Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

Abstract

Background
Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution.

Case presentation
C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal.

Discussion
The hypothesis is that C.J.’s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system.

Conclusions
This effect, we surmise, could be the result of a new dopamine balance, across C.J.’s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments.

Full text

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior
in a female, diagnosed with SUD and ADHD
THOMAS MCLAUGHLIN
1
, KENNETH BLUM
2,3,4,5,6,7,8,9,10
, BRUCE STEINBERG
11
, EDWARD J. MODESTINO
11
*, LYLE FRIED
9
,
DAVID BARON
4
, DAVID SIWICKI
6
, ERIC R. BRAVERMAN
8
and RAJENDRA D. BADGAIYAN
12
1
Department of Psychopharmacology, Center for Psychiatric Medicine, Lawrence, MA, USA
2
Department of Psychiatry, Boonshoft School of Medicine, Dayton VA Medical Center, Wright State University, Dayton, OH, USA
3
Department of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA
4
Department of Psychiatry and Behavioral Sciences, Keck Medicine University of Southern California, Los Angeles, CA, USA
5
Division of Applied Clinical Research & Education, Dominion Diagnostics, LLC, North Kingstown, RI, USA
6
Department of Precision Medicine, Geneus Health LLC, San Antonio, TX, USA
7
Department of Addiction Research & Therapy, Nupathways Inc., Innsbrook, MO, USA
8
Department of Clinical Neurology, Path Foundation, New York, NY, USA
9
Division of Neuroscience Based Addiction Therapy, The Shores Treatment & Recovery Center, Port Saint Lucie, FL, USA
10
Institute of Psychology, Eötvös Loránd University, Budapest, Hungary
11
Department of Psychology, Curry College, Milton, MA, USA
12
Department of Psychiatry, Icahn School of Medicine, Staten Island, NY, USA
(Received: July 9, 2017; revised manuscript received: September 4, 2017; second revised manuscript received: October 16, 2017;
accepted: November 27, 2017)
Background: Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of
dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that
dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when
simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation: C.J. is a
38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention
deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and
amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping
and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive
and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status
and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore,
her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control
shifted from external to more internal. Discussion: The hypothesis is that C.J.’s reported, behavioral, and
psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system.
Conclusions: This effect, we surmise, could be the result of a new dopamine balance, across C.J.’s brain reward
system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI
experiments.
Keywords: reward deficiency syndrome (RDS), pro-dopamine regulation (KB220Z), hoarding and shopping
behaviors, attention-deficit/hyperactivity disorder (ADHD)
INTRODUCTION
For longer than four decades, there has been an ongoing
debate about the role of brain dopamine (DA) in reward and
addiction. Nutt, Lingford-Hughes, Erritzoe, and Stokes
(2015) proposed that DA may be central to psychostimulant
dependence and possibly for alcohol dependence but not
requisite for opiates, nicotine, or even cannabis dependence
(Nutt et al., 2015). This view may be overly simplistic, as our
group has noted in earlier publications, distinction between
what constitutes “surfeit,”compared with “deficit,”regard-
ing short-term (acute) and long-term (chronic) brain reward
circuitry responsivity (Blum, Gardner, Oscar-Berman, &
Gold, 2012). Others have also argued that surfeit theories
of DA can explain, e.g., cocaine-seeking behavior as well as
responses concerning dominant rats with elevated DA
compared with subordinate rats (Jupp et al., 2016).
In an earlier study, we attempted to resolve controversy,
concerning the contribution of mesolimbic DA systems to
* Corresponding author: Edward Justin Modestino, PhD;
Department of Psychology, Curry College, 1071 Bluehill Ave-
nue, Milton, MA 02186, USA; Phone: +1 617 333 2226; Fax: +1
617 333 2316; E-mail: edward.modestino@gmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited.
© 2017 The Author(s)
CASE REPORT Journal of Behavioral Addictions
DOI: 10.1556/2006.6.2017.081

reward, by invoking three, competing, explanatory categories,
namely, “liking,”“learning,”and “wanting”(Blum et al.,
2012). Specifically, they are (a) the hedonic impact –“liking”
reward, (b) the ability to predict rewarding effects “learning,”
and (c) the incentive/salience of reward-related stimuli
“wanting.”
Concerning acute effects, most of the evidence favors the
“surfeit theory.”We know that because of preferential
DA release in the mesolimbic–ventral tegmental area
(VTA)–caudate–accumbens loci, many drugs of abuse and
reward deficiency syndrome (RDS). These behaviors have
been linked to heightened feelings of well-being and
hyperdopaminergic states (Beeler, Faust, Turkson, Ye, &
Zhuang, 2016;Beeler, Frazier, & Zhuang, 2012).
The “dopamine hypotheses”is now believed to be quite
complicated, encoding the set point of hedonic tone,
attention, reward expectancy, and incentive motivation
(Sternat & Katzman, 2016;Willuhn, Burgeno, Groblewski,
& Phillips, 2014). Willhuhn et al. (2014) have shown in a
self-administration paradigm (chronic), excessive use of
cocaine is associated with decreased, phasic DA signaling
in the striatum. Others have shown blunted reward
sites responsivity with chronic addictions, e.g., food
(Stice, Spoor, Bohon, & Small, 2008), nicotine (Harrell
et al., 2016), and gambling behavior (Gyollai et al., 2014;
Robinson, Fischer, Ahuja, Lesser, & Maniates, 2016).
The contention is that the differences in dopaminergic
function,which occur, as addictions progress can be impacted
by both genetics and negative and positive environmental
factors, such as epigenetics (Hamilton et al., 2017). One
significant effect of dopaminergic deficiency may be linked to
relapse and behavioral reinstatement (Cooper et al., 2014). In
particular, addictive-like behaviors (e.g., hoarding and
shopping) can result from the cumulative effects of dopami-
nergic and other neurotransmitter genetic variants as well as
elevated stress levels. Thus, DA homeostasis may be the
preferred goal in combating such challenging and unwanted
behaviors, when simple dopaminergic activation through
potent agonists may not provide any resolution.
DA AND MOTIVATION
DA neurons in the midbrain play a role in motivation as well
as in the regulation of mood and the induction of reward-
aversion (Ikemoto, Yang, & Tan, 2015;Love, 2014;Tomer,
Goldstein, Wang, Wong, & Volkow, 2008). While much of
this evidence points to the loci of this effect of DA being the
ventral tegmental area (VTA), other evidence suggests that
the motivational and other effects of DA on behavior may
also derive from the substantia nigra (Ikemoto et al., 2015;
Krawczyk et al., 2013).
It has been shown that, while high extracellular concentra-
tions of DA induce euphoria, low levels of DA induce
“seeking”and aversive behavioral states. For example, Ng
et al. (2016) have demonstrated that neuronal calcium
sensor-1, a substrate that regulates neuronal D2 expression
and subsequent release at the nucleus accumbens (NAc), when
deleted in the mouse’s brain, causes a reduced release of DA
and subsequently decreased motivation. Other very recent
work by Korte et al. (2017) evaluated the role of the 5-HT1A/
1B-receptor activation and showed that the 5-HT1A/
1B-receptor agonist, eltoprazine, increases both DA release
in the NAc and catecholamine release in the prefrontal cortex.
This agonist also decreases motivation for reward and
“waiting”impulsivity but increases “stopping”impulsivity.
In addition, the D1 DA receptor-mediated, long-
term potentiation, at gamma-aminobutyric acid (GABA)
synapses encodes motivation to self-administer cocaine in rats
(Krawczyk et al., 2013). We hypothesize that the enhanced
signal to increase cocaine self-administration agrees with the
report of Willuhn, Burgeno, Everitt, and Phillips (2012), which
demonstrated that as DA levels go down, as cocaine use
increases. This enhancement was further supported by the
work of others (Bello et al., 2011;de Jong et al., 2015).
The behavior of the woman, in this case study diagnosed
with attention-deficit/hyperactivity disorder (ADHD) and sub-
stance use disorder (SUD), is consistent with the findings of
Volkow’s group regarding DA reward pathway dysfunction.
They correlated positron emission tomography (PET) mea-
sures of DA D2/D3 receptor, as well as, DA transporter
availability (measured using [(11)C]raclopride and [(11)C]
cocaine, respectively) within the DA reward pathways. The
DA pathways included the midbrain and NAc, with a measure
of trait motivation (the achievement scale from the Multidi-
mensional Personality Questionnaire). These authors sug-
gested that disruption of the DA reward pathway is associated
with motivation deficits in ADHD adults, which may contrib-
ute to the observed attention deficits. This finding suggests
that pro-dopamine regulation, as a way of inducing “dopamine
homeostasis,”may constitute a means of normalizing moti-
vation in ADHD as well as SUD (Volkow et al., 2011).
DA AND EXCESSIVE HOARDING AND
SHOPPING BEHAVIORS
While generally, it is agreed that dopaminergic function
influences motivation and that certain deficits in the brain
reward pathway can impact impulsivity (hoarding and
shopping excesses), a piece of the treatment puzzle may
be missing.
A review of the literature (PUBMED 5/14/17) reveals that
there are many studies involving food-hoarding behavior
(Mogenson & Yang, 1991;Yang, Wang, Wang, & Wang,
2011), but a paucity of information on the role of DA in non-
food hoarding behavior. In fact, some reports are suggesting
that hoarding behavior is associated with a hyperdopaminergic
trait/state and subsequent blocking of D2 receptors seems to
improve the condition (Borker & Mascarenhas, 1991). Earlier
work by Kelley and Stinus (1985) showed that while
6-hydroxydopamine lesions of the mesolimbic DA neurons
eliminated hoarding behavior in rats, L-Dopa administration
was associated with a reinstatement of this behavior. Other
genetic work seems to support these earlier studies, with
female hoarders. These people tend to exhibit a greater
frequency of the low activity Met/Met genotype of Val158Met
polymorphism, compared with females, who did not express
this change, suggesting a higher concentration of DA in the
synapse (Melo-Felippe et al., 2016).
Fontenelle, Oostermeijer, Harrison, Pantelis, and Yucel
(2011) also suggested that obsessive–compulsive disorder,
Journal of Behavioral Addictions
McLaughlin et al.

impulse control disorders, and drug addiction have com-
mon, dopaminergic features and that therapeutic interven-
tion of these disorders should involve DA as a target.
Regarding excessive shopping behavior and dopaminergic
function, much less is known, except for reports regarding
these behaviors and Parkinson Disease (Claassen et al.,
2011;Raja & Bentivoglio, 2012;Voon et al., 2010). We
contend that whether there is a hyper or hypodopaminergia,
balancing the dopaminergic trait/state, especially, with a
well-researched, pro-dopamine regulator, KB220, should
show benefit the treatment of both excessive hoarding and
shopping in a middle-aged female, diagnosed with both
ADHD and SUD.
KB220
The most recent variant of KB220Z (powdered form) used in
this study is composed of the following ingredients: 10 mg
(500%) vitamin B6, 15 mg (1,033% of daily value) thiamine,
200 mcg (166%) chromium poly nictitate, and a fixed dose of
synaptose. Synaptose is a combination of amino acids and
herbs. The amino acids include L-tyrosine, DL-phenylalanine,
L-glutamine, and 5-hydroxytryptophan. The herbs include
passionflower extract and a complex containing astragalus,
arabinogalactans, N-acetylglucosamine, aloe vera, white pine
bark extract, frankincense resin Spirulina Rhodiola, as well as,
thiamine hydrochloride, pyroxidal-5-phosphate, pyridoxine
HCl, and N-acetylglucosamine, an amino sugar. The powder
was manufactured by Cephram, Inc. (New Jersey). One other
version used was the liquid nano form of the same ingredients.
Characteristics and neuropharmacology of KB220 variants
It is noteworthy that over 40 years of research over many
variants and 36 published articles, many clinical benefits
have been observed from double-blind placebo-controlled
trials, randomized placebo-control studies, case reports, and
neuroimaging studies in both humans and animals.
The following information should provide evidence for
clinical benefit of evaluating KB220Z in this study, begging
the question of neuromechanisms involved in producing DA
homeostasis. Variations of KB220 nutraceutical complex
have been studied extensively in preclinical and human trials.
As reported in a detailed review article (Blum, Febo, Fried,
et al., 2016), to date, KB220 variants have demonstrated the
ability to enhance brain enkephalin levels in in C57/BL mice,
thereby reducing alcohol-seeking behavior and pharmaco-
genetically convert acceptance in DBA ethanol preferring mice
to non-preference as in 2J mice (Blum, Briggs, Trachtenberg,
Delallo, & Wallace, 1987). In humans, KB220 has reduced
alcohol and drug and withdrawal symptomatology (Blum &
Gold, 2011;Blum, Trachtenberg,&Ramsay,1988). Specifi-
cally, lowering the need for benzodiazepines, reducing the
days with withdrawal tremors, no severe depression on the
Minnesota Multiphasic Personality Inventory, and a lower
score building up to drink score (Blum, Trachtenberg,
Elliott, et al., 1988). In recovery patients, demonstrated a
reduced stress response, measured by the level of skin con-
ductance, and significantly improved physical and behavioral,
emotional, social and spiritual scores (Blum, Trachtenberg,
Elliott, et al., 1988). After detoxification, the KB220 variant
group demonstrated a sixfold decrease in leaving against
medical advice (AMA) rates in comparison with the placebo
group (Blum, Allison, Trachtenberg, Williams, & Loeblich,
1988;Blum, Trachtenberg, Elliott, et al., 1988) and KB220
enhanced the focus of healthy volunteers (DeFrance et al.,
1997). There is also evidence that KB220 reduced craving for
alcohol (Chen et al., 2004), heroin, cocaine (Cold, 1996), food
(Beitscher-Campbell et al., 2016), inappropriate sexual behav-
ior (McLaughlin et al., 2013), and post-traumatic stress symp-
tomatology, such as lucid nightmares (McLaughlin, Blum,
Oscar-Berman, Febo, Agan, et al., 2015). Quantitative
Electroencephalogram (qEEG) studies in humans have found
that KB220Z modulates theta power in anterior cingulate
cortex (Blum et al., 2010). Compared with placebo, a single
dose of KB220Z in a pilot study of abstinent heroin addicts
resulted in NAc activation and improvement in activation
of the prefrontal–cerebellar–occipital neural network (Blum,
Liu, et al., 2015). Known obese carriers of the DRD2
A1 allele showed enhanced compliance with KB220Z treat-
ment, demonstrating weight loss and a significant Pearson’s
correlation, relative to carriers of the DRD2 A2 allele with a
usual complement DRD2 receptors (Blum et al., 2008). This
result suggests the importance of balanced DA function
equates to better treatment outcome.
To assist in understanding the intensive research on
KB220 variants, we encourage scrutiny of some reviews on
the subject (Blum, Febo, & Badgaiyan, 2016;Blum, Febo,
Fried, et al., 2016). These studies, including double-blinded
control studiesand qEEG, have demonstrated positiveeffects
on both craving attenuation and relapse prevention and
reduction in AMA rates; see review (Blum & Gold, 2011).
Are KB220 variants putative modulators of DA
homeostasis?
The development of KB220Z followed the first report
concerning the enkephalinase inhibitor D-phenylalanine
(Blum, Trachtenberg, Elliott, et al., 1988). The unique
design of the KB220Z complex follows the brain reward
cascade with the ultimate intent of facilitating DA release
throughout the reward circuitry. While, as yet, the actual
release of DA has not been determined we plan to study DA
release using a single scan dynamic molecular imaging
technique to understand the nature of DA released in the
human and animal brains following administration of
KB220Z (Badgaiyan, 2014). This specific technique allows
detection, mapping, and measurement of DA released
endogenously following a pharmacological or behavioral
challenge (Badgaiyan, 2013;Badgaiyan & Wack, 2011). This
molecular imaging technique was used to observe DA release
in some of the same areas where enhanced connectivity was
seen in the current experiment (Badgaiyan, 2010).
The hypothesis here is that these robust and selective results
are due to inhibition of GABA transmission within the sub-
stantianigraviaserotonergic–opioidergic–glutaminergic inter-
actions that reduce the inhibitory control of GABA over DA
release throughout the reward network (Volkow, Fowler,
Wang, Baler, & Telang, 2009). In support of these findings,
similar results were found in humans showing enhanced
regulation of deregulated widespread theta in the cingulate
Journal of Behavioral Addictions
Attenuation of compulsive hoarding and shopping

gyrus of abstinent psychostimulant abusers. Alpha and low
beta waves were increased 1 hr after KB220Z administration
(Blum et al., 2010). Previously, our laboratory found resting
state functional abnormalities in abstinent heroin-dependent
individuals affecting functional brain organization, which
could negatively impact decision-making and inhibitory
control (Miller et al., 2010). Moreover, compared with healthy
controls, heroin addicts showed reduced activation in right
amygdala in response to the affective pictures (Blum, Liu,
et al., 2015), consistent with previous reports of blunted
subjective experience for affective stimuli in obese carriers of
the DRD2 a1 allele (Stice et al., 2008). Brain scans of these
abstinent heroin addicts show evidence for “dopamine
homeostasis”following 1 hr KB220Z administration: BOLD
activation of caudate with reduced activation in putamen
(Blum, Liu, et al., 2015). Other studies showed persistent
abnormalities in the brain function following 1 month of
heroin withdrawal in the orbitofrontal cortex (Zijlstra, Booij,
van den Brink, & Franken, 2008). Zijlstra et al. also found
lower baseline D2R availability in opiate-dependent subjects
than in the left caudate nucleus of controls. After cue-
exposure, opiate-dependent subjects demonstrated higher
DA release in the right putamen than controls; this release
positively correlated with chronic craving and anhedonia.
DA 2R availability in the putamen was negatively correlated
with years of opiate use (Zijlstra, Veltman, Booij, van den
Brink, & Franken, 2009). Treatment strategies that increase
D2Rs may be an approach that could prevent relapse not
only in opiate addiction but also other behavioral addictions,
such as hoarding and excessive shopping (Dahlgren et al.,
2011). There is extensive evidence that indicates that current
and recently abstinent cocaine abusers compared with drug-
naive controls have decreased gray matter in regions, such as
the anterior cingulate, lateral prefrontal, and insular cortex
(Volkow et al., 2009). Following optogenetic stimulation of
the rat NAc, brain regions crucial for cognitive processing
including the dorsal hippocampus, anterior thalamus, and
regions the central striatal reward structure were also
observed to have changes in metabolic activity. Small animal
PET and [18F]2-fluoro-2-deoxy-D-glucose (Thanos et al.,
2013) or presentation of cues (Michaelides et al., 2013) were
used to observe these changes. Wang et al. have shown a
dysfunction of the frontostriatal and frontocerebellar circuits
in heroin addicts. The altered function implies an altered
balance between local neuronal assembly’s activities and
their integrated network organizational pattern that may be
involved in the process of moving from voluntary to habitual
and compulsive drug use and possibly behavioral compul-
sion (Wang et al., 2013). In a human pilot study, KB220Z
demonstrated improvement in the cerebellum, the cingu-
lated, and other areas of the reward circuitry in abstinent
heroin addicts (Blum, Liu, et al., 2015).
Importantly, the finding reported by Connolly, Bell,
Foxe, and Garavan (2013), of increased areas of activa-
tion could have therapeutic value, especially considering
the reduced brain gray matter volume during cocaine
administration to humans. It is plausible that KB220Z
due to COMT inhibition (via Rhodiola Rosea) could
result in larger amounts of DA in the synapse, and for
that reason enhanced DA activity (Blum, Allison, et al.,
1988).
One element of the reward circuitry, the mesolimbic DA
system in the brain, controls human responses to food, social
interactions, and money, and is, therefore, an influential deter-
minant of rewards and motivation. The midbrain DA neurons
that project to the striatum are involved in producing the
reward. In an animal study, Febo et al. (2017) illustrated
the modulatory actions of a putative DA agonist (KB220Z)
on the rsFC in association with a key region of the reward
system, the NAc. The finding is that KB220Z, like optogenetic
stimulation of the rat NAc (Thanos et al., 2013), caused an
increase in the connectivity between this central striatal reward
structure and the dorsal hippocampus and anterior thalamus,
areas crucial for cognition. Indeed, recent work from Ferenczi
et al. demonstrated that midbrain DA neuron stimulation drives
both reward-seeking behavior and striatal fMRI BOLD activi-
ty. They also showed that silencing of DA neurons drives
avoidance behavior (Blum et al., 1997;Ferenczi et al., 2016)
and suppresses response in the striatum, as well as other brain
regions like the hypothalamus. In addition, suppression of
striatal responses to DA and inhibition of the behavioral drive
to seek out natural rewarding stimuli through DA neuron
stimulation were observed following DA neuron silencing.
Most importantly, Ferenczi et al., demonstrated that medial
prefrontal cortex (mPFC) excitability that is consistently
elevated, synchronizes corticolimbic BOLD, and electrophys-
iological activity, which can, in turn, predict anhedonic behav-
ior in individual animals (Blum, Gold, et al., 2017;Ferenczi
et al., 2016). Interestingly, mPFC has glutaminergic neuronal
input, and as such, there is a need to balance and optimize
the fine interaction between mPFC–glutaminergic input to
striatal midbrain DA, so that the resultant release of DA at the
VTA–NAc is balanced (Blum, Febo, & Badgaiyan, 2016;
Blum, Febo, Fried, et al., 2016). These new findings
have direct implications for the notable observation that
KB220Z potentially may induce BOLD activation due to a
glutaminergic–dopaminergic optimization.
CASE REPORT
Identifying information
C.J. is a 38-year-old, unmarried, female, and living with her
mother. She is currently treated for ADHD, inattentive type,
and SUD. Her ADHD diagnosis was based on her performance
on the Connors’Continuous Performance Test II (CPT II V.5)
and her clinical history. Her SUD diagnosis was based upon
her history and psychiatric evaluations over a 7-year period.
Ethics
The patient signed a consent form and the case study is part
of an approved IRB from Path Foundation NY.
Past psychiatric history
Hospitalizations.
1. A psychiatric hospitalization at 16 years of age for a
“marijuana addiction;”
2. A psychiatric hospitalization at 15 years of age, when
patient was diagnosed with “bipolar disorder;”
Journal of Behavioral Addictions
McLaughlin et al.

3. A 6-month, psychiatric hospitalization, at the age of
14 for oppositional defiant disorder and intermittent
explosive disorder signs and symptoms.
Psychotherapy. Patient engaged in individual psycho-
therapy regularly from 25 years of age to the present.
Abuse history
The patient reports a history of verbal/emotional abuse by
her mother, who frequently called her a “bitch,”and a
“whore.”She claims physical abuse by her mother from
3 to 6 years of age.
Family psychiatric history
The patient maintains her mother had “untreated bipolar
disorder”(although the mother’s frequent use of coprolalia
raises the question about “vocal tics”and, possibly,
Tourette’s syndrome).
Family history
The patient’s mother is rageful, abusive, and hypercritical.
She was unaffectionate and, otherwise, inattentive to the
patient throughout her childhood.
The patient’s father is deceased. She mourned his death.
He is remembered as having been “kind, attentive, and
affectionate.”
Family addiction history
The patient’s father was addicted to alcohol and heroin. Her
mother is addicted to food, cigarettes, and hoarding. The
patient’s brother was addicted to opiates and is currently
treated with methadone. The patient’s sister was addicted to
heroin and is currently treated with methadone.
ADHD history
The patient states, during grade school, she was spacey,
dreamy, easily distracted, and bored.
Motor tics. The patient cracks her fingers frequently. She
also twists her torso, grinds her teeth, and picks her skin.
Vocal tics. The patient reports that, on a daily basis, she
hums, talks to herself, clears her throat, and engages in both
habitual coprolalia and palilalia.
Social history
The patient has a General Equivalency Diploma, with some
community college courses. She was never married and had
no children. She has had two abortions, one involving twins.
She lived in foster homes from age 13 to 17, because “my
mom was out of control.”
Past medical history
The patient denies any history of hypertension, heart dis-
ease, asthma, or any history of head injury.
Allergies. The patient denies any history of allergies to
food or medication.
Dreamlife. The patient notes an onset of lucid dreams at
about 5 years ofage. These dreams, which were characterized
as seeming “like... (she)... was “fully awake,”occurred
nightly into adulthood. Their content was unpleasant or
terrifying “100% of the time.”Thethemesofthedreams
usually involved fears of being chased, stabbed, or murdered.
These scary dreams led her to feel “paranoid”in the daytime
as well. She reports awareness, duringthese lucid dreams that
she is, in fact, dreaming. She reports an ability to control the
onset or offset of these lucid dreams.
The patient was given the nutraceutical, KB220Z at four
tablets a day, for 6 months, to influence her dreamlife,
because of the experience by one of the authors that its use
ameliorated such dreams. After following this regimen for
6 months, she reported her lucid dreams gradually remitted.
She also noted increased “mental energy;”during this time,
she took the KB220Z. Later, she reported that she no longer
had lucid dreams, despite having stopped the KB220Z
2 years prior (McLaughlin, Blum, Oscar-Berman, Febo,
Agan, et al., 2015;McLaughlin, Blum, Oscar-Berman, Febo,
Demetrovics, et al., 2015;McLaughlin et al., 2016).
Patient’s addiction history
The patient reported a remote history of marijuana addic-
tion, at 16 years of age. She also admitted to an opiate
addiction for 10 years as well as a history of both shopping
and hoarding addictions for this same period. The patient
smokes an average of one pack of cigarettes a day and drinks
20 cups of coffee a day.
Medication regimen. Buprenorphine/naloxone combina-
tion treatment history at her current clinic.
For 5 years, the patient has been maintained on
buprenorphine/naloxone combination of 8 mg/2 mg, one tablet
sublingual twice a day. In addition to counseling, she attends
monthly visits for her buprenorphine/naloxone combination
prescriptions. During the period, since she was firstseenatthe
clinic, she has denied any relapses, cravings, or drug use. She
has been able to decrease her dose to 1½ buprenorphine/
naloxone combination of 8 mg/2 mg sublingual a day.
From January 2016 to the present, the patient has also
been maintained on mixed amphetamine salts [NIH National
Library of Medicine] IR 30 mg every morning and 20 mg
every afternoon. In addition, she is maintained on gaba-
pentin 300 mg TID. The KB220Z compound was an
addition to these medications.
Random toxicology screens. The patient has had clean,
random, toxicology screens; during the 5 years, she has been
treated at the clinic.
Work stressors
The patient states that she has suffered from job stress for the
past 3 ½ years. This stress resulted from what she perceives to
be discrimination by supervisors as well as her need to work
the night shift and not getting enough sleep during the day.
Recent stressors
Three months prior, the patient reported frequent rage while
driving. She stated some of this emotion had to do with her
Journal of Behavioral Addictions
Attenuation of compulsive hoarding and shopping

being late for work (tardiness has been an ongoing
problem). During this same period, she complained of
increased apathy but denied cravings, relapse, or use of
substances. She continued to report stress at work.
Eventually, she lost her job, because she had overslept
and failed to call into work. She was denied unemployment
benefits and became severely “depressed”and unmotivated.
She was given the “liquid-nano”KB200z, to augment the
dopaminergic treatment (dextroamphetamine/amphetamine
mixture) of her presumed, RDS (Blum, Sheridan, et al.,
1996).
Phenomenological/psychological report of the effects of
KB200z in a patient evidencing RDS
At this point, the patient showed cell phone pictures of
her overly cluttered and hoarding-filled room, which
represented its state, before taking KB200Z. After taking
her KB220Z, each morning for 1 month, she had completely
decluttered her apartment as seen in her post-liquid nano
KB220Z photo (Figure 1) and the change in hours per week
spent shopping (Figure 2).
Even though there are, to date, 30 studies demonstrat-
ing the therapeutic and anti-addictive effects, there are
none which demonstrate an anti-shopping or an anti-
hoarding effect (Febo et al., 2017). Moreover, this is the
firstreportto(Archer, Oscar-Berman, Blum, & Gold,
2013) describe the psychological effect of the patient’s
ingestion of KB200z. These effects include her improved
self-esteem, her change from a “passive victim”to a more
active agent in control of her own life –in short, a change
in her experience of herself and her identity. The
following are the patient’s own words, presented in their
unedited form:
“The month of March 2017 is when I began to drink the
liquid nano KB220Z, and it worked fairly quickly for me.
In fact I feel like it was almost immediate. However,
realistically, it was a week or less. The first real benefit
was I did not feel the need to shop. I had this sudden burst
of hope or responsibility to get both my shopping and
hoarding under control. Since taking KB220Z in March,
my personal relationships with my family have dramati-
cally changed. Specifically, I feel that even though I have
always been kind and compassionate, I noticed that now I
feel more spiritually kind towards my family. I feel my
quest for spirituality (faith) has always been a struggle for
me and often confused, but ironically in the month of
March, I felt as though I was found, or that I found myself
opening up in a raw way to GOD. I selflessly opened up. I
cried for days when that happened to me. In terms of my
relationship with my mother, I am so much more patient,
and have not acted passionately toward her when she has
maybe said something hurtful or intentionally did some-
thing to hurt my feelings. My coping skills seemed to
allow me to let things slide off my back and that is a first
for me. Happily I report that I am softer towards her and
can do kind and loving things for her because I am
thinking about her feelings now. In the pre-KB220Z
period, there was so much hate and resentment. I am
learning how to like her/love her. In general I feel that
KB220Z and my doctor (TM) are responsible for these
beautiful changes in my life.”
Figure 1. Patient’s home before use of KB220Z (left: A) and after 30 days on KB220Z (right: B). This patient admitted to a history of ADHD,
opiate addiction, shopping addiction, and hoarding addiction. Traditionally, such diagnoses and behavioral addictions have been treated with
pharmacotherapy (ADHD) and, more recently, with nutraceutical formulas, such as KB200z. There are, to date, no reports of the alleviation
of shopping and hoarding addictions with any known pharmaceutical to our knowledge
Journal of Behavioral Addictions
McLaughlin et al.

DISCUSSION
Previously our laboratory provided a neuromechanism for
the pathogenesis of alcohol and non-alcohol-induced
depression in animals and possibly humans (Blum et al.,
1987). Since we found an effect of the KB220Z on the
subject’s mood (bipolar depression), it is incumbent upon us
to provide a brief discussion of this notable finding. In
fact, Archer et al. (2013) and our group discussed the role
of epigenetics in mood disorders concluding that mood
disorders manifest in in many forms, varying from
anxiety to severe major clinical depression. The disorders
are the complex interactive operations of environmental
and genetic factors expressed in individuals through man-
ifestations governed by the effects of genes on phenotypes
like comorbidities, symptom frequency, duration, and
severity.
The notion of endophenotypes, which contain markers for
several underlying disorders, may help to identify and detect
genetic risks for disease states and assist the unraveling
of the extreme complexity of disease states. Moreover,
Blum, Febo, et al. (2017) discussing SUD pointed out that
relapse rate is due, in part, to untreated post-withdrawal and
neurotoxicity. This impairment compromises resting state
functional connectivity, by changing neurotransmitter
signaling. The unwanted sequelae of these impairments
include depression, lack of satisfaction and impulsivity, sleep
disturbances, and sensation seeking. Neuroimaging studies
reveal that neurobiological recovery can take years. SUD has
a biological bidirectional (bio-directional) effect, like a
“double edge sword,”on the reward circuitry of the brain.
Acute psychoactive drug intake increases dopaminergic
activity, while, chronic intake the opposite, hypodopaminer-
gia occurs following with misuse (Blum, Febo, et al., 2017).
Moreover, untreated hypodopaminergia is a key to relapse
and may require not only 12 steps and fellowship but also
epigenetic repair involving manipulation of impaired brain
neurochemistry using pro-dopamine regulation directed at
concomitant depressive states.
The attenuation of bipolar depression in this case study
using KB220Z is in agreement with a number of other studies
showing significant attenuation of depressive states following
administration of this putative pro-dopamine regulator (Blum,
Allison, et al., 1988;Blum et al., 2014;Chen et al., 2007;
McLaughlin, Blum, Oscar-Berman, Febo, Agan, et al., 2015).
This patient provided a clinical history, consistent with
the diagnosis of ADHD, inattentive type. The results of her
Connors’Continuous Performance Test supported the
ADHD diagnosis. She admitted to having many vocal and
motor tics and reported that vocal tics occur in her mother as
well. She reported having been diagnosed with “bipolar
disorder”as an adolescent. The patient’s addictions to
opiates, caffeine, her prior history of marijuana addiction,
and her addictions to shopping as well as to hoarding;
all appear to be manifestations of RDS (Blum, Cull, &
Braverman, 1996). Her reported history of lucid dreams has
been reported in other patients, exhibiting RDS signs,
symptoms, and diagnoses. The amelioration of these
lucid dreams by KB200Z has been previously described.
Finally, the complete termination of lucid dreams, even
after the long-term cessation of KB200Z has also been
documented, with the explanation advanced that these
nutraceutical-induced neuroplasticity changes affected the
reward system of the brain (McLaughlin et al., 2016).
The KB220Z compound was an addition to C.J.’s usual
medications, including mixed amphetamine salts. The
dextroamphetamine/amphetamine mixture is a compound
combining four amphetamine isomers. The drug blocks the
reuptake and increases the release of catecholamines, spe-
cifically norepinephrine and DA (van Gaalen, van Koten,
Schoffelmeer, & Vanderschuren, 2006). However, long-
term use of amphetamines leads to tolerance, which may
be due to depletion of DA (Schechter, 1990). Therefore,
adding DA precursors and stabilizing the DA system, via the
adjunct therapy of KB220Z, may not only reverse this
tolerance but may also augment the stimulants by reversing
DA depletion (Ishikawa, Kadota, Kadota, Matsumura, &
Nakamura, 2005). Furthermore, regarding RDS, creating
DA homeostasis and stabilization can only be done by
influencing multiple neurotransmitter pathways that con-
verge on the DA brain reward cascade via a compound like
KB220Z (Blum, Febo, et al., 2015).
What is most striking in this patient’s report is not only
the cessation of her various addictive behaviors but also the
activation of her psychological ego, resulting in a change
from “passive victimhood”to her becoming an active agent,
in control of her life, and her identity. She had changed from
being a bored, hopeless, self-pitying victim to an activated
agent, who had taken charge of her life. Many studies have
evaluated the effect of this pro-dopaminergic regulator on
psychological functions. In addition to its demonstrated
anti-addiction effects, KB220Z or pro-dopamine regulation
constitutes a potentially new and exciting area of brain–
mind research.
Regarding both hoarding and shopping issues, the elimi-
nation of these unwanted behaviors in the patient is at the
core of the mechanism of action of KB220Z. Previous work
adequately showed not only selective DA activation across
Figure 2. Hours per week shopping before KB220Z and after
30 days of KB220Z. The above figure depicts the change in hours
spent per week shopping (42 hr/week for 2–3 years) to 0 hr/week after
taking KB200z for 1 month. The change has, in fact, persisted for
2 weeks beyond the active ingestion period of 1 month on a daily basis
at 1 oz a day (patient has recently reordered a new supply)
Journal of Behavioral Addictions
Attenuation of compulsive hoarding and shopping

the brain reward circuitry (Febo et al., 2017), but also
evidence for DA homeostasis in protracted heroin depen-
dence (Blum, Febo, et al., 2017;Blum, Liu, et al., 2015).
LIMITATIONS
Currently, we do not know the actual level of “dopamine
homeostasis”in the brain of this patient and although this
question requires, additional, in-depth research in a much
larger study her case provides an intriguing and provocative
rationale for the further study.
A case study is descriptive research and, unlike true
experimental placebo-control design, may help to generate
experimental hypotheses rather than showing direct causality.
The behavioral changes observed in this case study are
consistent with a larger body of work, specifically, that of
RDS and the use of the compound KB220Z. Based on
this intervention, it is appropriate to extrapolate that the
compound may have indeed influenced these profound
behavioral changes. Finally, the mechanisms of action of
KB220Z are well understood within the framework of the
literature reviewed herein.
CONCLUSIONS
Based on this case study, the authors have demonstrated the
elimination of many RDS-related behaviors, including lucid
dreams, uncontrollable hoarding and shopping along with
what appears to be enhanced motivation and activation of
her psychological ego. Surprisingly, the latter reported
change from “passive victimhood”to becoming an active
agent, in control of her life and her identity is most
intriguing.
The hypothesis that these benefits are the result of
pro-dopamine regulation through KB220Z (Blum, Liu,
et al., 2015), potentially leading to a needed balance of DA
across the brain reward system, requires testing in further
larger placebo-controlled studies.
Funding sources: Drs. KB and ERB are co-recipients of a
grant from The Life Extension Foundation, Ft. Lauderdale,
FL, USA to Path Foundation, NY, USA. Dr. RDB is
supported by the National Institutes of Health grants
1R01NS073884 and 1R21MH073624.
Authors’contribution: The original idea to perform this trial
was based on a previous clinical observation by TM and
KB. The final design of the study was developed by TM,
BS, and KB. The execution of the clinical data retrieval was
obtained by TM and KB. The basic write up the case was
developed by TM, BS, EJM, and KB. The initial writing of
the manuscript was executed by KB and TM. The interpre-
tation of the data was imputed by KB, TM, LF, RDB, EJM,
and DB. The development of the tables was executed by BS,
TM, and KB. The literature review was performed by KB,
TM, DB, RDB, EJM, and ERB. All authors approved the
final draft of the revised manuscript.
Conflict of interest: KB holds US and Foreign patents issued
and pending on KB220Z and receives royalties based on its
commercialization from various sources. He is also an
officer and stock holder of IGENE, LLC and Geneus Health,
LLC. He is a paid consultant of Dominion Diagnostics,
LLC, and The Shores Treatment & Recovery Center. He is a
member of the scientific advisory board of Dominion
Diagnostics, LLC and Rivermend LLC, New York,
NY. ERB owns Total Health Nutrients. Victory Nutrition
International, Sanus Biotech, and Nupathways distribute
nutritional supplements to the recovery marketplace based
in-part on KB’s patents. The authors have no other relevant
affiliations or financial involvement with any organization
or entity with a financial interest or financial conflict with
the subject matter or materials discussed in the manuscript
part from those disclosed. All authors have approved the
manuscript.
Acknowledgements: The authors would like to thank the
support of M. Hauser and a staff at Dominion Diagnostics,
LLC, North Kingstown, RI, USA. The authors would also
like to thank the support of T. Simpatico, MD, Department
of Psychiatry, The University of Vermont, VT, USA and
Margaret A. Madigan of Igene LLC. Finally, the authors
would like to thank Danielle Jean Kradin for formatting the
reference list.
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