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MARIJUANA EFFECTS ON HUMAN FORGETTING FUNCTIONS

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It has long been known that acute marijuana administration impairs working memory (e.g., the discrimination of stimuli separated by a delay). The determination of which of the individual com- ponents of memory are altered by marijuana is an unresolved problem. Previous human studies did not use test protocols that allowed for the determination of delay-independent (initial discrimina- tion) from delay-dependent (forgetting or retrieval) components of memory. Using methods devel- oped in the experimental analysis of behavior and signal detection theory, we tested the acute effects of smoked marijuana on forgetting functions in 5 humans. Immediately after smoking placebo, a low dose, or a high dose of marijuana (varying in 9-THC content), subjects completed delayed match-to-sample testing that included a range of retention intervals within each test session (0.5, 4, 12, and 24 s). Performances (discriminability) at each dose were plotted as forgetting functions, as described and developed by White and colleagues (White, 1985; White & Ruske, 2002). For all 5 subjects, both 9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination. The outcome is consistent with current nonhuman studies examining the role of the cannabinoid system on delayed matching procedures, and the data help illuminate one behavioral mechanism through which marijuana alters memory performance.
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Content Preview
JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR
2005, 83, 67–83
NUMBER 1 (JANUARY)
MARIJUANA EFFECTS ON HUMAN FORGETTING FUNCTIONS
SCOTT D. LANE, DON R. CHEREK, LORI M. LIEVING, AND OLEG V. TCHEREMISSINE
UNIVERSIT Y OF TEXAS HEALTH SCIENCE CENTER—HOUSTON
It has long been known that acute marijuana administration impairs working memory (e.g., the
discrimination of stimuli separated by a delay). The determination of which of the individual com-
ponents of memory are altered by marijuana is an unresolved problem. Previous human studies did
not use test protocols that allowed for the determination of delay-independent (initial discrimina-
tion) from delay-dependent (forgetting or retrieval) components of memory. Using methods devel-
oped in the experimental analysis of behavior and signal detection theory, we tested the acute effects
of smoked marijuana on forgetting functions in 5 humans. Immediately after smoking placebo, a
low dose, or a high dose of marijuana (varying in
9-THC content), subjects completed delayed
match-to-sample testing that included a range of retention intervals within each test session (0.5, 4,
12, and 24 s). Performances (discriminability) at each dose were plotted as forgetting functions, as
described and developed by White and colleagues (White, 1985; White & Ruske, 2002). For all 5
subjects, both
9-THC doses impaired delay-dependent discrimination but not delay-independent
discrimination. The outcome is consistent with current nonhuman studies examining the role of the
cannabinoid system on delayed matching procedures, and the data help illuminate one behavioral
mechanism through which marijuana alters memory performance.
Key words: marijuana, delayed match-to-sample, memory, human
For nearly 30 years, it has been well docu-
stimulus control at a temporal distance. Cur-
mented that acute marijuana smoking im-
rent behavioral accounts of remembering de-
pairs working memory in humans (Heish-
scribe a two-component system. One compo-
man, Arasteh, & Stitzer, 1997; Miller, Cornett,
nent entails an initial discrimination, in which
Brightwell, McFarland, Drew, et al., 1977;
correct performance is independent of the de-
Tinklenberg, Melges, Hollister, & Gillespie,
lay between sample and comparison. Other ar-
1970), as well as in nonhuman animals (Cas-
eas in the behavioral sciences, notably cognitive
tellano, Rossi-Arnaud, Cestari, & Costanzi,
psychology and neuroscience, generally refer to
2003; Heyser, Hampson, & Deadwyler, 1993;
this component as attention or encoding of in-
Schulze et al., 1989). In human experiments,
formation. A second component requires cor-
the methods used to evaluate these effects
rect discrimination of the comparison stimulus
have provided information about global im-
at a point in time after the sample has been
pairment, for example, impaired accuracy on
removed, and thus is in?uenced by the length
tests such as word recall, digit recall, and
of the delay (White, 1985, 2001; White & Wixt-
paired-associate word memory (Chait & Pier-
ed, 1999). In the other areas, the delay-depen-
ri, 1992; Earleywine, 2002).
dent component of discrimination is referred
Procedures in the experimental analysis of
to as recall or retrieval.
behavior used to measure memory typically
Because accurate remembering involves
employ delayed matching-to-sample (DMTS)
both delay-independent (initial) and delay-de-
testing in which two or more comparison stim-
pendent discriminations, disruption of either
uli are presented following the presentation of
(or both) may occur when performance is im-
a sample stimulus. The sample and comparison
stimuli are separated by some delay period, and
paired on memory tasks. Therefore, it has been
a correct response is operationally de?ned as
emphasized that accurate characterization of
responding to the comparison that was identi-
memory performance requires test procedures
cal to the sample (White, 1985; White & Ruske,
that allow measurement of both components
2002). Thus remembering may be de?ned as
(White, 1985; White & Ruske, 2002; White &
Wixted, 1999). To experimentally meet this re-
This research was made possible by NIDA grant DA
quirement, a range of retention (delay) inter-
R01 12968. We thank Jennifer Sharon, Sally Chee, and
vals must be used such that rates of forgetting
Laurie Thompson for valuable technical assistance in
can be assessed via a rate parameter from a
conducting the experiment.
function ?tted to the performance data, for ex-
Address correspondence to Scott D. Lane, Psychiatry & Be-
havioral Sciences, UTHSC-Houston, 1300 Mousund Street,
ample, a forgetting function (Rubin & Wenzel,
Houston, TX 77030 (e-mail: scott.d.lane@uth.tmc.edu).
1996; White & Ruske, 2002). Analyzing forget-
67

68
SCOTT D. LANE et al.
ting functions across a range of retention in-
be altered provided the impetus for the present
tervals allows delineation of delay-independent
investigation.
from delay-dependent components of stimulus
discrimination. To quantify performance on
METHOD
DMTS procedures, signal detection measures
of discriminability such as log d or logit p
Subjects
(Luce, 1963; Macmillan & Creelman, 1991)
Seven subjects were entered into the study
may be calculated and plotted across a range
after providing informed consent approved by
of retention intervals. Forgetting functions may
the local Institutional Review Board. Two sub-
then be generated by ?tting a negative expo-
jects were removed for noncompliance with
nential function to the data (see Method sec-
study requirements (see below). The remain-
tion for details). From the equation parame-
ing 5 subjects, 3 males and 2 females (ages 21
ters, the y -intercept and the slope are then
to 34 years), all completed the study; subse-
interpreted as representing initial discrimina-
quent demographics are based on these 5 sub-
tion and delay-dependent discrimination (or
jects. All 5 reported occasional marijuana use
rate of forgetting), respectively. White and col-
de?ned as 2 to 10 times per month, as well as
leagues (Parkes & White, 2000; Ruske, Fisher,
past use of at least one other drug, including
& White, 1997) used this approach to measure
alcohol, cocaine, opiates, and benzodiaze-
acute effects of cholinergic drugs in pigeons
pines. Past use of other drugs was intermittent
and showed that memory impairment or en-
and did not occur during the study, veri?ed
hancement was associated almost entirely with
by daily urinalysis (see below). Subjects were
changes in initial discrimination; rates of for-
recruited via local newspaper advertisements
getting were not affected.
for ‘‘behavioral research.’’ Based on informa-
Current research on the neurobiology of
tion obtained during initial telephone inter-
marijuana and the cannabinoid receptor sys-
views, potential subjects were brought to the
tem suggests—based on both the function and
laboratory for more extensive interviews cov-
the density of cannabinoid receptors in the hip-
ering physical and mental health status, and
pocampus (Hampson & Deadwyler, 1999, 2000;
drug and alcohol use history. Exclusion crite-
Iversen, 2003; Wilson & Nicoll, 2001) and the
ria included: (a) current or past medical prob-
importance of the hippocampal structure in
lems (e.g., traumatic head injury, asthma); (b)
memory function (Baxter & Murray, 2001;
current use of any medications; (c) current
Deadwyler, Bunn, & Hampson, 1996)—that
illicit drug use (except marijuana); and (d)
marijuana should impair memory by disrupt-
current or past history of an Axis I disorder
ing delay-dependent discrimination. Nonhu-
other than substance dependence, as de?ned
man studies have shown that modulation of
by the Structured Clinical Interview for the
cannabinoid receptors in the hippocampus by
DSM-IV (SCID-I, version 2.0, First, Spitzer,
cannabinoid agonists (including
9-THC) sig-
Gibbon, & Williams, 1996).
ni?cantly disrupts performance during DMTS
Although subjects reporting marijuana use
and (nonmatching) DNMTS procedures, and
2 to 10 times per month were recruited into
does so as a function of delay-interval value
the study, they were required to provide a
(Hampson & Deadwyler, 1998, 2000; Heyser et
clean urine sample prior to any testing. Fol-
al., 1993; Iversen, 2003). However, other data
lowing each active dose, a clean urine sample
suggest that
9-THC disrupts initial (delay-in-
was required before the next active dose was
dependent) discrimination, for example, by de-
administered. This typically took 3 to 4 days
grading performance on tasks purported to
following an active dose, and active doses were
measure attention processes (Chait & Pierri,
separated by at least 5 calendar days. After be-
1992; Curran, Brignell, Fletcher, Middleton, &
ginning the study, participation was discontin-
Henry, 2002; Earleywine, 2002). The impor-
ued following three drug-positive urine sam-
tance of hippocampal cannabinoid receptors in
ples (con?rmed by daily urinalysis) or
memory formation suggests that the delay-de-
breath-alcohol samples. This requirement was
pendent components (e.g., rates of forgetting)
used to rule out a potential interaction of
should be most disrupted by marijuana admin-
acute marijuana and residual effects from ex-
istration. The possibility that both delay-depen-
traexperimental drug use, including outside
dent and delay-independent components could
marijuana use. Urine drug screen analysis was

MARIJUANA EFFECTS ON MEMORY
69
carried out using enzyme multiple immuno-
free of any medical conditions that would pre-
assay (EMIT
d.a.u. , SYVA/DadeBehring
clude participation. Initial exposure to the task
Corp). Temperature monitoring and creati-
served to stabilize performance prior to initi-
nine determinations were performed to detect
ating dose administration.
attempts to alter urine samples. Two subjects
Each day of the study, subjects arrived at ap-
were removed from the study for repeated
proximately 8:00 a.m. Breath and urine sam-
positive drug tests (both for THC) at the be-
ples were collected at approximately 8:15 a.m.
ginning of the study, prior to active dosing.
Subjects participated in four experimental ses-
After several days of baseline testing, these in-
sions each lasting about 50 min. The ?rst test-
dividuals had not discontinued marijuana use.
ing session began at 8:30 a.m., prior to admin-
istration of the dose for that day. Following
Apparatus
dose administration at 9:45, subjects complet-
During marijuana administration, subjects
ed three more test sessions (10:00 a.m., 1:00
sat in a 1-m by 1-m chamber with two Plexi-
p.m., and 2:00 p.m.). Between sessions, sub-
glas sides and an exhaust fan mounted at the
jects stayed in a waiting room with magazines,
top to ventilate smoke from the chamber. In-
books, and a TV. Lunch was provided at 12:00
side the chamber were an ashtray, a pair of
p.m. Subjects were not allowed to eat any oth-
tweezers to hold the cigarette near the bot-
er food or smoke cigarettes between 8:00 a.m.
tom, a cuff connecting to an oscillometric
and 3:00 p.m. Compliance with nonsmoking
digital blood pressure and pulse monitor
instructions was veri?ed by expired CO sam-
(Critikon Dynamap, Tampa, FL), and a car-
ples taken at 8:25 a.m. and 12:30 p.m.
bon monoxide indicator (Vitalograph, Inc.,
Lenexa, KS). One Plexiglas wall faced a com-
Behavioral Testing Procedures
puter video monitor used to cue events dur-
On the ?rst day of the experiment, prior
ing the smoking protocol.
to the ?rst testing session, subjects were read
During experimental test sessions, subjects
the following instructions:
worked alone in 1.2-m by 1.8-m sound-atten-
uating test chamber equipped with a 14-in.
In this task, you will be required to match
(36.5-cm) VGA color monitor and a mouse.
shades of the color gray that are presented as
Experimental events and data collection were
squares on the computer screen. To perform
handled by a remote Microsoft Windows OS
this task, you will use the computer mouse.
PC using custom software written in Microsoft
First, you will see the word CLICK near the
Visual Basic .
center of the computer screen. Move the cursor
(or arrow) over the word CLICK and press the
Subject Payment and Schedule
right button on the mouse. As soon as you press
the button, the word CLICK will disappear and
Subjects were paid daily for performance
a gray square will appear just above it in the cen-
during experimental sessions (four sessions per
ter of the screen.
day; earning approximately $6 to $10 per ses-
The gray square will stay on the screen for a
sion; see below), attendance and clean urine
few seconds, then it will disappear and the
samples ($10 per day for each), and were given
screen will be blank for a while. This period in
a completion bonus at the end of the experi-
which the screen is blank will vary from about a
ment ($10 for each day of participation). Ex-
half second to more than 20 seconds. After the
cluding the completion bonus, subjects earned
screen is blank, four more gray squares will ap-
an average of $57.67 (
$4.40) per day during
pear in each of the four corners of the screen.
the experiment. The testing protocol lasted 4
To make a correct response you must move the
to 6 weeks, with subjects participating either 2
cursor (arrow) over the gray square that is iden-
or 3 days per week, dictated by their schedules.
tical to the one that was shown in the middle of
the screen, and then press the right mouse but-
Subjects completed an average of 44.8 sessions
ton. You have a limited amount of time to make
(range 40 to 52) during the experiment. Dur-
your selection.
ing the initial day of the study, subjects were
If you move the mouse over the correct square
given an examination by a physician and pro-
and press the mouse button, the squares will go
vided initial exposure to the laboratory task (no
off the screen and a money counter will appear
marijuana doses were administered). The phys-
at the top showing that you have earned 10
ical examination served to ensure subjects were
cents. If you choose the wrong square or wait too

70
SCOTT D. LANE et al.
long, the squares will go off the screen and the
from discriminating duration of the session
counter will show zero.
completed and to anchor each trial to a com-
You will be presented with many trials during
mon baseline (e.g., Kahnemann & Tversky,
this session. Please stay in the room until you see
1979). Each session consisted of 128 trials, al-
a message that reads ‘‘Session Over.’’ This mes-
lowing for all variables to be counterbalanced:
sage will also show how much money you earned
during the session. Do you have any questions?
each sample stimulus (16 times), comparison
(16 times), location (each comparison in each
Memor y testing employed a delayed
location four times), and retention interval
match-to-sample (DMTS) procedure. Stimuli
(32 times) occurred an equal number of
consisted of eight grayscale squares, approx-
times. The same sample stimulus could not oc-
imately 3 cm by 3 cm, presented against a
cur on more than two consecutive trials. The
black background. The grayscale stimuli were
correct comparison location could not be the
created in Microsoft Paint with the following
same on more than four consecutive trials. At
properties: hue
160, saturation
0, lumi-
the end of each session, all stimuli were re-
nosity
220 to 115 in 15-unit increments. At
moved from the screen and a message box ap-
the beginning of each trial, the message
peared with the text ‘‘Session Over. You have
‘‘Click’’ was shown slightly below the center
earned $[cumulative total] this session.’’
of the screen. Placing the cursor over the
message and making a mouse click removed
Marijuana Cigarettes and Administration
the message and immediately presented the
Marijuana cigarettes supplied by NIDA were
sample stimulus (gray square) directly in the
used and ranged across three doses: placebo
center of the screen. This requirement was
cigarettes containing 0.0001% w/w
9-THC;
used as an orienting procedure. The sample
half of 2.20%
9-THC (one half placebo and
stimulus remained on the screen for 2 s fol-
one half active cigarette, hereafter referred to
lowed by one of four delays: 0.5, 4, 12, or 24
as M1); and 3.89% 9-THC (both halves active,
s, during which the screen was blank. After
hereafter referred to as M2). Cigarettes were
the delay (or retention interval), four com-
stored at
20 C and cut in half and humidi-
parison stimuli appeared in each of the four
?ed before smoking. The purpose of dividing
corners of the screen.
the cigarettes into two halves was to achieve a
A correct match-to-sample response was de-
low dose (M1) suf?ciently effective to demon-
?ned as moving the mouse onto the compar-
strate an intermediate effect that was distin-
ison that was identical to the sample and mak-
guishable from both the high dose and place-
ing a mouse click within 4 s of the
bo. Subjects smoked the two cigarette halves
presentation of the comparisons. The 4-s time
immediately prior to the beginning of the sec-
constraint was employed to make the task suf-
ond experimental session of the day (9:45
?ciently dif?cult so as to produce differential
a.m.). Smoking was cued by a series of textual
performance (e.g., Baron & Menich, 1985;
instructions that appeared on the monitor
Critch?eld & Perone, 1993), in this case as a
screen: ‘‘get ready’’ for 2 s; ‘‘inhale’’ for 3 s;
function of retention interval length. Pilot
‘‘hold your breath’’ for 10 s; ‘‘exhale’’ for 1 s
testing con?rmed that this time constraint
and then a blank screen for 29 s. The sequence
was necessary. Once subjects became familiar
repeated continuously until both halves of the
with the DMTS trial requirements and per-
cigarette were smoked. Number of inhalations
formance became stable (typically within a
per dose was recorded by observation and ver-
few sessions) few too-slow errors were made
i?ed via the computer program that presented
across the remainder of the experiment. Af-
the smoking cues and that also tracked the
ter either a mouse click occurred or 4 s had
number of 45-s cycles completed. Inhalations
elapsed, the comparison stimuli were re-
were compared across all conditions. This cur-
moved and a monetary counter showed the
rent paced, cued smoking procedure has been
outcome of that trial: $0.10 (shown in green)
widely used and produces reliable physiologi-
for a correct response or $0.00 (shown in
cal- and subjective-effects data indicative of
white) for an incorrect response. Each trial
acute marijuana intoxication (Chait, 1989;
was separated by a 3-s intertrial interval.
Cherek, Lane, & Dougherty, 2002; Haney,
Cumulative earnings were not displayed
Comer, Ward, Foltin, & Fischman, 1997; Lane
during the session in order to prevent subjects
& Cherek, 2002).

MARIJUANA EFFECTS ON MEMORY
71
Dosing Sequence
two stimuli and two comparison locations
(Parkes & White, 2000; White, 1985; White &
Doses were administered in ascending order
Ruske, 2002). Because the present procedure
with intervening placebo doses preceding each
active dose. Two determinations of each active
used eight stimuli and four comparison lo-
dose were obtained, and thus the dose se-
cations, discriminability was calculated as log-
quence was placebo, M1; placebo, M2; placebo,
it p
log[p/(1
p)], where p is the propor-
M1; placebo, M2. Placebo doses were adminis-
tion correct. Logit p values were calculated at
tered until the DMTS performance data stabi-
each delay interval, then plotted graphically
lized. Data were considered stable when the co-
and ?tted to the negative exponential func-
ef?cient of variation (SD/M) of the percentage
tion y
a·exp( b ·
t) (see White, 1985;
correct scores from all four test sessions within
White & Ruske, 2002). Expressed in this man-
a day was below 0.15, with no linearly increas-
ner, the parameters a (intercept) and b
ing or decreasing trend. Therefore, multiple
(slope, or rate of decline) provide an index
placebo doses were sometimes administered
of initial discriminability and rate of forget-
between active doses. For all analyses herein,
ting (delay-dependent discriminability). The
only data from the stable placebo sessions that
parameter t corresponds to time, or the in-
preceded the active doses are reported.
dividual delay values. When performance is
less than 50% accurate the calculated value
Cardiovascular and Self-Repor t Measures
of logit p is negative and cannot be ?tted to
Immediately prior to and following mari-
a function of the form y
a·exp( b ·
t).
juana smoking, the subject’s breath carbon
Mathematically, the equation does not con-
monoxide level, heart rate, and systolic and
form to a function with a value below 0. To
diastolic blood pressure were measured. Im-
correct for this problem, all data were scored
mediately after obtaining the postsmoking
as logit p
1. Adding a constant of 1 allowed
cardiovascular measures, subjects completed
the use of the equation for forgetting func-
a rating form. They were asked to estimate
tions. The behavioral data also were analyzed
the subjective effects of the marijuana ciga-
at a molar level by calculating overall per-
rette on a 5-point scale (anchored by ‘‘0—not
centage correct for each dose, collapsed
at all’’ and ‘‘4—extremely’’) by rating the fol-
across retention intervals, thereby providing
lowing statements: ‘‘I feel an effect of the
a global assessment of the effects of marijua-
marijuana smoke,’’ ‘‘My heart is pounding
na smoking on DMTS performance.
faster than normal,’’ ‘‘I feel dizzy, lighthead-
The impact of the marijuana doses on per-
ed,’’ and ‘‘I feel a typical marijuana high.’’
centage correct and on the a and b parameters
Data Analyses
from the ?tted functions was evaluated for sta-
tistical signi?cance via repeated measures AN-
The dependent measures related to cardio-
OVA, with Tukey HSD tests of all pairwise
vascular and subjective effects were analyzed for
comparisons for post hoc analyses. All calcu-
statistical signi?cance via analysis of variance
lations and analyses were performed using
(ANOVA). For number of inhalations, cardio-
Jandel Sigma Plot , Jandel Sigma Stat (SPSS,
vascular, breath CO, and subjective effects data,
Chicago, IL) and custom software written in
one-way repeated measures ANOVAs were con-
Microsoft Visual Basic (Redmond, WA).
ducted with repeated measures on dose (pla-
All behavioral data were taken from the
cebo, M1, M2). Cardiovascular and breath CO
data were calculated as change scores from pre-
second test session of the day. The onset of
to postsmoking. Tukey HSD tests of all pairwise
acute subjective, biological, and behavioral ef-
comparisons were used for post hoc analyses.
fects of smoked marijuana occurs within 5
The primary measurement goal was to de-
min of smoking (Azorlosa, Greenwald, &
termine how the acute marijuana administra-
Stitzer, 1995; Huestis, Henning?eld, & Cone,
tion affected forgetting functions with respect
1992), and the peak behavioral effects are
to initial discrimination and rate of forgetting.
typically reported within the 1st hr of smok-
Previous studies that have examined forget-
ing (Chait & Pierri, 1992). Thus we limited
ting functions in nonhumans have calculated
our analyses to Session 2, which began im-
log d based on experimental procedures with
mediately after drug administration.

72
SCOTT D. LANE et al.
Table 1
Shown are the number of inhalations, carbon monoxide (CO) boost, cardiovascular, and
subjective effects following marijuana administration. Values represent mean (
SEM) of all
5 subjects. Values for CO, systolic and diastolic blood pressure (BP), and heart rate represent
change scores (post- minus presmoking). The rightmost column shows statistical outcomes
from comparisons across doses with one-way repeated measures ANOVA.
Dependent measure
Placebo
M1
M2
F(2, 18), p
Inhalations
9.90 (0.27)
10.03 (0.26)
11.60 (0.45)
8.38,
.004
CO
12.45 (0.66)
12.50 (1.12)
13.30 (0.86)
1.17, ns
Systolic BP
4.35 (2.48)
0.60 (4.35)
0.30 (2.97)
0.22, ns
Diastolic BP
0.70 (1.56)
3.70 (2.60)
2.00 (2.02)
1.57, ns
Heart Rate
2.95 (1.62)
24.90 (5.01)
33.40 (4.67)
19.91,
.001
‘‘I feel an effect of
marijuana smoke’’
0.85 (0.20)
2.40 (0.43)
3.20 (0.20)
29.15,
.001
‘‘My heart is pounding
faster than normal’’
0.40 (0.13)
1.50 (0.31)
1.90 (0.23)
9.64,
.002
‘‘I feel dizzy, light-headed’’
0.50 (0.17)
1.10 (0.23)
1.50 (0.31)
5.33,
.016
‘‘I feel a typical
marijuana high’’
0.65 (0.18)
2.50 (0.37)
3.20 (0.13)
46.61,
.001
RESULTS
.05) showed heart rate changes at both mar-
Marijuana Administration
ijuana doses to be statistically different (great-
er) than placebo. Heart rate increase is
Table 1 shows data from the marijuana ad-
among the most reliable dose-related indica-
ministration procedure at each dose, includ-
tors of acute marijuana administration (Hues-
ing the number of inhalations, the cardiovas-
tis et al., 1992). There was not a signi?cant
cular and breath CO pre/post change scores,
effect of dose on either systolic or diastolic
and the subjective effects measures. Table 1
blood pressure. For the subjective effects
also provides F values and degrees of freedom
data, there was a signi?cant effect of dose on
for each ANOVA. The means of the repeated
all four questions: ‘‘I feel an effect of mari-
administrations of each dose, as well as the
juana smoke,’’ p
.001; ‘‘My heart is pound-
details of the statistical outcomes from the
ing faster than normal,’’ p
.002; ‘‘I feel diz-
one-way repeated measures ANOVAs are pre-
zy, light-headed,’’ p
.016; and ‘‘I feel a
sented. For the number of inhalations, there
typical marijuana high,’’ p
.001. Signi?cant
was a signi?cant main effect of dose, p
.004.
differences on Tukey post hoc tests (
.05)
Tukey post hoc tests (
.05) showed the
were observed between placebo and both the
number of inhalations at the M2 dose to be
M1 and M2 doses for every question except
greater than both M1 and placebo. This dif-
‘‘I feel dizzy, light-headed,’’ in which only the
ference implies that subjects adjusted (or de-
higher M2 dose was different from placebo.
creased) their smoke intake at the high dose
Collectively, these data serve to document
and required roughly one and one half extra
and replicate the well-known physiological
inhalations to smoke an equivalent amount of
and subjective effects of smoking marijuana.
the cigarette. Adjustment of inhalation has
been observed in previous studies, and has
Behavioral Data
been attributed to subjects’ rapid discrimi-
nation of the psychoactive effects of the high-
All data presented in the Results section were
THC content marijuana (Heishman, Stitzer,
taken from Session 2 during peak marijuana
& Yingling, 1989; Kelly, Foltin, & Fischman,
effects (see Methods section). Approximately
1993; Lane & Cherek, 2002). However, CO
4% of all errors made in Session 2 were too-
boost levels were not signi?cantly different,
slow errors. These were included in the analy-
suggesting that overall smoke intake was
ses but were not systematically related to delay
equivalent across the three doses.
or dose (see below). On days of active THC
There was a large signi?cant effect of mar-
administration, during Sessions 3 and 4 (which
ijuana dose on heart rate change from pre-
occurred in the afternoon following lunch) sev-
to postsmoking, p
0.001. Tukey tests (
eral subjects showed signs of sedation, and per-

MARIJUANA EFFECTS ON MEMORY
73
Fig. 1.
Mean (
SD) percentage correct DMTS data for the 5 subjects and the group (
SEM) at each dose.
Each bar pattern represents a different dose, with multiple determinations at each dose. PLC indicates placebo; M1
indicates half placebo and half 2.2%
9-THC; M2
3.89%
9-THC. See text for dose administration details.
formance was marked by frequent too-slow er-
for each dose for each of the 5 subjects, as
rors. These errors were not related to delay
well as the group average. The ?gure reveals
length, but accounted for highly variable per-
that, typically, the marijuana-induced disrup-
formance during these sessions. The Appendix
tion in DMTS performance increased as a
provides the number of too-slow errors and log-
function of retention interval. Note that ir-
it p values with and without too-slow errors for
respective of baseline (placebo) levels of per-
all subjects, sessions, and doses.
formance, marijuana disrupted remembering
Figure 1 displays the overall percentage cor-
systematically at the longer retention inter-
rect value for each subject across the three dos-
vals. For example, under placebo Subject
es, expressed as the mean (
SD for individuals,
2896 showed a nearly ?at forgetting function
SEM for group) of the multiple administra-
whereas Subject 2869 had a much larger de-
tions of each dose. For all 5 subjects, at least one
cline in logit p as a function of retention in-
of the marijuana doses produced a global dec-
terval. Yet the forgetting functions of both
rement in performance compared to placebo.
subjects were altered by the same relative
Four subjects showed a decrement in perfor-
amount under the M2 dose. For Subjects
mance at the M2 dose; 4 showed a decrement
2869, 2871, and 2896 changes in forgetting
at the M1 dose; and 3 showed a decrement at
functions were dose related. For Subjects
both doses. One-way ANOVA with repeated
2860 and 2604, both the M1 (half 2.2%) and
measures across dose revealed that these differ-
M2 (3.89%) doses produced equivalent dec-
ences were statistically signi?cant, F(2, 18)
rements in DMTS performance. Importantly,
10.73, p
.001. Tukey tests (
.05) showed
performance was systematically impaired at
both marijuana doses to be different from pla-
the longer retention intervals, but very little
cebo (lower overall percentage correct). Note
decrement in DMTS performance occurred
that, because these data were collapsed across
at the short (0.5 s) retention interval. Subject
retention intervals, Figure 1 somewhat obscures
2871 is the only subject with any notable dec-
the magnitude of the decline in performance.
rement in logit p at the shorter interval.
However, the global decrement in performance
Table 2 shows parameter values (a
inter-
documents the known effect of marijuana on
cept, b
slope) for each subject, obtained
memory impairment.
from ?tting the negative exponential equa-
Figure 2 displays the forgetting functions
tion to the data from each dose (i.e., from

74
SCOTT D. LANE et al.
Fig. 2.
Mean discriminability, calculated as logit p
1, as a function of delay interval between sample and comparison
stimuli. Each panel shows an individual subject, with the group mean (
SEM) in the bottom right panel. In each panel,
each symbol represents the mean (
SEM) of a different dose with multiple determinations at each dose. Curves represent
negative exponential forgetting functions ?t to the data from each dose.
and solid curve indicate placebo;
and dashed
curve indicate half placebo and half 2.2%
9-THC (M1);
and solid curve indicate 3.89%
9-THC (M2). Note different
scaling on y axis for Subject 2896. See text for details on the calculation of logit p
1 and the negative exponential function.
the data shown in Figure 2). Individual sub-
among the doses, F(2, 8)
1.72, ns. There
ject data from each of the four daily test ses-
was a large signi?cant difference among the
sions and of each individual dose are shown
doses for the b parameter, F(2, 8)
11.66, p
in the Appendix. The data were generally
.004. Tukey tests (
.05) revealed that
well described by the equation. R2 values
only the M2 dose was different from placebo.
ranged from 0.70 to 0.98, and only 1 subject
Two features of the design and analysis may
had an R2 value below 0.80. An ANOVA on
have produced an unintended systematic in-
the parameter values statistically con?rmed
?uence on the data: the inclusion of the too-
the patterns shown in Figure 2. For the a pa-
slow errors and the repeated ascending dose
rameter, there was not a signi?cant difference
sequence. To evaluate the possibility that ei-

MARIJUANA EFFECTS ON MEMORY
75
Table 2
measures on both factors. There was no sig-
Parameter (a
intercept, b
slope) and goodness-of-?t
ni?cant main effect of dose order, F(3, 12)
(R2) values from the negative exponential forgetting
1.12, ns and no signi?cant dose order by delay
functions shown in Figure 2. Values are provided for each
interaction, F(9, 36)
0.63, ns. Additionally,
dose, each of the 5 subjects, and the group function. See
text for details on the negative exponential function.
to assess if any systematic change in baseline
performance occurred over time, the four pla-
Subject
Dose
a
b
R2
cebo values were evaluated via two-way repeat-
2860
Placebo
1.26
0.06
0.92
ed measures ANOVA comparing the logit p
M1
1.18
0.09
0.92
values across the four placebo doses and delay
M2
1.43
0.14
0.91
values with repeated measures on both factors.
2869
Placebo
1.40
0.08
0.86
There was not a signi?cant main effect of or-
M1
1.42
0.12
0.86
M2
1.66
0.24
0.98
der across the placebo doses, F(3, 12)
3.02,
2871
Placebo
1.53
0.04
0.80
ns and no signi?cant placebo by delay inter-
M1
1.79
0.13
0.97
action, F(9, 36)
1.13, ns. These analyses in-
M2
1.51
0.10
0.91
dicate that the dosing design used in the study
2896
Placebo
1.88
0.03
0.88
did not systematically effect stimulus discrimi-
M1
1.91
0.08
0.70
M2
2.14
0.15
0.94
nation, as measured by logit p.
2604
Placebo
1.54
0.06
0.82
M1
1.57
0.11
0.84
DISCUSSION
M2
1.72
0.13
0.94
Group
Placebo
1.52
0.05
0.92
The acute administration of smoked mari-
M1
1.57
0.10
0.97
juana to adult humans produced changes in
M2
1.68
0.15
0.98
rates of forgetting but not in initial discrimi-
nability. Relative to performance after place-
bo administration, these impairments were a
ther of these features affected the data, in-
dependent analyses were carried out using
function of delay interval length. Speci?cally,
9
the data from Session 2. Too-slow errors were
-THC increased the slope parameter of
evaluated by conducting a three-way ANOVA
negative exponential forgetting functions in
comparing the logit p values on error type
all 5 subjects. The use of a DMTS procedure
(with vs. without too-slow errors) as a between
with a range of retention intervals thus al-
factor and repeated measures on the factors
lowed for determination of the mechanism
of dose and delay interval. There was not a
through which marijuana disrupted memory
signi?cant main effect of error type on logit
performance by delineating between delay-in-
p value, F(1, 74)
0.09, ns, and there were
dependent and delay-dependent effects. As
no signi?cant interactions: F values for dose
noted by White (1985), ‘‘In the absence of a
by error type, delay by error type, and dose
delay-interval manipulation, discriminability
by delay by error type were 0.00, 0.08, and
recorded at a single delay confounds a par-
0.03, respectively. Additionally, a Pearson cor-
ticular level of initial discriminability with a
relation analysis on logit p values with and
certain rate of decrement in discriminability’’
without too-slow errors produced a correla-
(p. 31). To our knowledge, previous studies
tion coef?cient of 0.99, p
.0001. These
of marijuana effects on human memory have
analyses make clear that inclusion of the two-
not separated these components.
slow errors in the data analyses did not affect
Generally, the data are consonant with
the calculation of the logit p values or the
many previous studies of acute marijuana ef-
forgetting functions. Further details of the
fects on human memory performance (Chait
too-slow errors are available in the Appendix,
& Pierri, 1992), but at least one recent study
which provides the raw number of too-slow
stands in contrast to the present ?ndings.
errors and the logit p values calculated with
Curran et al. (2002) examined the effects of
and without too-slow errors for all subjects,
oral
9-THC on human memory using an ex-
sessions, doses and delay values.
tensive battery of 12 neuropsychological tests
The effects of dose order were evaluated via
measuring, among other things, implicit
two-way repeated measures ANOVA compar-
memory (selective reminding, free recall,
ing the logit p values on active dose order (M1,
prose recall), working memory (serial digit
M2, M1, M2) and delay value with repeated
manipulation, rapid visual information pro-

76
SCOTT D. LANE et al.
cessing), and attention (choice reaction time,
both administration of cannabinoid agonists
digit search and identi?cation). The results
(including 9-THC) and hippocampal lesions
indicated no effect on working memory tasks,
produced signi?cant impairment in perfor-
signi?cant impairment on implicit memory
mance. Importantly, their data also revealed
tasks, and selective but inconsistent impair-
that memory impairment was a systematic
ment on attention tasks. Unfortunately, dif-
function of delay interval and dose. The pres-
ferences in (a) route of drug administration,
ent data are quite consistent with Hampson
(b) the inclusion of a continuously presented
and Deadwyler et al.’s ?ndings and extend
series of different tasks (e.g., sequence and
support to human subjects, suggesting that
fatigue factors), and (c) substantial differenc-
marijuana impairs memory function by in-
es in test procedures hinder direct compari-
creasing the rate of forgetting. This impair-
sons of the present study with Curran et al.
ment may be related to disruption of canna-
Previous studies with nonhuman subjects
binoid receptor (e.g., CB1) function in the
have used DMTS procedures with the data ex-
hippocampus, and provides one explanation
pressed as forgetting functions to examine
for the behavioral differences in memory per-
the effects of other memory-impairing drugs.
formance induced by
9-THC versus those
Using a delayed auditory conditional discrim-
observed by White and colleagues (Kirk et al.,
ination procedure with a range of delay in-
1988; Parkes & White, 2000; Ruske et al.,
tervals, Kirk, White, and McNaughton (1988)
1997; White and Ruske, 2002) following ad-
showed that the anticholinergic drug scopol-
ministration of other classes of drugs. It
amine produced de?cits in performance. Ini-
should be acknowledged that White et al.’s
tial discriminability was decreased at all doses,
work using nonhuman subjects has been
but rate of forgetting was only impaired at the
carefully designed, systematically conducted,
two highest doses. In subsequent studies,
and has achieved greater levels of control
White and colleagues demonstrated that the
than can be attained when administering
administration of both muscarinic agonists
smoked substance to human subjects in an
(Ruske et al., 1997) and glucose (Parkes &
outpatient setting. This level of experimental
White, 2000) attenuated the impairing effects
control also may be a factor in the above-not-
of scopolamine on DMTS performance, and
ed differential outcomes. It is possible that
did so by improving performance at short de-
extraexperimental variables may have in?u-
lay intervals. Thus the diminution of memory
enced our subjects’ performances in an un-
impairment was related directly to improve-
identi?ed but nontrivial manner.
ment in the initial discriminability. Based on
The action of different neurobiological sys-
both pharmacological data and studies of pa-
tems may correspond to different aspects of
tients with Alzheimer’s disease, White and
behavioral performance on laboratory tests
Ruske (2002) have concluded that disruption
of memory. Procedures that distinguish indi-
of memory related to the cholinergic (i.e.,
vidual memory components will help eluci-
acetylcholine) system is due to impairment in
date the biological and behavioral interaction
initial discrimination rather than rates of for-
involved in memory processes. The present
getting. One factor that may account for the
data take a step in that direction using hu-
discrepancy between White et al.’s conclu-
man subjects. Replication of this experiment
sions and the present data is that marijuana
with cannabinoid antagonists and drugs with
has a unique neurobiological mechanism of
different neurobiological mechanisms of ac-
action unrelated to the cholinergic system.
tion will further this agenda.
In a series of studies with rodents, Hamp-
son, Deadwyler, and colleagues (Deadwyler et
REFERENCES
al., 1996; Hampson & Deadwyler, 1999;
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Hampson, Simeral, Kelly, & Deadwyler, 2003;
Marijuana smoking: Effects of varying puff volume
Heyser et al., 1993) demonstrated that (a)
and breathhold duration. Journal of Pharmacology and
cannabinoid receptors on hippocampal neu-
Experimental Therapeutics, 272, 560–569.
rons were highly active during delayed match-
Baron, A., & Menich, S. R. (1985). Age-related effects of
ing (and delayed nonmatching) perfor-
temporal contingencies on response speed and memory:
An operant analysis. Journal of Gerontology, 40, 60–70.
mance; (b) that their activity was directly
Baxter, M. G., & Murray, E. A. (2001). Opposite relation-
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