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. 2022 Aug 9;7(4):388–408. doi: 10.1089/can.2021.0113

Table 1.

Included samples on acute exercise (N=40 samples reported in N=22 articles)

Type First author (year) Condition Strain of animal Sample size (n) Age (mean±SD) Gender (% female) Race/ethnicity (%) Type of exercise Exercise modality Exercise duration Exercise intensity eCB collection method eCB collection timepoints Significant reported change in AEA Significant reported change in 2-AG Significant reported change in other eCBs Additional outcomesa
Human studies
 Patients, including those with pre-existing conditions
  Crombie (2020)88 Patients with PTSD N/A HC: n=12
TE: n=14
PTSD: n=14
HC: 21.4±3.9
TE: 23.0±5.4
PTSD: 27.6±6.6
HC: 100% F
TE: 100% F
PTSD: 100% F
HC: 92% W, 8% B, 0% A, 0% M, 0% O
TE: 86% W, 0% B, 7% A, 0% M, 7% O
PSTD: 64% W, 21% B, 7% A, 0% M, 7% O
Endurance Treadmill running 30 min of running on a treadmill at a moderate-intensity exercise with 5 min warm-up and cool-down 70–75% AAMHR Standard blood draw Collected immediately before and after exercise HC: AEA ↑
TE: AEA ↑
PTSD: AEA ↑
HC: 2-AG ↑
TE: 2-AG ↑
PTSD: 2-AG ↑
HC:
OEA ↑
PEA ↑
2-OG ↑
TE:
OEA ↑
PEA ↑
2-OG ↑
PTSD:
OEA ↑
PEA ↑
2-OG ↑
HC:
Anxiety ↓
Fear ↓
Improvements in mood
TE:
Anxiety ↓
Fear ↓
Improvements in mood
PTSD:
Anxiety ↓
Fear ↓
Improvements in mood
  Meyer (2019)58 Patients with MDD N/A n=17 40.8±14.8 100% F N/R Endurance Electronically braked cycle ergometer 30 min of cycling, either (1) at a moderate intensity or (2) at a preferred intensity, each with 5 min warm-up and cool-down Ratings of perceived exertion of “13” Standard blood draw Collected immediately before and as quickly as possible after the session ended, always within 10 min post-exercise Prescribed: AEA ↑
Preferred: No AEA changes
Prescribed: No 2-AG changes
Preferred: No 2-AG changes
Prescribed:
OEA ↑
No PEA, 2-OG changes
Preferred:
No OEA, PEA, 2-OG changes
Prescribed: Improvements in mood related to eCB changes
Preferred: Improvements in mood not related to eCB changes
  Crombie (2019)80 Patients with PTSD N/A HC: n=10
PTSD: n=10
HC: 22.0±6.1
PTSD: 25.2±8.1
HC: 70% F
PTSD: 80% F
HC: 70% W, 0% B, 20% A, 10% M, 0% O
PTSD: 90% W, 0% B, 10% A, 0% M, 0% O
Endurance Treadmill running or incline walking 30 min of running or walking on a treadmill at a moderate-intensity exercise with 5 min warm-up and cool-down 70–75% AAMHR Standard blood draw Collected immediately before and after exercise HC:
AEA ↑
PTSD:
AEA ↑
HC:
2-AG ↑
PTSD:
No 2-AG changes
HC:
OEA ↑
No PEA, 2-OG changes
PTSD:
OEA ↑
No PEA, 2-OG changes
N/A
  Stensson (2019)49 Patients with CNSP N/A HC: n=11
CNSP: n=21
HC: 37.7±15.9
CNSP: 50.8±12.9
HC: 55% F
CNSP: 76% F
N/R Endurance Arm cycling A 30-min session of arm cycling N/R Standard blood draw Collected immediately before and 60 min after exercise HC:
AEA ↓
CNSP: No AEA changes
HC:
No 2-AG changes
CNSP:
No 2-AG changes
HC:
No OEA, PEA, SEA changes
CNSP:
No OEA, PEA, SEA changes
HC: Glutamate/AEA ratio ↑
CNSP: No glutamate/AEA ratio changes
  Brellenthin (2019)44,b Patients with
Substance Abuse Disorder
N/A Treatment as usual with exercise:
n=21
35.1±10.2 45% F 64% W, 2% B, 0% A, 1% M, 1% O Endurance Treadmill incline walking 30 min of moderate-intensity treadmill incline walking 70–75% AAMHR Standard blood draw Collected within 5 min before and after exercise AEA ↑ No 2-AG changes N/A Acute improvements in mood and reductions in perceived stress and drug craving
  Crombie (2018)30 Patients with PTSD N/A HC:
n=12
PTSD:
n=12
HC:
22.0±4.7
PTSD:
26.1±6.7
HC:
75% F
PTSD:
75% F
N/R Endurance Treadmill running or incline walking 30 min of walking or running on a treadmill at a moderate intensity with 10 min warm-up 70–75% AAMHR Standard blood draw Collected immediately before and after exercise HC:
AEA ↑
PTSD:
AEA ↑
HC:
2-AG ↑
PTSD:
2-AG ↑
HC:
OEA ↑
No PEA, 2-OG changes
PTSD:
OEA ↑
No PEA, 2-OG changes
HC:
Improvements in mood
Pain ↓
PTSD:
Improvements in mood
Pain ↓
 Healthy volunteers
  Marin Bosch (2020)46 Healthy volunteers N/A n=15 23.2±4.2 0% F N/R Endurance Cycling A 30-min session of cycling at a moderate intensity
and 15 min of cycling at a high intensity the next day, each with a 3 min warm-up and cool-down
Moderate intensity:
70% MHR
High intensity:
80% MHR
Standard blood draw Collected immediately before and after exercise Moderate intensity:
AEA ↑
High intensity:
AEA ↑
N/A N/A Hippocampus activation ↑
Motor sequence learning ↑
  Hughes (2020)89 Healthy, recreationally active volunteers N/A n=12 29.0±6.0 17% F N/R Strength Light load RE, BFR-RE, BFR-RE with high pressure, and heavy load RE Light load RE, BFR-RE, BFR-RE with high pressure: 4 sets (30, 15, 15, and 15 repetitions, respectively) of unilateral leg press exercise with 30 sec interset rest periods.
Heavy load RE: 4 sets of 10 repetitions of unilateral leg press exercise with 53 sec interset rest periods.
Light load RE, BFR-RE, BFR-RE with high pressure: 30% one rep max
Heavy load RE: 70% one rep max
Standard blood draw Collected immediately before, 5 min after, 10 min after, and 24 h after exercise N/A Light load RE, BFR-RE, BFR-RE with high pressure, and heavy load RE: No 2-AG changes (decrease for heavy load RE after 24 h) N/A Beta-endorphin concentration ↑
Pain ↓
  Stone (2018)90 Healthy volunteers N/A n=9 61.0 100% F N/R Endurance Cycling and dancing One 30-min session of cycling and one 30 min session of dancing N/R Standard blood draw Collected immediately before and after exercise Cycling: No AEA changes
Dancing: No AEA changes
N/A Cycling: OEA ↑, no PEA changes
Dancing: no OEA changes, no PEA changes
Cycling: ↓ hunger/appetite
Dancing: Improved mood
  Crombie (2018)91,c Healthy volunteers (placebo condition) N/A n=58 21.0±3.0 50% F 57% W, 17% B, 14% A, 12% M, 0% O Strength Isometric handgrip Isometric handgrip exercise for 3 min 25% MVC Standard blood draw Collected immediately before and within 5 min after exercise AEA ↑ 2-AG ↑ OEA ↑
PEA ↑
2-OG ↑
See Koltyn (2014)29
  Brellenthin (2017)40 Healthy volunteers N/A Low PA exercisers (preferred and prescribed): n=11
Moderate PA exercisers (preferred and prescribed): n=12
High PA exercisers (preferred and prescribed): n=13
Low PA exercisers (preferred and prescribed): 20.6±2.4
Moderate PA exercisers (preferred and prescribed): 19.8±1.1
High PA exercisers (preferred and prescribed): 22.6±5.5
Low PA exercisers (preferred and prescribed): 50% F
Moderate PA exercisers (preferred and prescribed): 50% F
High PA exercisers (preferred and prescribed): 50% F
N/R Endurance Prescribed treadmill exercise and preferred intensity treadmill exercise. Order was randomized and counterbalanced across participants Prescribed exercise: 45 min session of treadmill walking or running
Preferred exercise: participants' choice of treadmill exercise intensity and duration
Prescribed: 70–75% VO2max
Low PA preferred: 74.7±7.8
Moderate PA preferred: 80.4±7.6
High PA preferred: 74.6±15.5
Standard blood draw Collected immediately before and within 5 min after exercise Low PA exercisers (preferred and prescribed): AEA ↑
Moderate PA exercisers (preferred and prescribed): AEA ↑
High PA exercisers (preferred and prescribed): AEA ↑
Low PA exercisers (preferred and prescribed): 2-AG ↑
Moderate PA exercisers (preferred and prescribed): 2-AG ↑
High PA exercisers (preferred and prescribed): 2-AG ↑
Low PA exercisers (preferred and prescribed):
OEA ↑
PEA ↑
Moderate PA exercisers (preferred and prescribed):
OEA ↑
PEA ↑
High PA exercisers (preferred and prescribed):
OEA ↑
PEA ↑
Low PA exercisers (preferred and prescribed): Improvements in mood
Moderate PA exercisers (preferred and prescribed): Improvements in mood
High PA exercisers (preferred and prescribed): Improvements in mood
  Cedernaes (2016)47 Healthy volunteers N/A n=16 22.9±0.7 0% F N/R Endurance Ergometer cycling Ergometer cycling for 35 min Watts equivalent to 75% of VO2 reserve Standard blood draw Collected immediately before, 15 min after, and 4 h after exercise No AEA changes 2-AG ↑ OEA ↑
No PEA changes
Sleep deprivation ↑2-AG levels but no modulation in exercise response
  Koltyn (2014)29 Healthy volunteers (placebo condition only) N/A n=58 21±3.0 50% F 57% W, 17% B, 14% A, 12% M, 0% O Strength Isometric handgrip Isometric handgrip exercise for 3 min 25% MVC Standard blood draw Collected immediately before and within 5 min after exercise AEA ↑ 2-AG ↑ OEA ↑
PEA ↑
2-OG ↑
DHEA ↑
PPT ↑
PPR ↓
  Raichlen (2013)31 Healthy volunteers N/A n=10 31.9±12.1 40% F N/R Endurance Treadmill running or walking 30 min of treadmill walking or running at one of four intensities. Intensities were randomized across four separate laboratory visits. Intensity 1: <50% AAMHR
Intensity 2: 70% AAMHR
Intensity 3: 80% AAMHR
Intensity 4: 90% AAMHR
Standard blood draw Collected immediately before and after exercise Intensity 1: No AEA changes
Intensity 2: AEA ↑
Intensity 3: AEA ↑
Intensity 4: No AEA changes
Intensity 1: No 2-AG changes
Intensity 2: No 2-AG changes
Intensity 3: No 2-AG changes
Intensity 4: No 2-AG changes
N/A Improved positive affect
  Raichlen (2012)59 Healthy volunteers N/A n=10 N/R N/R N/R Endurance Treadmill running or walking 30 min of treadmill walking on day 1 and 30 min of treadmill running on day 2 Running: 72.5%±2.54% MHR (Froude of 0.71±0.03)
Walking: 44.6%±1.25% MHR (Froude of 0.26±0.01)
Standard blood draw Collected immediately before and after exercise Running: AEA ↑
Walking: No AEA changes
Running: No 2-AG changes
Walking: No 2-AG changes
N/A N/A
  Feuerecker (2012)48 Healthy, trained hikers N/A n=12 27.6 0% F N/R Endurance Hiking Protocol A: Hiking at lower altitude for 4–4.5 h
Protocol B: Hiking at higher altitude for 3.5–5.5 h
Protocol A: Hiking at lower altitude of ∼1650 m
Protocol B: Hiking at higher altitude of ∼3380 m (1780 m difference compared with lower altitude)
Standard blood draw Collected before, immediately after, 18 h after, and 24 h after exercise Protocol A: AEA ↑
Protocol B: AEA ↑
Protocol A: No 2-AG changes
Protocol B: No 2-AG changes
N/A Hypoxia (higher altitudes) ↑ eCB system activation
  Heyman (2012)56 Healthy, trained cyclists N/A n=11 23.3±5.1 0% F N/R Endurance Cycling 60 min of pedaling on an ergometric bicycle, followed by predetermined amount of work equal to 30 min at higher intensity. The total exercise period was 90 min 55% of maximal power output for 60 min, followed by 75% of maximal power output for 30 min Standard blood draw Collected at rest, after 60 min of exercise at 55% maximal power output, immediately after the 90 min time trial, and 15 min after exercise. AEA ↑ after a 90-min exercise period No 2-AG changes N/A BDNF levels ↑ significantly during
exercise and ↓ during the 15 min of recovery
BDNF and AEA concentrations correlated after exercise
  Sparling (2003)41 Healthy, trained volunteers N/A Running: n=8
Cycling: n=8
23.8±9.4 Running: 0% F
Cycling: 0% F
N/R Endurance Running or cycling 45 min of prescribed exercise 70–80% MHR Standard blood draw Collected immediately before and after exercise Running: AEA ↑
Cycling: AEA ↑
Running: No
2-AG changes
Cycling: No 2-AG changes
N/A N/A
 Animal studies
  King-Himmelreich (2017)64 Mice treated with CB1R antagonist and AMP-activated protein kinase C57BL/6 mice N/R 6–8 weeks N/R N/R Endurance Treadmill running 60 min of treadmill running N/R Standard blood draw Collected immediately after, 30 min after, 2 h after, 4 h after, and 24 h after exercise AEA ↑ N/A N/A CB1 ↑, FAAH ↓
Found a significant ↓ in the nociceptive response after a single bout of 1 h treadmill running
  Fuss (2015)92 Mice C57BL/6J mice n=16 10 weeks N/R N/R Endurance Wheel running 5 h of wheel running N/R Mice tissues (e.g., heart, lung, skeletal muscle, brain), cerebrospinal fluid, and plasma Collected 5 h after exercise AEA ↑ 2-AG ↑ OEA ↑
PEA ↑
AA ↑
Anxiety-like behavior ↓
Pain (thermal sensitivity) ↓
Absence of CB1R on GABAergic neurons and blockade of central and peripheral CBRs inhibits anxiolytic and analgesic effects, respectively.
  Galdino (2014)93 Rats injected with CB receptor inverse agonists, eCB metabolizing enzyme inhibitors and an AEA reuptake inhibitor Male Wistar rats N/R N/R 0% F N/R Strength RE (i.e., electrical stimulation to the animal's tail causing them to flex their leg muscles) 15 sets of 15 repetitions, with a 120 sec rest between each set. The total exercise period was 7.5 min Load was 70% of one rep max Cardiac puncture Collected immediately after exercise AEA ↑ 2-AG ↑ OEA ↑
PEA ↑
Injection of AM251 and AM630 prevents the antinociceptive effect induced by acute RE
  Galdino (2014)94 Rats injected with CB receptor inverse agonists, eCB metabolizing enzyme inhibitors and an AEA reuptake inhibitor Male Wistar rats N/R N/R 0% F N/R Endurance Treadmill running Animals ran with a progressive speed at 20 m/min (average time of 49.06 min) and 0% inclination until fatigue N/R Cardiac puncture Collected immediately after exercise AEA ↑ 2-AG ↑ OEA ↑
PEA ↑
Injection of AM251 and AM630 prevents the antinociceptive effect induced by acute aerobic exercise
  Raichlen (2012)59,d Dogs and ferrets Mixed-breed dogs and ferrets Dogs: n=8
Ferrets: n=8
N/R N/R N/R Endurance Treadmill running and walking 30 min of walking on day 1 and 30 min of running on day 2 Running (Dogs and Ferrets): Froude numbers of ∼0.70
Walking (Dogs and Ferrets): Froude numbers of ∼0.25
Standard blood draw Collected immediately before and after exercise Dogs: AEA ↑
Ferrets: No AEA changes
Dogs: No 2-AG changes
Ferrets: No 2-AG changes
N/A N/A

Reported sample size is only for the sample that performed the exercise condition.

a

Outcomes, including mood, anxiety, stress, pain, fear, hunger, cravings, etc. were all self-reported unless otherwise stated.

b

Also appears in chronic exercise section.

c

Same sample as in Koltyn (2014).29

d

Same article as human study by Raichlen (2012).31

2-AG, 2-arachidonoylglycerol; 2-OG, 2-oleoylglycerol; A, Asian; AA, arachidonic acid; AAMHR, age-adjusted maximum heart rate; AEA, anandamide; AMP, adenosine monophosphate; B, Black; BDNF, brain-derived neurotrophic factor; BFR-RE, blood flow restriction resistance exercise; CB1R, cannabinoid type 1 receptor; CNSP, chronic neck and shoulder pain; DHEA, docosahexaenoyl ethanolamide; eCB, endocannabinoid; F, female; FAAH, fatty acid amide hydrolase; HC, healthy control; M, mixed; MDD, major depressive disorder; MHR, maximum heart rate; MVC, maximum voluntary contraction; N/A, not applicable; N/R, not reported; O, other; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; PPR, pressure pain ratings; PPT, Pressure pain thresholds; PTSD, post-traumatic stress disorder; RE, resistance exercise; SD, standard deviation; TE, trauma-exposed individuals without PTSD; W, White.