The Psychological Record (2023) 73:481–500

https://doi.org/10.1007/s40732-023-00554-0

ORIGINAL ARTICLE

Environmental Cues Can Indirectly Acquire Cocaine‑Eliciting Changes

in Heart Rate: A Pilot Study of Derived Relational Responding,
the Transfer of Function among Cocaine Users
Kenneth M. Carpenter1,2 · Richard W. Foltin1,2 · Margaret Haney1,2 · Suzette M. Evans1,2

Accepted: 1 August 2023 / Published online: 19 September 2023

© Association for Behavior Analysis International 2023

Abstract
Identifying the processes by which environmental stimuli can come to influence drug use is important for developing more
efficacious interventions. This study investigated derived relational responding and the transfer of differential conditioned
effects of environmental stimuli paired with “smoked” cocaine in accordance with the relations of symmetry, transitivity,
and equivalence using Heart Rate as the measure of conditioning among 12 adults with significant histories of cocaine use.
Match-to-sample (MTS) procedures were used to test for emergent relations among two four-member stimulus groupings.
One member of a group was then paired with 25 -mg of smoked cocaine and one member of the other group was paired with
0 -mg of smoked cocaine. Ten participants completed the MTS protocol: four participants demonstrated two four-member
equivalence classes, three participants demonstrated two three-member equivalence classes, and two participants
demonstrated symmetry only. One participant demonstrated no derived relations. Differential respondent elicited changes in
HR was demonstrated in the presence of stimuli paired with smoked cocaine among four of the six participants completing
the conditioning phase; all four of the participants demonstrated a bidirectional transfer of these functions in accordance
with symmetry. Transfer was not reliably demonstrated in accordance with transitive or equivalence relations. The results
suggest that respondent elicitation in the context of drug use may be a function of both direct conditioning and derived
relational processes. These findings have implications for studying and understanding the processes by which stimuli in the
natural ecology can set the occasion for cocaine use and developing cocaine use disorder.

Keywords Stimulus equivalence · Respondent conditioning · Derived relations · Cocaine use disorders ·
Transfer of respondent eliciting functions

Introduction There have been notable advances in the treatment of CUD.

Approximately 1.3 million Americans meet criteria for a
cocaine use disorder (CUD; Center for Behavioral Health
Statistics and Quality, 2021). Individuals struggling with
CUD experience significant social, psychological, and medi-
cal problems, which also affects the family and community.
* Kenneth M. Carpenter
ken.carpenter@nyspi.columbia.edu
1
New York State Psychiatric Institute, Division on Substance
Use Disorders, 1051 Riverside Drive, Box 120, New York,
NY 10032, USA
2
Department of Psychiatry and Columbia University Irving
Medical Center, Columbia University Vagelos College
of Physicians and Surgeons, 630, West 168th Street,
New York, NY 10032, USA
Behavioral interventions have demonstrated efficacy (Car-
roll & Onken, 2005; Higgins et al., 1993). However, in gen-
eral, treatment effects tend to be modest (Dutra et al., 2008;
Magill et al., 2019) and the mechanisms promoting change
within these interventions remain unclear (Magill et al.,
2020). Thus, continued efforts to identify key processes by
which the problematic use of cocaine develops and is main-
tained offers the promise of more targeted and efficacious
intervention strategies.
Environmental stimuli (external) that are directly paired
with drug taking can acquire emergent functions over time
including the ability to elicit craving and alter physiologi-
cal functioning that may occasion drug use. Respondent or
classical conditioning, a process by which a drug neutral
stimulus (a pipe for smoking cocaine; CS) can come to elicit
physiological responses or subjective experiences (increased

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heart rate, craving; CR) based on its temporal associations
with stimuli that initially elicited such responses (cocaine;
UCS) is an important process by which new stimulus func-
tions can emerge. Respondent conditioning has been a central
feature in models of drug use (Stewart et al., 1984), drug
withdrawal (Wikler, 1973), and tolerance (Siegal, 1975). It
has also provided an explanatory framework for understand-
ing the etiology of several indicators of CUD. For example,
stimuli continuously paired with cocaine use can come to
produce physiological responding that is similar to cocaine
administration under human laboratory conditions (Carter &
Tiffany, 1999; Foltin & Haney, 2000) and elicit the subjective
experience of craving (Childress et al., 1993). In addition,
treatment protocols based on respondent conditioning princi-
ples (Cannon et al., 1981; O'Brien et al., 1990) decrease cue
elicited responding in certain contexts. However, the effects
of these treatment protocols have not consistently generalized
to other contexts, nor have they yielded prolonged reductions
in substance use (Conklin & Tiffany, 2002). Thus, delineating
other potential processes by which stimuli may come to influ-
ence drug taking remains an important issue for developing
more effective intervention strategies.
Humans can demonstrate relational repertoires, in which
a diverse array of stimuli (i.e., stimuli not sharing physi-
cal features along a continuum) can come to be related and
acquire functions in accordance with these relations without
the direct pairing of stimuli or conditioning events (Barnes
& Holmes, 1991; Sidman, 1994). Thus, stimuli acquiring
new functional properties can occur indirectly. Responding
to one stimulus in relation to another stimulus can take a
variety of forms (e.g., A is larger than B or A is the same
as B) and can encompass a complex combination of rela-
tions (Hayes et al., 2001). For example, studies employing
Matching to Sample (MTS) training procedures, in which
participants are reinforced for choosing one stimulus in the
presence of another (i.e. the relations are arbitrary because
they are decided by the experimenter not by the physical
attributes of the stimuli), demonstrate that if individuals
are trained to select Stimulus A in the presence of Stimulus
B (B➔A) and Stimulus C in the presence of Stimulus A
(A➔C), then it is likely individuals will demonstrate several
relational responses that have never been directly trained
(i.e., the relations are derived): (1) selecting B in the pres-
ence of A (A➔B); (2) selecting A in the presence of C
(C➔A) (this bidirectional relation has been denoted as sym-
metry); (3) selecting C in the presence of B (B➔C; transi-
tivity); and (4) selecting B in the presence of C (C➔B). The
later relationship (CB), which is a combination of symmet-
ric and transitive relations, has been denoted as equivalence
(Sidman, 1994). It has been argued that a significant propor-
tion of everyday learning involves the formation and modi-
fication of derived relations (Barnes-Holmes et al., 2000;
Fields et al., 1995; Fields & Reeve, 2001; Leslie et al., 1993;
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The Psychological Record (2023) 73:481–500
Valdivia-Salas et al., 2013) including relations by which per-
ceptually different stimuli can come control an individual’s
behavioral response in the natural ecology (Fields & Moss,
2008).
Importantly, stimuli can come to acquire functions in
accordance with their relations with other stimuli, that is,
functions of one stimulus may transfer to, or transform, the
functions of other stimuli in the context of derived relations
(i.e., an example of an indirect acquisition). Studies have
demonstrated the transformation of a wide range of stimulus
functions in accordance with derived relations (Auguston
& Dougher, 1997; Barnes-Holmes et al., 2000; Dymond &
Barnes, 1995; Greenway et al., 1996; Hayes et al., 1991;
Roche et al., 2000), including eliciting functions (Dougher
et al., 2007). These later findings may provide an important
conceptual lens for understanding ongoing substance use
and the development of substance use disorders becauseas
they suggest a process by which a wide range of stimuli
can come to occasion drug use without a history of hav-
ing been directly paired with drug taking. For example,
Dougher et al. (1994) demonstrated that stimuli, when in
an equivalent relation with a stimulus that was paired with
shock, also came to elicit similar physiological responding
(i.e., increased skin conductance). That is, the respondent
eliciting functions of the stimulus paired with shock was
acquired by other stimuli in the context of derived relations,
not through the direct pairing of each stimulus with shock or
higher-order conditioning. Furthermore, De Grandpre et al.
(1992) demonstrated an individual’s interoceptive response
to a drug (triazolam) could also take on the discriminative
functions of environmental stimuli (exteroceptive) when in
a derived equivalence relation with them. Thus, physiologi-
cal and subjective effects of drug administration can come
to function like environmental cues that increase the proba-
bility of drug seeking and drug use. Together these findings
suggest stimuli internal and external to an individual may
come to exert a significant effect on substance use through
a complex mixture of direct conditioning and derived rela-
tional learning processes. It is important to note that the
parameters surrounding relational processes may not be
fully addressed in behaviorally based interventions for sub-
stance use disorders; a significant limitation as procedures
that directly incorporate, or address, relational repertoires
can facilitate the extinction of conditioned physiological
responding (Dougher et al., 1994) as well as promote the
acquisition of complex cognitive (Fields et al., 2009) and
psychological skills (Rehfeldt & Barnes-Holmes, 2009),
important components in promoting successful changes
in substance use behavior (Smout et al., 2010; Wilson &
Hayes, 2000).
Although a large body of research has established the
emergence of mutual and combinatorial stimulus relations
(i.e. derived relational responding) under different training
The Psychological Record (2023) 73:481–500
conditions and across different populations, comparatively
there has been a notable paucity of research on the derived
transformation of stimulus functions. Further, the direct
investigation of derived relational responding and the trans-
formation of eliciting functions of drug-associated-stimuli
in accordance with these relations have not been conducted
among individuals with a significant history of substance use.
Thus, the extent to which relational processes can come to
bring a diverse array of stimuli to bear on an individual’s
physiological responding, which may set the occasion for
drug use, remains primarily conceptual. As such, the present
investigation sought to develop a human laboratory model for
investigating the indirect acquisition of elicited physiologi-
cal responding in the context of drug use disorders. Human
laboratory procedures for training and testing the emergence
of derived relations (Adams et al., 1993) and for establish-
ing emergent eliciting functions of stimuli that have been
directly paired with smoked cocaine (Foltin & Haney, 2000)
were combined. This combination provided a framework for
assessing the acquisition of several derived relations (i.e.,
symmetry, transitivity, and equivalence) and the transfer of
drug-eliciting functions to drug-neutral stimuli in accordance
with these relations among stimulus groupings that included
stimuli that were directly paired with smoked cocaine among
individuals meeting criteria for CUD.
The pilot study had three aims: (1) to investigate the
extent to which experienced cocaine users with CUD dem-
onstrate the emergence and maintenance of symmetry, tran-
sitivity, and equivalence among 3 and 4 member stimuli
groups across multiple training sessions; (2) to investigate
the extent to which these experienced cocaine users dem-
onstrate differential emergent eliciting functions ([i.e.,
increased heart rate [(HR)]) in the presence of stimuli that
have been directly paired with two different doses of smoked
cocaine (i.e. 0 mg and 25 mg); (3) to test if the differential
eliciting functions of the stimuli directly paired with smoked
cocaine transferred to drug-neutral stimuli in accordance
with the derived relations participants demonstrated during
the MTS training and testing sessions.
Methods
Participant Recruitment
Participants, solicited via word of mouth and newspaper adver-
tisements in New York City, signed a consent form approved
by the Institutional Review Board of The New York State
Psychiatric Institute, which described the study, outlined the
possible risks, and indicated that cocaine would be adminis-
tered. All participants completed a structured clinical interview
(SCID; First & Gibbon, 2004) administered by a doctoral level
psychologist, a psychiatric interview, and completed medical
483
examinations (i.e., urine toxicology, ECG, standard hematol-
ogy, pregnancy test) as part of the screening process. All par-
ticipants met the inclusion criteria of having a current DSM-IV
cocaine dependence diagnosis, being between the ages of 21
and 50, reported smoking to be their primary route of cocaine
administration, and the frequency and amount of their cocaine
use in the natural ecology paralleled or exceeded the amount
of cocaine to be administered in the study. Repeated queries
were made to ensure that no potential participant was seeking
or recently had been in treatment for drug or alcohol use. No
participant met criteria for other active DSM-IV AXIS I psychi-
atric diagnoses (e.g., major depression, schizophrenia, bipolar
disorder), another substance dependence diagnosis (excluding
nicotine and caffeine), demonstrated notable cognitive impair-
ments (e.g., dementia), had unstable physical conditions (e.g.,
hypertension, seizures, abnormal liver functioning, heart dis-
ease), were pregnant, or were currently being prescribed psy-
chotropic medication.
Design
Setting and Apparatus
Participants were admitted to the Irving Institute for Clinical
and Translational Research in the Columbia University Irving
Medical Center that housed both the laboratory room in which
all assessment and testing procedures were conducted and pri-
vate resident rooms for a 10-day inpatient stay. Participants
were admitted to the unit only for the purpose of participating
in this study. All experimental sessions were conducted over
a 7-day period, plus 2 weekend days spent on the unit, and
participants were discharged on the morning of the 1­ 0th day.
Participants resided on the research unit and were not permitted
to leave and come back to the unit while enrolled in the study.
Urine toxicologies were done daily to ensure that no nonproto-
col drug use occurred. Each of the private rooms was equipped
with a TV and video player, and participants were permit-
ted to interact with other residents in a unit lounge. Nicotine
replacement (Nicorette gum 2 mg, 4- mg doses) was provided
to tobacco smokers during their stay to minimize nicotine crav-
ing or withdrawal symptoms. No gum use was permitted during
the laboratory sessions. All participants received compensation
based on the number of days they stayed on the inpatient unit
(US$50/day; ) and for their participation in the training and
testing sessions (e.g., $18– to $20 per MTS training session;
money earned on key pressing task).
Procedures The experimental sequence included four
phases.
Phase 1. Stimulus Preference and Reflexivity Participants
were admitted to the research facility in the morning and
completed a stimulus preference task and reflexivity testing
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(generalized identity matching) on the afternoon of Day 1.
Prior to a participant’s preference task, to assess a differen-
tial preference for selecting a nonsense syllable among those
to be used in the study, the 12 nonsense syllables (VAK,
YIM, LUR, BOH, ZID, NUP, PAF, ROG, CUG, JOM, KIZ,
DAX) were randomly assigned into one of three stimulus
groups (the syllables will be denoted as A, B, C, and D
within each of the three groups (e.g., Group 1: VAK(A1),
JOM(B1), DAX(C1), NUP(D1); Group 2: YIM(A2),
ROG(B2), CUG(C2), KIZ(D2); Group 3: LUR(A3),
BOH(B3), ZID(C3), PAF(D3)). The grouping defined how
the syllables were going to be used in the MTS training and
cocaine conditioning trials: Stimulus Group 1 contained the
syllable to be paired with 25 mg cocaine, Stimulus Group
2 contained the syllable to be paired with 0 mg cocaine,
whereas no syllable in Stimulus Group 3 was to be paired
with cocaine, stimuli from this group were used during the
stimulus preference task, identity matching, and as a com-
parison stimulus during an attention probe in the condition-
ing trials. This yielded a total of three (25 mg, 0 mg, no
cocaine), four-member (A, B, C, D) stimulus groupings.
Participants were presented three stimuli (a sample stimu-
lus, Sa+) and two comparison nonsense stimuli (Co+; which
was identical to Sa+) and (Co-; a nonsense syllable from the
neutral stimulus group 3) in the identity matching training
and testing procedure. A correct response was picking the
comparison (Co+) that was the same as the sample stimulus
(Sa+). For example, participants were shown RUW (Sa+),
and they were then presented with two comparison stimuli
(RUW, Co+) and (DAY, Co-). Picking RUW would be the
correct choice. Identity matching training blocks consisted
of 20 trials with successively less feedback provided (“COR-
RECT” or “WRONG”) across each successive block (100%,
75%, 25%, 0% of the trials). Participants needed to dem-
onstrate 100% correct performance for each training block
before moving to the next one. Performance below mastery
criteria (100% correct) resulted in a repeat of the training
block. The testing block consisted of 30 trials in which no
feedback was provided. All of the participants met the mas-
tery criterion, 100% correct performance, on the identity test-
ing trials and no participant demonstrated a preference for a
nonsense syllable prior to the beginning the MTS protocol.
Phase 2. Matching‑to‑Sample Procedure: Overview The con-
ditional discrimination training and the testing of derived rela-
tions (i.e., symmetry, transitivity, and equivalence) occurred
across three consecutive ½- day sessions (Day 2 am and pm;
Day 3 am) before any of the cocaine-pairing sessions occurred.
Participants were initially taught four baseline conditional dis-
criminations across the two designated cocaine dose stimuli
groups: (Cocaine 25 mg group, B1A1; A1C1; Cocaine 0 mg
group, B2A2; A2C2) and were tested for the emergence of sev-
eral derived relations (symmetry A1B1/A2B2, C1A1/C2A2;
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transitivity B1C1/B2C2; and two 3-member equivalence
classes (A1-B1-C1/A2-B2-C2). Participants who demon-
strated the emergence of 3-member equivalence classes were
then taught two additional baseline discriminations (Cocaine
25 mg group, D1A1; Cocaine 0 mg group, D2A2) and were
tested for the emergence of two 4-member equivalence classes
(A1-B1-C1-D1/A2-B2-C2-D2). A serial training protocol was
used to train the baseline relations and a simultaneous testing
protocol was used to assess the maintenance of the baseline
relations and all emergent relations (i.e., symmetry, transitivity,
and equivalence) for both the three- member and four- member
classes (Adams et al., 1993). It is important to note the training
was structured so that the C and D stimuli were only one nodal
distance (A) from the B stimuli used in the conditioning tri-
als. This training structure was utilized to reduce the effects of
nodal distance on the likelihood of transfer of function across
the derived relations (Fields et al., 1995). Further, the com-
parison stimuli (Co-) used in a training trial consisted of the
respective stimulus from the other dosing group. For example,
in a B1A1 training trial using stimuli from the 25 mg group,
the Co+ was A1 and the Co- was A2. Likewise, B2A2 training
utilized the A1 stimulus as the Co-. This presentation format
was employed to reduce the probability that any differential
transfer effects would be due to a difference in the frequency
of sample (Sa+) and comparison stimuli presentations (Co+
and Co-) or the effects of an unbalanced pairing of sample and
comparison stimuli during the training and testing phases. In
addition, the equal number of A1 and A2 presentations in the
presence of both Sa+ stimuli (i.e. the B1 and B2 CSs) was
included to reduce the probability that a demonstrated trans-
fer of differential physiological responding could be strictly
due to associative processes (i.e. sensory preconditioning or
higher-order conditioning). The syllables designated to the
“‘no cocaine”’ group (Group 3) were not used for the MTS
training or testing blocks.
As with the identity matching trials, each MTS trial
involved the presentation of a sample (Sa+) and two com-
parison stimuli (Co+; Co-). The sample was presented first
at the upper top center portion of the computer screen fol-
lowed by the two comparisons to the left and the right below
the sample (correct comparison stimuli were randomly alter-
nated from left to right positioning to rule out the possibil-
ity of stimuli location controlling the selection response).
Participants were instructed to point and click on the com-
parison stimulus they choose. The sample stimulus remained
on the screen while the comparison stimuli were presented.
Each trial in the initial training block provided informa-
tive feedback (i.e., 100% of the trials in the block), which
consisted of presenting “CORRECT” or “WRONG” after a
comparison was selected. This training block was presented
repeatedly until the trials yielded 100% correct responding,
which was designated as the mastery criterion. Subsequent
training blocks provided feedback that was systematically
The Psychological Record (2023) 73:481–500 485

reduced to 75%, 25%, and 0% of the trials, provided the
mastery criterion was maintained in each block. The tri-
als providing feedback were randomly selected within each
block. Performance below criterion in a given block resulted
in the repeated administration of that block. A training block
could be repeated up to six times. A training session was
ended if the participant did not achieve mastery criterion by
the sixth administration of a given training block. All MTS
sessions had a maximum time limit of 3 hr. Participants were
instructed at the beginning of each training and testing ses-
sion that they would earn money based on their performance.
This incentive was provided to maintain motivation during
the task. However, a reimbursement amount was randomly
selected from a range of $18– to $20 prior to the session, the
amount was not linked to task performance and the amount
“earned” was only displayed on the computer screen at the
end of a training session. Table 1 presents the sequence of
the MTS training and testing blocks.
Training BA, AC, and DA Baseline Relations BA relations
were trained in a block of 16 trials with 100% feedback
until mastery criterion was achieved. Subsequent training
blocks consisted of eight trials and the systematic reduction
of feedback from 100%, to 75%, and 25%, then 0% as long
as mastery criterion was demonstrated for a given block.
Below mastery performance resulted in the repeated admin-
istration of that block. Mastery performance of BA relations
with 0% feedback prompted the beginning of AC training.
AC relations were trained in a block of 16 trials with 100%
feedback, which also included BA probes, until mastery cri-
terion was achieved. Subsequent training blocks consisted
of eight trials and the systematic reduction of feedback from
100%, to 75%, and 25%, then 0% if mastery criterion was
demonstrated for a given block. Below mastery performance
resulted in the repeated administration of that block. DA
relations were only trained following 100% correct perfor-
mance on the tests of symmetry, transitivity, and equiva-
lence in the three-mixed-probe test blocks (“three-mixed”;
see below). DA training blocks consisted of 20 trials with
100% feedback, which also included BA and AC probes,
until mastery criterion was achieved. Subsequent training
blocks consisted of 12 trials and the systematic reduction of

Table 1  The Sequence of Blocks (in order of training) Trials with feedback Mastery Relations trained and/or
Conditional Discrimination Criterion tested within each block
Training and Derived Relations (The no. of trials presented
Testing Blocks Employed in the in each block)
Matching-to-Sample Sessions
Train BA 100% 100% B1:A1 (8) B2: A2 (8)
Train BA 75%, 25%, 0% 100% B1:A1 (4) B2: A2 (4)
Train AC & BA 100% 100% A1:C1 (6) A2:C2 (6)
B1:A1 (2) B2:A2 (2)
Train AC & BA 75%, 25%, 0% 100% B1:A1 (2) B2:A2 (2)
A1:C1 (2) A2:C2 (2)
3-mixed-probe tests for symmetry, 0% 100% B1:A1 (5) B2:A2 (5)
transitive, equivalence relations (80 A1:C1 (5) A2:C2 (5)
Trials per block; 3 block maximum)* A1:B1 (9) A2:B2 (9)
C1:A1 (6) C2:A2 (6)
B1:C1 (6) B2:C2 (6)
C1:B1 (9) C2:B2 (9)
Train DA (with BA & AC probes) 100% 100% D1:A1 (6) D2:A2 (6)
B1:A1 (2) B2:A2 (2)
A1:C1 (2) A2:C2 (2)
Train DA (with BA & AC probes) 75%, 25%, 0% 100% D1:A1 (2) D2:A2 (2)
B1:A1 (2) B2:A2 (2)
A1:C1 (2) A2:C2 (2)
4-mixed-probe tests for symmetry, tran- 0% 100% A1:B1 (4) A2:B2 (4)
sitive and equivalence relations (72 C1:A1 (4) C2:A2 (4)
trials per block; 6 block maximum) A1:D1 (4) A2:D2 (4)
B1:C1 (4) B2:C2 (4)
D1:C1 (4) D2:C2 (4)
D1:B1 (4) D2:B2 (4)
B1:D1 (4) B2:D2 (4)
C1:B1 (4) C2:B2 (4)
C1:D1 (4) C2:D2 (4)
*
Below mastery performance prompted a sequence of serial testing blocks for symmetry, transitivity, and
equivalence relations prior to the beginning of DA training

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feedback from 100%, to 75%, 25%, then 0% as long as mas-
tery criterion was demonstrated for a given block. Mastery
of the DA conditional discrimination trials with 0% feedback
prompted the simultaneous testing for all emergent relations
among the four-member stimuli groups.
Testing for the Derived Relations of Symmetry, Transitivity, and
Equivalence A test block of 80 trials was conducted following
the successful completion of the BA and AC training blocks.
The three-mixed-test block included the presentation of all the
relation probes in one block: trained conditional relations (BA,
AC), and the derived relations: symmetry (AB, CA) transitivity
(BC), and equivalence (CB). No feedback was provided during
test trials and mastery performance was defined as 100% cor-
rect. Mastery performance resulted in entering the DA training
sequence. Below mastery performance resulted in the repeated
administration of the three-mixed test block for a maximum of
three times (a total of 240 trials). After the third administra-
tion, participants who did not demonstrate mastery entered a
serial testing phase that consisted of blocks separately assessing
each of the derived relations. No performance feedback was
provided for the serial test blocks. The serial testing sequence
followed this order: CB (equivalence, 24 trials), AB (symmetry,
16 trials), CB (24 trials), CA (symmetry, 24 trials), CB (24
trials), BC (transitivity, 24 Trials), and CB (24 trials). Mastery
performance during any of the CB testing blocks (equivalence
relations) resulted in the administration of the three-mixed test
block. Below mastery performance on a CB test block resulted
in the administration of the next block in the sequence. Below
mastery performance on the symmetry and transitivity serial
test blocks resulted in a repeat of that block for a maximum of
12 times. If mastery performance was not demonstrated after
the ­12th administration the session was ended.
A test block of 72 trials was conducted following the suc-
cessful completion of the DA training blocks. The test block
(“four-mixed”) test included probes for all the relations in one
block: the trained conditional relations (BA, AC, DA) and the
derived relations: symmetry (AB, CA, AD), transitivity (BC,
DC), and equivalence (DB, BD, CB, and CD). No feedback
was provided for the test probes and mastery performance
was defined as 100% correct. Mastery performance ended the
session. Below mastery performance resulted in the repeated
administration of the four-mixed block for a maximum of six
times (432 total trials). If mastery performance was not dem-
onstrated after the ­sixth administration the session was ended.
The MTS procedures were conducted across three sepa-
rate sessions. If a participant demonstrated the emergence
of four-member equivalence during a session, that session
ended. The next session then started with the administration
of the four-mixed test block to assess the maintenance of
the derived relations. Mastery performance on the test ter-
minated the session. Below mastery performance prompted
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the beginning of the training and testing sequence starting
with the BA conditional training block.
Phase 3. Respondent Conditioning: The Direct Pairing of Non‑
sense Syllables (B1 and B2) with Smoked Cocaine Following
the MTS training and testing sessions, participants began
the respondent conditioning phase of the study. During this
phase, the administration of 25 mg dose of cocaine followed
the presentation of the “B1” stimulus (CS+, a member of the
designated 25 mg Cocaine group) and the administration of
0 mg dose of cocaine followed the presentation of the “B2”
stimulus (CS-, a member of the designated 0 mg Cocaine
group). The preparation and administration of cocaine during
a respondent conditioning session followed the procedures
implemented in previous studies (Foltin & Haney, 2000).
Cocaine base, derived from cocaine hydrochloride (Mallinck-
rodt Pharmaceuticals, St. Louis MO), was prepared in 25 mg
pellets by the New York State Psychiatric Institute Pharmacy
(Foltin et al., 1990). The 0 mg dose consisted of inhaling
warm air from the glass stem. During dose administration,
participants were blindfolded and presented with cocaine base
in a glass pipe (“stem”) fitted with mesh smoke screens and
were instructed to take one large inhalation and hold the vapor
as long as they would outside of the laboratory. The cocaine
base was aerosolized by a nurse holding the flame from a pipe
lighter beneath the pipe. Zero- mg administration involved the
presentation and heating of an empty glass pipe. Neither dose
was given if cardiovascular activity was above the criteria for
safe drug administration: systolic pressure (SP) > 160 mm
Hg; diastolic pressure (DP) > 100 mm Hg or a heart rate (HR)
≥ 200 – (participant’s age x 0.85); sustained for more than 6
min prior to the next scheduled dose administration. Cocaine
use only occurred during the study sessions. Each session
ended 30 min after the last dose was administered.
Eight conditioning sessions were conducted across 5 days
(Day 3 pm; Days 4, 5, and 6, am and pm; Day 7 am). Each con-
ditioning session was designated as either a 25- mg session or
a 0- mg session. For each designated session, the same cocaine
dose was administered six times. Participants were scheduled
to complete four 25-mg conditioning sessions and four 0-mg
conditioning sessions during the study (a total of eight sessions
that entailed 24 conditioning trials for each cocaine dose). All
laboratory sessions occurred on the weekdays. Morning ses-
sions began at 0900 h, and the afternoon sessions began at
1500 h. Each session lasted approximately 2 hr. During a con-
ditioning session, participants were seated in a reclining chair
in front of a laptop computer with a mouse manipulandum. A
22-guage catheter (Quik-Cath, Travenol Laboratories, Deer-
field, IL) was inserted in a subcutaneous vein of one arm to
permit ready intravenous access if needed in an emergency. A
physician, nurse, and research assistant located in an adjacent
control room monitored and communicated with participants
The Psychological Record (2023) 73:481–500
via a one-way mirror and intercom. Electrocardiograms
(ECGs) were monitored continuously (BioPAC, with Acq-
knowledge software) and blood pressure was recorded every 2
min (Sentry II-Model 6100 automated vital signs monitor NBS
Medical, Costa Mesa, CA) beginning 20 min prior to the first
dose administration. The automated collection of ECG and
blood pressure data was facilitated by computers also located
in the adjacent control room.
Conditioning sessions started with a 20-min baseline
period. Following the first 10 min, participants completed a
computerized subjective-effects questionnaire. The battery
consisted of a series of visual analog scales ranging from 1
“not at all” to 100 “extremely.” Participants were instructed
to register their subjective state by selecting a number along
a separate VAS for each of the statements “I feel stimulated,”
“I feel high,” “I feel anxious,” “Good drug effect, and “Bad
drug effect.” Participants were asked to rate the statement
“I want cocaine,” once during the session, 14-min after the
last cocaine dose was administered.
Following the 20-min baseline period, the session consisted
of six dosing blocks and two posttraining subjective assess-
ments. Each dosing block was 14-min in duration and was
the same sequence. First, consistent with the conditioning
framework employed by Dougher et al. (1994), participants
were prompted to begin a key-pressing task. Participants could
earn $0.10 for maintaining a consistent response (between 12
and 20 clicks per 10 seconds) on a button using the mouse
manipulandum. The key-pressing task occurred for approxi-
mately 4-min (a randomly generated time interval between 240
and 260 seconds) and the cumulative amount being earned
was presented on the screen during the task. The key-pressing
task and monetary earnings were used to keep a participant’s
attention focused on the computer screen on which the CS
(B1 and B2 stimuli) was presented during the session and to
maintain participant motivation throughout the experimental
procedures. After four min, the screen went blank, and the B
stimulus used for the dose being administered (i.e., B1 25 -mg;
B2 0 -mg) was presented for a randomly generated time pro-
grammed to be between 50 and 65 seconds. Participants could
not shorten the time of the stimulus presentation. Following
the stimulus presentation, participants were presented with
the B stimulus and a randomly selected stimulus from Group
3 and were instructed to “click on the stimulus that was just
presented.” This step was included to assess if the participant
attended to the presented B stimulus during the time interval.
Clicking on the correct stimulus (CSs; B stimulus) cleared the
computer screen (a “wrong” response presented the choice
again); the research assistant then asked the participant via
intercom to put on a blindfold and the research nurse entered
the room with the cocaine dose to be administered. Partici-
pants were instructed they could remove their blindfold and
to remain seated in their chair following dose administration.
Four min after dose administration, participants completed the
487
subjective-effects questionnaire. Five min after the question-
naire was presented, the next 14-min block was initiated with
a prompt to begin the key-pressing task. Each conditioning
session ended 30 min after the last dose was administered.
Phase 4. Tests for the Transfer of Respondent Eliciting Func‑
tions of Stimuli Paired with Smoked Cocaine The test for
the transfer of the respondent eliciting functions of stimuli
that were paired with cocaine to drug neutral stimuli was
conducted during the last session of the study sequence in
the afternoon on Day 7. This session was used to test if the
differential changes in HR in the presence of the stimuli
directly paired with smoked cocaine (B1 (CS+), 25-mg
dose; and B2 (CS-), 0- mg dose) would also be demonstrated
in accordance with the emergent relations demonstrated dur-
ing the MTS testing blocks. The test of transfer began with
the presentation of the B1 and B2 stimuli with the stipulation
that the B1 stimulus was always presented first. Each presen-
tation was followed by the administration of the respective
cocaine doses (25 mg and 0 mg). The active dosing was
included to set the expectations that cocaine may be received
throughout the testing session. This ordering also allowed
for a 41-min period before the presentation of the other
stimuli from each class (e.g., A, C and D), so a participant’s
physiological responding due to active cocaine inhalation
could return to baseline. Following the randomly ordered
presentation of the A, C, and D stimuli, the B stimuli were
presented for a second time. Procedures for the transfer test
sessions followed the conditioning sessions in most regards.
However, the instructional set for this session differed from
the training sessions. Participants were told that there was a
probabilistic chance they would receive cocaine following
the presentation of each presented stimulus (“you may or
may not have the opportunity to smoke cocaine following
the presentation of each symbol”). Further, it is important
to note that the presentation of all stimuli (A, C, D, and
the second presentation of B) were under extinction condi-
tions (no cocaine was administered). Previous studies have
demonstrated a linear decrease of physiological activity over
the course of extinction sessions. Thus, the assessment of
changes in HR during the transfer session (i.e., relative to
baseline) was conducted in the context of a reduction in the
overall level of physiological activity over the course of the
session.
The test for transfer session started with a 20-min baseline
period and participants completed subjective ratings at the
10-min mark. The key-pressing task began following the base-
line period. The key-pressing task was presented in approxi-
mately a 4-min block and the cumulative amount being earned
was presented on the screen during the task. After four minutes
of key pressing, the screen went blank and a selected stimu-
lus was presented for a time interval randomly generated to be
between 50 and 65 seconds. Participants could not shorten the
13
488
presentation time. The order in which stimuli were presented
was randomly generated prior to the transfer session for each
participant. Participants were asked to click on the stimulus
when the instruction appeared. After clicking on the stimulus,
it was removed from the screen, and participants were instructed
to place a blindfold over their eyes via intercom (so as to intro-
duce the possibility of cocaine administration). After five sec-
onds, participants were instructed to remove their blindfolds and
completed the subjective-effects questionnaire four min later.
Following the completion of the questionnaires the next segment
began with a prompt to begin the key-pressing task.
Physiological Recording during Respondent Conditioning
and the Test for Transfer Sessions HR was monitored con-
tinuously throughout the conditioning sessions and the test
for transfer session. Baseline HR was determined by aver-
aging HR over the last 10 min of the 20 min rest period at
the beginning of each session. The averaged baseline HR
value was then subtracted from the recorded value during
the approximately one-minute presentation of the B stimuli
utilized in the MTS training sessions. This yielded the dif-
ference scores in which positive values indicated an increase
in HR responding from baseline in the presence of a stimu-
lus and a negative difference score indicated a decrease in
responding from the baseline HR value in the presence of the
stimulus. Differences scores were also calculated for each
stimulus presentation (A1, A2, B1, B2, C1, C2, D1, and D2)
during the test for transfer session.
Criteria Used to Denote the Establishment of Respondent
Conditioning A change in heart rate (HR) was the outcome
of primary interest during the conditioning trials and the
transfer of eliciting function tests (Foltin and Haney, 2000).
Changes in HR following the first B stimulus presentation
during the first conditioning session and the first presenta-
tion of that stimulus in last conditioning session were calcu-
lated to assess for the establishment of respondent eliciting
functions of the nonsense syllables that were directly paired
with each cocaine dose (B1, 25 mg and B2, 0 mg). Par-
ticipants were designated as having evidenced differential
elicited responses in HR if they demonstrated (1) increased
HR in the presence of the B stimulus paired with 25 mg
of cocaine (CS+) between the first and fourth conditioning
sessions; (2) greater increases in HR in the presence of the
25- mg paired stimulus (B1, CS+) compared to the 0- mg
paired stimulus (B2, CS-) in the beginning of the fourth con-
ditioning session for each respective dose; and (3) differen-
tial HR responding in the presence of the B1 and B2 stimuli
in the transfer testing session. The values presented for each
B stimulus in the test for transfer were based on the second
presentations of these stimuli at the end of the session (as
the first presentation was followed by the administration of
the two respective cocaine doses).
13
The Psychological Record (2023) 73:481–500
End of Study Interviews Participants were scheduled for
follow-up interviews 1- and 12 -weeks after the study ended
in which they were invited to provide feedback about the
experiment and to assess their level of cocaine use and cur-
rent cocaine problems. If participants expressed interest in
treatment, they were provided referrals for treatment facili-
ties close to their place of residence.
Results
Participants
Twelve individuals (10 males; 2 females) completed the screen-
ing procedure, met all inclusion and exclusion criteria, and con-
sented to participate in the study. Table 2 presents descriptive
data for each participant. On average, participants were 43.5
years of age (SD = 4.2), completed 12.3 years of school (SD
= 1.3) and were regularly smoking cocaine (at least 3x/ week)
for 20.6 years (SD = 5.2). Participants reported using cocaine
on 4.8 days (SD = 1.7) and spending approximately $422.3
(SD = $301.5) per week during the month prior to enrolling
in the study. Of the 12 individuals enrolled in the experiment,
10 completed all three MTS training and testing sessions. Six
participants completed all phases of the experiment. There were
several reasons why individuals did not complete the study. P2
failed to show up for his admission appointment. P8 had ECG
abnormalities following admission, thus was removed from the
study prior to participating in any of the experimental proce-
dures and was provided referrals for continued cardiac assess-
ment and care. Participants 1, 6, 11, and 12 left the study during
the respondent conditioning phase of the experiment for the
following reasons: P1 decided to seek treatment while interact-
ing with the research staff and was exited from the study. P6
reported that family matters needed his attention and discon-
tinued his participation. He subsequently reported, during a
follow-up interview, that he sought treatment soon after leaving
the unit. P11 and P12 were discontinued from the trial as their
physiological responding exceeded the criteria we employ for
safe drug administration (i.e., abnormal cardiac rhythms and
significantly elevated blood pressure, respectively).
BA and AC Baseline Relations
All 10 participants initiating the MTS protocol met mas-
tery criterion for BA and AC conditional discrimination
training over the course of the three training sessions.
However, there was considerable variability in the number
of trials needed to proceed to the three-mixed test blocks.
The number to trials needed to learn these initial base-
line relations was inversely associated with the number of
derived relations demonstrated. On average, participants
The Psychological Record (2023) 73:481–500 489

Table 2  Demographic ID Gender; Race; Age Yrs of Educ Cocaine use: Cocaine Use: $ Yrs of Regular
Characteristics and Smoked Ethnicity days per week spent per week Cocaine Use
Cocaine Use for All the
Participants Enrolling in the P1* M; Black; NH 36 10 7 $900 16
Study
P2 M; Black; NH 39 12 3.5 $600 29
P3** M; Black; NH 46 12 5 $325 20
P4 M; Black; NH 46 12 3.5 $800 10
P5 M; Black; NH 46 12 7 $150 27
P6* M; Black; H 38 12 2 $125 23
P7 M; White; H 41 12 2 $250 20
P8 M; Black; NH 49 14 7 $700 14
P9* F; White; NH 40 15 6 $200 21
P10** M; Black; NH 45 14 7 $700 22
P11** F; White; H 47 11 3 $200 23
P12** M; Black; NH 48 13 4.5 $100 26
*
Demonstrated the emergence of three-member equivalence in the mixed probe tests
**
Demonstrated the emergence of both three and four-member equivalence classes in mixed probe tests
M = male; F = female. H = Hispanic, NH = non-Hispanic. Participants in boldface completed all four
phases of the study. P2 and P8 (italicized) did not initiate any phase of the study

who advanced to the DA extension training and demon-
strated two 4-member equivalence classes needed 307 (SD
= 102.8) BA and AC baseline conditional discrimination
training trials to meet the mastery criterion. Participants
demonstrating only 3-member equivalence classes (i.e.,
did not advance to the four-mixed-tests) required 482 (SD
= 34.7) baseline conditional discrimination training trials.
Those demonstrating no derived relations in the mixed
probe test blocks over the course of the experiment needed
the greatest number of conditional discrimination train-
ing trials to meet the mastery criterion (M = 563; SD =
69.0). Figure 1 presents the MTS training and testing per-
formances for each participant by each session. Table 3
presents the total number of conditional discrimination
training and testing trials for each participant during the
MTS phase of the experiment.
Testing Derived Relations after BA and AC Baseline
Discrimination Training
Seven of the 10 participants (70%) shown in Fig. 1 demon-
strated symmetry, transitivity, and equivalence in the three-
mixed testing blocks (P3, P10, P11, P12, P1, P9, P6). Six
of these seven participants demonstrated the maintenance
of derived relations over multiple MTS sessions. P6 dem-
onstrated two 3-member equivalence classes in the first
training session although failed to meet mastery criterion
during the subsequent two MTS sessions. Figure 2 pre-
sents the average response times for the conditional dis-
crimination and the emergent relation probes presented in
the mixed-probe test blocks for all the participants. Con-
siderable variability was noted across the relation probes
within and across participants. Average response times
were shorter for the probes of the baseline discrimination
trials and longer for the probes of emergent transitive and
equivalence relations among participants demonstrating
three-member equivalence classes. Further, participants
demonstrating equivalence relations tended to demonstrate
increasingly faster responding to the relational probes over
the three testing and training days (e.g., P1, P9, P12). How-
ever, among participants who did not meet mastery crite-
rion for three-member equivalence, response times gener-
ally increased over the three training and testing sessions
(i.e., P4, P5, P7).
Training DA Conditional Relations and Testing
the Extension of Equivalence Classes
Six participants entered the extension part of the training
in which DA relations were introduced, and the emergence
of two 4-member equivalence classes were tested. Four
of the six participants entering this phase of the training
(67%; 40% of the total sample) demonstrated the emergence
and maintenance of two 4-member equivalence classes in
the mixed-probe testing blocks (i.e., P3, P10, P11, P12).
Three of the four participants meeting mastery criterion for
the four-member equivalence classes demonstrated a rela-
tively rapid acquisition with the emergence of four-member
equivalence classes occurring during the first MTS training
and testing session (P3, P10, P11). P12 entered the serial
probe tests during the first MTS session and demonstrated
four-member equivalence classes during the second training
session. These relations were maintained during the third
testing session and response times to the relation probes in
the four-mixed test block generally decreased over the three

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490 The Psychological Record (2023) 73:481–500

4-Member Equivalence Demonstrated (a)

Session 1 Session 2 Session 3
P3 P10
100
* *** 100
* * ***

80 80

60 60

40 40

20 20

0 0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV

P11 P12

100
*** *** 100
** **

80 80

60 60

40 40

20 20

0 0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV

3-Member Equivalence Demonstrated (b)

P1

**
100

80

60

40
Percentage Correct

20

0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV

P6 P9

100 * 100
**

80 80

60 60

40 40

20 20

0 0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV

Fig. 1  The percentage of correct responses on the training and
testing trial blocks during each of the three MTS sessions. Base-
line conditional discrimination trials (AB, BC), derived relation
probes for the 3-mixed testing blocks (Symmetry (SYM), Transi-
tivity (TRAN), Equivalence (EQUIV)), the extension conditional
discrimination training (DA), and derived relation probes for the
4-mixed testing blocks (SYM, TRAN, EQUIV) are presented on
the horizontal axis. The vertical axis presents the percentage of cor-
rect responses across all the probes for each relation. Participants
are grouped according to their performance on the derived relations
probes in the mixed testing blocks (panels a, b, and c). Demon-
strated mastery performance indicating emergent equivalence in a
mixed-probe testing block is denoted by *

13
The Psychological Record (2023) 73:481–500 491

No Equivalence Demonstrated (c)

P4
100

80

60

40

20

0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV

P5 P7
100 100

80 80

60 60

40 40

20 20

0 0
BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV BA AC SYM TRAN EQUIV DA SYM TRAN EQUIV
Baseline 3-Mixed BL 4-Mixed Baseline 3-Mixed BL 4-Mixed

Fig. 1  (continued)

testing sessions (see Fig. 2). The overall yield (Fields et al.,
2020), or percentage of participants in this study demonstrat-
ing the immediate emergence of four-member equivalence
classes on the first or second four-mixed probe test block
was 10% (P3).
Serial Derived Relations Test Probes
Participants demonstrating below mastery performance on
the three-mixed test blocks (P4, P5, P7), evidenced improve-
ment and mastery performance on the baseline conditional
discrimination trials (BA and AC) across the three training
sessions. P4 and P5 demonstrated symmetry (P4 (A1B1/
A2B2); P5 (A1B1/A2B2 and C1A1/C2A2)) during the serial
testing blocks only. P7 demonstrated no emergent relations
in either the mixed or serial probe test blocks across all three
training and testing sessions.
Respondent Conditioning
Six of the 10 participants completing the MTS training and
testing phase also completed the respondent conditioning
phase and the test for transfer session. The left panel of
Fig. 3 presents changes in HR in the presence of each B
stimulus at the beginning of the first (Trial 1) and fourth
(Trial 19) conditioning sessions for each cocaine dose (25
mg and 0 mg). The right panel presents changes in HR
responding in the presence of each MTS stimulus during
the test for transfer session (A1, A2, C1, C2, D1, D2, second
presentation of B1 and B2).
Four of the six participants (67%; P9, P10, P4, P5) evi-
denced differential conditioning over the course of the
experiment based on the three preestablished criteria: (1)
greater HR response in the presence of the 25- mg cocaine
paired stimulus (B1) in the fourth conditioning session com-
pared to the first; (2) greater HR responding in the presence
of the 25- mg stimulus (B1) compared to the 0- mg stimulus
(B2) at the beginning of the fourth conditioning session;
and (3) demonstrated differential HR responding to each B
stimulus at the end of the test for transfer session. P3 failed
to demonstrate differential increases in HR in the presence of
the B1 stimuli during the transfer testing session. P7 demon-
strated relatively greater HR in the presence of the B stimuli
paired with the 0- mg dose (CS-) over the course of the
conditioning sessions and this differential response was not
demonstrated in the test for transfer session.
The right portion of each panel in Fig. 3 presents changes
in HR during the tests of the transfer of differential condi-
tioned elicitation in the presence of stimuli paired with
cocaine (B stimuli) to the previously neutral A, C, and D stim-
uli (i.e., stimuli that were never directly paired with cocaine

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492 The Psychological Record (2023) 73:481–500

Table 3  The Total Number Total Number of Total number of Derived Relations Probes (no feedback)
of Baseline Conditional- Baseline
Discrimination and Derived Discrimination Trials
Relation Testing Probes (with and without
Presented across the Three feedback)
MTS Sessions for Participants.
Participants are grouped by Symmetry Transitivity Equivalence
their performances on the a a a a
derived relation test probes ID BA AC DA AB CA AD BC BD DC CB CDa DBa

4-Member equivalence demonstrated (Mixed-Probe Test Blocks)

P3 144 104 72 48* 60* 24* 48* 24* 24* 60* 24* 24*
P10 284 252 204 108* 138* 48* 108* 48* 48* 84* 48* 48*
P11 344 276 256 108* 138* 48* 108* 48* 48* 48* 48* 48*
P12 192 128 52 132* 130* 40* 100* 40* 40* 151* 40* 40*
3-Member equivalence only demonstrated (Mixed-Probe Test Blocks)
P1 336 296 120 229* 284* 48 277* 104 104 222* 104 104
P9 300 256 108 192* 244* 40 200* 40 40 280* 40 40
P6 318 204 72 270* 144* -- 96* -- -- 168* -- --
Derived relations demonstrated in serial test blocks only
P4 284 292 -- 132* 551 -- 108 -- -- 234 -- --
P5 284 204 -- 300* 210* -- 234 -- -- 246 -- --
No derived relations demonstrated
P7 332 292 -- 310 156 -- 92 -- -- 177 -- --
Participants are grouped by their performances on the derived relation test probes
a
Derived relation probes were only presented following mastery performance on the DA extension training
probes with no feedback
*
100% accuracy demonstrated for these derived relation probes in a requisite testing block

administration). The results support a transfer of differential
conditioned elicitation (HR responding) in the context of sym-
metry among all four of the participants (100%; P4, P5, P9,
P10) who demonstrated both derived relations during the MTS
testing phase and differential conditioned elicitation during
the cocaine administration phase. In particular, changes in HR
responding in the presence of the A stimulus in a derived sym-
metrical relation (A1B1) with the 25- mg-paired B stimulus
(CS+) was greater than the change in HR response in the pres-
ence to the A stimulus in a derived symmetrical relationship
(A2B2) with 0- mg-paired B stimulus (CS-). This outcome
occurred for participants demonstrating emergent symmetry
in either the mixed-probe test blocks (P10, P9) or the serial-
probe blocks (P4, P5). Of note, the probability of observing
this pattern across participants in the test session (i.e. four of
six participants demonstrating differential respondent elicita-
tion in the presence of the A stimuli) by chance alone was
low (approximately .002). P3, demonstrated four-member
equivalence but did not demonstrate differential respondent
conditioning and P7 demonstrated no emergent relations dur-
ing the MTS training sessions and also did not demonstrate
differential respondent conditioning. Thus the observed lack
of transfer of differential conditioned elicitation was consist-
ent with what was predicted for each participant. Of note,
no concordant symmetric transformations of functions were
demonstrated for the subjective-effect ratings.
The transfer of conditioned elicitation in accordance with
combinatorial entailed relations (i.e., to C and D stimuli) was
predicted for P10 (four-member equivalence) and P9 (three-
member equivalence class). Neither participant showed differ-
ential elicitation in the presence of the C stimuli. P10 demon-
strated differential elicitation in the presence of the D stimuli,
consistent with predictions. However, P4, P5, and P7, none of
whom showed equivalence or transitive relations, also demon-
strated greater HR responding in the presence of the D stimuli
in the 25- mg stimulus group. The differential elicitation could
not be a function of emergent relations for these participants,
becauseas they did not advance to the DA extension part of
the MTS training protocol.
Discussion
Identifying the processes by which stimuli in the natural
ecology can lead to substance use is critical for develop-
ing effective treatment strategies. Human laboratory models
that combine well- established procedures for investigating
the acquisition of emergent stimulus functions by the direct

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The Psychological Record (2023) 73:481–500 493

4-Member Equivalence Demonstrated (a)

Session 1 Session 2 Session 3
P3 P10
7.0
7.0
6.5
6.5
6.0 6.0

5.5 5.5

5.0 5.0

4.5 4.5

4.0 4.0

3.5 3.5

3.0 3.0
2.5 2.5
2.0 2.0
1.5 1.5
1.0 1.0
0.5 0.5
0.0 0.0
BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB

12.5 P12
12.0
11.5
11.0
P11 10.5
7.0
10.0
6.5 9.5
6.0 9.0
8.5
5.5 8.0
5.0 7.5
7.0
4.5 6.5
4.0 6.0
5.5
3.5 5.0
3.0 4.5
4.0
2.5 3.5
2.0 3.0
2.5
1.5
2.0
1.0 1.5
1.0
0.5
0.5
0.0 0.0
BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB

3-Mixed Test Probes 4-Mixed Test Probes 3-Mixed Test Probes 4-Mixed Test Probes

3-Member Equivalence Demonstrated (b)

7.0 P1
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
Response Time (Seconds)

1.0
0.5
0.0
BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB

9.0 P6 7.0 P9
8.5 6.5
8.0
6.0
7.5
7.0 5.5
6.5 5.0
6.0
4.5
5.5
5.0 4.0
4.5 3.5
4.0 3.0
3.5
2.5
3.0
2.5 2.0
2.0 1.5
1.5
1.0
1.0
0.5 0.5
0.0 0.0
BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB BA AC AB CA BC CB AB CA AD BC BD DC DB CD CB

3-Mixed Test Probes 4-Mixed Test Probes 3-Mixed Test Probes 4-Mixed Test Probes

Fig. 2  All baseline and derived relation probes that were presented response time for a specified relation probe in seconds. Participants
during the 3-mixed-probe test blocks and 4-mixed-probe test blocks are grouped according to the equivalence relations evidenced during
are along the horizontal axis. The vertical axis presents the average the mixed-probe test blocks (panels a, b, and c)

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494 The Psychological Record (2023) 73:481–500

No Equivalence Demonstrated (c)

P4
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
BA AC AB CA BC CB

P5 P7
7.0 7.0
6.5 6.5
6.0 6.0
5.5 5.5
5.0 5.0
4.5 4.5
4.0 4.0
3.5 3.5
3.0 3.0
2.5 2.5
2.0 2.0
1.5 1.5
1.0 1.0
0.5 0.5
0.0 0.0
BA AC AB CA BC CB BA AC AB CA BC CB

3-Mixed Test Probes 3-Mixed Test Probes

Fig. 2  (continued)

pairing of stimuli with cocaine use and the indirect acquisi-
tion of emergent stimulus functions via the transfer of elicita-
tion functions in accordance with derived relational respond-
ing offers a promising framework for studying behavioral
processes underlying the development and maintenance of
substance use disorders. Nine out of 10 individuals with a
significant history of cocaine use demonstrated the mutually
entailed relation of symmetry, 7 of 10 evidenced complex
combinatorial relations as demonstrated by the emergence of
two 3-member equivalence classes. The formation of three-
member equivalence classes occurred quite readily for most
participants, i.e., during the first or second training session,
and was maintained over subsequent sessions. The emer-
gence of two 4-member equivalence classes following an
extension-training phase was more difficult to demonstrate,
with only four participants (40% of the total sample trained)
demonstrating emergent four-member equivalence classes.
The acquisition of differential conditioned elicitation in
the presence of nonsense syllables that were directly paired
with two different doses of smoked cocaine was demon-
strated for four of the six participants who completed this
phase of the experiment. All four participants demonstrat-
ing differential respondent elicitation also demonstrated a
transfer of these conditioned effects to other stimuli, i.e.,
nonsense syllables, in accordance with the derived relation
of symmetry. These findings extend the pathways by which
previously neutral stimuli can come to acquire drug-related
functions in the natural ecology, and highlight direct and
indirect conditioning processes that likely play important
roles in establishing ongoing substance use and a substance
use disorder. The present results also suggest methodologi-
cal refinements may be needed to further delineate the con-
textual parameters influencing the derivation of more com-
plex combinatorial relations and the transfer of respondent
eliciting functions in the context of these relations, reduce
participant attrition, and enhance the safety of the condition-
ing paradigm.
Derived relational responding has been a central compo-
nent of behavioral analytic accounts of human language and
cognition (Hayes et al., 2001; Sidman, 1994) and is hypoth-
esized to play an important role in substance use disorders
(Wilson & Hayes, 2000). However, few studies have directly

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The Psychological Record (2023) 73:481–500
studied this behavior among individuals with extended his-
tories of substance use. Sixty percent of the participants
meeting criteria for a cocaine use disorder evidenced three-
member equivalence classes in an MTS protocol using
stimuli that did not have previously established drug-related
functions (i.e., nonsense syllables). Although these relations
emerged within the first or second training session for most
participants, a proportion of participants did not demonstrate
emergent equivalence relations. The proportion of partici-
pants who demonstrated equivalence in this training protocol
was less than what has been shown in nondrug-using popu-
lations (Adams et al., 1993) but aligns with studies among
other substance-using populations (Vadhan et al., 2014;
Wilson, 1998). Together, the evidence suggests that combi-
natorial entailed relations may be less readily demonstrated
among individuals with substance use disorders compared
to individuals without substance use disorders. However, the
present findings also indicate establishing relational reper-
toires in the context of drug neutral stimuli can be readily
accomplished among a significant proportion of individu-
als with extended substance use histories. It is important to
note that studies indicate the process of establishing new
relations among stimuli may be significantly impacted by
the presence of preeestablished drug-related functions of
the stimuli being related. The personal relevance of stimuli
has been shown to affect the acquisition of new relational
classes in other clinical populations (Leslie et al., 1993) and
only 42% of individuals seeking treatment for CUD showed
derived equivalence in a single training and testing session
when cocaine associated words were included in the stimu-
lus groups (Carpenter et al., 2016). Thus, identifying factors
that influence the flexibility of relational processes among
individuals with a significant substance use history may offer
important insight into the effects of chronic substance use on
this behavioral process. In addition, identifying contextual
factors that can help strengthen and alter relational reper-
toires in this population may be critical for improving the
efficacy of verbally based interventions that look to modify
well-established patterns of substance use.
The present results also highlight 9 of the 10 participants,
with significant histories of substance use, readily demon-
strated symmetry, a building block for more complex rela-
tions. This basic component of derived relational responding
captures the foundational bidirectionality of emergent stimu-
lus relations and highlights a process by which a wide range
of stimuli can come to exert control over responding without
a history of directly training each relation. It is important
to note that mastery performance on the symmetry probes
was demonstrated under different testing conditions. Seven
of 9 participants demonstrated mastery performance in test
blocks containing all the relational probes and 2 participants
demonstrated mastery performance in test blocks contain-
ing only symmetry probes. Further, participants evidencing
495
equivalence relations in the three-mixed test blocks dem-
onstrated more rapid responding on the symmetry probes
(AB; CA) across all three testing sessions compared to those
meeting mastery criteria in the testing blocks presenting
symmetry probes alone.
The variability in the both the acquisition and the con-
textual control of relational responding suggests important
differences in the strength of relational repertoires across
participants. Interindividual differences in cognitive and
verbal abilities account for variability in CUD treatment
response (Aharonovich et al., 2006), and the relationship
between verbalized commitments to make changes in
cocaine use during counseling sessions and subsequent
changes in drug using behavior may require complex
relational repertoires (Carpenter et al., 2016). However,
altering how evidenced-based therapies are delivered has
not consistently improved treatment outcomes among
those with compromised cognitive and verbal perfor-
mances (Aharonovich et al., 2018). Symmetry has been
highlighted as an important building block for establish-
ing cognitive and verbal abilities as well as more com-
plex relational repertoires (O’Toole et al., 2009; Sidman,
1994). Thus, including more formal relational assessment
and training protocols (Adams et al., 1993) into substance
use disorder treatment programs may help identify indi-
viduals more likely to benefit from cognitive-behavioral
treatment strategies and offer an avenue to establish and
expand relational responses among individuals who may
not have the requisite relational repertoires that can bring
verbal behavior to bear on their drug- seeking and drug-
use behaviors.
Increases in HR occurred most reliably in the presence of
the nonsense syllables paired with the 25- mg cocaine dose
(B1) compared to the nonsense syllables paired with the
0- mg cocaine dose (B2) for a majority of the participants
entering this phase of the experiment (4/6). All instruc-
tional sets, key pressing tasks, experimental settings, and
dose administration procedures were identical for the four
25-mg and the four 0-mg conditioning sessions. Thus, the
emergence of differential physiological responding to the
neutral nonsense syllables is likely attributable to the direct
stimulus-cocaine dose-pairing procedures. These findings
are consistent with previous studies that have documented
the acquisition of emergent stimulus properties using direct
classical conditioning procedures under laboratory condi-
tions (Cascella et al., 1989; Foltin & Haney, 2000). The
emergent HR responses were demonstrated under labora-
tory conditions after a total of 36 trials (eighteen 25-mg
trials; eighteen 0-mg trials). In the natural ecology, there are
significantly more conditioning trials (pairing of drug and
cues), and fairly robust and reliable physiological respond-
ing in the presence of drug cues has been demonstrated
among those with extensive drug use histories (Ehrman
13
496 The Psychological Record (2023) 73:481–500

HR (25mg) HR (0mg) 4-member equivalence demonstrated

(Mixed-Probe Test)

P3 40 P10

30

20

-5

10
-10

0
-15

3-member equivalence demonstrated Symmetry demonstrated

(Mixed-Probe Test) (Serial Testing AB)
Change from Baseline (BPM)

P9 10 P4
15

10
5

0 0

-5

-5
-10

Symmetry demonstrated No derived relations demonstrated

(Serial Testing AB and CA)
8 P5 20 P7

15
6

10
4

2
0

0
-5

-2
-10

1 4 B A C D 1 4 B A C D
Conditioning Transfer Tests Conditioning Transfer Tests
Session Session

13
 The Psychological Record (2023) 73:481–500
◂Fig. 3  Changes in HR are presented for each cocaine dose (light gray
25 mg; dark gray 0mg) during the first trial in the first conditioning
session for that dose, the first trial in fourth conditioning session for
that dose (left-side panel), and for each of the stimuli presented dur-
ing the test for transfer session (right-side panel) on the horizontal
axis. The vertical axis presents the magnitude of change in beats per
minute between a participant’s HR during the baseline period of a
given session and in the presence of a given stimulus during the test
for transfer session. Participants are grouped according to the type
of derived relations demonstrated during the mixed or serial testing
blocks
et al., 1992). The present findings further highlight the
importance of direct conditioning processes as an integral
part of the explanatory models offered to individuals who
are seeking to understand their drug-seeking and drug-taking
behavior in the natural ecology (Carroll, 1998). Of note, P3
evidenced the emergence of four-member equivalence classes
and P7 failed to demonstrate any derived relations in either
the mixed or serial probe tests prior to the conditioning phase
of the experiment. Both participants also failed to demon-
strate responding that met the criteria for the emergence of
conditioned effects of smoked cocaine to the nonsense syl-
lables during the conditioning trials. It is possible that provid-
ing more personalized cocaine dosing based on individual
levels of use in the natural ecology, rather than a standard
25-mg dosing, may have yielded more consistent respond-
ent elicitation effects across all participants. Future research
investigating how relational repertoires affect the emergence
of respondent-elicited functions may also provide important
information on the verbal parameters impacting the acquisi-
tion of conditioned responding (Mitchell et al., 2009).
This was one of the first investigations to examine the
transfer of differential respondent elicited functions of
stimuli directly paired with drug use to other drug-neutral
stimuli in accordance with derived relations. The emergence
of differential elicited HR responding to stimuli that was
directly paired with the 25- mg or 0- mg doses of smoked
cocaine to other stimuli that were in a derived relation with
each respective cocaine-paired stimulus was most consist-
ently demonstrated in the context of symmetry (i.e., mutual
entailment). All four participants who demonstrated greater
increases in their HR in the presence of the 25- mg cocaine
paired stimuli (B1) evidenced greater increases in HR in the
presence of the mutually entailed A stimulus (A1B1) com-
pared to HR responding in the presence of the stimulus in a
mutually entailed relation with the 0- mg stimulus (A2B2).
A reliable transfer of function was not clearly demonstrated
for the combinatorial entailed relations of transitivity (CB)
or equivalence (DB). Overall, these findings highlight that
symmetry, a foundational bidirectional stimulus relation, is
readily observable among individuals reporting a significant
history of substance use and may play an important role by
497
which stimuli can come to acquire respondent elicited func-
tions, not as a result of direct drug-stimulus parings, but
through derived relational processes.
The failure to demonstrate a complete transfer of function
in accordance with transitive or equivalence relations was
inconsistent with previous investigations demonstrating the
transfer of a wide range of stimulus functions, including
respondent eliciting functions through stimulus equivalence
classes in a nonsubstance dependent population (Dougher
et al., 1994; Valverde et al., 2009). Several structural factors
may have mitigated the coequality of functional equivalence
among the stimuli comprising the equivalence classes in this
study including: nodal distance, the number of times a stim-
ulus was presented during the conditional discrimination
training, the order of introducing stimuli during the train-
ing sequence (Fields, Adams, Verhave, & Newman, 1993),
and the number of functions the A nodal stimulus served
(Belanich & Fields, 2003). Each of these processes may have
increased the probability that the transfer effects would be
most evident in the presence of symmetry (AB) but not in
the context of combinatorially entailed relations (CB, DB).
However, the present study was not designed to isolate
the impact of each structural factor on the transfer of the
respondent elicited functions. Furthermore, the possibil-
ity that the demonstrated transfer of differential respondent
eliciting functions in accordance with symmetry was due to
associative processes such as higher-order conditioning or
sensory preconditioning could not be completely ruled out.
Both the A1 and A2 stimuli were presented as comparison
stimuli (Co+/Co-) in all the B1A1 and B2A2 training trials.
Structuring the training and testing trials this way resulted
in each comparison stimulus (A1/A2) being presented with
both cocaine- paired (CS+ and CS-) sample stimuli (B1/
B2) the same number of times. This may have mitigated
the likelihood that the demonstrated differential respondent
elicitation was strictly due associative processes. However,
given the absence of transfer between stimuli not directly
paired during MTS training (i.e., separated by at least one-
anode) the overall impact of associative processes could not
be definitively ruled out. Thus, further studies are needed
to isolate which factors affect the relatedness of stimuli in
equivalence classes and other combinatorial entailed rela-
tions, as well as parameters impacting the magnitude of
respondent elicited functions and their transfer in the context
of repeated drug use within this methodological framework.
This pilot study demonstrated that it is feasible to model
derived relational responding and the extent to which this
process influences the emergence of drug-related respondent-
eliciting functions without a history of direct drug-stimulus
pairings under a controlled human laboratory setting among
individuals with histories of persistent substance use. Over-
all, three relational responding training and testing sessions
13
498
were acceptable to 10 of the 12 participants and the 2 par-
ticipants who did not complete the MTS procedures left
the study for reasons not related to the training procedures.
This project also highlighted methodological modifications
that could improve the experimental paradigm. First, par-
ticipant dropout appeared to be affected by the number of
drug conditioning sessions as 40% of the participants begin-
ning this phase of the study exited the protocol. Two par-
ticipants were withdrawn from this portion of the study due
to their physiological response to the conditioning sessions;
repeated smoked cocaine administration has also increased
cardiovascular responding among experienced cocaine users
in other studies (Reed et al., 2009). Reducing the number
of conditioning sessions could both shorten study duration
and reduce the amount of cocaine exposure thus potentially
mitigating heightened physiological responding following
repeated cocaine administration. Second, the present study
did not assess the maintenance of the emergent relations prior
to the transfer session. Thus, the inconsistent transfer results
may also have been due to the complexity of the protocol
and/or the combinatorial entailed relations (e.g., transitivity,
equivalence) not being maintained over time. Employing a
more sequential protocol in which the transfer of respondent
elicitation is first investigated in accordance with symme-
try, then is followed by an investigation of a reliable trans-
fer in accordance with transitive relations, with the aim of
establishing both processes before addressing the transfer of
function in the context of equivalence relations, may offer a
more systematic framework for refining and implementing
this experimental protocol. Third, the test of transfer ses-
sion differed from the conditioning sessions in several ways.
The transfer of function test session included the random
presentation of numerous stimuli and the presentation of
each stimulus occurred under extinction; cocaine was not
administered after their presentation. In contrast, the condi-
tioning sessions presented only one stimulus and the admin-
istration of cocaine occurred after each stimulus presenta-
tion. Further, active doses of cocaine were presented at the
beginning of the transfer testing session. This was done to
set the expectation that cocaine may be administered, which
resulted in the necessity of presenting the B stimuli twice
(i.e., beginning and end) and extending the overall length of
the session. The longer testing session, the use of numerous
extinction trials, and the presentation of numerous stimuli
may have affected the level of physiological responding and
the subjective ratings of “wanting cocaine” because transfer
was being assessed under different contextual parameters. It
has also been demonstrated that the magnitude of physiologi-
cal reactivity decreases among participants over the course
of experimental sessions in which drug is not administered
(Foltin & Haney, 2000). Methodological refinements that
bring the contextual parameters surrounding the conditioning
and transfer sessions into closer alignment may offer a better
13
The Psychological Record (2023) 73:481–500
platform for studying the transfer of function in accordance
with more complex relations (e.g., Valverde et al., 2009).
Finally, all participants completed the MTS training prior
to the conditioning phase. The stimuli were not meaningful
to participants during the relational training and testing trials.
In the natural ecology, individuals engaging in substance use
frequently interact with stimuli that have been associated with
drug ingestion. As such, intervention strategies often attempt
to alter relations among stimuli that have preestablished drug
elicitation and discriminative functions. Further, evidence
suggests a preexperimental history with stimuli can affectthe
acquisition of equivalence classes (Haydu et al., 2015). Thus,
future studies investigating the impact of establishing drug-
related functions among the stimuli before relational training
and testing trials may offer important insight into the extent
to which the drug relatedness of stimuli affect the emergence
and modification of derived relations among individuals with
significant histories of substance use. Overall, refining the
methodological procedures may offer a more efficient plat-
form for establishing and testing the derived transformation
of cocaine-related functions and provide a stronger founda-
tion for future investigations seeking to replicate the outcomes
observed in this pilot study. Future replications are particularly
important given the small sample size in this study and the
smaller subset (4/10) of participants demonstrating differential
respondent elicitation and transfer. It is important to note the
demonstrated outcomes were highlighted and discussed in the
context of the observed data for each participant not the use of
within participant statistical modeling that would offer more
formal tests of the probability of observing the intra-participant
patterns of responding demonstrated in this study.
In sum, the present investigation developed a human labo-
ratory paradigm that demonstrated individuals with a history
of chronic cocaine use readily evidenced a relational rep-
ertoire of mutual entailment and the bidirectional stimulus
relation of symmetry promoted the acquisition of respond-
ent eliciting functions by stimuli that were previously drug
neutral. These results are consistent with the hypothesis that
derived relational responding may be an important mecha-
nism by which substance use can indirectly come under the
control of a larger range of stimuli over time. The findings
also invite further investigation into the factors that affect
the derivation and transfer of cocaine eliciting functions in
the context of more complex stimulus relations, which may
strengthen the proof-of-concept of the impact that derived
relational responding may have on long- term substance use.
Acknowledgments Participants resided on the Irving Institute for
Clinical and Translational Research at Columbia University Medical
Center which is supported by the National Center for Advancing Trans-
lational Sciences (National Institutes of Health Grant UL1RR0241576).
Special thanks to Drs. Lanny Fields and Edward V. Nunes for their
mentoring during the career development award. Feedback provided
by Dr. Michael Dougher and the assistance of Nicholas Urban, Alicia
The Psychological Record (2023) 73:481–500
Couraud, Brenda Fay, Drs. Krysten W. Bold, Eric Rubin and Nehal
Vadhan during the study are gratefully acknowledged.
Funding This research was supported by National Institute of Drug
Abuse grant K23 DA021850 (PI: Carpenter). The National Institute
of Health and National Institute of Drug Abuse had no further role
in study design, in the collection, analysis, and interpretation of data,
writing of the report or the decision to submit the paper for publication.
Data Availability The data generated and presented from this investiga-
tion are available from the corresponding author upon request.
Declarations
Informed Consent All participants signed an informed consent describ-
ing the procedures as approved by the Institutional Review Board of
The New York State Psychiatric Institute.
Conflict of Interest The authors of the study report no conflict of interest.
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