Table 1.
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.
Outcomes, including mood, anxiety, stress, pain, fear, hunger, cravings, etc. were all self-reported unless otherwise stated.
Also appears in chronic exercise section.
Same sample as in Koltyn (2014).29
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.