to freebase in effects, this method delivers lower

concentrations to the brain and adverse physical reactions may result

from Ingestion of the solvents used In the extraction process (Seigel,

1962)

When treated w ith hydrochloric acid, coca paste becomes the white

powder known as cocaine, the preparation which is used for tntranasel

and intravenous modes of administration. Intranosal use, or “snorting,”

gained popularity during the early 1970's, end while addicting, the

expense and less e ffic ien t delivery to the brain likely prevented the

epidemic thot crack smoking has become The powder is absorbed into the

nasal mucous membranes when inhaled. Routinely diluted w ith a variety

of other substances ( e g , amphetamine, sugar, caffeine, laxatives,

powdered m ilk) to increase profits, purity of cocaine hydrochloride

vanes from 2 0 * to 9 0 * The drug takes effect w ith in two to three

minutes ond the "high" lasts from 30 to 40 minutes. Complications of this

method include nasal bleeding ond sores, sinus irr ita t io n ond congestion,

in addition to septum damage (Verebey& Gold, 1988).

Cocoine hydrochloride produces a powerful, rapid response when it is

dissolved in w a te r ond Injected Into a vein (Flschmen, 1988) The drug

exerts its effect on the brain w ith in 30 to 45 seconds following

15

injection, producing feelings of intense euphoria which subside w ithin 10

to 20 minutes, This is a highly e ff ic ie n t method of absorption w ith nearly

1 0 0 * bioavailability. A cogent contraindication of intravenous injection

of cocaine is the risk of contracting Acquired Immune Deficiency

Syndrome (AIDS) by shenng a needle w ith an individual who Is Infected

w ith the Human Immunodeficiency Virus (HIV) Other, less fa ta l,

health risks

associated w ith this route of administration Include phlebitis and

hepatitis (Allen, 1907b)

Oral administration, via coca leaf chewing or ingestion of cocoine

hydrochloride, is the least e ffec tive mode of administration (Verebey &

Gold, 1968). A malleable substance made of toasted coco leaves end an

alkaline, e g , lime or ash, is chewed or stored between the cheek and gum

to produce mild feelings of well-being, anorexia, and energy which last

for up to one ond a half hours. Coco leaf purity is 0.5 to 1.8 % (A r if , 1987).

This is the most popular type of ingestion in South America Cocaine

hydrochloride may be swallowed to achieve a slow-acting e ffec t w ith

absorption rates s im ila r to intranasol use (Verebey & Gold, 19B8).

Although nausea may occur, this method appears to be devoid of senous

physical or psychological side effects.

16

NeuropsucholQQU ond Subslance Abuse

Effects of Specific Drugs on Memory

Alcohol. Memory Impairment is an integral port of the constellation of

neuropsychologicol Impairments common among alcoholics (T arter &

Edwards, 1995) Until the hypothesis— that low celling effects on

standard memory assessment instruments preclude manifestation of

alcohol induced d e f id ts - -w e s tested and upheld by Butters, Cermak,

Montgomery, & Adinolfi (1977 ), memory impairments were not

consistently found in alcoholics (Jonsson, Cronholm, & Iz ikow ltz , 1962,

Parsons &. Prigatano, 1977, Welngartner, Foillice, & Merkley, 1971), Since

more sensitive measures have been developed ond administered, defic its

have been identified in several areas, e.g., storage, encoding and retrieval

of verbal (Brandt, Butters, Ryan, Bayog, 1963, Ryan, I9 6 0 , Ryan &. Butters,

i9 6 0 ) ) ond nonverbal (Cutting, 1978, Miglioll, Buchstel, Companini, &

DeRisio, 1979, Parsons & Farr, 1901) material. Additionally, most

evidence suggests that new learning ond recent memory ore more

compromised than remote memory (A lbert, Butters, Brandt, I9 6 0 ,

T a rte r Edwards, 1985)

Length of abstinence has proven to be on important voriable in

assessing memory functions in alcohol abusers, that is, the most obvious

17

dysfunctions are evidenced during the f irs t week of abstinence, a fter

which significant, but incomplete, recovery of function occurs, and

continues until approximately 6 weeks following cessation of alcohol

Ingestion (Ryan& Butters, 19B6). Data suggest that following this in itia l

period of recovery, mnestic impairments remain re lative ly stable over

time, i. e , persistent memory dysfunctions have been reported following

one year (Ryan, DiDario, Butters, & Adinolfi, 1980, Voman, Parsons, Leber,

1985) and 7 years of sobriety (Brandt, Butters, Ryan, & Bayog, 1983).

Maniuana Results of neuropsychological studies of the effect of

marijuana on memory are inconsistent (Hartman, 1988), While some

researchers have found short-term memory impairments in chronic

marijuana users ( Casswell &. Marks, 1973, Melges, Tinklenberg, Hollister,

Gillespie, 1970), others report no memory dysfunction (Grant, Rochford,

Fleming, & Stunkard, 1973, Mendelson & Meyer, 1972; Schaeffer,

Andrysiek, & Ungerleider, 1981,)

Opioids Although one study reported that heroin addicts performed in

the impaired range on the memory score of the Tactual Performance Test

(Hill & Mikhael, 1979), most evidence suggests that abuse of heroin end

other opioids does not adversely e ffec t neuropsychological functioning

(Fields & Fullerton, 1975, Press, 1983, Rounsaville, Jones, Novelly, &

10

Kleber, 1982)

Poludrua Abuse It Is estimated that 5 0 * of Individuals belonging to

this classification experience neuropsychological defic its (T arter &

Edwards, 1965). Studies of cognitive functioning in Individuals who

abuse m ultiple substances have not focused on memory functions

specifically, but general neuropsychological dysfunction Is evident In

investigations employing the Halstead-Relten Battery (Grant, Mohns,

Miller, Reiten, 1976, Grant & Judd, 1976; Grant, Adams, Carlin, Renntck,

Judd, Schooff, Reed, 1976)

Cocaine While investigation of neuropsychological sequelae of

abused substances has received modest attention in general, such

investigations regarding cocaine abuse are v irtua lly nonexistent. While

lacking rigorous empirical investigation, allusions have been made to the

possibility of cognitive dysfunctions attendant to cocaine abuse, for

example, 20 percent of chronic cocaine freebase users surveyed, reported

memory problems and 37.5 percent reported concentration problems

(Verebey & Gold, 1986) Fifty-seven percent of the target population

endorsed memory problems In a survey conducted by Washton end Gold

(1984) Additionally, items relating to memory and concentration

problems are included in the newly developed Cocaine Abuse Assessment

19

Profile (Washton, Stone, & Henrickson, 1986),

Empirical investigation of mnestic e ffects of cocaine is sparse.

Current studies include a doctoral dissertation (Press, 1983) which

investigated neuropsychological functioning in opiate end cocaine users

using the Luria-Nebraska Neuropsychological Battery Participants in the

cocaine group e ither smoked freebase or snorted cocaine hydrochloride,

however, of the 16 subjects, the exact number using each of the

administration methods was not reported. While cocaine users, as a group,

evidenced no significant memory impairment, a s im ila r pattern of

memory defic its was identified in two freebase users, leading Press to

hypothesize that route of administration d iffe ren tia lly effected memory

functions, that is, freebase users may be more likely than intranasal

users to evidence memory impairment

Two studies have examined the e ffec t of cocaine intoxication on

m emory, that is, subjects were assessed while under the Influence of the

drug Resnick (1978 ) found a fte r insufflation of cocaine, individuals

made more errors on a verbal learning task then did controls.

Additionally, a study by Fischmen (1984 ) found that the number of errors

made on a test of new learning Increased as a function of route of

administration, and consequently, cocaine plasma levels, that is, subjects

20

who received intravenous injections as opposed to intranasal

administration performed more poorly

Withdrawal Effects

Both alcohol and heroin have w ell described physical withdrawal

syndromes, however, such symptoms are not Inherent to abrupt cessation

of cocaine use The revision of the Diagnostic and S ta tis tica l Manual of

Mental Disorders-Third Edition (D SM -III-R ) includes a classification for

cocaine w ithdrawal comprised of specific depressive symptomology (e.g.,

fatigue, sleep disturbance, psychomotor agitation) which must be present

for more than one day in order to warrant diagnosis.

In contrast to the unidimensional syndrome identified by DSM-III-R ,

Gowin ond Kleber (198G) hove developed a more elaborate explication of

withdrawal which d ifferentia tes three distinct phases. Phase 1, referred

to os the "crosh," ensues when the cocaine supply is depleted Intense

cravings for the drug are followed by depressive symptomology (e.g.,

anhedonia, insomnia. Ir r i ta b i l i ty ) lasting from 1 to 40 hours. The

following 8 to 50 hours ore marked by extreme fatigue end Increased

appetite. Phase 2, or w ithdraw al, begins w ith a 1 to 5 day period of

normal mood which shortly deteriorates Into a pervasive anhedonic state

It is ot this point that relapse is highly likely; however, i f the individual

21

remains abstinent, symptoms w il l abate w ith in 6 to 19 weeks. With the

cessation of anhedonic symptoms, phase 3 begins. Periodic drug cravings,

typically triggered by environmental cues, are the hallmark of this final

phase. Extinction occurs during this phase i f the abstinent Individual does

not succumb to the cravings. While Gawin and Klebers examination of the

affec tive and biological aspects of cocaine withdrawal

demonstrates considerable treatment validity, equally cogent

Investigations of concurrent neuropsychological functioning are needed.

Rationale

Research examining the neuropsychological sequelae of cocaine abuse

and withdrawal is conspicuously absent from the burgeoning cocaine

l ite ra ture This topic Is of particular importance considering the

epidemic proportions of cocaine use and the paucity of data on the

neuropsychological concomitants of the drug in general, and specifically

In relation to the new, more e ffec tive , routes of administration currently

in vogue Furthermore, evidence suggests that cognitive functioning is

correlated w ith treatm ent outcome in alcohol abusers, hence

investigation of neuropsychological in tegrity w ith in abstinent cocaine

abusers may be of considerable treatm ent va lid ity For example, in a

study conducted by Guthrie & Elliot (1980 ) patients who actively

2 2

participated In an aftercare regime were significantly more likely than

their counterparts who did not attend aftercare to remain abstinent,

however, alcohol abusers who exhibited neuropsychological impairments

at the beginning of the treatment program were significantly less likely

to attend aftercare end hence less likely to remain abstinent. S im ilarly,

results of a study conducted by Walker, Donovan, Kivlahan, & O'Learu

(1983 ) indicate that participants in an alcohol treatment program who

evidenced cortical dysfunction during the f i rs t week of treatment were

less likely to have remained abstinent nine months following discharge

Additionally, current treatment approaches in the fie ld of substance

abuse, eg., relapse prevention, include a significant educational

component If neuropsychological defic its (e.g., impairments in new

learning and memory) exist, then educational m ateria l, which is presented

in both visual and verbal form, may not be assimilated Therefore, i t is of

significant practical importance for this construct to be explored

Furthermore, identification of defic its in consolidation of new

memones may help to localize the pathophysiology of cocaine. That is, if

cocaine abusers demonstrate impairments in learning and retention of

new information, then i t may be hypothesized, for example, that the

temporal lobes are affected by chronic cocaine Ingestion

23

The present study wos conducted to examine the effects of cocaine on

learning ond memory Given the paucity of data examining the

neuropsychological effects of cocaine abuse, the nature of the present

study wos deemed exploratory. Memory test scores were utilized to

evoluate the following empirical questions

1. Is there a difference between cocaine abusers ond controls?

2 Is there a difference between those who in ject cocaine

intravenously ond those who smoke cocaine?

3 Ooes length of abstinence correlate w ith degree of impairment?

Chapter II

Method

Subjects.

A total of 45 subjects participated In this study. The experimental

group consisted of 30 Individuals consecutively admitted to the Drug

Dependence Treatment Unit (DDTU) at the New Orleans Veterans

Administration Medical Center (VAMC) who met the following criteria: 1)

fu lf i l lm en t of DSM -III-R c r ite r ia for cocaine dependence os assessed by

the Structured Clinical Interview for DSM ll l -R (SCID; Spltzer &

Williams, 1986), 2) Stated preferred route of cocaine administration of

either intravenous injection, IV, (n=15) or cocaine freebase, or "crock",

smoking (n=15). Individuals employing Intronosol Ingestion rarely present

for treatment at the DDTU of the New Orleans VAMC and hence were not

be studied, 3) estimated I.Q not less than 1 standard deviation below the

mean, i.e., 05 or below, as measured by the Shipley Institute of Living

Scale (Shipley, 1967); 4) 6 months or longer duration of cocaine use,

Patients who reported a history of neurological Impairment, including

loss of consciousness due to head trauma, were excluded.

Data sugger t that chronic alcohol abuse may cause neuropsychological

24

25

impairment, hence participants w ith a history of severe alcohol abuse

were excluded. Because previous research has indicated that a high

proportion of individuals addicted to cocaine also meet c r ite r ia for

alcohol dependence ( M iH e r G o ld , I9 6 0 ) , i t was concluded that to exclude

ell individuals who met minimum cr ite r ia for alcohol dependence would

drastically decrease the number of potential subjects and more

importantly, that such a sampling procedure may have yielded a sample

which wos not representative of the population of interest. Responses to

the SC ID crite ria for alcohol dependence were utilized to assess level of

severity, i.e., individuals who endorsed seven or more of the nine items

were classified in the severe range and thus were excluded from the

study

Likewise, polydrug abuse has been found to cause neuropsychological

compromise, hence individuals who met the threshold for current

addiction to more than one i l l ic i t drug other than cocaine were excluded.

Additionally, the Minnesota Multiphaslc Personality Inventory (MMPI;

Hathaway and McKinley, 1954) F scale was employed to screen for

individuals who potentially were unwilling or unable to participate due

to various reasons, e.g., i l l ite racy , psychosis, malingering That is,

individuals whose MMPI F scale T-score was greater than 90 were

26

excluded from participation in the study This protocol was

completed routinely by all DDTU residents as a component of ongoing

psychological assessment on the unit.

In addition to the exclusionary c r ite r ia described above, potential

control subjects who had ever smoked or Injected cocaine, had used

cocaine via the intranasel route more than tw ice, or met minimum

crite ria for alcohol dependence were excluded from the control group The

SCID was utilized to assess alcohol dependence

Group 1 (intravenous Infection)

Members of this cohort included 15 males between the ages of 27 ond 46

( * = 37.B6, SC = 4.76 ), Mean number of years of education completed wos

13 30 (SC = 1 73) All participants in this group were male, predominately

black (86.67 * ) , w ith mean estimated WAIS-R IQ of 97.73 (SC = 7.42)

Group 2 (Smokers):

This group was comprised of 15 individuals (2 females) ranging In age

from 27 to 48 years (a = 33 20, SC = 5.32). Ninety-three percent were

block, mean number of years of formal education reported was 13.00

(SC r 1.45 ), ond mean estimated IQ equaled 95.20 (SC = 7.88).

The percentage of blacks versus whites ond males versus females

w ith in these groups is representative of the population characteristics of

27

individuals treated on the DDTU

Group 5 (Control)

The control group consisted of 15 individuals (2 females) enlisted in

the Army National Guard who ranged in age from 20 to 42 years old and

reported a mean level of education of 13 17 years (SC = 1.70 ). This sample

was predominately black (80S) and attained an estimated mean IQ of

102 80 = 9.23). A summary of demographic variables for each group is

presented in Table I

Insert Table 1 about here

Materials

The following screening Instruments were administered to all new

DDTU admissions who reported cocaine as their drug of choice and

employed either smoking or intravenous in jection as their primary route of

administration

1) Minnesota Multiphasic Personality Inventory (MMPI): This is a 566

item criterion-keyed instrument designed to assess psychological status

This measure is the most widely used personality assessment Instrument

and hes been been employed in over 6000 studies (Graham, 1907). The test

2 0

yields T-scores on ten clinical scales, three va lid ity scales, end a Cannot

Say scale

2) Structured Clinical Interview for DSM -III-R (SCID, Spitzer &

W illiams, 1986) : Cocaine abuse was assessed using this instrument

Subject responses to questions assessing Diagnostic and S tatis tica l

Manual of Mental Disorders Third Edition - Revised (DSM -III-R ) c r ite ria for

the disorder are rated as absent, subthreshold, or threshold. The SCID has

received support as an objective approach to diagnosis and for its

re lia b ility end va lid ity (Mackinnon & Yudofsky, 1986, Riskind, Beck,

Berchick, Brown, & Steer, 1987) Only individuals w ith 3 or more c rite ria

scored at threshold level for cocaine abuse were included in the

experimental group Abuse of other i l l ic i t drugs end alcohol was also

assessed using this structured interview The total number of c r ite ria

scored at the threshold level provided a measure of the severity of

addiction, i.e., 3 /9 = minimum severity, 9 /9 = maximum severity

3) Shipley Institute of Living Scale (Shipley, 1967): This

self-adm inistered intelligence screening test consists of two subtests

the vocabulary subtest which Is comprised of 40 multiple-choice word

definition items ond the abstraction subtest, comprised of 20 Items which

29

assess ab ility to determine the next logical item in a pre-established

pattern or sequence The number of words correctly defined is the

vocabulary score, the number of correct answers multiplied by 2 is

the abstraction score. An estimated Wechsler Adult Intelligence

Scale-Revised (WAIS-R) I.Q. may be derived from the sum of scores on the

two subtests (Zachary, Crumpton, & Spiegel, 1905), A .07 correlation was

achieved between the WAIS-R and the Shipley using the conversion

outlined by Zachary, et el. (1965). Estimates of in tellectual functioning

were attained using this method

4) Background Information Questionnaire (BIQ); Demographic

information were e lic ited vie this brief questionnaire which is currently

in use at the VAMC-New Orleans

Individuals who met pre-established c r ite r ia were chosen as subjects

and received alternate forms of several tests of verbal ond non-verbal

memory on two separate occasions during the ir treatment on the DDTU.

Data suggests that more challenging tests are required in order to detect

subtle defic its in substance abusing populations Therefore, when

selecting this battery, neuropsychological tests deemed sensitive to

subtle cortical defic its were included (i.e., AVLT ond Complex Figure Test)

in addition to less demanding tests of word generation (i.e., Verbal

30

Fluency) ond ottention/concentrotlon (I.e., Digit Spon ond Visuol Memory

Spen). All tests ore frequently employed to measure memory.

Administration time for this bettery wos approximately 1 /2 hour

A Verbal Memory

1) Verbal Fluency Test (VFLU): This test, which Is frequently

Included in batteries which assess mental status, requires subjects to

generate words that begin w ith a specified le t te r of the alphabet. One

minute is allowed for each le t te r The le tters C, F, ond L were used during

the pretest ond P, R, ond W were used during the posttest. Norms adjusted

for age, sex and education ore available for these le tters (Benton &

Hamsher, 1976) Scores equal total number of correct responses given

w ith in the allotted time Although this Instrument Is commonly employed

os a measure of frontal lobe integrity, i t may also measure memory

functioning, specifically le f t hemisphere in tegrity , since the subject is

required to remember the task demands in addition to retrieving

appropriate words

2) Auditory-Verbal Learning Test (AVLT; Rey, cited in Lezok, 1903):

This demanding test measures Immediate memory, learning over repeated

tr ia ls , and delayed recall It consists of 5 administrations of a 15-word

l is t , in addition to on interference tr ia l (a second lis t of equal length).

which is followed by a sixth tria l of the original l is t Following each

presentation of the f irs t lis t, the individual was asked to recall as many

words from the l is t os possible. The same procedure was followed for the

second lis t , a f te r which the subject wos instructed to once again recall

the f irs t lis t (t r ia l 6) A 30-m inute delayed recall of the original lis t wos

included This instrument yields several scores; number of words

correctly recalled for each tr ia l , the number recalled during tr ia l 6, end

the number of words recalled following the 30-m inute delay. An alternate

l is t is available ond wos administered at fo llow -up in order to control for

practice effects Norms ore available for this measure which is likely

more sensitive to le ft hemisphere compromise

3) Digit Span The f i rs t presentation of this measure of

attention/concentration for verbal stimuli consisted of the Wechster

Memory Scale-Revised (WMS-R, Wechsler, 1987) Digit Span subtest

Number sequences used in the Digit Span subtest from the Wechsler Adult

Intelligence Scale-Revised (WAIS-R, Wechsler, 1981) were given during

the posttest In it ia lly , subjects were asked to repeat a series of numbers,

beginning w ith 3 numbers and increasing by 1 number (to a maximum of 8)

each time one or both of the tr ia ls is correctly repeated. Testing wos

32

discontinued when both tr ia ls of any given series were failed Following

completion of "digits fo rw a rd / the subject wos asked to repeat a

different set of number series In the reverse order from Its presentation

Testing began w ith 2 digits and proceeds, in a fashion sim ilar to digits

forward, to a maximum of 0 digits. One point was given for each correct

repetition tr ia l Tes t-re tes t re l ia b il ity coefficients for this test range

from 8 2 - 89 D iff icu lty w ith this task is generally regarded as a possible

indicator of d iff icu lt ies in attention/concentration

This test is sensitive to diffuse and or le ft hemisphere dysfunction

B Non-Verbal Memory

1) Complex Figure Test (CFT, Taylor, cited in Lezek,1983) This

challenging test of visual-spatial constructional ab ility provides a

measure of visual memory (immediate and delayed) Subjects were

presented w ith a drawing of a complex geometric design and asked to copy

the design on a blank sheet of paper Upon completion of this task, the

original drawing and copy was removed, and the subject was asked to draw

the design from memory on another blank sheet, constituting a measure of

immediate memory. Approximately 30 minutes later, he was again asked

to reconstruct the figure from memory, constituting a measure of delayed

3?

recall Figures were scored via a unit scoring method devised and normed

by Osterrieth (cited in Lezak, 1983). Alternate forms, objective scoring

crite ria , and adult norms ere available for this assessment tool. Following

the immediate recall task of both the pretest ond posttest, Individuals

were informed of the delayed recall measure. This measure of visual

memory is deemed more sensitive to right hemisphere dysfunction

2) Visual Memory Span (VMS) This subtest from the WMS-R, which

requires the examinee to touch colored boxes printed on a card in the some

or reversed order as presented by the examiner, wos employed to measure

attention/concentration for visual stimuli The "topping forward" subtest

required the subject to touch boxes in the same order as touched by the

examiner (beginning w ith 2 boxes, to a maximum of 8) Two tr ia ls of each

length were given Testing wos discontinued when both tr ia ls of any length

were failed "Topping backward" followed a similar procedure, however, at

this time the subject was directed to top boxes in the reverse order of

presentation Tapping backward began w ith 2 taps ond has a maximum of

7 taps One point wos earned for each correct sequence The total row

score for topping forward ond topping backward is converted to a standard

score, for which norms are available. T e s t-re tes t re liab ility for this

34

test is between .83 and .88 Because this test requires organization and

memory of visually-mediated stim uli, i t is deemed more sensitive to right

hemisphere dysfunction.

Procedure

Phase I of the DDTU program consisted of a 21 day Inpatient

treatment Upon discharge from this phase, residents began Phase II, a 14

day outpatient stay in a residential treatment fac ility . During this phase,

participants in the program are required to attend 4 meetings per week on

the DDTU In itia l memory testing wos conducted 7 -1 0 days following

admission into Phase I In order to permit adequate tim e for detoxlficotion

(Sheehy, 1907). The posttest wos administered at the end of Phase II of

treatment, i.e., 3 0 -3 5 following admission. Routine drug testing is

mandatory during this phase of treatment, hence only individuals who

remained sober during Phase II received the postttest. It wos assumed that

conducting the posttest while subjects were s t i l l actively participating in

treatment would bolster compliance Screening was conducted

approximately one week following admission to the DDTU. The SCID was

administered by the examiner, the Shipley was then completed by the

subject while supervised by the examiner. The subject completed the MMPI

unsupervised

35

Subjects who met c r ite ria for participation in the study then

received the battery of memory tests. During all sessions, in order to

promote standardization, these tests were given in the following

sequence 1) Auditory Verbal Learning Test, 2) Complex Figure Test, 3)

Digit Span, 4) Visual Memory Span, 5) Verbal Fluency. The post-test was

conducted approximately 4 weeks subsequent to the in it ia l testing.

The same procedure was utilized in testing the control group. A brief

interview was conducted w ith potential subjects in which the study was

explained and demographic information was obtained A consent form

summarizing the study and the risks and benefits of participation was

signed by those who agreed to participate (see Appendix). These subjects

then completed the MMPI end Shipley During the second session, the SCID

for alcohol dependence was administered The memory battery was then

administered if ell c r ite r ia for participation were met. The posttest

memory battery was re-administered in a single session four weeks

subsequent to the in it ia l testing

Chapter III

Results

The control group ond experimental groups which were examined in

this study were essentially homogeneous. No differences were found

among groups on demographic variables which may a ffec t performance on

memory tests, e.g., IQ, age, race, and education, hence on analysis of

covariance wos not conducted

Significant differences were found between Individuals w ith a history

of cocaine abuse ond controls on performance of demanding tasks

designed to measure the ab ility to learn end recall new information

presented in both non-verbal ond verbal form. Furthermore, Individuals

who employ intravenous injection os the ir usual route of administration

evidenced greater defic its in performance than those who smoke cocaine

No significant differences were found on verbal and non-verbal measures

of attention/concentration or verbal fluency. No significant differences

among groups in changes in performance were observed os a function of

the time factor, i.e., there wos no significant difference in performance

between the control group end the experimental groups between in itia l

ond fo llow -up memory test scores. Table 2 presents means ond

36

37

standard deviations of scores achieved by the three groups on each

dependent variable during pretest and posttest assessments

Insert Table 2 about here

Nine univariate analysis of variance (ANOVA) tests using a repeated

measures design w ith factors of 3 (groups) x 2 (t im e) were employed to

compere performance on measures of memory functioning, i.e., three

scores form the Auditory Verbal Learning Test (sum of words recalled

over tr ia ls 1-5, total number of words recalled on tr ia l 6 [tria l following

the interference tr ia l l , total number of words recalled on tr ia l 7 [30

minute delayed r e c a l l ] ); three scores from the Complex Figure Test (copy

score, immediate memory score, 30 minute delayed recall). Digit

Span-Total; Visual Memory Span-Total; Verbal Fluency-Total A summary

of the results from the Analyses of Variance are presented in Table 3

Insert Table 3 about here

Using a univariate analysis of variance, a group mein e ffec t was found

on two measures of learning of new material: the sum of AVLT tr ia ls 1-5 ,

38

£ (2, 42) r 5 68, g < .006 ond on the immediate memory score of the

Complex Figure Test, £ (2 ,42 ) = 3.88, g < .028. In order to control the Type

I experimentwise error rote, Tukey's Studentlzed Ronge Test wos

performed ond indicoted thot controls scored slgnificontly higher then the

IV cocoine group on both voriobles. While in the expected direction, the

difference in performance between controls ond smokers on these two

meosures wos not significont Significont differences were olso found

between the control group ond both experimentol groups on the AVLT

meosure of deloyed recoil (trio l 7) £ (2 ,42) = 6.42, g < .004. Tukey's Test

indicoted thot controls recoiled o slgnificontly greoter number of AVLT

words following o 30 minute deloy thon e ither the IV group or the smoker

group A group effect wos olso evidenced on deloyed recoil of the Complex

Figure Test, £ (2 ,42) = 4.35, g < .019. Tukey's Test reveoled significontly

better performonce by the control group thon by the IV group, os well os

slgnificontly better performonce by smokers thon by the IV group, on this

meosure Controls scored slightly higher thon smokers on the delayed

recoil component of the Complex Figure Test, however, the difference

between these two groups wos not significont

Univoriote onolysis of vorionce revealed o significont moin e ffec t for

time of odmimstrotlon on AVLT trio l 6, £ (1 ,42) r 5.04, g < 030 ond tr ia l

39

7 F (1 ,42) = 12.39, e < .001. Tukey's Test Indicated that posttest scores

for all three groups were lower than pretest scores on both tasks

Differences were also found between testing administrations on

immediate memory, F (1 ,42) = 32.92, e < 0001 and delayed recall, £ (1 ,42)

= 46.62, p < 0001 of the Complex Figure Test. Tukey’s Test indicated that

for all three groups, posttest scores were higher thon pretest scores on

these two measures

Univariate analysis of variance yielded no significant main effects or

interactions among the three groups on Digit Span-Total, Visual Memory

Span-Total, or Verbal Fluency-Total. No significant Interaction effects

were found on the Complex Figure Test or AVLT.

The strength of association between the independent and dependent

variables was measured using eta square Table 4 lis ts eta square values

for each dependent ond Independent variable.

Insert Table 4 about here

Chapter IV

Discussion

The current project was conceptualized as an exploratory examination

of the neuropsychological sequelae of cocaine abuse, specifically the

drug's effect on new learning and clinical memory. The results of this

study indicate thot chronic ingestion of cocaine has an adverse effect on

learning and recall of both verbally end non-verbally mediated tasks

Additionally, the degree of impairment appears related to the route of

administration employed to ingest the drug, i.e., individuals who reported

intravenous injection as their preferred route of administration

demonstrated greater defic its than the ir counterparts who chose smoking

as the ir primary route of ingestion

A major differences between intravenous and Intrapulmonary routes of

administration is bioavailability, or the percent of the drug which is

absorbed Intravenous ingestion is the most e ff ic ien t route of

administration w ith 1 0 0 * bioavailability. When heat is applied to cocaine

preparations which ere smoked, a significant amount of its active

ingredient is lost, therefore, the btoavailability of crack or freebase

cocaine, in comparison, is only 6-32% (Verebey & Gold, I9 6 0 ) In light of

40

41

this inherent difference m rote of absorption, it may be hypothesized that

cocaine is a neurotoxin w ith a dose dependent effect on memory

functioning That is, the degree of Impairment may be conceptualized on o

continuum, w ith degree of memory impairment dependent upon the amount

of cocaine delivered to the brain The current data support this hypothesis,

i.e., mnestic dysfunction is less pronounced in those employing the less

effic ient intrapulmonery route, while greater impairment is manifested in

those employing the more e ffic ien t IV route.

Additionally, i t may be hypothesized that there is a connection between

severity of addiction and route of administration, i.e., those using the

more invasive mode of ingestion, IV injection, may manifest a more severe

addiction and hence demonstrate greater impairment. It is likely that

individuals w ith a more severe addiction have used the drug over a longer

period of tim e and have consumed a higher total volume, therefore

incurring greater toxic effects to the brain. It has been stated that "in the

progression of obsessive self-destructive cocaine dependence, Intravenous

cocaine abuse follows Intranasal use" (Verebey & Gold, 196G, p. 515),

however, the current review of the lite ra ture failed to discover a

systematic investigation of correlations between route of administration

end seventy of cocaine addiction. Future research which assesses this

42

correlation is warranted

Purity is another factor to be considered when addressing the

differences between the two routes of administration of interest. As

opposed to crock and freebose, which are purified forms of cocaine, the

preparation which is Injected typically contains a variety of adulterants,

e g , amphetamine, manitol. Perhaps these unstudied substances exert

discrete neurotoxic effects either alone or in Interaction w ith one another.

This area merits further examination.

Significant improvement in neuropsychological performance occurs in

abstinent alcohol abusers during the In itia l weeks of sobriety (Ryan &

Butters, 1986), however, such recovery of function was not noted in

cocaine abusers who participated in this study The experimental groups

did not demonstrate any unique, significant improvements In performance

during the posttest In fact, performance of all three groups was less

proficient during retesting on AVLT tr ia ls 6 and 7. Motivational factors,

fatigue, or boredom w ith the task may have contributed to the consistent

decrements in performance exhibited across all three groups. This task

may be considered monotonous by some, hence scores on the posttest may

hove been lowered because of boredom The novelty of the task during the

in it ia l testing may have contributed to motivation. However, this measure

43

is rather demanding and requires active attention for a sustained period of

time, therefore, during the posttest, subjects may have recalled the

orduous nature of the task end may have been less motivated to exert a

s im ila r e ffo rt during the second testing. Additionally, members of the

experimental groups were in a significantly d ifferent phase of treatment

at the tim e of the posttest. That Is, during the in it ia l testing, these

individuals were enrolled In Phase I of treatment (21 day inpatient stay)

During this facet of treatment, residents ere reasonably sheltered from

outside stresses The posttest was conducted during the final days of

Phase ll (14 day stay in a residential treatment fac il ity ). Upon completion

of this phase of treatment, these individuals return to the community and

I ts attendant stressors, e.g., returning to drug Infested environments,

unemployment, interpersonal and financial d iff icu lt ies While all

participants were highly cooperative w ith the testing protocol, I t is

conceivable that w ith such weighty issues to consider, optimal levels of

motivation may not have been demonstrated when asked to perform a

demanding and repetitious task w ith l i t t le perceived reward. In addition

to motivational factors, because of the ir involvement w ith the Notional

Guard, members of the control group had been required to work extended

hours prior to the posttest, therefore, decreased performance by this

44

cohort may hove been due to fatigue Lastly, although presumed parallel,

psychometric data to support the equivalency of the AVLT alternate l is t is

unavailable, hence the lis t which was employed during the fo llow-up

testing may hove been inherently more d if f ic u lt than the l is t used during

the in itia l testing

The only other significant change from pretest to posttest was noted

on the Complex Figure Test all three groups received higher posttest

scores on the immediate memory and delayed recall measures of this test

This may be attributed to practice effects or perhaps, again, to

unequivelent alternate forms of the test, i.e., the stimuli employed for the

posttest may have been inherently simpler. Because s im ilar, stable tim e

effects were seen across all three groups, these discrepancies in

performance cannot be attributed to the e ffec t of cocaine on the brain

The findings of the current study are consistent w ith previous research

in regard to the relationship between level of d iff icu lty of memory

assessment Instruments and manifestation of deficits. That is, prior

research has concluded that mnestic impairments were not demonstrated

in alcohol abusers until more sensitive measures were employed (Albert,

Butters, & Brandt, I9 6 0 , Ryan, 1980). Ryan &. Butters (1 9 8 6 ) state that in

order for subtle memory dysfunction to be identified in substance abusers,

45

the tasks u til ized to assess memory In tegrity must "require subjects to

process a great deal of un fam ilia r In form ation . . . In a short period of

time" (p.390). Both instruments which yielded significant differences

among groups (i.e., AVLT and Complex Figure T e s t) meet these

requirements, w h ile the tests which did not yield differences are

generally regarded as conceptually s im pler tasks (I.e., D igit Span, Visual

Memory Span, Verbal Fluency)

A final explanation of the significant differences found among groups

on the AVLT and Complex Figure Test is that these findings may hove been

a chance happening or an a r t i fa c t of the assessment instruments which

were employed While these tests are w idely used, and endorsed by

individuals who are prominent In the fie ld of general neuropsychological

assessment (Le2ak, 1963) end the specific area of neuropsychological

toxicology (Hartman, 1980), the psychometric properties of these tests

hove not been rigorously Investigated. Therefore, I t could be hypothesized

that significant results may be attr ibu tab le to a lack of In teg rity of these

Instruments, and hence that s im ila r results may not be replicable or that

the construct being measured was something other than memory.

Lim itations of the Studu

The practice of u t i l iz in g esoteric measures to assess memory

46

functioning hos received considerable c r it ic is m because performance on

these measures does not generalize to behaviors which are integral to

practica l, everyday functioning (Crook, 1906; Erickson & Scott, 1977).

Based on previous research which concluded that memory de fic its In

substance abusing population are only apparent on performance of

demanding tasks (Ryan & Butters, 1966), i t was assumed that typical

measures of everyday memory would be unsuccessful in e lic it in g more

subtle memory impairments. However, ecological va lid ity of future

research in this area may be bolstered by devising such measures which

would be appropriate in studying substance abusing populations For

example, a test designed to measure assim ilation of concepts presented

during treatm ent would provide a more meaningful assessment of memory.

For instance, if a treatm ent program employed the relapse prevention

model of substance abuse, then a tes t of relapse prevention concepts

which were presented during trea tm ent would measure a construct deemed

integral to the individuals' sobriety While appealing in theory, such a

measure is not w ithout its d i f f ic u lt ie s as this approach may be measuring

constructs besides memory, e g , m otivation, tes t taking ab ility

Another l im ita t io n of this study is that severity of addiction, amount

consumed, and duration of abuse w ere not system atica lly investigated

47

Examination of these constructs is fraught w ith methodological

d iff ic u lt ie s since i t would be necessary to rely upon self report data to

obtain this information. Nevertheless, future research which rigorously

examines these dimensions of addiction would be a significant

contribution to the literature.

C lin ica l im p lic a tio n s

Results of this study may guide future investigations of the

pathophysiology of cocaine While i t appears that cocaines effec t on the

brain is likely diffuse, from a grossly oversimplified view of localization

of brain dysfunction, decreased performance by cocaine abusers on tasks

requiring learning of new information presented in both verbal and visual

form implies temporal lobe Involvement of the le f t and right hemispheres

Data suggest that individuals enrolled in alcohol treatment programs

who exhibit neuropsychological Impairments are less like ly to remain

sober than their unimpaired counterparts (Guthrie & Elliot, 1980, Walker,

et al.) Results of the present study suggest that individuals enrolled in

treatment for cocaine abuse exhibit neuropsychological Impairments,

specifically, those who in ject cocaine demonstrate d iff ic u lty learning

verbal and non-verbal material. Additionally, data indicate that th is group

experiences d iff ic u lty recalling visually mediated stimuli following a

46

period of deioy Those who smoke os well os those who in ject cocoine

evidence d iff icu lty recoiling newly Acquired verbel infomnotlon following

o period of delay. These preliminary findings may be c lin ica lly solfent in

regard to treatment outcome For example, treatment outcome may be

adversely effected in cocoine rehabilitation programs which rely heavily

upon on educational component since a substantial number of cocoine

abusers may evidence d iff icu lty assimilating material presented in both

visual and verbal form If fu rther research supports these finding,

treatment outcome may be enhanced by incorporating methods of

improving retention of this material into the treatment program, e.g.,

repetition, more individualized modes of presentation. Future research

which assesses the relationship between neuropsychological impairment

in cocoine abusers and treatment outcome is indicated.

As the neuropsychological concomitants of cocoine abuse ore better

understood, e fforts to discourage use of the drug may be bolstered by

providing the public w ith actual descriptions of the adverse consequences

of chronic use on brain functioning. Such an approach would odd a more

empirical, fact-based component to the more emotionally based anti-drug

campaigns currently in vogue (e.g., comparing the e ffec t of drugs on the

brain to on egg in a frying pan) A broad spectrum approach incorporating

49

both factual and sensational presentations of the adverse consequences of

cocaine abuse may access a greater proportion of the population

Conclusion

Impairments in performance of cocoine obusers relative to controls on

challenging tests designed to measure new learning and delayed recall of

both verbal end visually mediated tasks suggest that chronic cocaine

administration adversely affects mnestic integrity. Furthermore, the

degree of impairment appears to be related to the route of administration

employed to ingest the drug, I.e., the iV group evidenced greater

impairment than the smoker group No significant differences were noted

among groups on measures of attention/concentration and verbal fluency

While it is not prudent to conclude that an unequivocal cause and effect

relationship exists, these preliminary results suggest the possibility of a

dose dependent neurotoxic relationship between cocaine and brain

functioning and that further research examining this construct is

indicated

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Teb le 1

Mean Subj ect Demoarophic Characteristics

64

Group

Age IQ Education

X X SB x S£

IV 36 06 4 7 8 97.73 7.42 13.30 1.73

Smokers 33.20 5.32 95.20 7.68 13.00 1.45

Controls 32 66 0 13 102 80 9.23 13 16 17 9

65

Table 1 (con't)

Hean Subject Demographic Characteristics

Group

Race

%

Black White

IV 66.67 13.33

Smokers 93 00 7.00

Controls 60.00 20.00

Table 2

Mean Scores on Memoru Tests for Each Groups

66

Variable

IV

Pretest

Smokers Controls

X SC X SC X SC

AVLT 1-5 * 39 3 9 6 43 1 7.7 5 0 4 7.4

AVLT 6 8 5 2 7 9 0 2.8 10 3 2 5

AVLT 7 * * 7.2 3 2 6 8 3 0 10 6 2 7

CFT-Copy 33.3 2 5 34.1 1 5 34.1 1.9

CFT-IM * 20 4 7 1 2 3 4 5.7 2 4 8 4 7

C F T -D R *** 1 0 5 7 6 2 2 6 5.1 2 4 5 5 3

Digit Span-Total 13 9 3 5 15 3 2.9 14.3 4.1

VMS-Total 14.6 2.1 15 7 3 5 17 5 3.3

VFLU-T otal 4 4 5 1 1 4 45 4 1 0 9 3 9 7 13 8

* Controls s ign if icantly be tte r than IV group (p < .05)

* * Controls s ign if ican tly be tte r than IV and Smoker group (p < .05)

* * * Controls and Smokers s ign if ican tly b e tte r than IV group (p < .05)

67

Table 2 (con’t)

neon Scores on flemoru Tests for Each Groups

Vorioble

IV

Posttest

Smokers Controls

X SC X SC X SC

AVLT 1-5 11 39 1 7.1 430 76 45.2 0 8

AVLT 6 7.2 2.3 8 6 2.6 9.1 2 3

AVLT 7 * * 5 5 18 6 8 3 0 8.1 2 8

CFT-Copy 33.2 3.5 34 8 1.0 35.1 0 7

CFT-IM* 250 6.4 29.5 5 9 299 4 4

C FT -D R *** 24.8 6 5 29.8 5 1 28 4 4.4

Digit Spon-Totol 13.4 3 2 14 5 3.3 15 1 4.0

VMS-Total 14.6 3.5 16 1 3.4 16.3 3.4

VFLU-Totol 4 1 4 9.5 446 11.0 390 14.2

* Controls significantly better thon IV group (p < .05)

* * Controls significantly better thon IV ond Smoker group (p < .05)

* * * Controls ond Smokers significantly better thon IV group (p < .05)

Table 3

Summary of Results from the Analyses of Variance

6b

Group Main Effect

Variable F Ratio (2 ,42) F Probability Levels

AVLT 1-5 5.68 .0066

AVLT 6 2.94 .0639

AVLT 7 6.42 .0037

Complex Figure Test-Copy 3 28 .0476

Complex Figure Test-IM 3.88 .0285

Complex Figure Test-DR 4.35 .0193

Digit Span-Total 0.58 .5632

Visual Memory Span-Total 2 41 .1022

Verbal Fluency-Total 0.94 .3995

6 9

Table 3 (con’t)

Time Main Effect

Variable F Ratio (1 ,42) F Probability Levels

AVLT 1-5 2.13 .1520

AVLT 6 5 0 4 .0301

AVLT 7 12.39 .0011

Complex Figure Test-Copy 1.69 .1767

Complex Figure Test-IM 32 92 .0001

Complex Figure Test-DR 46.82 .0001

Digit Span-Total 0.16 .6932

Visual Memory Span-Total 0 44 .5090

Verbal Fluency-Total 2.30 .1371

70

Table 3 (con’t)

Group x Time Interaction

Variable F Ratio (2 ,42 ) F Probability Levels

AVLT 1-5 1.03 .1730

AVLT 6 2 4 3 1266

AVLT 7 52 5966

Complex Figure Test-Copy 0.78 4663

Complex Figure Test-IM 0.23 7926

Complex Figure Test-DR 1.35 .2702

Digit Span-Total 1.74 .1876

Visual Memory Span-Total 1.09 .3459

Verbal Fluency-Total 0 59 5583

71

Table 4

Summaru of eta square values

Independent Variable

Dependent Variable Group Time

AVLT 1-5 16 .01

AVLT 6 .09 .03

AVLT 7 17 .05

CFT-Copy 08 .01

CFT-IM to .16

CFT-DP .11 .19

Digit Span-Total .02 01

VMS-Total .08 .01

VFLU-Total .03 .01

APPENDIX

7 2 A

72

ADDENDUM TO VA FORM 1 0 - 1006 INFORMED CONSENT AGREEMENT

EFFECTS OF COCAINE USE AND WITHDRAWAL ON CLINICAL MEMORY AND NEW LEARNING

1. I understand that I have been asked to partic ipate in a research investigation designed to study memory. I have been informed that the project moy not benefit me d irec tly but that I t Is hoped that i t w i l l increase our understanding of the e ffec ts of cocaine abuse on neuropsychological functioning.

2 Madeline Uddo Crane has explained the deta ils and procedures Involved in my partic ipation in this study I am aware that I w i l l be asked to divulge personal information regarding my physical and mental health and my drug and alcohol consumption. I hove been Informed that all information received from me w i l l be kept confidential and at no tim e w il l my replies or responses be associated w ith my name. Further, I hove been informed that the fo llow ing coding system w i l l be employed to assure confidentia lity

Each participant w i l l be assigned a subject number which w i l l be recorded on the Informed Consent Agreements. All records w i l l be identif ied ond filed by number only Informed Consent Agreements ond identifying information w i l l be stored ond locked in a separate m aster f i le . The m aster f i le w i l l be located in a d iffe ren t s ite from the working f i le which w i l l contain non-personal information

3. There are minimal r isks /d iscom forts associated w ith the collection of memory data. I understand that possible anxiety re lated to revealing personal information and/or frus tra tio n from lock of success on tests of memory may occur.

4. I understand that my partic ipation in th is research study is voluntary and that I may w ithdraw whenever I might choose. I fu rth er understand that a decision to w ithdraw would in no way adversely a f fe c t me.

7 3

Poge 2, informed Consent AgreementEffects of Cocoine Use ond Wlthdrowol on Clinical Memory ond New Leoming

5 if I hove ony questions regarding this study or the procedures required of me, I moy oddress my questions to Madeline Uddo Crone, PsychologyService, New Orleans VAMC, telephone (504) 5 8 9 -5 2 3 5 . I also understand thet I moy contact Ms. Crone ot the above number in the event of a study-related emergency

6 In cose of ony adverse e ffec t or physical In jury resulting from this study, i t is my understanding that eligible veterans ore entitled to medical core ond treatment. Compensotion moy be payable under 38 USC 351 or in some instances under the Federal Torts Claims Act. Non-eligible veterans or nonveterons ore entitled to medical emergency core ond treatment on o humanitarian basis. Compensotion would be controlled by the provisions of the Federal Torts Claims Act

7 Before giving consent by signing this form, I hove been suffic iently informed of the purpose of the study, of the nature of the procedures ond interviews I w il l undergo, ond the inconveniences, hazards, or adverse effects thot might result from the procedures and Interviews.

8 Having reed ond understood the information stated above, I sign this consent form w illing ly ond keep a copy for my records.

Signature of P a rt ic ip a n t___________________________ D ote_________

Signature of Witness Date

CURRICULUM VITAE

PERSONAL DATA

Nome T itle Birthdate Place of Blrtn Social Security' Marital Status

Model 1 rie Uddo Crane Psychology intern November 9, 1960 New Orleans, LA 433-23-9672 named

Home Address

Home Phone

5926 St. Roch Avenue New Orleans. LA 70122 504-282-2815

EOUCATION

B / 1 9 6 9 -Expected PhD

12/1937

5 / ' 9 6 2

MS

BA

Louisiana State University Baton Rouge, Louisiana Major: Clinical Psychology

University of Southwestern LouisianaLafayette, LouisianaMajor: Experimental Psychology

Loyola University NewOrleans, Louisiana Major: Psychology

AWARDS and HONORS

1979 1985 nemDer.Psi Chi National Honor Society.

1962 Graduated cum laude

CLINICAL INTERNSHIP

9 / 198B-8/1989 Psychology internveterans Administration Medical Center New Orleans. Louisiana

Drug Dependent* T rea tm ent Pregrain-comprehensive psychological assessment, individual and group psychotherapy with inpatient and outpatient populations, discharge planning, relapse prevention.

Surgery end Medicine C onsultation-assessment and treatment ol medically-related psychological problems, Including control and adaptation to chronic hemodialysis, training in biofeedback, progressive relaxation, stress management, and cognitive restructuring therapies.

7 4

75

PROFESSIONAL

4/1980 B / 1988

0/1987 1/19B8

t /1986 -1 /1988

0 /1986-1 /1938

B / 1 9 8 6 5 /1 9 0 7

PROFESSIONAL

Neuropsychology S p ec ia ltyGeriatric Neun>D?MChPlQqy

-comprehensive neuropsychological and personality assessment of former Prisoners of War of World war li and the Korean conflict; oral end written clinical description of results.

- w ill be completed June-August. 1969

Research-ongoing assessment of neuropsychological sequelae of cocaine abuse

EXPERIENCE

Psychology Technician, Psychology Service veterans Administration Medical Center NewOrleans, Louisiana

Neuropsychology Assessment Practicum Louisiana State University Baton Rouge, Louisiana Supervisor W Drew Douvter, PhD

Clinical Psychology Proctlcum Louisiana State University Be ton Rouge, Louisiana Supervisors William F Waters, PhD and Johnny L Matson, Ph D

ReseerchAsslstant Louisiana State University Professors: W Drew Gouvler, PhD. ond John Junginger, Ph D.

intellectual Assessment of Deaf Children Louisiana State School for the Deaf Baton Rouge, Louisiana Supervisor Phyllis Stevens, MS

AFFILIATIONS

Student A ffilia te, American Psychological Association

Student Member, American Psychological Society

Student Member, Society of Psychologists in Addictive Behaviors

76

PRESENTATIONS

tienaoze, J. E., Uddo-Crone. h Ik Moon*, J. N. Clock drawing deficiencies as aI unction of dock sl2e Poster accepted for presentation ot the annuel convention

of the American Psychological Association, New Orleans, Louisiana, August 1939

nenoozc, J E , Moore, J N , & Uddo-Crene, n A qualitative scoring approach for the Rey-Ostemeth Complex Figure Paper accepted for presentation ot the annual

convention of the Amen con Psychological Association, New Orleans,Louisiana, August 1969.

PUBLICATIONS

Gouvler, W.D., Uddo Crane, M. , & Brown, L M. (1986). Base rates ofpost-concussional symptoms. Archives ofCHnicalNeuropsycholoqu. 5 , 273-276

Gouvier, W.D, & Uddo-Crone, M (1967). Feeding proolems of head 1 njured clients: Psychological Factors Network; Dietetics In Phuslcal riedldne and RenatlUtotlon 2. w

nalow. R M i Uddo-Crene, fl illic it drug abuse ond dependence disorders in P. B Sutker 4. H E Adams (Eds ), Comprehensive handbook of Dsuchopathoioou (2nd ed ) New Vork Plenum Publishing Corporation, in preparation

Uddo-Crene, 11. & Gouvler. W.D (19B7) Feeding problems of head I njured clients Physiological Factors Network: Dietetics In Physical nedldne and Rehabilitation 3. 1-4

Uddo Crane M , Roussel, L S., Gouvier, w D . & Bloncherd-Flelds, F (in press)Nutritional considerations In head injury and geriatric disorders In D.J Gmes (Ed ). Nutritional support lnrehabilltetlon Rockville, MD Aspen Publishers.

RESEARCH/PROFESSIONAL INTERESTS

NeuropsychologySubstanceAbuse

DOCTORAL EXAMINATION AND DISSERTATION REPORT

C a n d id a te

M ajo r Field:

T i t l e o f D isserta tion

Madeline Uddo Crane

Psychology

Effects of Cocaine Use and Withdrawal on Clinical Memory and New learning

M a jo r ProfFssor and C h a irm a n

D e a n o f th e G ra d u a te

E X A M 1 N 1 N C C O M M I T T E E

Date of Examination