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Purpose: To examine eCB and mood responses to prescribed and preferred exercise among individuals with low, moderate, and high levels of physical activity. Methods: Thirty-six healthy adults (21±4yrs) were recruited from low (≤60min moderate-vigorous physical activity [MVPA]/wk), moderate (150-299min MVPA/wk), and high (≥300 MVPA/wk) physical activity groups. Participants performed both prescribed (approx. 70-75% max) and preferred (i.e., self-selected) aerobic exercise on separate days. Mood states and eCB concentrations were assessed before and after exercise conditions. Results: Both preferred and prescribed exercise resulted in significant increases (p < 0.01) in circulating eCBs (AEA, 2-AG); however, increases in AEA (p < 0.05) were larger in the prescribed condition. Likewise, both preferred and prescribed exercise elicited positive mood improvements compared to pre-exercise values, but changes in state anxiety, total mood disturbance, and confusion were greater in the preferred condition (p < 0.05). Changes in 2-AG concentrations were found to negatively correlate with changes in depression, tension, and total mood disturbance in the preferred condition (p < 0.05), and changes in AEA were positively associated with changes in vigor in the prescribed condition (p < 0.05). There were no significant group differences for mood or eCB outcomes. Conclusion: These results indicate that eCB and mood responses to exercise do not differ significantly between samples with varying physical activity levels. This study also demonstrates that in addition to prescribed exercise, preferred exercise activates the eCB system, and this activation may contribute to positive mood outcomes with exercise.
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Endocannabinoid and Mood Responses to
Exercise in Adults with Varying Activity Levels
Department of Kinesiology, University of Wisconsin–Madison, Madison, WI; and
Neuroscience Research Center and
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI
BRELLENTHIN, A. G., K. M. CROMBIE, C. J. HILLARD, and K. F. KOLTYN. Endocannabinoid and Mood Responses to Exercise in
Adults with Varying Activity Levels. Med. Sci. Sports Exerc., Vol. 49, No. 8, pp. 1688–1696, 2017. Acute aerobic exercise improves
mood and activates the endocannabinoid (eCB) system inphysically active individuals; however, both mood and eCB responses to exercise
may vary based on habitual levels of physical activity. Purpose: This study aimed to examine eCB and mood responses to prescribed and
preferredexercises among individuals with low, moderate, and high levels ofphysical activity. Methods: Thirty-six healthy adults (21 T4yr)
were recruited from low (e60 min moderate–vigorous physical activity [MVPA] per week), moderate (150–299 min MVPA per week),
andhigh(Q300 MVPA per week) physical activity groups. Participants performed both prescribed (approximately 70%–75% max) and
preferred (i.e., self-selected) aerobic exercise on separate days. Mood states and eCB concentrations were assessed before and after ex-
ercise conditions. Results:Bothpreferredandprescribedexerciseresultedinsignificantincreases(PG0.01) in circulating eCB
(N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol); however, increases in AEA (PG0.05) were larger in the prescribed con-
dition. Likewise, both preferred and prescribed exercise elicited positive mood improvements compared with preexercise values, but changes
in state anxiety, total mood disturbance, and confusion were greater in the preferred condition (PG0.05). Changes in 2-arachidonoylglycerol
concentrations were found to negatively correlate with changes in depression, tension, and total mood disturbance in the preferred condition
(PG0.05), and changes in AEA were positively associated with changes in vigor in the prescribed condition (PG0.05). There were no
significant group differences for mood or eCB outcomes. Conclusion: These results indicate that eCB and mood responses to exercise do
not differ significantly between samples with varying physical activity levels. This study also demonstrates that in addition to prescribed
exercise, preferred exercise activates the eCB system, and this activation may contribute to positive mood outcomes with exercise.
It is widely acknowledged that exercise is associated with
many psychological benefits, including reductions in
stress, tension, and anxiety (53). Although the specific
neurobiological mechanisms responsible for these outcomes
remain largely unknown, recent work in both animals and
humans indicates that the endocannabinoid (eCB) system,
which is activated by an acute bout of exercise, may play a
significant role (9,17,41).
The eCB is an expansive neuromodulatory network that
regulates synaptic excitability and neurotransmitter release. It is
composed of two primary receptors, CB1 and CB2, and two pri-
mary endogenous ligands, the eCB N-arachidonoylethanolamine
(AEA) and 2-arachidonoylglycerol (2-AG), as well as the
metabolizing enzymes for the eCB. CB1 receptors have been
found in almost all major regions of the brain and are heavily
expressed in areas that have been implicated in diverse
psychological processes such as reward and emotional regu-
lation (e.g., limbic system), memory (e.g., hippocampus),
nociception (e.g., periaqueductal gray), and higher level
cognitive functions (e.g., prefrontal cortex; for an extensive
review of the eCB system, see [27]).
Animal evidence indicates that various psychological re-
sponses to exercise as well as exercise behaviors are depen-
dent on eCB signaling. For example, blocking or mutating CB1
receptors before exercise abolishes anxiolytic and antinociceptive
effects typically observed with acute exercise (17,18). From a
behavioral standpoint, the eCB system has been found to reg-
ulate voluntary wheel running in rodents (16). Rodents that are
lacking CB1 receptors or have their CB1 receptors blocked
engage in 30%–40% less wheel running than control animals
(12). This reduction has been found to be specifically related to
the motivational aspects of wheel running (as opposed to the
ability to run) (43) and has been associated with eCB-induced
inhibition of GABA and facilitation of dopamine transmission
in reward-processing brain regions (8). Together, these results
suggest that the eCB system could contribute to the diverse
psychological benefits that result from exercise and may also
contribute to motivated exercise behaviors.
In humans, several studies have found that an acute bout
of exercise leads to significant increases in circulating eCB
(23,32,41,42,50), and one of these studies reported that
exercise-induced eCB increases were associated with increases
Address for correspondence: Angelique Brellenthin, Ph.D., University of
Wisconsin–Natatorium, Room 1160 2000, Observatory Drive, Madison, WI
53706; E-mail:
Submitted for publication November 2016.
Accepted for publication March 2017.
Copyright Ó2017 by the American College of Sports Medicine
DOI: 10.1249/MSS.0000000000001276
Copyright © 2017 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
in positive affect in a small sample of recreationally fit in-
dividuals (41). Other than this preliminary investigation, the
relationship between eCB and mood outcomes after exercise
in humans remains largely unexplored. In addition, the afore-
mentioned studies focused on moderately active individuals,
so it is unknown whether the eCB response to exercise differs
among people who engage in varying amounts of physical
activity. Outside of the acute eCB response to exercise, basal
physiological differences in the eCB system between in-
dividuals with varying physical activity levels may also exist
(13,19), further emphasizing the need to understand how acute
eCB responses shape chronic exercise behaviors in humans.
Therefore, the aims of this investigation were to expand
upon the relationships between mood and eCB responses to
a prescribed exercise bout in healthy individuals with vary-
ing levels of physical activity (inactive/low, moderate, and
high). A secondary objective of this study was to charac-
terize mood and eCB responses to preferred exercise, which
in some instances has been shown to elicit greater mood
improvements than prescribed exercise (38,55).
Study Participants
A power analysis (G*Power 3.1) was conducted to deter-
mine the sample size needed per group (three groups) to detect
a significant group difference in a repeated-measures (four
measurement points), between–within interaction design. The
analysis was powered at 0.80, with an alpha of 0.05, and a
Cohen’s f, medium effect size value of 0.25. Previous studies
have indicated there are large effect sizes for differences in
psychological outcomes between inactive and active partici-
pants (4,10,20), as well as large effect sizes for increases in
AEA after acute exercise (41,50). Because eCB responses to
exercise have not been compared across activity groups, a me-
dium rather than a large effect size was selected for this initial
investigation. The power analysis indicated that 10 participants
per group (n= 30) would be needed. To account for possible
participant attrition, the sample size was increased to 12 par-
ticipants per group (6 men and 6 women).
Before coming into the laboratory, potential participants
were screened via telephone about their estimated levels of
physical activity to ensure that invited participants would be
representative of all three activity groups (inactive/low, mod-
erate, and high). Thirty-six healthy young adults (18 men and
18 women) between the ages of 18–34 yr and without a history
or present diagnosis of any physical or psychiatric disorder
were recruited to participate in this study. All procedures were
approved by the University of Wisconsin Health Sciences In-
stitutional Review Board.
Seven-day Physical Activity Recall. The Physical
Activity Recall (PAR) has been found to be a valid
assessment of general levels of physical activity and has
demonstrated acceptable reliability, with test–retest periods
ranging from 2 wk to 2 yr, indicating that it is reflective of
long-term activity patterns (45,48,49). The PAR was conducted
by a trained interviewer who was blinded to the physical ac-
tivity information provided during the phone screen. Through
a series of guided, standardized prompts, the participants
reported their morning, afternoon, and evening bouts (mode,
intensity, and duration of at least 10 min) of physical activity,
which occurred in the past 7 d. Results of the PAR were
used to group participants based on physical activity levels.
For the inactive/low active group, participants had to report
less than 60 min of moderate–vigorous physical activity
(MVPA) per week, within 150–299 min MVPA per week for
the moderately active group, and greater than 300 min MVPA
per week for the highly active group. Group distinctions were
basedonthe2008 Physical Activity Guidelines for Americans.
According to the guidelines, inactive adults do not engage in
physical activities beyond those required through daily living,
and health benefits are observed starting at 60 minIwk
MVPA. Moderately active individuals attain 150–300 min
MVPA per week, and highly active individuals attain more
than 300 min of MVPA per week (40).
Profile of Mood States. The Profile of Mood States
(POMS) is a 65-item questionnaire that was administered to
examine the mood states of the participants before and after
each session. Six mood states are evaluated using the POMS:
tension, depression, anger, vigor, fatigue, and confusion, with
internal consistencies of each mood state ranging from >=
0.84–0.95 (36). The POMS has been shown repeatedly to be a
valid and sensitive measure of general mood (36). Total mood
disturbance was calculated by summing the scores from the
negative mood states, subtracting the vigor score, and adding
100 to account for negative values.
State–Trait Anxiety Inventory. The State–Trait Anx-
iety Inventory (STAI) is a 40-item questionnaire that was used
to assess participants’ anxiety (51). The STAI has repeatedly
been shown to have sound construct validity, and internal con-
sistencies are high, ranging from >= 0.86 to 0.95 (51). The
20-item trait anxiety subscale (general levels of anxiety)
was administered on the first day of testing, and the 20-item
state anxiety subscale (present levels of anxiety) was admin-
istered before and after exercise on preferred and prescribed
exercise days.
Commitment to Exercise Scale. For exploratory pur-
poses, the eight-item Commitment to Exercise Scale (CES)
was administered to assess participants’ psychological com-
mitment to and subjective feelings surrounding exercise (7).
This tool uses a series of visual analog scales anchored with
‘never’’ and ‘always’’ to assess for the presence of a path-
ological relationship with exercise. For example, items in-
quire about the degree to which a person feels a sense of guilt
when missing workouts, compromises social relationships for
exercise, or exercises despite being injured or sick. Responses
on the eight items demonstrated excellent internal consistency
(Cronbach’s >= 0.90). Composite scores from the CES range
eCB ACROSS PHYSICAL ACTIVITY LEVELS Medicine & Science in Sports & Exercise
Copyright © 2017 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
from 0 to 10 and represent the average distance along the
visual analog scales. Higher scores on the CES suggest a
greater degree of exercise dependency.
Participants completed three experimental sessions. Ses-
sions for individual participants occurred at the same time of
day and were separated by 1 wk. Participants were instructed
not to eat within 2 h or exercise within 24 h of testing to
minimize eCB variations and any potential carryover effects
from previous exercise sessions.
Session 1. During the first session, participants pro-
vided written informed consent indicating they agreed with
and would adhere to outlined procedures. They next completed
a basic demographic questionnaire, the CES (7), and the trait
subscale of the STAI (51). They then reported their physical
activity behaviors by completing the 7-Day PAR with a trained
interviewer (48). Participants were grouped based on their self-
reported activity levels.
After completing questionnaires, participants completed a
submaximal V
treadmill test. Participants wore a heart rate
monitor (Polar, Lake Success, NY) and a face mask (Hans-
Rudolph, Kansas City, MO), and expired through a tube
connected to a Parvo Medics True One 2400 Metabolic cart
(TrueOne; ParvoMedics, Sandy, UT). Following the American
College of Sports Medicine Bruce protocol guidelines for
submaximal treadmill testing, participants walked or jogged
on a treadmill at an increasing rate and incline until 85% of
age-predicted max heart rate was achieved (15).
Sessions 2 and 3. Sessions 2 and 3 consisted of preferred
and prescribed exercise conditions, with the order randomized
and counterbalanced for each participant. Before exercise,
participants completed the POMS (36) and the state anxiety
subscale of the STAI (51) and then had their baseline blood
sample drawn. Standardized scripts were used to explain each
exercise condition as well as Borg’s RPE scale (6–20) (3).
The prescribed exercise condition consisted of a 10-min
warm-up at low to moderate intensity (40%–60% estimated
), followed by 45 min at 70%–75% estimated V
(monitored using heart rate ranges determined from the
submaximal test), and then finished with a 5-min walking
cool down. This duration and intensity of exercise has pre-
viously been shown to result in significant elevations in cir-
culating eCB (23,42,50). Heart rate and RPE were assessed
every 5 min during the exercise.
The preferred exercise condition consisted of a 10-min
warm-up at a low to moderate intensity, followed by the
participants’ choice of treadmill exercise intensity and du-
ration. When they indicated they had completed their ses-
sion, participants finished with a 5-min walking cooldown.
Heart rate and RPE were assessed every 5 min during ex-
ercise. For both conditions, participants were allowed to
drink water at any time during exercise, and the postexercise
blood draw was collected within 5 min of the end of exer-
cise. After the blood draw, they completed the postexercise
mood assessments (i.e., POMS and state anxiety).
eCB Assays
Blood draws were performed while participants were seated,
and samples were collected into ethylenediaminetetraacetic acid
vacutainers. Blood samples were immediately centrifuged at
4-C, and the plasma was separated into aliquots before freezing
at j80-C. After preparation, AEA and 2-AG as well as related
biogenic lipids, palmitoylethanolamide (PEA) and oleoylethano-
lamide (OEA), were quantified using isotope dilution, atmo-
spheric pressure, and chemical ionization liquid chromatography/
mass spectrometry as described previously (32).
Statistical Analyses
A one-way ANOVA was used to detect the presence of group
differences in baseline variables. A series of mixed-design,
repeated-measures ANOVAs were performed to assess activ-
ity group and condition changes in eCB and mood states from
pre- to postexercise. The overall alpha family-wise was set at
= 0.05. Simple effects were calculated based on significant
interaction effects. Pearson’s rcorrelation coefficients were
determined to assess relationships among pre- to postexercise
changes in mood scores and eCB concentrations. To meet the
normality assumption for parametric tests, lipid concentrations
were logarithmically transformed before analyses.
Participant characteristics. Thirty-six men and women
with a mean age of 21 T4 yr were recruited for this study.
There were no significant differences between groups for age,
body mass index, or trait anxiety (P90.05). There were
significant group differences for estimated V
7.31, PG0.01), exercise commitment scores (F
= 15.97,
PG0.001), and amount of time spent in MVPA (F
31.72, PG0.001). Pairwise comparisons indicated that esti-
mated V
and exercise commitment were significantly
lower (PG0.01) in the low activity group compared with the
moderate and high activity groups. Self-reported MVPA
minutes were significantly different (PG0.05) between all
three activity groups (see Table 1), and MVPA was signifi-
cantly correlated with estimated V
(r= 0.57, PG
0.001). Average preexercise concentrations in AEA were
inversely associated with MVPA (r=j0.33, P= 0.05) but
TABLE 1. Sample characteristics.
(n= 11)
Age (yr) 20.6 T2.4 19.8 T1.1 22.6 T5.5 21.1 T3.8
BMI (kgIm
) 23.8 T5.3 22.7 T2.0 23.4 T3.4 23.4 T3.4
Estimated V
41.3 T6.8** 49.9 T5.0 51.1 T7.9 47.6 T7.8
MVPA (minIwk
)* 37.2 T22.2 203.0 T43.9 570.5 T261.2 285.1 T280.6
CES 2.4 T1.3** 6.7 T2.8 6.6 T1.8 5.4 T2.8
Trait anxiety 33.4 T8.4 33.0 T9.2 33.2 T9.3 33.2 T8.7
Data are presented as mean TSD.
BMI, body mass index.
*Significant difference (PG0.05) between all three groups.
**Low activity group was significantly different (PG0.01) from moderate and high activity
http://www.acsm-msse.org1690 Official Journal of the American College of Sports Medicine
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not estimated V
(r=j0.05, P= 0.77). No significant
associations were found between baseline lipid concentra-
tions and other variables.
Preferred and prescribed condition characteris-
tics. In the prescribed condition, there were significant group
differences for treadmill speed (F
Pairwise comparisons indicated that the low activity group
had slower treadmill speeds (PG0.01) than the high activity
group. There were no group differences for RPE in either the
prescribed or the preferred conditions (P90.05), although
there was a significant condition difference for estimated ex-
ercise intensity such that participants elected to exercise at a
relatively higher percentage of their estimated V
in the
preferred compared with the prescribed condition (F
7.74, PG0.01). In the preferred condition, there were sig-
nificant group differences for preferred duration (F
PG0.01) and treadmill speed (F
Pairwise comparisons indicated that the high activity group
exercised for significantly longer durations (PG0.05) than
the low and moderate groups, and the low activity group se-
lected significantly slower treadmill speeds (PG0.001) than
the moderate and high groups. There were no significant
differences in the timing of blood draws between groups or
between conditions (P90.05) (see Table 2).
eCB and mood responses to exercise. The results
indicated that there were significant time effects for 2-AG
=24.46,PG0.001) and PEA (F
with the concentrations of both lipids increasing signifi-
cantly from pre- to postexercise. There were also significant
condition–time interactions for AEA (F
= 5.12, PG0.05)
and OEA (F
= 7.04, PG0.05). AEA and OEA increased
significantly after both exercise conditions; however, analysis
of simple effects indicated that postexercise plasma concen-
trations of AEA (F
=4.47,PG0.05) and OEA (F
10.04, PG0.01) were greater in the prescribed compared with
the preferred condition. There were no main effects or in-
teractions for activity group for any eCB or lipid responses to
either preferred or prescribed exercise (P90.05), and effect
size estimates (G
) for group–time interactions were small
(AEA = 0.015, PEA = 0.020, OEA = 0.019, 2-AG = 0.039)
(see Fig. 1).
The results indicated that there were significant decreases
in tension (F
= 4.1, PG0.05), depression (F
= 8.09,
PG0.01), anger (F
= 5.51, PG0.05), and increases in
vigor (F
= 23.84, PG0.001) after both exercise condi-
tions. There were significant condition–time interactions for
confusion (F
= 4.39, PG0.05), total mood disturbance
= 5.03, PG0.05), and state anxiety (F
= 5.45, PG
0.05), and analysis of simple effects indicated that re-
ductions in confusion (F
= 10.19, PG0.01), total mood
disturbance (F
= 18.14, PG0.001), and state anxiety
= 6.55, PG0.05) occurred in the preferred but not the
prescribed condition (P= 0.26–0.65). There were no sig-
nificant main effects or interactions for activity group for
any mood state responses to either preferred or prescribed
exercise (P90.05), and effect size estimates (G
) for group–
time interactions were small to medium (tension = 0.081,
depression = 0.023, anger = 0.055, vigor = 0.093, fatigue =
0.029, confusion = 0.063, total mood disturbance = 0.083,
and state anxiety = 0.041) (see Fig. 2).
Associations between eCB and mood responses
to exercise. In the preferred condition, changes in 2-AG
were negatively associated with changes in tension (r=
j0.59, PG0.01), depression (r=j0.45, PG0.01), and
total mood disturbance scores (r=j0.40, PG0.05) after
exercise. In the prescribed condition, changes in AEA were
associated with changes in vigor (r= 0.37, PG0.05).
eCB responses to exercise. Aerobic exercise was
found to activate the eCB system, which agrees with previ-
ous work conducted in humans (23,42,50). There were sig-
nificant increases in AEA as well as 2-AG after both
preferred and prescribed exercise bouts. With the exception
of Cedernaes et al. (5), previous studies using aerobic ex-
ercise have reported nonsignificant increases in circulating
2-AG. Data from a few of these studies indicated that there
were medium to large effect size increases (14,41) or an
observable trend for increases in 2-AG after exercise (50).
These studies had small sample sizes, ranging from 8 to 16
exercising participants, suggesting they may have been in-
sufficiently powered to detect changes in 2-AG. Cedernaes
et al. (5) (n= 16) did report a significant increase in 2-AG
after 30 min of cycling and speculated that a portion of the
increase in 2-AG might have been related to the natural
circadian rhythm of 2-AG. One investigation has found no
discernable pattern of 2-AG for 24 h (54), whereas another
reported that 2-AG levels increased steadily throughout the
morning (approximately 15%–20% per hour) and plateaued
around 12:30 p.m., regardless of food intake (i.e., lunch)
(21). Therefore, although it is possible that some of the in-
crease in 2-AG was related to its circadian rhythm while it
was approaching this midday peak, it remains plausible that
TABLE 2. Exercise session characteristics.
Low Moderate High
Duration (min) Prescribed 45 45 45
Preferred 26.5 T7.2 25.4 T5.0 36.1 T12.3*
RPE Prescribed 12.8 T0.9 12.4 T0.9 12.9 T1.0
Preferred 12.3 T1.6 13.9 T1.3 13.4 T2.0
Prescribed 75.3 T8.6 72.1 T6.5 68.6 T8.4
Preferred**** 74.7 T7.8 80.4 T7.6 74.6 T15.5
Speed (kmIh
) Prescribed 7.4 T1.1*** 8.5 T1.0 9.2 T1.8
Preferred 7.6 T1.0** 10.6 T1.1 10.5 T1.3
Time of blood
collection (h:min)
Pre 11:27 (1:21) 11:53 (1:23) 11:18 (1:23)
Post 12:32 (1:22) 12:57 (1:22) 12:23 (1:21)
Pre 11:17 (1:15) 11:54 (1:24) 11:22 (1:18)
Post 12:03 (1:18) 12:39 (1:23) 12:13 (1:23)
Data are presented as mean TSD.
*Significant difference (PG0.05) from other groups.
**Significant difference (PG0.001) from other groups.
***Significant difference (PG0.05) between low and high active groups.
****Significant difference between sessions, with preferred session performed at higher
relative V
eCB ACROSS PHYSICAL ACTIVITY LEVELS Medicine & Science in Sports & Exercise
Copyright © 2017 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
2-AG responded to exercise because it increased approxi-
mately 28% and 55% from baseline in the preferred and
prescribed conditions, respectively.
The current investigation also found that there were sig-
nificant increases in PEA and OEA after aerobic exercise.
Although not classified as true eCB because they do not
bind to cannabinoid receptors, both PEA and OEA are
N-acyletha nolamines, which share synthetic and degradative
mechanisms with AEA, so it is not surprising that they
would increase in circulation alongside AEA (27). Because
they do not bind to CB1 receptors, PEA and OEA have not
comes, which are thought to be influenced by CB1 activity
in the central nervous system. However, they may contribute
to other well-documented effects of exercise. For instance,
PEA has been found to be neuroprotective, having both anti-
inflammatory and antinociceptive effects within the central
nervous system (35), whereas OEA has anorexigenic prop-
erties potentially contributing to appetite suppression after
intense exercise (22,46).
There were no differences in eCB at baseline or in their
responses to exercise between the low, moderate, and high
activity groups. The evidence for basal differences in eCB
among groups with varying physical activity levels remains
equivocal. Although the present investigation did not find
group differences in eCB concentrations at baseline, there
was a significant inverse association between self-reported
MVPA and baseline AEA concentrations. Conversely, others
have found that AEA levels were positively correlated with
objectively measured MVPA in overweight women (13),
whereas another study found that AEA levels were depressed
in a group of highly active runners who also endorsed criteria
for exercise dependence (1). Gasperi et al. (19) found no
differences in basal levels AEA and 2-AG between active and
sedentary, normal weight men; however, they did find dif-
ferences in fatty acid amide hydrolase activity (the enzyme
that degrades AEA) particularly in response to increases in
IL-6, a proinflammatory cytokine, among the physically ac-
tive men compared with the sedentary men. The authors
speculated that the effect of IL-6 on fatty acid amide hydro-
lase activity was a metabolic adaptation that occurred to ne-
gotiate the repeatedly increased eCB concentrationsthat occur
with habitual exercise (19). This notion makes sense given the
large body of evidence indicating that the eCB system acts to
both mount an appropriate, systemic stress response and bring
the body back to homeostasis once the stressor has passed
(for a review, see [25]). It is possible that the lack of group
differences in eCB responses to exercise were a result of
good general health and fitness in this young adult sample
because the estimated V
values for all three groups
were in the good to excellent categories based on normative
data for 20–29 yr olds (24). Similarly, Gasperi et al. (19) found
FIGURE 1—Mean and SE for the two eCB, AEA (anandamide) and 2-AG (2-AG), and related lipids, PEA and OEA, before and after prescribed and
preferred exercisesin the low, moderate, and high active groups as well as the overall sample. *Significant main effect of time for 2-AG and PEA (PG0.001).
Significant condition–time interaction for AEA and OEA (PG0.05). Changes in pre- to postexercise AEA and OEA plasma concentrations were greater
in the prescribed than the preferred condition. There were no significant group effects.
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no differences in eCB concentrations between sedentary and
active men and also observed that both groups had relatively
high cardiorespiratory fitness.
Increases in AEA and OEA were greater in the prescribed
versus the preferred condition. Overall, participants performed
significantly more work (% V
duration in minutes) in
the prescribed versus the preferred condition, and these find-
ings did not differ between groups. The greater amount of total
work (and thus greater physicalstress) may simply explain the
differential AEA and OEA responses. However, although to-
tal work within the prescribed condition did not differ between
groups, it is still possible that the prescribed condition was
especially physically stressful for the low activity group. For
instance, because estimated V
did not differ between the
moderate and high activity groups, they were combined into
one ‘‘high’’ group for an exploratory analysis and compared
with the low activity group. Although most lipid and mood
outcomes remained nonsignificant between the newly formed
low and high groups, there were significant group–condition
interactions for both AEA and OEA. Post hoc analyses in-
dicated that increases in AEA and OEA were greater in the
prescribed than preferred condition for the low activity group,
but increases in AEA and OEA were not different between
the conditions for the high activity group.
As an extension of the greater work performed in the
prescribed condition, it is also possible that larger AEA and
OEA concentrations arose from differences in hydration status
and plasma volume changes between the two conditions
(23,30). Fluid intake and plasma volume were not measured
in this study to test this possibility. Finally, another potential
explanation is that eCB values could have continued to in-
crease after the termination of preferred exercise, reaching the
levels observed after prescribed exercise. For instance, AEA,
OEA, PEA, and 2-AG continue to increase in concentration
for up to 15 min after exercise (5,23). Because our prescribed
bout was 45 min long and the average preferred bout was
29 min long, it is possible that eCB concentrations in the
preferred condition could have approached the greater levels
observed in the prescribed condition had there been another
blood draw 15 min after exercise (thus approximating the
45 min total duration in the prescribed bout).
In addition to stress processes, eCB have also been linked
to motivational aspects of physical activity in animals. For
instance, the amount of daily wheel running, which is often
considered to be a reinforcing behavior in rodents (16), has
been found to negatively correlate with basal concentrations
of AEA in mice (2), and disrupting CB1 receptors has been
showntosignificantlyreducevoluntary wheel running (11,12).
The effects of eCB manipulation are more pronounced among
animals that have been selectively bred to engage in high
amounts of wheel running compared with control animals (31).
Additional reports have shown that eCB signaling contrib-
utes specifically to the motivational aspects of wheel running
possibly through eCB and GABA interactions influencing
FIGURE 2—Means and SE for mood outcomes before and after prescribed and preferred exercises. Preexercise values depicted by BLACK bars.
Postexercise values depicted by WHITE bars. Prescribed condition responses on the left, preferred condition responses on the right. *Significant time
effect (PG0.05). Significant condition–time interaction (PG0.05), with mood improvements being greater in the preferred compared with the
prescribed condition. There were no significant activity group differences for any mood outcome so entire sample averages are shown.
eCB ACROSS PHYSICAL ACTIVITY LEVELS Medicine & Science in Sports & Exercise
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dopamine transmission in reward-processing brain regions such
as the striatum and ventral tegmental area (8,11,17,43).
From a motivational perspective, it was hypothesized that
individuals who engaged in varying amounts of voluntary
physical activity may have underlying differences in their eCB
system. Although there were no differences in eCB responses
to exercise between the physical activity groups in either con-
dition, it is interesting that baseline AEA levels were inversely
associated with self-reported MVPA but were not significantly
associated with V
strongly associated with each other. These results suggest that
the eCB system may relate to motivated exercise behaviors
apart from basic physiological adaptations to stress (i.e., im-
proved fitness) that occur with routine physical activity.
Similarly, Antunes et al. (1) reported that runners with high
activity levels who also met criteria for exercise dependence
according to the Exercise Dependence Scale had lower basal
levels of eCB, greater mood disturbance, and a blunted eCB
response to acute exercise compared with highly active in-
dividuals who had the same level of activity as the ‘‘dependent’’
group but did not fit the criteria for exercise dependency (i.e.,
they may have had differences in underlying motivational
processes). Compared with Antunes et al. (1), the moderate and
high activity groups in the present study did not score signifi-
cantly different on the CES. This suggests that although the
moderate and high activity groups had significantly different
self-reported physical activity levels, they may not have had
differences in their eCB responses because they did not differ
in their self-reported commitment to or motivations surround-
ing exercise, and there was little evidence suggesting that this
sample exhibited a pathological relationship with exercise.
Mood responses to exercise. Acute aerobic exer-
cise, whether preferred or prescribed, was able to elicit im-
provements in several mood states, including reductions in
tension, depression, and anger, and increases in vigor. Pre-
ferred exercise was able to elicit additional improvements in
confusion, total mood disturbance, and state anxiety. There
were no differences between physical activity groups in mood
outcomes to exercise in either condition. Several studies have
found that psychological improvements (e.g., reductions in
state anxiety and mood disturbance) are greater after exercise
in physically active compared with nonactive individuals
(20,39), although others have found no differences in mood
changes after exercise in low and high active groups (47), or
that mood improvements are the greatest in individuals with
more negative mood states before exercise, regardless of physical
activity level (44). Although there appeared to be greater levels
of mood disturbance and state anxiety before the preferred
condition, paired samples t-tests examining baseline levels of
mood states between the two conditions were all nonsignifi-
cant (Pvalues from 0.14 to 0.53). Furthermore, in both con-
ditions, preexercise values for mood disturbance and state
anxiety were below published norms for a young adult popu-
lation (51,52). It has also been suggested that allowing in-
dividuals to choose or ‘‘self-select’’ parameters of their exercise
session may lead to greater psychological benefits (55), and
this notion could be particularly relevant in populations with
varied exercise experiences and histories (38). Although the
evidence supporting this idea is mixed and seems to vary
based on the sample and instruments used to assess affect and
mood, initial reports indicate that allowing adults to engage in
preferred or self-selected exercise (as opposed to prescribing
exercise) may promote increased physical activity participa-
tion in the future, potentially by enhancing mood outcomes
during and after exercise bouts (33).
Associations between eCB and mood responses
to exercise. Increases in 2-AG and AEA were associated
with positive mood outcomes, including reductions in ten-
sion, depression, and total mood disturbance (2-AG) as well
as increases in vigor (AEA). These findings are in line with
previous work indicating that increases in AEA were asso-
ciated with increases in positive affect after exercise (41).
Beyond mood, additional studies have examined exercise-
induced changes in eCB and other psychological outcomes
such as perceived stress (5) and perceived exertion (23) and
have not found significant associations. This study also did
not find significant associations between RPE and eCB.
These mixed findings suggest that although eCB are mobi-
lized in response to a stressor, they may not be synthesized
in a linear fashion with the perceived magnitude of the stress.
These results also suggest that eCB may be particularly influ-
ential on emotional- or pleasure-related processes. For instance,
the evidence demonstrating that peripheral concentrations of
eCB are able to influence central processes originates from
preclinical research showing that animals will self-administer
intravenous injections of both AEA and 2-AG, and this reward-
seeking behavior is mediated by CB1 receptors (28,29). Also
related to reward and reinforcement processes, Antunes et al.
(1) found that AEA concentrations were decreased at baseline
and during a 14-d period of abstinence from physical activity,
which aligned with worsening mood outcomes in ‘‘exercise-
dependent’’ adults compared with highly active control par-
ticipants, although mood states and AEA were not directly
correlated in that study.
In the broader literature, eCB dysfunction has been asso-
ciated with several psychiatric conditions, including major
depressive disorder, posttraumatic stress disorder, and sub-
stance use disorders (26,34). In addition, it was documented
in healthy adults that chronic administration of rimonabant,
a CB1 inverse agonist, during weight loss trials led to increased
symptoms of depression and suicidal thoughts compared with a
placebo control (6), suggesting a causal relationship between
low CB1 activity and psychopathology. In animals, the eCB
system is important for adapting to chronic stress (25), so it is
possible that a dysfunctional eCB system could contribute to
maladaptive stress responses, such as the manifestation of de-
pressive symptoms. In humans, there is preliminary evidence
which suggests that physically active individuals are better able
to modulate their eCB activity in the context of inflammatory
and immune processes compared with sedentary individuals,
despite there being no significant differences in basal eCB
levels (19). There is considerable evidence that interactions
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Copyright © 2017 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
between inflammation and the brain may underlie the etiol-
ogy of depression, suggesting that the ability to regulate in-
flammatory processes could be instrumental in lowering the
risk of depression or other stress-related psychological dis-
orders (37). Moving forward, it will be important to deter-
mine whether exercise is protective against the long-term
psychological effects of stress because of its ability to activate
or perhaps regulate the eCB system.
In conclusion, both prescribed and preferred exercises elic-
ited beneficial mood outcomes and increased concentrations of
AEA and 2-AG among inactive to highly active individuals.
An important extension of this research will be to determine
whether eCB adaptations occur with an exercise training
program not only in healthy adults but also in patient
populations where eCB dysfunction has been observed and
where exercise has been shown to have therapeutic effects
(e.g., major depressive disorder).
This work was supported by the American College of Sports
Medicine, the University of Wisconsin Virginia Horne Henry Fund,
and the Research and Education Component of the Advancing
a Healthier Wisconsin Endowment at the Medical College of
The authors of this manuscript have no conflicts of interest to de-
clare. The results of this study do not constitute endorsement by the
American College of Sports Medicine. The results are presented
clearly, honestly, and without fabrication, falsification, or inappropriate
data manipulation.
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... This includes the endogenous opioid [91] and endocannabinoid systems [99], which can act as a mood enhancer and help reduce the desire for drug use [69,71,[100][101][102]. Specifically, exercise can be a non-pharmacological intervention for enhancing the eCB system due to increasing the circulating levels of endocannabinoids in healthy individuals [103][104][105]. This is because it can activate the eCB system in patients with SUD, leading to mood improvements, better stress management, and attenuated withdrawal symptoms [63,64]. ...
... Indeed, acute increases in the levels of AEA (eCBs) in circulation have been reported after exercise, documenting an exercise-induced activation of the eCB system in both patients with SUD and healthy subjects [132]. More specifically, in healthy individuals, elevated levels of AEA after exercise have been associated with many beneficial psychological effects, including positive emotion and courage, as well as reduced reactivity to stressful stimuli [105]. Exercise-induced AEA increases can restore the eCB system, which is often downregulated due to the chronic use of addictive substances [146]. ...
Full-text available
It is generally accepted that chronic opioid use is associated with structural and functional changes in the human brain that lead to an enhancement of impulsive behavior for immediate satisfaction. Interestingly, in recent years, physical exercise interventions have been used as an adjunctive treatment for patients with opioid use disorders (OUDs). Indeed, exercise has positive effects on both the biological and psychosocial basis of addiction, modifying neural circuits such as the reward, inhibition, and stress systems, and thus causing behavioral changes. This review focuses on the possible mechanisms that contribute to the beneficial effects of exercise on the treatment of OUDs, with emphasis placed on the description of a sequential consolidation of these mechanisms. Exercise is thought to act initially as a factor of internal activation and self-regulation and eventually as a factor of commitment. This approach suggests a sequential (temporal) consolidation of the functions of exercise in favor of gradual disengagement from addiction. Particularly, the sequence in which the exercise-induced mechanisms are consolidated follows the pattern of internal activation—self-regulation—commitment, eventually resulting in stimulation of the endocannabinoid and endogenous opioid systems. Additionally, this is accompanied by modification of molecular and behavioral aspects of opioid addiction. Overall, the neurobiological actions of exercise in combination with certain psychological mechanisms appear to promote its beneficial effects. Given the positive effects of exercise on both physical and mental health, exercise prescription is recommended as a complement to conventional therapy for patients on opioid maintenance treatment.
... In line with previous studies, our results showed that a single effect of PA or DQ was significantly associated with mental health [40,41]. This association is explained by the reaction of the endocannabinoid system to acute neuroendocrine stimulation and inflammation [42] and long-term brain adaptations, such as changes in neural architecture [43]. A Mendelian randomization study has investigated more than 100 potentially modifiable factors for their association with incident depression, but it only identified several modifiable risk factors for the prevention of depression, including PA-related domains and dietary [44]. ...
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Background: Depression escalating public health concern and the modest efficacy of currently available treatments have prompted efforts to identify modifiable risk factors associated with depression symptoms. Physical inactivity, poor nutrition, or other lifestyle behaviors are among the potentially modifiable risk factors most consistently linked with depression. Past evidence regarding the single effect of physical activity (PA) or dietary quality (DQ) on reducing the risk of depression symptoms has been well-documented. However, the association of the joint effect of PA and DQ on depression symptoms has never been investigated in a representative sample of adults. Objective: This study investigates the association between PA and depression symptoms and between DQ and depression symptoms, and their combined effects on US adults. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2018 cycles. The primary exposures were DQ and PA, measured using the Healthy Eating Index (HEI)-2015 and the metabolic equivalent (MET) minutes per week reported in questionnaires, respectively. Depression symptoms were defined as a 9-item Patient Health Questionnaire (PHQ-9) score of ≥10. We created 4 lifestyle categories: healthy diet and active individuals, unhealthy diet but active individuals, healthy diet but inactive individuals, and unhealthy diet and inactive individuals. Participants were considered to have a healthy diet if they fell within the 60th percentile of the HEI-2015 or to be active if they met the current guidelines for PA. A survey-multivariable logistic regression approach was used to model adjust the variables relevant to the associations, and an age-adjusted prevalence for depression symptoms was calculated following the NHANES guidelines. Results: In total, 19,295 participants represented a weighted number of 932.5 million adults aged 20 to 80 years in the noninstitutionalized US population. The total age-adjusted prevalence of depression symptoms among all respondents was 7.08% (1507/19,295). Of the respondents, 81.97% (15,816/19,295) met the PA recommendation and 26.79% (5170/19,295) scored at or above the 60th percentile on the HEI-2015. Depression symptoms were inversely associated with a higher level of PA (adjusted odds ratio [AOR] 0.819, 95% CI 0.716-0.938) and healthy DQ (AOR 0.809, 95% CI 0.701-0.931), respectively. A healthy diet combined with recommended PA was associated with a significantly lower risk of depression symptoms (AOR 0.658, 95% CI 0.538-0.803) than those who consumed an unhealthy diet but were physically active (AOR 0.890, 95% CI 0.765-1.038) or consumed a healthy diet but were physically inactive (AOR 1.077, 95% CI 0.817-1.406). Conclusions: Our findings indicate that people with a healthy diet and recommended PA have a lower risk of depression symptoms than those with an unhealthy diet and a low level of PA. A healthy dietary habit and regular PA are potential precautions against depression.
... The weekly physical activity did not impact the eCB. Moreover, accordingly to the questionnaires taken regarding depression, anxiety, or anger, the overall mood improved better in the prescribed conditions [135]. ...
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The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions. Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endogenous cannabinoids. Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time. A runner’s high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects. This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.
Introduction Heavy‐load free‐flow resistance exercise (HL‐FFRE) is a widely used training modality. Recently, low‐load blood‐flow restricted resistance exercise (LL‐BFRRE) has gained attention in both athletic and clinical settings as an alternative when conventional HL‐FFRE is contraindicated or not tolerated. LL‐BFRRE has been shown to result in physiological adaptations in muscle and connective tissue that are comparable to those induced by HL‐FFRE. The underlying mechanisms remain unclear; however, evidence suggests that LL‐BFRRE involves elevated metabolic stress compared to conventional free‐flow resistance exercise (FFRE). Aim The aim was to evaluate the initial (<10 min post‐exercise), intermediate (10–20 min), and late (>30 min) hormonal, immune, and oxidative stress responses observed following acute sessions of LL‐BFRRE compared to FFRE in healthy adults. Methods A systematic literature search of randomized and non‐randomized studies was conducted in PubMed, Embase, Cochrane Central, CINAHL, and SPORTDiscus. The Cochrane Risk of Bias (RoB2, ROBINS‐1) and TESTEX were used to evaluate risk of bias and study quality. Data extractions were based on mean change within groups. Results A total of 12525 hits were identified, of which 29 articles were included. LL‐BFRRE demonstrated greater acute increases in growth hormone responses when compared to overall FFRE at intermediate (SMD 2.04; 95% CI 0.87, 3.22) and late (SMD 2.64; 95% CI 1.13, 4.16) post‐exercise phases. LL‐BFRRE also demonstrated greater increase in testosterone responses compared to late LL‐FFRE. Conclusion These results indicate that LL‐BFRRE can induce increased or similar hormone and immune responses compared to LL‐FFRE and HL‐FFRE along with attenuated oxidative stress responses compared to HL‐FFRE.
Individuals with PTSD often exhibit deficits in executive functioning. An unexplored aspect of neurocognitive functions associated with PTSD is the type of learning system engaged in during decision-making. A model-free (MF) system is habitual in nature and involves trial-and-error learning that is often updated based on the most recent experience (e.g., repeat action if rewarded). A model-based (MB) system is goal-directed in nature and involves the development of an abstract representation of the environment to facilitate decisions (e.g., choose sequence of actions according to current contextual state and predicted outcomes). The existing neurocognitive literature on PTSD suggests the hypothesis of greater reliance on MF vs MB learning strategies when navigating their environment. While MF systems may be more cognitively efficient, they do not afford flexibility when making prospective predictions about likely outcomes of different decision-tree branches. Emerging research suggests that an acute bout of aerobic exercise improves certain aspects of neurocognition, and thereby could promote the utilization of MB over MF systems during decision making, although prior research has not yet tested this hypothesis. Accordingly, the current study administered a lab-based two-stage Markov decision-making task capable of discriminating MF vs MB decision making, in order to determine if moderate-intensity aerobic exercise (either shortly after or 30-minutes after the exercise bout has ended) promotes greater engagement in MB behavioral strategies compared to light-intensity aerobic exercise in adult women with and without PTSD (N=61). Results revealed that control women generally displayed higher levels of MB behavior that was further increased following immediate exercise, particularly moderate-intensity exercise. By contrast, the PTSD group generally displayed lower levels of MB behavior, and exhibited greater MB behavior when completing the task following moderate-intensity aerobic exercise compared to light-intensity aerobic exercise regardless of whether there was a short or long delay between exercise and the task. Additionally, women with PTSD demonstrated less impairment in MB decision-making compared to controls following moderate-intensity aerobic exercise. These results suggest that an acute bout of moderate-intensity aerobic exercise boosts MB behavior in women with PTSD, and suggests that aerobic exercise may play an important role in enhancing cognitive outcomes for PTSD.
Background: The use of cannabis with various forms of exercise (e.g., running) has received increased media attention in recent years, contradicting the popular stereotype that cannabis is associated with sedentary behavior. Although cross-sectional evidence suggests a positive association between cannabis use and exercise engagement, to date, the acute effects of cannabis on exercise remain unclear. Methods: The present within-subjects crossover study compared participants' experiences of running after ad libitum use of legal market cannabis (cannabis run) to running without cannabis (non-cannabis run) in a real-world setting. Participants (n=49) were cannabis users between the ages of 21 and 49 years (mean=30.82, standard deviation [SD]=6.21). The majority of participants were male (61.5%) and non-Hispanic White (81.6%). Results: Participants (n=49) ran an average of 3.88 miles (SD=2.28) during their cannabis and non-cannabis runs. Although participants ran an average of 31 seconds/mile slower during their cannabis run, this difference was not statistically significant (p=0.12). Participants reported experiencing (1) less negative affect (p=0.03), (2) greater feelings of positive affect (p<0.001), tranquility (p=0.004), enjoyment (p=0.004), and dissociation (p=0.001), and (3) more runner's high symptoms (p<0.001) during their cannabis (vs. non-cannabis) runs. Participants also reported lower pain levels after their cannabis (vs. non-cannabis) run (p=0.03). Perceived exertion did not differ between runs (p=0.33). Cannabis form, cannabinoid content, and feelings of "high" were largely unrelated to participants' experience of exercise while under the influence of cannabis. Conclusions: Results suggest that acute cannabis use may be associated with a more positive exercise experience among regular cannabis users. Research using varied methodologies, a range of exercise modalities, and diverse populations is needed to establish the long-term harms and benefits associated with this behavior, as well as the generalizability of these findings to other populations and settings.
Background: The health benefits of domain-specific physical activity (PA) on depressive symptoms were inconclusive. Few studies explored PA patterns and depressive symptoms. This study aimed to investigate the associations of PA domains and patterns with depressive symptoms. Methods: We conducted a cross-sectional study in China with 5047 adults. Latent class analysis was applied to identify the PA patterns and logistic regression analysis was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). Results: The ORs (95 % CIs) for the active versus inactive groups were 0.79 (0.69-0.91) for leisure-time PA, 0.57 (0.49-0.65) for transport PA, 0.95 (0.82-1.09) for household PA, and 1.38 (1.18-1.62) for occupational PA. We found non-linear associations between leisure-time PA, transport PA and depressive symptoms, with the lowest risk at 11 METs-h/week of leisure-time PA (equal to 147 min/week moderate PA or 88 min/week vigorous PA) and 23 METs-h/week of transport PA. There was a marginal inverse association with household PA for men while not for women. We identified four PA patterns and found a lower risk of depressive symptoms associated with "low occupational PA pattern" versus "moderate PA level pattern" (0.45 (0.38-0.52)). Limitations: Given the cross-sectional design, causality cannot be inferred. Conclusions: Our study supported an inverse association of leisure-time PA and transport PA with depressive symptoms and a positive association of occupational PA. The observed inconsistent association of household PA among men and women, and the finding that "low occupational PA pattern" was associated with a lower risk of depressive symptoms warrant further investigation.
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Background: Exercise can effectively attenuate withdrawal symptoms and reduce relapse, but it is unknown whether exercise of different intensities produces different results. This study aimed to systematically review the effects of different exercise intensities on withdrawal symptoms among people with substance use disorder (SUD). Methods: Systematic searches for randomized controlled trials (RCTs) on exercise, SUD, and abstinence symptoms were conducted via electronic databases, including PubMed, up to June 2022. Study quality was evaluated using the Cochrane Risk of Bias tool (RoB 2.0) for assessment of risk of bias in randomized trials. The meta-analysis was performed by calculating the standard mean difference (SMD) in outcomes of interventions involving light-, moderate-, and high-intensity exercise for each individual study using Review Manager version 5.3 (RevMan 5.3). Results: In total, 22 RCTs ( n = 1,537) were included. Overall, exercise interventions had significant effects on withdrawal symptoms, but the effect size varied with exercise intensity and by outcome measure (i.e., for different negative emotions). Light-, moderate-, and high-intensity exercise reduced cravings after the intervention [SMD = −0.71, 95% CI = (−0.90, −0.52)], and there were no statistical differences between the subgroups ( p > 0.05). Light-, moderate-, and high-intensity exercise reduced depression after the intervention [light, SMD = −0.33, 95% CI = (−0.57, −0.09); moderate, SMD = −0.64, 95% CI = (−0.85, −0.42); high, SMD = −0.25, 95% CI = (−0.44, −0.05)], with moderate-intensity exercise producing the best effect ( p < 0.05). Only light- and moderate-intensity exercise relieved anxiety after the intervention [light, SMD = −0.48, 95% CI = (−0.71, −0.26); moderate, SMD = −0.58, 95% CI = (−0.85, −0.31)]. Only high-intensity exercise worked in alleviating stress [SMD = −1.13, 95% CI = (−2.22, −0.04)]. Both irritability and restlessness could be improved by light- and moderate-intensity exercise [irritability, SMD = −0.74, 95% CI = (−0.98, −0.50); restless, SMD = −0.72, 95% CI = (−0.98, −0.47)], and there were no statistical differences between the subgroups ( p > 0.05). Moderate- and high-intensity exercise decreased withdrawal syndrome after the intervention [moderate, SMD = −0.30, 95% CI = (−0.55, −0.05); high, SMD = −1.33, 95% CI = (−1.90, −0.76)], with high-intensity exercise producing the best effects ( p < 0.01). Conclusion: Overall, exercise leads to improvements in withdrawal symptoms in individuals with SUD, but these effects vary significantly between the exercise of different intensities and according to the type of withdrawal symptoms. Moderate-intensity exercise has the greatest benefits in improving depression and anxiety; high-intensity exercise has the greatest benefits in improving withdrawal syndrome. Systematic Review Registration: , identifier, CRD42022343791
Studies in recent years have shown that the endocannabinoid (eCB) system is activated by exercise and modulates several physiological processes. Thus, the present review aimed to summarize the literature about the involvement of the eCB system in the control of pain, obesity, and metabolism by exercise. MEDLINE, EMBASE, and Web of Science were searched for experimental studies that investigated the presence of the eCB system in animal models of pain and obesity, in which the animals were subjected to different exercise modalities. The primary outcomes were pain, obesity, and metabolism. The databases were searched for articles from their inception up until March 2020. Two independent reviewers extracted the data and assessed the methodological quality of the included studies. Thirteen studies were considered eligible for this review. The results indicated that there was increased expression and levels of cannabinoid receptors and eCBs, respectively, after aerobic and resistance exercise, and that this effect was associated with antinociception. The eCB system was modulated by exercise in obese rats, confirming that it may also be involved in the control of obesity and metabolism when these are modulated by aerobic training. Exercise can be effective in controlling pain, partly through the involvement of the eCB system. In addition, exercise can modulate the imbalance of the eCB system in obesity and metabolic disorders, thus also controlling these pathologies through this signaling system.
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Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-hr sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-hr sleep opportunity, 2:45-7am each night) vs. normal sleep (8.5-hr sleep opportunity, 10:30pm-7am each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5 hr after awakening (vs. normal sleep, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15 min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration.
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The low rates of regular exercise and overall physical activity (PA) in the general population represent a significant public health challenge. Previous research suggests that, for many people, exercise leads to a negative affective response and, in turn, reduced likelihood of future exercise. The purpose of this paper is to examine this exercise–affect–adherence relationship from an evolutionary perspective. Specifically, we argue that low rates of physical exercise in the general population are a function of the evolved human tendency to avoid unnecessary physical exertion. This innate tendency evolved because it allowed our evolutionary ancestors to conserve energy for physical activities that had immediate adaptive utility such as pursuing prey, escaping predators, and engaging in social and reproductive behaviors. The commonly observed negative affective response to exercise is an evolved proximate psychological mechanism through which humans avoid unnecessary energy expenditure. The fact that the human tendencies toward negative affective response to and avoidance of unnecessary physical activities are innate does not mean that they are unchangeable. Indeed, it is only because of human-engineered changes in our environmental conditions (i.e., it is no longer necessary for us to work for our food) that our predisposition to avoid unnecessary physical exertion has become a liability. Thus, it is well within our capabilities to reengineer our environments to once again make PA necessary or, at least, to serve an immediate functional purpose. We propose a two-pronged approach to PA promotion based on this evolutionary functional perspective: first, to promote exercise and other physical activities that are perceived to have an immediate purpose, and second, to instill greater perceived purpose for a wider range of physical activities. We posit that these strategies are more likely to result in more positive (or less negative) affective responses to exercise, better adherence to exercise programs, and higher rates of overall PA.
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Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.
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Exercise is rewarding, and long-distance runners have described a runner’s high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner’s high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.
Beneficial effects of voluntary wheel running on hippocampal neurogenesis, morphology and hippocampal-dependent behavior have widely been studied in rodents, but also serious side effects and similarities to stereotypy have been reported. Some mouse strains run excessively when equipped with running wheels, complicating the comparability to human exercise regimes. Here, we investigated how exercise restriction to 6 h/day affects hippocampal morphology and metabolism, stereotypic and basal behaviors, as well as the endocannabinoid system in wheel running C57BL/6 mice; the strain most commonly used for behavioral analyses and psychiatric disease models. Restricted and unrestricted wheel running had similar effects on immature hippocampal neuron numbers, thermoregulatory nest building and basal home-cage behaviors. Surprisingly, hippocampal gray matter volume, assessed with magnetic resonance (MR) imaging at 9.4 Tesla, was only increased in unrestricted but not in restricted runners. Moreover, unrestricted runners showed less stereotypic behavior than restricted runners did. However, after blockage of running wheels for 24 h stereotypic behavior also increased in unrestricted runners, arguing against a long-term effect of wheel running on stereotypic behavior. Stereotypic behaviors correlated with frontal glutamate and glucose levels assessed by 1H–MR spectroscopy. While acute running increased plasma levels of the endocannabinoid anandamide in former studies in mice and humans, we found an inverse correlation of anandamide with the daily running distance after long-term running. In conclusion, although there are some diverging effects of restricted and unrestricted running on brain and behavior, restricted running does not per se seem to be a better animal model for aerobic exercise in mice.
The aim of this study was to identify the possible association between biochemical markers of exercise addiction and affective parameters in a sample of athletes during 2 weeks of withdrawal exercise. Eighteen male runners were distributed into a control group (n = 10) composed of runners without exercise addiction symptoms and an exercise addiction group (n = 8) composed of runners with exercise addiction symptoms. The volunteers performed a baseline evaluation that included affective questionnaires, blood samples, body composition and an aerobic test performed at ventilatory threshold I. After the baseline evaluation, the groups started an exercise withdrawal period that was sustained for 2 weeks. During exercise withdrawal, an actigraph accelerometer was used to monitor the movement index, and CK and LDH were measured in blood samples to validate the non-exercise practice. At the end of the exercise withdrawal period, a blood collection, aerobic test and mood scale was performed in the re-test. The results showed that at the end of the experimental protocol, when compared with the control group, the exercise addiction group showed an increase in depression, confusion, anger, fatigue and decreased vigor mood that improved post-exercise, along with low levels of anandamide at all time-points evaluated and a modest increase in β-endorphin post-exercise. Moreover, the exercise addiction group showed a decrease in oxygen consumption and respiratory exchange ratio after the exercise withdrawal period, which characterized a detraining phenomenon. Our data suggest that a 2-week withdrawal exercise period resulted in an increase of negative mood in exercise addiction; additionally, exercise addiction showed low levels of anandamide.