REVIEW ARTICLE
Exercise and Neural Adaptations: Designing a
Novel Treatment for Alcohol Addiction
Terence Moriarty, PhD; Kelsey Bourbeau, MS; Micah Zuhl, PhD
ABSTRACT
Context • Multiple forms of behavioral therapies have
been developed to treat alcohol abuse disorders (AUDs).
Despite positive outcomes during and immediately after
behavioral treatment, 60% to 90% of patients relapse in
the year after treatment. Combined approaches have also
been developed, but similar high relapse rates have
occurred. Aerobic exercise may be an appropriate
complimentary treatment for behavioral therapy in AUDs.
However, it is critical to identify the appropriate dose of
exercise to gain maximal benefit.
Objective • This literature review intended to explore the
neural components of alcohol addiction, identify the
mechanisms by which exercise might influence brain
function, characterize the appropriate exercise intervention
for AUDs, and ascertain strategies for implementing
exercise into behavioral therapy treatment.
Design • The research team searched the literature for
systematic reviews, descriptive studies, case reports,
cross-sectional, along with experimental design studies
(both randomized controlled trials and nonrandomized
single group). Mechanisms of AUD, neurophysiological
Terence Moriarty, PhD, is a research assistant in the
Department of Health, Exercise, and Sports Sciences,
University of New Mexico, in Albuquerque, New Mexico,
and assistant professor in the Department of Kinesiology,
University of Northern Iowa, in Cedar Falls, Iowa. Kelsey
Bourbeau, MS, is a research assistant in the Department of
Health, Exercise, and Sports Sciences, University of New
Mexico, in Albuquerque, New Mexico. Micah Zuhl, PhD, is
an assistant professor in the Department of Health, Exercise,
and Sports Sciences, University of New Mexico, in
48 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3
adaptations to physical exercise, and exercise interventions
in AUD treatment were the primary areas of interest.
PubMed, ScienceDirect, Cochrane Library, and Google
Scholar databases were searched between 1970 and 2019.
Results • Neural mechanisms of AUD identified included
abnormal neurotransmission, prefrontal cortex function,
and neurogenic processes. Exercise may serve the
underlying neurophysiological mechanisms of AUD, and
this has been demonstrated in a handful of exercise
therapies studied among alcohol abusers.
Conclusions • Given the current reviews findings on the
neural mechanisms of alcohol addiction, the
neurophysiological basis of exercise treatment, and the
results of exercise interventions during alcohol treatment
the current research team has developed a novel approach
to treatment of alcohol addiction by incorporating aerobic
interval exercise into traditional, evidence-based, cognitive
behavioral therapy. The benefits of exercise may promote
and compliment CBT treatment and lead to reduced
drinking outcomes (Altern Ther Health Med. 2020;26(3):48-
57).
Albuquerque, New Mexico, and an associate professor at
the School of Health Sciences, Central Michigan University,
in Mount Pleasant, Michigan.
Corresponding author: Micah Zuhl, PhD
E-mail address: zuhl09@unm.edu
Moriarty—Exercise and Alcohol Use Disorder
INTRODUCTION
Alcohol use disorder (AUD) is defined as a chronic
relapsing brain disease and affects nearly 16 million people in
the United States.1 The reported overall health care and
related costs exceed $249 billion in 2010, which includes
costs associated with addiction treatment, effects on the
physical and mental health of addicted persons, and related
crime.2,3 Although many adults suffering from AUD can
benefit from treatment, as of 2016 only an estimated
7% receive treatment each year.1
In addition, high rates of alcohol relapse are reported
among those who participate in treatment.4,5 Multiple forms
of psychosocial therapy with varying components, such as
length (number of sessions) and settings (group or individual)
are commonly used to treat substance abusers. Alcohol
addiction researchers have recently focused their efforts on
several behaviorally-based therapies, which include
motivational interviewing (MI), cognitive behavioral therapy
(CBT), alcohol behavioral couple therapy (ABCT), and
12-step (TS) programs.6 Despite some positive results for
early abstinence and at a 3- to 9-month follow-up in
randomized controlled trials, high rates of relapse remain.4
To enhance the effects of psychosocial therapy, researchers
have used combination treatments, such as medications
combined with CBT or MI.7 The added improvement in
abstinence has been small when compared to psychosocial
therapy alone.7
Since the early 1970s, various types of physical activity
interventions have been implemented in outpatient and
inpatient alcohol treatments. The early activities included
basketball, jogging, calisthenics, muscle stretching, and
cross-country skiing.8 More recently, several randomized,
controlled exercise trials have been incorporated into
treatment-as-usual (TAU) behavioral therapy and have
included aerobic-exercise and yoga interventions.9-11 Positive
results have been demonstrated for drinking behaviors, such
as number of drinking days and drinks per drinking day, as
well as for mood, depression, and anxiety. Conversely, several
studies have reported no added benefit for adding exercise to
alcohol- or substance-abuse treatment.12,13
A possible explanation for mixed results is that the
appropriate exercise intervention has yet to be fully
characterized in this population. Critical programming
variables must be considered, such as exercise intensity,
duration, and frequency as well as exercise timing and level
of monitoring or feedback. A suitable exercise program must
target the underlying mechanisms of alcohol addiction and
be balanced with logical formats to sustain exercise adherence.
The theory that explains how aerobic exercise can
benefit alcoholic individuals is based on the underlying
mechanisms of alcohol addiction. Chronic alcohol
consumption causes neurophysiological dysfunction and
may ultimately influence the ability of an alcohol abuser to
retain skills learned in behavioral therapy. Neurophysiological
dysfunction is demonstrated by abnormal neurotransmission,
such as dopamine and serotonin levels; global brain atrophy;
Moriarty—Exercise and Alcohol Use Disorder
and dysfunction in the brain’s prefrontal cortex (PFC) and
hippocampus.14-17 The neurological dysfunction manifests
through poor decision-making, cognitive deficits, memory
loss, and destructive behaviors—self and relationship.18
Exercise has been shown to manipulate neurotransmitter
levels, increase brain-derived neurotrophic factor (BDNF) to
promote neurogenesis, and enhance activation in the PFC
and hippocampus.19-21 Exercise’s positive neural benefits
include improvements to cognitive performance, memory,
and learning.22 This may translate to improved retention of
coping skills learned in behavioral therapy and support
sustained abstinence in drinkers. These findings demonstrate
that exercise can be a suitable treatment for AUDs. However,
it’s critical to identify the appropriate dose of exercise to gain
maximal benefit.
This review intended to explore the neural components
of alcohol addiction, identify the mechanisms by which
exercise might influence brain function, characterize the
appropriate exercise intervention for AUDs, and ascertain
strategies for implementing exercise into behavioral therapy
treatment. The overarching goal of the current research team
was to create a framework for exercise that can become a
standard of treatment for substance abuse. The economic
burdens of medical treatments continue to escalate, and
exercise is a low-cost therapy with potentially high returns.
METHODS
Procedures
The research team searched PubMed, ScienceDirect,
Cochrane Library, and Google Scholar databases between
1970 and 2019. Systematic reviews, descriptive studies, case
reports, cross-sectional, along with experimental design
studies (both randomized controlled trials and
nonrandomized single group) were targeted.
Primary areas of interest were neural mechanisms of
alcohol addiction, neurophysiological adaptations to exercise,
and exercise interventions in AUD treatment. Various
combinations of key searched terms were conducted, and
included alcohol addiction, alcohol use disorder, behavioral
treatment, exercise, neurogenesis, neurotransmission, and
prefrontal cortex.
RESULTS
Neural Mechanisms of Alcohol Addiction
The underlying mechanisms of addiction are complex,
with a multitude of factors involved, including social,
environmental, genetic, and neurobiological ones. The
mechanistic focus of this review was primarily the neurally
and biologically mediated abnormalities that can lead to
impaired decision making and cognitive decline (Figure 1).
Neurotransmission. Several neurotransmitters play a
role in the etiology of alcohol addiction. Excess dopamine
(DA) production in the nucleus accumbens occurs during
consumption of alcohol and is thought to enhance motivation
and reward during intoxication.23 DA release appears to be
dependent on the amount of alcohol consumed and may play
ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 49
Figure 1. The Neural Mechanisms of Heavy, Chronic, Alcohol Use
Note: Alcohol plays a role in PFC, neurogenesis, and neurotransmitter dysfunction, which contribute to overall cognitive
decline.
Abbreviations: BDNF, brain-derived neurotrophic factor; GABA, gamma-aminobutyric acid; PFC, prefrontal cortex.
a role in alcohol tolerance.24 When alcohol-preferring rats were
injected with ethanol, they demonstrated an increase in
extracellular DA levels in the nucleus accumbens; however,
levels did not change among alcohol-nonpreferring rodents.25
The DA response among rats also appeared to influence future
alcohol consumption behavior, meaning that those who had
the greatest DA response might continue heavy drinking
patterns.26 To further demonstrate the role of DA in alcohol
addiction, researchers have used neurotoxins to destroy DA
neurons in the nucleus accumbens in rats.27 In that study, the
ablation of the DA neurons resulted in a 60% decrease in
alcohol consumption among alcohol-dependent rats.
In alcohol-dependent humans, DA regulation in
response to ethanol is less clear. In 1996, Volkow et al28
demonstrated that heavy drinkers have a reduced expression
of DA receptors (D1 and D2) but no difference in DA
transporter levels in the striatum.28 Polymorphisms in the
DRD2 gene among humans are associated with a higher risk
for alcohol abuse.29-31
In 1999, Laine et al32 used single photon emission computed
tomography (SPECT) to demonstrate that DA transporters were
also reduced among alcoholics.32 Together, these findings
indicate that DA release and receptor binding are disrupted in
response to chronic alcohol consumption. The regulation of DA
release and uptake is confounding during alcohol consumption
in addicted humans; it has been well established that alcohol
withdrawal causes a decrease in DA release from the striatum.33,34
The decline in DA release may contribute to the negative
symptoms of withdrawal leading to relapse.
50 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3
Serotonin (5-HT) is a monoamine derived from
tryptophan and is mainly produced by neurons in the raphe
nuclei of the brain stem. Upon release, this neurotransmitter
binds to 5-HT receptors—such as 5-HT1B, 5-HT2, and 5-HT3—
located on cell bodies, which causes downstream
neurotransmission.35 It plays important roles in mood, sleep,
anxiety, compulsivity, and depression,35 and 5-HT reuptake
inhibitors, such as sertraline, increase 5-HT levels in the brain
and are the first-line pharmacological treatments for
depression.36 Acute alcohol consumption causes an increase in
5-HT levels, whereas chronic alcohol abuse leads to an overall
decline in 5-HT transmission.29 An established connection
between low basal 5-HT and an impulse to drink among
alcohol-dependent humans has been supported by alcohol
researchers.37,38 The 5-HT release in response to alcohol
consumption is involved in the rewarding effects of alcohol.39,40
Acute and chronic alcohol abuse also disrupts the
function of various 5-HT receptors. Isolated alcohol exposure
can increase the stimulation of the 5-HT1B isoform and
contribute to the intoxicating effects of alcohol.41 Long-term
alcohol exposure can result in increased expression of 5-HT2
and enhanced 5-HT activity, which has a rewarding effect for
the user during chronic episodes of consumption.42 A decline
in 5-HT2 function has been reported during alcohol
withdrawal and is thought to contribute to negative
symptoms, such as anxiety and aggression, that are associated
with abstinence.42 In summary, alcohol abuse leads to a
dysfunctional serotonergic system—both release and
uptake—and contributes to excessive drinking behavior.
Moriarty—Exercise and Alcohol Use Disorder
 Gamma-aminobutyric acid (GABA) is a major inhibitory
neurotransmitter, whereas glutamate serves as the major
excitatory neurotransmitter in the brain. Both GABA and
glutamate are thought to play roles in the etiology of alcohol
addiction.29 Acute alcohol consumption increases GABA
release while reducing glutamate activity in the striatum and
PFC.43,44 The suppression of glutamate function is most likely
mediated through alcohol alterations of the N-methyl-D-
aspartate (NMDA) receptor.45 Acute alcohol-induced GABA
action has been found to be a result of the increased activity
of the GABAA receptor complex, which is thought to mediate
mood enhancement together with cause the motor
dysfunction effects of alcohol.46,47
Long-term alcohol consumption can have the opposite
effect on GABAA activity, reducing inhibitory
neurotransmission. Conversely, NMDA receptor activity
increases after chronic alcohol exposure, and excessive
glutamate activity occurs during early alcohol withdrawal
and is manifested through devastating side effects such as
seizures and psychosis.48,49 The reduced inhibitory (GABAA)
and heightened excitatory (NMDA) signaling in the brain of
alcohol-dependent humans influences both memory and
cognitive function and increases the risk for epilepsy,
Wernick-Korsakoff syndrome, major depression, and other
mental disorders.49-51
Prefrontal Cortex. The PFC is considered an executive
network involving planning, attention, and decision-making,
ultimately controlling goal-directed behavior. Regions of the
PFC that have been implicated in addiction are the
orbitofrontal cortex (OFC), anterior cingulate cortex (ACC)
and DLPFC.14 The OFC is involved with stimulus reward and
reinforcement of behavior, while the ACC is highly involved
in cognition and well-being.52,53 The DLPFC is the site for
working memory and executive function.54 However, it’s
important to understand the PFC is highly interconnected
with other brain areas, including the hippocampus and other
deeper sites. For this reason, the role of the PFC in addiction
is highly complex. Goldstein and Volkow55 have proposed
that PFC dysfunction in substance abuse leads to a syndrome
characterized by excessive clarity in response to drug cues
and an inability to resist maladaptive behaviors.55
From a neurophysiological approach, hyperactivation of
the PFC occurs among substance abusers when presented
with drug-of-choice cues.56 This has been shown in studies
using functional magnetic resonance imaging (fMRI) and
functional near-infrared spectroscopy (fNIRS), where users
have demonstrated enhanced metabolism and blood flow in
the PFC during alcohol cues.56,57 Drinkers also have shown
decreased activation in response to natural reward cues, such
as highly palatable food.56 Upon entry into alcohol treatment,
patients have shown less PFC stimulation to alcohol cues and
increased responses to natural cues, which may determine
the abstinence outcomes of long-term treatment.56
Drinkers also have shown a delayed ability to exert
inhibitory control over drinking decisions and executive
function for the PFC.14 This may be mediated through
Moriarty—Exercise and Alcohol Use Disorder
changes in PFC metabolism and activation in response to
alcohol consumption among drinkers.58 Glucose metabolism
is reduced in the medial frontal and left dorsolateral PFC
among alcoholics and is associated with poor performance
on cognitive-reasoning tasks.59 Alcohol-dependent
individuals have shown delays in PFC activation during
decision-making tasks similar to those with brain lesions.60
It has been well established that those with AUD
demonstrate cognitive and motor function impairment.61-63
PFC function may underlie the cognitive deficits that occur
as a result of excessive alcohol abuse.64 Hypoactivation in
regions of PFC has been shown during working-memory and
cognitive tasks among drinkers.65 The cognitive impairment
may negatively affect the ability of an alcohol abuser to retain
coping skills learned in behavioral treatment.
Brain Growth Factors and Morphology. Brain-derived
neurotropic factor (BDNF) is a neurotrophic polypeptide
expressed heavily in the hippocampus and cerebral cortex.66
BDNF is involved in synapse development, synaptic plasticity,
neuronal connectivity, and enhanced survival of adult
neurons.67 A common, single-nucleotide polymorphism of
BDNF, Val66Met, has been associated with lower hippocampal
volumes and various neuropsychiatric disorders.68 Several
studies have suggested a possible role for BDNF deficiency in
alcohol dependence. For example, in 2007 Joe et al69 reported
that levels of peripheral circulating BDNF were lower in
alcohol-dependent patients compared to healthy controls.69
Interestingly, alcohol-dependent patients with a family
history of alcoholism had consistently lower levels of
Val66Met than alcohol-dependent patients with no family
history, suggesting that BDNF may play a role in genetic
predispositions to alcohol addiction.68 Furthermore,
overexpression of BDNF in the PFC has been shown to
minimize alcohol drinking behavior among transgenic
mice.70 It has recently been suggested that BDNF gene
polymorphism plays a substantial role in the development of
alcoholism and serves as a modulating factor in regulating
drinking behavior.70,71
Mechanistically, a deficiency in BDNF appears to
contribute to alcohol dependence through cell-signaling
pathways that ultimately regulate synaptic plasticity in the
PFC, hippocampus, striatum, and amygdala.72,73 This
contributes to dysfunctional neural cell maintenance
through inadequate repair and neurogenesis and is
ultimately manifested through alcohol drinking behavior.72
It has been well established that global brain atrophy or
shrinkage occurs among drinkers of excessive amounts of
alcohol.74 Altered densities in both white- and grey-matter
regions has been shown to contribute to dysfunctional brain
connectivity.75 More specifically, alcohol-dependent adults
show lower total volumes in the hippocampus, PFC, thalamus,
cerebellum, and pons.75,76 In 1989, Muuronen et al77
demonstrated that 72% of alcohol-dependent humans
seeking treatment showed brain atrophy, and 49% had
intellectual impairment. At a five-year follow-up, those who
maintained abstinence showed a regression in atrophy and
ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 51
Figure 2. The Effects of Aerobic Exercise on the Underlying Neural Aspects of Alcohol Abuse

Note: Aerobic exercise promotes changes in the PFC region, promotes neurogenesis (BDNF), and increases various
neurotransmitter expression. These changes may improve cognition among alcohol abusers.

Abbreviations: BDNF, brain-derived neurotrophic factor; GABA, gamma-aminobutyric acid; PFC, prefrontal cortex.

further improvement in cognitive ability.77 Furthermore,
recovery of grey-matter volume was demonstrated after
14 days of abstinence among alcohol-dependent patients.78
This demonstrates that changes in brain morphology and
dysfunction may be reversible upon alcohol cessation.
In summary, alcohol dependency is linked to BDNF
deficiency and further promotes excessive and chronic
alcohol consumption, which contributes to overall brain
atrophy and cognitive decline.76
Neurophysiological Basis of Exercise Treatment
This section discusses the neural benefits of exercise to
address the mechanistic underpinnings of alcohol addiction
(Figure 2). The findings on the efficacy of aerobic exercise as
a serviceable treatment for alcohol dependency are compelling
and require exploration. Recent research has focused on
neurological adaptations in response to both acute and
chronic exercise. Exercise may provide an alternative
reinforcement against substance abuse behavior mediated
through neurological changes. This can be demonstrated in
animal models where alcohol-preferring rats that were given
concurrent access to wheel running and alcohol, exercised
more and consumed less alcohol.79
Exercise and Neurotransmission. The previous section
indicated that alcohol interacts with a variety of
neurotransmission pathways in the central nervous system,
including the glutamatergic, dopaminergic, serotonergic, and
GABAergic receptor systems.80-83 Although the central
neurobiological pathway of exercise’s positive reinforcing
effects remains to be clarified, data in this area suggest that
exercise stimulates the same motivation and reward pathways
that are activated by alcohol or other addictive drugs.8 The
bulk of research in this area has been performed with animals.
DA levels have been shown to increase nearly 2-fold in rat
hippocampal and midbrain tissues after 20, 40, and 60 minutes
of intense treadmill running, and they remained elevated for
2 hours postexercise.19,84 This acute elevation has also been
shown in the nucleus accumbens of mice after 1 hour of
swimming exercise.85 The response is believed to be independent
of exercise training status, indicating that aerobically trained and
untrained animals have similar acute responses.86
Furthermore, DA upregulation after exercise may be
dependent on exercise intensity in some tissue; the more intense,
greater is the DA release.84 DA release after exercise may be a
substitute for the DA response to alcohol and reduce the appetite
for alcohol among users. However, in 2000 in the only known
human study, Wang et al87 did not detect any increase in striatal
DA release using PET imaging after 30 minutes of treadmill
running in healthy adults.87 The differing results may possibly be
due to the intensity of the exercise in the study, the fact that the
researchers conducted the measurements in otherwise healthy
individuals, and/or the brain location used.
Some evidence has suggested that habitual aerobic exercise
can increase DA expression and prolong neurotransmission.88
The rate-limiting enzyme in DA synthesis, tyrosine hydroxylase,
has been shown to increase nearly 4-fold in the regions of the
midbrain of animals after 6 weeks of free wheel running.88 In
the same study, levels of DA receptor D2 mRNA increased in
the caudate putamen regions.88
Acute aerobic exercise has been shown to increase
serotonin levels by nearly 140% in the hippocampal region of
rats.89 Increased circulating tryptophan from contracting
muscle, which increases brain-serotonin synthesis, is thought
to be a potential mechanism.90 The 5-HT response to exercise
may contribute to the mood-enhancing benefits of exercise.91
The 5-HT upregulation after exercise may replace the

52 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 Moriarty—Exercise and Alcohol Use Disorder
rewarding effects of alcohol among drinkers. Increasing
5-HT levels through SSRI administration has been shown to
be effective in reducing drinking behavior, and aerobic
exercise may be a comparable treatment.92
Evidence suggests that aerobic exercise may also preserve
GABA and glutamate signaling in the brain of chronic
alcohol drinkers. For example, treadmill exercise in rodents
has been shown to inhibit excessive release of glutamate by
increasing the release of GABA.93 As discussed previously,
chronic alcohol consumption leads to reduced inhibitory
(GABAA) and heightened glutamate signaling in the brain,
and the exercise response provides further evidence of
neurotransmitter regulation through aerobic exercise.49,93
Exercise and the PFC. Recent implementation of brain
imaging technology, such as functional magnetic resonance
imaging (fMRI) and functional near-infrared spectroscopy
(fNIRS), in exercise studies has allowed researchers to better
understand how exercise influences brain activity. In 2016,
Bediz et al94 demonstrated that prefrontal-cortex activity
increases during cognitive testing when a single bout of
high-intensity cycling (Wingate anaerobic test) is performed
prior to concentration tasks.94 In support of this, in 2010
Yanagisawa et al95 had reported improved PFC activation
during cognitive testing after 20 minutes of low-intensity
cycling (50% VO2max).95 Increased PFC activity after exercise
may support the delayed activation that occurs among drinkers
during cognitive-testing experiments. In addition, acute
exercise has been shown to decrease PFC activity among
smokers presented with cigarette cues, which correlated with
reduced cravings.96 If these results translate to chronic drinkers,
then acute exercise may inhibit the hyperactivity response to
alcohol cues and potentially reduce cravings.
Exercise and Neural Growth Factors. Several studies
have shown that exercise may promote brain growth and
volume.21,97 In 2006, Colcombe et al21 had reported increases
in both grey- and white-matter regions in the brain among
sedentary older adults after 6 months of aerobic exercise.
Similarly, in 2011 Erickson et al had demonstrated an
increase in hippocampal volume, which correlated with
improved functional memory in an older population after
aerobic training.20 Wheel running promoted hippocampal
neurogenesis in a rat binge-drinking model, and reversed
ethanol inhibition of neural stem-cell proliferation.98,99
A commonly proposed mechanism for these
improvements is upregulated BDNF expression.100 Multiple
researchers have reported that acute bouts of aerobic exercise
increase circulating BDNF levels.100,101 Some evidence has
also suggested that the increase in BDNF was dependent on
exercise intensity, with high-intensity exercise promoting a
stronger BDNF response.102 When comparing the BDNF
response in high-intensity interval training (HIIT) versus
continuous training, Suucedo et al103 in 2015 had reported
that HIIT training was more effective in elevating circulating
BDNF.103 The evidence that aerobic exercise, specifically
high-intensity exercise, increases BDNF levels suggests that
integrating high-intensity exercise into treatment programs
Moriarty—Exercise and Alcohol Use Disorder
for individuals with alcohol dependence may improve
outcomes by modifying the BDNF response.
Exercise Interventions and Drinking Behavior
The implementation of exercise programs during alcohol
treatment has a sporadic history with several acute
interventions—single exercise sessions—and exercise
training studies being conducted since the 1970s.
Interventions have ranged from basketball and physical
games to aerobic exercise specifically prescribed in intensity
and duration.104-106 In these studies, no potential mediators
were evaluated in determining whether or not exercise was
more effective than standard treatment for alcoholic behavior.
Interestingly, alcohol-drinking behavior was measured in
only 6 studies, and in many of the studies, only 1 measure
was used.107-111 It has been reported that use of a single, best
measure for alcohol consumption is unrealistic and possibly
counterproductive, and, therefore, a more comprehensive
approach should be implemented.112
The acute benefits of exercise in alcohol treatment have
been linked to suppression of the impulse to drink. Acute
moderate-intensity aerobic exercise lasting 10 to 20 minutes
has been shown to reduce alcohol urges among detoxified
drinkers.113,114 This result is similar to the effects of acute
exercise on reducing cigarette cravings among smokers.96
Researchers have demonstrated that a reduced craving
among smokers after exercise can be mediated through
delayed activation of the PFC; however, it is unknown if a
similar mechanism is present among drinkers.96
It has also been demonstrated that each individual session
of aerobic exercise during a 12-week trial improved mood and
reduced anxiety among drinkers.114 This finding demonstrated
that the magnitude of change in the course of a single session
is not influenced by training and that alcohol abusers gain
continued acute benefits throughout an aerobic exercise
program. However, whether or not the acute improvements in
mood, anxiety, and reduction in urges translate to an overall
decline in long-term alcohol use is not known.
Only 5 known studies exist where the effects of an exercise
intervention on alcoholic behavior has been explored. In early
work in 1986, Murphy et al110 introduced an 8-week running
program among university students who consumed a high
volume of alcohol.110 The exercise program was not well
defined and was described as 30 minutes of running or
walking performed 3 times per week. The university students
reported an overall 44% reduction in ethanol consumption.110
In 2009, Brown et al106 developed and implemented a
traditional aerobic exercise program into a 12-week alcohol
treatment program. The program included 1 weekly supervised
exercise session lastingly 20 to 40 minutes at 55% to 69%
(moderate) intensity, and 2 additional unsupervised, home-
based exercise sessions per week.106 Participants were required
to keep daily logs of exercise activity to evaluate compliance.
An increase in the percentage of days of abstinence was
reported at the end of treatment; however, the effect was lost as
of a 3-month follow-up posttreatment.
ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 53
Figure 3. Exercise Priming
Note: Engaging in aerobic exercise prior to behavioral therapy may enhance the effectiveness of treatment and ultimately
promote a further reduction in drinking. The proposed exercise intervention is high-intensity aerobic exercise. For example,
patients would complete 4-10 bouts of 30-s efforts, followed by 90 s of recovery. Total time can range between 18 and 30 min.
Other highlights include a 20- to 60-min delay before behavioral treatment to allow for the transient cognitive benefits of
exercise to appear.
Abbreviations: CBT, cognitive behavioral therapy.
In a follow-up randomized controlled trial in 2014,
Brown et al9 compared an exercise group to a health-education
control and demonstrated fewer drinking and heavy drinking
days relative to the health-education group at the end of
treatment.9 Similarly, the effect was lost as of a 3-month
follow-up, but in exploratory regression analyses, the
researchers found that those who were adherent to exercise
had fewer drinking days at follow-up. The work by Brown’s
group must be highlighted as the most complete in study
design, alcohol measures, and exercise interventions to date.
In 2017, Roesssler et al108 measured alcoholic behavior
after 6 months of outpatient therapy, combined with either
group or individual exercise, and the researchers also
performed a 6-month follow-up.108 The group exercise was
supervised, and participants met as a group twice per week to
perform a running exercise. The individual exercisers
received an individualized running program, which
encouraged exercise twice per week. No specific exercise
guidelines, such as duration or intensity, were reported for
either intervention. The researchers reported an exercise
dose response at the end of treatment after 6 months,
described as a reduction in alcohol consumption by 4% for
each increase in exercise day.108
In 2017, Georgakouli et al109 also showed reduced,
self-reported alcohol consumption among heavy drinkers
after 8 weeks of supervised exercise, which was reported as a
progressive program using increases in both exercise
frequency and intensity. The authors hypothesized that
reduced alcohol consumption would be mediated by changes
in the HPA axis; however, no changes in hormones were
identified.109 To the current research team’s knowledge, this
was the first study to analyze associated mechanisms of
exercise effects on alcohol consumption.
These studies have established efficacy and effectiveness
for both acute exercise and aerobic-exercise programs in
alcohol treatment. However, for clinicians to fully adopt
54 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3
exercise into treatment, the potential mechanisms that mediate
exercise improvements must be explored. In addition,
adherence to exercise among AUD patients is estimated at only
63% and demonstrates room for improvement.9,108 A lack of an
exercise effect on drinking outcomes among alcohol users is
thought to be linked to a lack of adherence, which suggests that
efforts to remove barriers to exercise should be considered
when implementing exercise programs.111,115
Ideal Exercise During Treatment
The ideal exercise intervention has yet to be clarified by
researchers for drinkers. In 2011, Abrantes et al116 reported
exercise preferences of alcohol abusers and determined that
(1) 68% of drinkers would participate in exercise if offered it
during treatment, (2) 50% would want to start exercising
during substance treatment, and (3) 75% preferred to exercise
at moderate-to-high intensities.116 These results indicated
interest among drinkers in adopting an exercise program that
specifies intensity during treatment.
Alcohol abusers may gain the full advantage of the benefits
of exercise by incorporating moderate-to-high intensity, aerobic-
interval exercise into therapy. Acute cognitive improvements
after exercise are intensity dependent, and higher intensity
results in larger improvements in memory and processing
speed.22 The cognitive response may be mediated by increased
activation of the PFC postexercise.94 In addition, the BDNF
response to exercise is intensity dependent and may support
brain neurogenesis among drinkers when performed routinely.103
Aerobic interval exercise may be suitable for drinkers since it can
be easily implemented because it requires no major equipment;
can be short in duration, approximately 20 minutes; is tolerable,
and has fitness improvements that are commonly reported to be
higher than those for traditional exercise.117,118
For example, in 2018, Cabral et al119 designed a
four-week interval program for polysubstance users—alcohol
and cocaine, consisting of four 30-second, maximal running
Moriarty—Exercise and Alcohol Use Disorder
sprints performed 3 times per week. The researchers reported
improvements in both PFC function and psychological
symptoms, which are potential mediators of addiction, as
was discussed in previous sections of this article.119 These
results must be taken lightly as this was a case study.
Nonetheless, this recent report has demonstrated that interval
exercise can be safely performed and may affect some
underlying mechanisms of addictions.
Furthermore, a recent review highlighted the importance
of, but lack of studies on, using high-intensity exercise among
substance abusers.120 It is important to mention that for a high-
intensity interval program to be safely put into action among
AUD patients, it must begin at moderate-intensity exercise and
progress to higher-intensity efforts. According to previous
studies, problem drinkers report low cardiorespiratory fitness
levels—bottom tenth percentile for age and gender, so exercise
should begin at a tolerable level.9,106,111 This approach to
interval exercise has been successfully employed among
cardiac patients, who routinely report interval exercise to be
more tolerable and enjoyable, which results in more sessions
attended and improved fitness.117,121
In addition to the type of exercise, the appropriate
implementation of exercise is equally important. Evidence-
based alcohol treatment, such as CBT, focuses the patient on
developing strategies for handling high-risk drinking
situations and is rooted in promoting self-efficacy and coping
skills and addressing anxiety and depression.6,122 Exercise
ideally compliments cognitively focused treatment by
promoting self-efficacy; however, a reported barrier to
exercise among AUD patients is implementing exercise too
soon into treatment.115,123 The initiation of behavioral
treatment forces patients to deal with previously neglected
personal issues, and adding exercise may overwhelm them
and ultimately lead to discontinuation of exercise.115
Therefore, exercise should begin after several weeks of
stabilization within, and adaptation to, behavioral treatment.
For example, if behavioral therapy is a 12-week program,
then exercise should be initiated in weeks 3 or 4.115
Another implementation approach indicates the timing,
or placement of exercise, within CBT. Cognitive decline that
accompanies alcohol abuse may reduce the ability of a patient
to fully engage in CBT treatment. Therefore, performing
exercise prior to CBT sessions may take full advantage of
transient, exercise-induced cognitive improvement that may
translate into improved CBT retention. This exercise priming
approach has been incorporated into motor therapy for
stroke patients. In some studies, an aerobic bout of exercise
prior to motor therapy improved retention of the skills
learned.124,125 Moreover, high-intensity bouts of exercise
performed prior to motor-training tasks have been shown to
improve retention and learning of new skills in healthy
adults.126 Completing exercise before behavioral therapy—
exercise priming—together with delaying the initiation of
exercise, builds upon developing an appropriate exercise-
implementation strategy.
Moriarty—Exercise and Alcohol Use Disorder
DISCUSSION
The National Institute on Alcohol Abuse and Alcoholism
characterizes AUD as a chronic relapsing brain disease.127 The
underlying mechanisms of AUD are highly complex, and
abnormalities in neurotransmission, the PFC, and brain
morphology have been highlighted in this review. Although
behavioral therapy is effective in treating AUD, relapse remains
high and, therefore, novel ad hoc treatments are being
developed to enhance the benefits of traditional treatment. In
several studies, the benefits of exercise on alcohol behavior
have shown promising results; however, both mechanisms and
appropriate exercise programs have yet to be clarified.
Engaging in aerobic exercise prior to behavioral therapy
may enhance the effectiveness of treatment and ultimately
promote a further reduction in drinking. The current research
team’s hypothetical model for its exercise program is
presented in Figure 3. The proposed exercise intervention is
high-intensity aerobic exercise. For example, patients would
complete 4 to10 bouts of 30-second efforts, followed by
90 seconds of recovery. Total time can range between 18 and
30 minutes. Other highlights include a 20- to 60-minute
delay before behavioral treatment to allow for the transient
cognitive benefits of exercise to appear.
Limitations and Future Studies
This review is not without limitations. First, many reported
mechanisms of the benefits of exercise were studied in animal
models, which may not translate to humans. Second, exercise
has been successfully implemented into AUD and SUD
treatment, but potential mediators have not been explored. For
this reason, the proposed mechanisms are theory based. Third,
the novel exercise program—interval exercise—and
implementation strategies are also theory based, and to explore
the benefits of an exercise intervention, it must operate side-
by-side with behavioral treatment and not in opposition to it.
Therefore, future research efforts should be made to examine
the benefits of exercise in combination with specified behavioral
treatment’ such as CBT, MI, or TS.
CONCLUSIONS
Given the current reviews findings on the neural
mechanisms of alcohol addiction, the neurophysiological
basis of exercise treatment, and the results of exercise
interventions during alcohol treatment the current research
team has developed a novel approach to treatment of alcohol
addiction by incorporating aerobic interval exercise into
traditional, evidence-based, CBT. The benefits of exercise
may promote and compliment CBT treatment and lead to
reduced drinking outcomes.
AUTHOR DISCLOSURE STATEMENT
The authors declare no conflicts of interests.
REFERENCES
1. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE, Miech R. Monitoring
the future: National survey results on drug use, 1975-2015. 2016;2:19-55.
2. Sacks JJ, Gonzales KR, Bouchery EE, Tomedi LE, Brewer RD. 2010 national and
state costs of excessive alcohol consumption. Am J Prev Med. 2015;49(5):e73-e79.
ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 55
 3. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J.
Global burden of disease and injury and economic cost attributable to alcohol use
and alcohol-use disorders. Lancet. 2009;373(9682):2223-2233.
4. Miller WR, Walters ST, Bennett ME. How effective is alcoholism treatment in the
United States? J Stud Alcohol Drugs. 2001;62(2):211-220.
5. Swift RM. Drug therapy for alcohol dependence. N Engl J Med. 1999;340(19):1482-
1490.
6. Magill M, Kiluk BD, McCrady BS, Tonigan JS, Longabaugh R. Active ingredients
of treatment and client mechanisms of change in behavioral treatments for alcohol
use disorders: Progress 10 years later. Alcohol Clin Exp Res. 2015;39(10):1852-1862.
7. Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and
behavioral interventions for alcohol dependence: the COMBINE study: A
randomized controlled trial. JAMA. 2006;295(17):2003-2017.
8. Manthou E, Georgakouli K, Fatouros IG, Gianoulakis C, Theodorakis Y, Jamurtas
AZ. Role of exercise in the treatment of alcohol use disorders. Biomed Rep. 2016;
4(5):535-545.
9. Brown RA, Abrantes AM, Minami H, et al. A preliminary, randomized trial of
aerobic exercise for alcohol dependence. J Subst Abuse Treat. 2014;47(1):1-9.
10. Hallgren M, Romberg K, Bakshi A-S, Andréasson S. Yoga as an adjunct treatment
for alcohol dependence: a pilot study. Complement Ther Med. 2014;22(3):441-445.
11. Reddy S, Dick AM, Gerber MR, Mitchell K. The effect of a yoga intervention on
alcohol and drug abuse risk in veteran and civilian women with posttraumatic
stress disorder. Altern Complement Med. 2014;20(10):750-756.
12. Donaghy ME. The Investigation of Exercise as an Adjunct to the Treatment and
Rehabilitation of the Problem Drinker. Glasgow, UK: University of Glasgow; 1997.
13. Gary V, Guthrie D. The effect of jogging on physical fitness and self-concept in
hospitalized alcoholics. Q J Stud Alcohol. 1972;1(1):1-11.
14. Abernathy K, Chandler LJ, Woodward JJ. Alcohol and the prefrontal cortex. Int
Rev Neurobiol. 2010;91:289-320.
15. Mukherjee S, Das SK, Vaidyanathan K, Vasudevan D. Consequences of alcohol
consumption on neurotransmitters-an overview. Curr Neurovasc Res.
2008;5(4):266-272.
16. Chastain G. Alcohol, neurotransmitter systems, and behavior. J Gen Psychol.
2006;133(4):329-335.
17. Bjork JM, Grant SJ, Hommer DW. Cross-sectional volumetric analysis of brain
atrophy in alcohol dependence: effects of drinking history and comorbid
substance use disorder. Am J Psychiatry. 2003;160(11):2038-2045.
18. Volkow N, Li T-K. The neuroscience of addiction. Nat Neurosci. 2005;8(11):1429.
19. Goekint M, Bos I, Heyman E, Meeusen R, Michotte Y, Sarre S. Acute running
stimulates hippocampal dopaminergic neurotransmission in rats, but has no
influence on brain-derived neurotrophic factor. J Appl Physiol. 2011;112(4):535-541.
20. Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of
hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-3022.
21. Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain
volume in aging humans. J Gerontol A Biol Sci Med Sci. 2006;61(11):1166-1170.
22. Chang Y-K, Labban J, Gapin J, Etnier JL. The effects of acute exercise on cognitive
performance: A meta-analysis. Brain Res. 2012;1453:87-101.
23. Boileau I, Assaad JM, Pihl RO, et al. Alcohol promotes dopamine release in the
human nucleus accumbens. Synapse. 2003;49(4):226-231.
24. Weiss F, Lorang MT, Bloom FE, Koob GF. Oral alcohol self-administration
stimulates dopamine release in the rat nucleus accumbens: genetic and
motivational determinants. J Pharmaco Exp Ther. 1993;267(1):250-258.
25. Smith AD, Weiss F. Ethanol exposure differentially alters central monoamine
neurotransmission in alcohol-preferring versus-nonpreferring rats. J Pharmaco
Exp Ther. 1999;288(3):1223-1228.
26. Katner SN, Weiss F. Neurochemical characteristics associated with ethanol
preference in selected alcohol‐preferring and‐nonpreferring rats: a quantitative
microdialysis study. Alcohol Clin Exp Res. 2001;25(2):198-205.
27. Myers R, Melchior CL. Alcohol drinking in the rat after destruction of serotonergic
and catecholaminergic neurons in the brain. Res Comm Chem Pathol
Pharmacol.1975;10(2):363-378.
28. Volkow ND, Wang GJ, Fowler JS, et al. Decreases in dopamine receptors but not in
dopamine transporters in alcoholics. Alcohol Clin Exp Res. 1996;20(9):1594-1598.
29. Banerjee N. Neurotransmitters in alcoholism: A review of neurobiological and
genetic studies. Indian J Hum Genet. 2014;20(1):20.
30. Prasad P, Ambekar A, Vaswani M. Dopamine D2 receptor polymorphisms and
susceptibility to alcohol dependence in Indian males: A preliminary study. BMC
Med Genet. 2010;11(1):24.
31. Hirth N, Meinhardt MW, Noori HR, et al. Convergent evidence from alcohol-
dependent humans and rats for a hyperdopaminergic state in protracted
abstinence. Proc Natl Acad Sci U S A. 2016;113(11):3024-3029.
32. Laine T, Ahonen A, Torniainen P, et al. Dopamine transporters increase in human
brain after alcohol withdrawal. Mol Psychiatry. 1999;4(2):189.
33. Darden J, Hunt W. Reduction of striatal dopamine release during an ethanol
withdrawal syndrome. J Neurochem. 1977;29(6):1143-1145.
34. Volkow ND, Fowler JS, Wang G-J, Swanson JM, Telang F. Dopamine in drug abuse
and addiction: Results of imaging studies and treatment implications. Arch
Neurol. 2007;64(11):1575-1579.
35. Murphy DL, Andrews AM, Wichems CH, Li Q, Tohda M, Greenberg B. Brain
serotonin neurotransmission: An overview and update with an emphasis n
serotonin subsystem heterogeneity, multiple receptors, interactions with other
neurotransmitter systems, and consequent implications for understanding the
actions of serotonergic drugs. J Clin Psychiatry. 1998;1(1):1-11.
56 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3
36. Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or
venlafaxine-XR after failure of SSRIs for depression. N Engl J Med.
2006;354(12):1231-1242.
37. McBride WJ, Murphy JM, Yoshimoto K, Lumeng L, Li TK. Serotonin mechanisms
in alcohol drinking behavior. Drug Dev Res. 1993;30(3):170-177.
38. Herman AI, Philbeck JW, Vasilopoulos NL, Depetrillo PB. Serotonin transporter
promoter polymorphism and differences in alcohol consumption behaviour in a
college student population. Alcohol Alcohol. 2003;38(5):446-449.
39. Koob G, Rassnick S, Heinrichs S, Weiss F. Alcohol, the reward system and
dependence. Toward a molecular basis of alcohol use and abuse: New York, NY:
Springer; 1994.
40. Schweighofer N, Bertin M, Shishida K, et al. Low-serotonin levels increase
delayed reward discounting in humans. J Neurosci. 2008;28(17):4528-4532.
41. Crabbe JC, Phillips TJ, Feller DJ, et al. Elevated alcohol consumption in null
mutant mice lacking 5–HT1B serotonin receptors. Nature Genetic. 1996;14(1):98.
42. Lal H, Prather PL, Rezazadeh SM. Potential role of 5HT1C and/or 5HT2 receptors
in the Mianserin‐induced prevention of anxiogenic behaviors occurring during
ethanol withdrawal. Alcohol Clin Exp Res. 1993;17(2):411-417.
43. Valenzuela CF. Alcohol and neurotransmitter interactions. Alcohol Res Health.
1997;21(2):144.
44. Sytinsky I, Guzikov B, Gomanko M, Eremin V, Konovalova N. The Gamma‐
aminobutyric acid (GABA) system in brain during acute and chronic ethanol
intoxication. J Neurochem. 1975;25(1):43-48.
45. Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current
in hippocampal neurons. Science. 1989;243(4899):1721-1724.
46. Olsen RW, Hanchar HJ, Meera P, Wallner M. GABAA receptor subtypes: The “one
glass of wine” receptors. Alcohol. 2007;41(3):201-209.
47. Wallner M, Olsen R. Physiology and pharmacology of alcohol: The
imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors
as an opportunity for drug development? Br J Pharmacol. 2008;154(2):288-298.
48. Engberg G, Hajós M. Alcohol withdrawal reaction as a result of adaptive changes
of excitatory amino acid receptors. Naunyn-Schmiedeberg Arch Pharmacol. 1992
346(4):437-441.
49. Tsai G, Coyle JT. The role of glutamatergic neurotransmission in the
pathophysiology of alcoholism. Ann Rev Med. 1998;49(1):173-184.
50. Brook DW, Brook JS, Zhang C, Cohen P, Whiteman M. Drug use and the risk of
major depressive disorder, alcohol dependence, and substance use disorders. Arch
Gen Psychiatry. 2002;59(11):1039-1044.
51. Saunders PA, Copeland JR, Dewey ME, et al. Heavy drinking as a risk factor for
depression and dementia in elderly men: findings from the Liverpool longitudinal
community study. Br J Psychiatry. 1991;159(2):213-216.
52. Walton ME, Behrens TE, Buckley MJ, Rudebeck PH, Rushworth MF. Separable
learning systems in the macaque brain and the role of orbitofrontal cortex in
contingent learning. Neuron. 2010;65(6):927-939.
53. Stevens FL, Hurley RA, Taber KH. Anterior cingulate cortex: Unique role in
cognition and emotion. J Neuropsychiatry Clin Neurosci. 2011;23(2):121-125.
54. Curtis CE, D’Esposito M. Persistent activity in the prefrontal cortex during
working memory. Trends Cogn Sci. 2003;7(9):415-423.
55. Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological
basis: Neuroimaging evidence for the involvement of the frontal cortex. Am J
Psychiatry. 2002;159(10):1642-1652.
56. Bunce SC, Izzetoglu K, Izzetoglu M, Ayaz H, Pourrezaei K, Onaral B. Treatment
status predicts differential prefrontal cortical responses to alcohol and natural
reinforcer cues among alcohol dependent individuals. Paper presented at:
International Conference on Brain Inspired Cognitive Systems; 2012.
57. Kroczek AM, Haeussinger FB, Fallgatter AJ, Batra A, Ehlis AC. Prefrontal
functional connectivity measured with near‐infrared spectroscopy during
smoking cue exposure. Addict Biol. 2017;22(2):513-522.
58. Moreno-López L, Stamatakis EA, Fernández-Serrano MJ, et al. Neural correlates
of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in
polysubstance abusers: A resting-PET brain metabolism study. PloS one.
2012;7(6):e39830.
59. Goldstein RZ, Leskovjan AC, Hoff AL, et al. Severity of neuropsychological
impairment in cocaine and alcohol addiction: association with metabolism in the
prefrontal cortex. Neuropsychologia. 2004;42(11):1447-1458.
60. Sullivan EV, Mathalon DH, Zipursky RB, Kersteen-Tucker Z, Knight RT,
Pfefferbaum A. factors of the Wisconsin Card Sorting Test as measures of frontal-
lobe function in schizophrenia and in chronic alcoholism. Psychiatry Res.
1993;46(2):175-199.
61. Sullivan E, Rosenbloom M, Pfefferbaum A. Pattern of motor and cognitive deficits
in detoxified alcoholic men. Alcohol Clin Exp Res. 2000; 24(5):611-621.
62. Tivis R, Beatty WW, Jo Nixon S, Parsons OA. Patterns of cognitive impairment
among alcoholics: Are there subtypes? Alcohol Clin Exp Res.1995;19(2):496-500.
63. Sullivan EV. Compromised pontocerebellar and cerebellothalamocortical systems:
Speculations on their contributions to cognitive and motor impairment in
nonamnesic alcoholism. Alcohol Clin Exp Res. 2003;27(9):1409-1419.
64. Jernigan TL, Butters N, DiTraglia G, et al. Reduced cerebral grey matter observed
in alcoholics using magnetic resonance imaging. Alcohol Clin Exp Res.
1991;15(3):418-427.
65. Crego A, Rodriguez-Holguín S, Parada M, Mota N, Corral M, Cadaveira F.
Reduced anterior prefrontal cortex activation in young binge drinkers during a
visual working memory task. Drug Alcohol Depend. 2010;109(1):45-56.
66. Hong C-J, Liou Y-J, Tsai S-J. Effects of BDNF polymorphisms on brain function
and behavior in health and disease. Brain Res Bull. 2011;86(5-6):287-297.
Moriarty—Exercise and Alcohol Use Disorder
67. Aguado F, Carmona MA, Pozas E, et al. BDNF regulates spontaneous correlated
activity at early developmental stages by increasing synaptogenesis and expression
of the K+/Cl-co-transporter KCC2. Development. 2003;130(7):1267-1280.
68. Harrisberger F, Smieskova R, Schmidt A, et al. BDNF Val66Met polymorphism
and hippocampal volume in neuropsychiatric disorders: A systematic review and
meta-analysis. Neurosci Biobehav Rev. 2015;55:107-118.
69. Joe KH, Kim YK, Kim TS, et al. Decreased Plasma brain-derived neurotrophic
factor levels in patients with alcohol dependence. Alcohol Clin Exp Res.
2007;31(11):1833-1838.
70. Warnault V, Darcq E, Morisot N, et al. The BDNF valine 68 to methionine
polymorphism increases compulsive alcohol drinking in mice that is reversed by
tropomyosin receptor kinase B activation. Biol Psychiatry. 2016;79(6):463-473.
71. Pandey SC. A critical role of brain-derived neurotrophic factor in alcohol
consumption. Biol Psychiatry. 2016;79(6):427-429.
72. Kyzar EJ, Pandey SC. Molecular mechanisms of synaptic remodeling in
alcoholism. Neurosci Lett. 2015;601:11-19.
73. Moonat S, Sakharkar AJ, Zhang H, Pandey SC. The role of amygdaloid brain‐
derived neurotrophic factor, activity‐regulated cytoskeleton‐associated protein
and dendritic spines in anxiety and alcoholism. Addict Biol. 2011;16(2):238-250.
74. Harper C, Kril J. Brain atrophy in chronic alcoholic patients: A quantitative
pathological study. J Neurol Neurosurg Psychiatry. 1985;48(3):211-217.
75. Mechtcheriakov S, Brenneis C, Egger K, Koppelstaetter F, Schocke M, Marksteiner
J. A widespread distinct pattern of cerebral atrophy in patients with alcohol
addiction revealed by voxel-based morphometry. J Neurol Neurosurg Psychiatry.
2007;78(6):610-614.
76. Kubota M, Nakazaki S, Hirai S, Saeki N, Yamaura A, Kusaka T. Alcohol
consumption and frontal lobe shrinkage: Study of 1432 non-alcoholic subjects. J
Neurol Neurosurg Psychiatry. 2001;71(1):104-106.
77. Muuronen A, Bergman H, Hindmarsh T, Telakivi T. Influence of improved
drinking habits on brain atrophy and cognitive performance in alcoholic patients:
A 5‐year follow‐up study. Alcohol Clin Exp Res. 1989;13(1):137-141.
78. Eijk J, Demirakca T, Frischknecht U, Hermann D, Mann K, Ende G. Rapid partial
regeneration of brain volume during the first 14 days of abstinence from alcohol.
Alcohol Clin Exp Res. 2013;37(1):67-74.
79. Ehringer MA, Hoft NR, Zunhammer M. Reduced alcohol consumption in mice
with access to a running wheel. Alcohol. 2009;43(6):443-452.
80. Seidemann T, Spies C, Morgenstern R, Wernecke K-D, Netzhammer N. Influence
of volatile anesthesia on the release of glutamate and other amino acids in the
nucleus accumbens in a rat model of alcohol withdrawal: A pilot study. PloS one.
2017;12(1):e0169017.
81. Yoder KK, Albrecht DS, Dzemidzic M, et al. Differences in IV alcohol-induced
dopamine release in the ventral striatum of social drinkers and nontreatment-
seeking alcoholics. Drug Alcohol Depend. 2016;160:163-169.
82. Polina ER, Contini V, Hutz MH, Bau CHD. The serotonin 2A receptor gene in alcohol
dependence and tobacco smoking. Drug Alcohol Depend. 2009;101(1):128-131.
83. Carta M, Mameli M, Valenzuela CF. Alcohol enhances GABAergic transmission
to cerebellar granule cells via an increase in Golgi cell excitability. J Neurosci.
2004;24(15):3746-3751.
84. Bailey SP, Davis JM, Ahlborn EN. Neuroendocrine and substrate responses to
altered brain 5-HT activity during prolonged exercise to fatigue. J Appl Physiol.
1993;74(6):3006-3012.
85. Bliss EL, Ailion J. Relationship of stress and activity to brain dopamine and
homovanillic acid. Life Sci. 1971;10(20):1161-1169.
86. Meeusen R, Smolders I, Sarre S, et al. Endurance training effects on
neurotransmitter release in rat striatum: an in vivo microdialysis study. Acta
Physiologica. 1997;159(4):335-341.
87. Gene-Jack W, Volkow ND, Fowler JS, Franceschi D. PET studies of the effects of
aerobic exercise on human striatal dopamine release. J Nucl Med. 2000;41(8):1352.
88. Foley TE, Fleshner M. Neuroplasticity of dopamine circuits after exercise:
Implications for central fatigue. Neuromol Med. 2008;10(2):67-80.
89. Bequet F, Gomez‐Merino D, Berthelot M, Guezennec C. Exercise‐induced
changes in brain glucose and serotonin revealed by microdialysis in rat
hippocampus: Effect of glucose supplementation. Acta Physiologica.
2001;173(2):223-230.
90. Davis JM, Alderson NL, Welsh RS. Serotonin and central nervous system fatigue:
Nutritional considerations. AM J Clin Nutr. 2000;72(2):573S-578S.
91. Dey S, Singh R, Dey P. Exercise training: significance of regional alterations in
serotonin metabolism of rat brain in relation to antidepressant effect of exercise.
Physiol Behav. 1992;52(6):1095-1099.
92. Higley J, M Hasert M, Suomi S, Linnoila M. The serotonin reuptake inhibitor
sertraline reduces excessive alcohol consumption in nonhuman primates: effect of
stress. Neuropsychopharmacology. 1998;18(6):431-443.
93. Jia J, Hu Y-S, Wu Y, et al. Pre-ischemic treadmill training affects glutamate and
gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral
ischemia. Life Sci. 2009;84(15-16):505-511.
94. Bediz CS, Oniz A, Guducu C, et al. Acute Supramaximal exercise increases the brain
oxygenation in relation to cognitive workload. Front Hum Neurosci. 2016;10:1.
95. Yanagisawa H, Dan I, Tsuzuki D, et al. Acute moderate exercise elicits increased
dorsolateral prefrontal activation and improves cognitive performance with
Stroop test. Neuroimage. 2010;50(4):1702-1710.
96. Van Rensburg KJ, Taylor A, Hodgson T, Benattayallah A. Acute exercise
modulates cigarette cravings and brain activation in response to smoking-related
images: An fMRI study. Psychopharmacology. 2009;203(3):589.
Moriarty—Exercise and Alcohol Use Disorder
97. Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW. Physical activity increases
mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain.
Brain Res. 1996;726(1-2):49-56.
98. Helfer JL, Goodlett CR, Greenough WT, Klintsova AY. The effects of exercise on
adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure
during the brain growth spurt. Brain Res. 2009;1294:1-11.
99. Crews FT, Nixon K, Wilkie ME. Exercise reverses ethanol inhibition of neural
stem cell proliferation. Alcohol. 2004;33(1):63-71.
100. Rasmussen P, Brassard P, Adser H, et al. Evidence for a release of brain‐derived
neurotrophic factor from the brain during exercise. Exp Physiol. 2009;94(10):1062-1069.
101. Brunelli A, Dimauro I, Sgrò P, et al. Acute exercise modulates BDNF and pro-BDNF
protein content in immune cells. Med Sci Sports Exerc. 2012;44(10):1871-1880.
102. Schmidt-Kassow M, Schädle S, Otterbein S, et al. Kinetics of serum brain-derived
neurotrophic factor following low-intensity versus high-intensity exercise in men
and women. Neuroreport. 2012;23(15):889-893.
103. Saucedo Marquez CM, Vanaudenaerde B, Troosters T, Wenderoth N. High-
intensity interval training evokes larger serum BDNF levels compared with
intense continuous exercise. J Appl Physiol. 2015;119(12):1363-1373.
104. Tsukue I, Shohoji T. Movement therapy for alcoholic patients. J Stud Alcohol
Drugs. 1981;42(1):144-149.
105. Palmer J, Vacc N, Epstein J. Adult inpatient alcoholics: Physical exercise as a
treatment intervention. J Stud Alcohol Drugs. 1988;49(5):418-421.
106. Brown RA, Abrantes AM, Read JP, et al. Aerobic exercise for alcohol recovery:
Rationale, program description, and preliminary findings. Behav Modif.
2009;33(2):220-249.
107. Sinyor D, Brown T, Rostant L, Seraganian P. The role of a physical fitness program
in the treatment of alcoholism. J Stud Alcohol Drugs.1982;43(3):380-386.
108. Roessler KK, Bilberg R, Nielsen AS, Jensen K, Ekstrøm CT, Sari S. Exercise as
adjunctive treatment for alcohol use disorder: A randomized controlled trial. PloS
one. 2017;12(10):e0186076.
109. Georgakouli K, Manthou E, Georgoulias P, et al. Exercise training reduces alcohol
consumption but does not affect HPA-axis activity in heavy drinkers. Physiol
Behav. 2017;179:276-283.
110. Murphy TJ, Pagano RR, Marlatt GA. Lifestyle modification with heavy alcohol
drinkers: Effects of aerobic exercise and meditation. Addict Behav. 1986;11(2):175-186.
111. Jensen K, Nielsen C, Ekstrøm CT, Roessler KK. Physical exercise in the treatment
of alcohol use disorder (AUD) patients affects their drinking habits: A randomized
controlled trial. Scand J Public Health. 2018:1403494818759842.
112. Dawson DA, Room R. Towards agreement on ways to measure and report
drinking patterns and alcohol-related problems in adult general population
surveys: the Skarpö Conference overview. Elsevier; 2000.
113. Ussher M, Sampuran AK, Doshi R, West R, Drummond DC. Acute effect of a
brief bout of exercise on alcohol urges. Addiction. 2004;99(12):1542-1547.
114. Brown RA, Prince MA, Minami H, Abrantes AM. An exploratory analysis of
changes in mood, anxiety and craving from pre-to post-single sessions of exercise,
over 12 weeks, among patients with alcohol dependence. Ment Health Phys Act.
2016;11:1-6.
115. Sari S, Muller AE, Roessler KK. Exercising alcohol patients don’t lack motivation
but struggle with structures, emotions and social context-a qualitative dropout
study. BMC Fam Pract. 2017;18(1):45.
116. Abrantes AM, Battle CL, Strong DR, et al. Exercise preferences of patients in
substance abuse treatment. Ment Health Phys Act. 2011;4(2):79-87.
117. Lee LS, Tsai M-C, Oh PI, Brooks D. The effectiveness of progressive aerobic
interval training in cardiac rehabilitation. Med Sci Sports Exerc. 2017;1(1):1-11.
118. O’Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training
in patients with chronic heart failure: HF-ACTION randomized controlled trial.
JAMA. 2009;301(14):1439-1450.
119. Cabral DA, Costa KG, Costa AM, et al. Alcohol addiction-improving brain
oxygenation and cognition through a three-month running program. Med Sci
Sports Exerc. 2017;49(5S):352-353.
120. Colledge F, Gerber M, Puhse U, Ludyga S. Anaerobic exercise training in the
therapy of substance use disorders: A systematic review. Front Psychiatry.
2018;9:644.
121. Keteyian SJ, Hibner BA, Bronsteen K, et al. Greater improvement in
cardiorespiratory fitness using higher-intensity interval training in the standard
cardiac rehabilitation setting. J Cardiopulm Rehabil Prev. 2014;34(2):98-105.
122. Morgenstern J, Longabaugh R. Cognitive–behavioral treatment for alcohol
dependence: A review of evidence for its hypothesized mechanisms of action.
Addiction. 2000;95(10):1475-1490.
123. McAuley E, Jerome GJ, Marquez DX, Elavsky S, Blissmer B. Exercise self-efficacy
in older adults: social, affective, and behavioral influences. Ann Behav Med.
2003;25(1):1.
124. Mang CS, Campbell KL, Ross CJ, Boyd LA. Promoting neuroplasticity for motor
rehabilitation after stroke: considering the effects of aerobic exercise and genetic
variation on brain-derived neurotrophic factor. Physical Ther. 2013;93(12):1707-1716.
125. Quaney BM, Boyd LA, McDowd JM, et al. Aerobic exercise improves cognition
and motor function poststroke. Neurorehabil Neural Repair. 2009;23(9):879-885.
126. Roig M, Skriver K, Lundbye-Jensen J, Kiens B, Nielsen JB. A single bout of exercise
improves motor memory. PloS one. 2012;7(9):e44594.
127. Grant BF, Dawson DA, Stinson FS, Chou PS, Kay W, Pickering R. The alcohol use
disorder and associated disabilities interview schedule-IV (AUDADIS-IV):
Reliability of alcohol consumption, tobacco use, family history of depression and
psychiatric diagnostic modules in a general population sample. Drug Alcohol
Depend. 2003;71(1):7-16.
ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3 57
 CASE REPORT
Case Report: Fainting During Acupuncture
Treatment
YuHui Zhang, MD; Xin Zhao, MD; Yinjuan Lv, PhD; Mei-Ling Chen, MD; Wei Chen, MD; XunHua Xu, MD
ABSTRACT
Context • The first issue to be considered in acupuncture
is the safety of and adverse effects from treatment.
Fainting is an uncommon adverse reaction. Some
researchers believe that fainting is related to the mechanism
underlying acupuncture treatment, but due to moral and
technical issues, studies involving fainting during the
acupuncture process haven’t been conducted.
Objective • The study intended to determine if specific
risk factors are associated with fainting during acupuncture
treatment.
Design • The research team performed 2 case studies
involving fainting during acupuncture.
Setting • The study took place in the Physiotherapy
Departments of the Leribe Motebang Hospital and the
Mamohau Hospital in the Kingdom of Lesotho.
Participants • Participants were 2 out of 2050 patients
who received acupuncture treatment between October
2017 and April 2018 at one of the hospitals. They had
YuHui Zhang, MD, Associate Chief Physician, Orthopedic
Department, Wuhan Hospital of Traditional Chinese
Medicine, Wuhan, HuBei, China. Xin Zhao, MD, Resident,
Tuina Department, Wuhan Hospital of Traditional Chinese
Medicine, Wuhan, HuBei, China. Yinjuan Lv, PhD, Associate
Professor, Hubei University of Chinese Medicine, Wuhan,
Hubei, China. Mei-Ling Chen, MD, Resident, Cardiology
Department, Wuhan Hospital of Traditional Chinese
Medicine, Wuhan, HuBei, China. Wei Chen, MD, Associate
Chief Physician, Department of Internal Medicine, the
Affiliated Hospital of Jianghan University, Wuhan, HuBei,
China. XunHua Xu, MD, Associate Chief Physician,
Department of Radiology, CR and WISCO General
Hospital, Wuhan, HuBei, China.
Corresponding author: Yinjuan Lv, PhD
E-mail address: yj_luy@yeah.net
58 ALTERNATIVE THERAPIES, MAY/JUNE 2020 VOL. 26 NO. 3
fainted, with different clinical manifestations, during
acupuncture treatment. Their main symptoms were
dizziness, general weakness associated forehead sweating,
palpitations, dyspnea, and nausea.
Results • In both cases, the patient had complained of
hunger before treatment. Both claimed that they had
never experienced such a situation previously.
Conclusions • The research team suggests that the fainting
occurred for the patients in the two case studies secondary
to the hungry state. Hunger may be one of the most
important causes of fainting connected to acupuncture.
The failure of a practitioner to perform treatment for
fainting in a timely and effective manner, or his or her
improper handling of it, can lead to serious consequences.
Therefore, factors that may cause fainting should be
minimized to avoid their occurrence during acupuncture
therapy. (Altern Ther Health Med. 2020;26(3):58-60).
INTRODUCTION
Acupuncture has increasingly been accepted worldwide,1
but endless reports on its safety have appeared, with that
topic attracting the attention of many people.2-6 The adverse
reactions to acupuncture include fainting, acupuncture-
induced infections, bent needles, bleeding, broken needles,
sequelae allergies, delayed needles, visceral bleeding and
organ damage, and pneumothorax.1,7-12
Fainting is an uncommon adverse reaction associated
with acupuncture, with an incidence of 0-0.3%7 wordwide
and practitioners commonly learn methods to revive patients.
During the course of acupuncture treatment, patients
suddenly exhibit symptoms, such as pallor, dizziness, cold,
and coma, which is called fainting.13 Delayed fainting occurs
several minutes after treatment, and carelessness can easily
cause serious injuries. The practitioner should observe the
patient closely.
Zhang—Fainting During Acupuncture
Reproduced with permission of copyright owner. Further reproduction
prohibited without permission.