Effects of Cocaine Use and Withdrawal on Clinical Memory ...
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LSU Historical Dissertations and Theses Graduate School
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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E ffects o f c o c a in e u se an d w ith d r a w a l o n c lin ica l m e m o r y a n d n e w le a r n in g
U d d o -C ran e , M ad e lin e , P h .D .
The Louisiana S ta te U nivers ity and A g ric u ltu ra l and M echanical C o l., 1989
C o p y r ig h t © 1 9 9 0 b y U d d o -C r a n e , M a d e lin e . A ll r ig h ts r e serv e d .
MX) N Zccb RdAnn Arbor, M l 4810ft
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
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