| Cluny et al., 2011 [88] |
in vitro/ex vivo |
Resting tissue tension (grams tension, S. murinus whole intestine) Carbachol and EFS contractile response (grams tension, S. murinus whole intestine) KCl response (grams tension, S. murinus whole intestine) |
AM251
AM630
TTX |
10 nM–30 μM, organ bath |
Carbachol response reduction (% reduction):
CBD (3 μM) + carbachol (10 μM, 30 μM) on proximal intestine: 14.3 ± 3.3∗, 13.9 ± 3.3∗, respectively CBD (10 μM) + carbachol treated proximal and central intestine: contractions ↓ significantly∗ CBD (10 μM) + carbachol on terminal intestine: ↓ contractions significantly∗
EFS:
KCl response:
CBD + TTX or CB antagonist response:
|
CBD ↓ resting tissue tension in all parts of the intestine CBD ↓ contraction response to carbachol & EFS CBD ↓ contraction response to KCl AM251, AM630, & TTX did not modify effect of CBD |
| Jamontt et al., 2010 [90] |
in vitro/ex vivo |
Spontaneous activity (amplitude & duration, Charles River Wistar rat colon segments) Carbachol response; EFS contractile response (potency and duration; amplitude, Charles River Wistar rat colon segments) |
Carbachol
THC
TNBS |
5–20 mg/kg, i.p |
Spontaneous contractions, amplitude (gram/gram dry tissue weight); duration (seconds):
Control (no TNBS tx): 195 ± 19; 26.9 ± 1.7 Vehicle (TNBS tx): 37 ± 5; 62.8 ± 4.5 CBD 10 mg/kg: 67 ± 11∗; 46.2 ± 6.5∗ CBD 20 mg/kg: 55 ± 10; 38.7 ± 2.8∗ CBD (10 mg/kg) + THC (5 mg/kg): 66 ± 10; 46.3 ± 3.4∗ CBD (10 mg/kg) + THC (10 mg/kg): 89 ± 9∗; 44.5 ± 5.6∗
Carbachol response, potency (LogEC50); max contraction (gram/gram dry tissue weight):
Control: 6.76 ± 0.24; 329 ± 35 Vehicle: 7.06 ± 0.30; 107 ± 11 CBD (10 mg/kg): 6.52 ± 0.39; 230 ± 45∗ CBD (10 mg/kg) + THC (10 mg/kg): data reported in figure∗
EFS:
|
TBNS ↓ amplitude & duration of spontaneous contractions in rat colon strips & carbachol response CBD ↑ amplitude & duration of spontaneous contractions in colon strips from TNBS treated rats CBD + THC ↑ amplitude & duration of SC in colon strips from TNBS treated rats CBD ↑ contractions to carbachol in colon strips from TNBS treated rats CBD did not impact the tissue response to EFS; CBD + THC had a significant effect CBD doses followed a bell-shaped activity curve & CBD + THC demonstrated an additive effect |
| Li, 2013 [76] |
in vitro/ex vivo
& in vivo
|
Evans blue solution (whole gut transit %, Charles River CD1 mice) Time to colonic bead expulsion (% of control, Charles River CD1 mice) EFS contraction response (Charles River CD1 mouse ileum & colon segments) |
In vivo: O-1602, WIN55,212-2
In vitro: O-1602, WIN55,212-2 |
In vivo: 0.5 mg/kg, i.p;
20 μg, i.c.v.
In vitro: 0.001–0.1 μM |
Whole gut transit (% of control), in vivo:
CBD (0.5 mg/kg, IP): Counteracted effect of O-1602∗ CBD (20 μg ICV): Counteracted effect of O-1602∗ and WIN55,212-2∗
Time to bead expulsion (% of control), in vivo:
EFS contraction response, in vitro:
CBD (0.1 μM) (colon): 37.6 ± 5.7%∗ CBD (0.001–0.01 μM) + O-1602 (ileum): CBD blocked the inhibitory effect of O-1602 (data reported in figure)∗ CBD (0.01 μM) + O-1602 (colon): CBD blocked the inhibitory effect of O-1602 (data reported in figure)∗
|
O-1602 and WIN55,212-2 ↓ whole gut transit and colonic bead expulsion CBD alone had no effect on whole gut transit CBD blocked effect of O-1602 on whole gut transit and bead expulsion CBD ↓ EFS contraction response in colon at the highest dose tested CBD blocked the effect of O-1602 in the colon and ileum |
| De Filippis et al., 2008 [75] |
in vitro/ex vivo
& in vivo
|
|
In vivo: AM251, LPS
In vitro: Capsaicin |
In vivo: 10 mg/kg, i.p.
In vitro: 0.01–10 μM |
Geometric center (GC), in vivo:
Control (no LPS): CBD did not have a significant effect on the GC LPS: Significant reduction in GC compared to control∗ LPS + CBD: Significant reduction in GC compared to control∗ and LPS alone∗ LPS + CBD + AM251: Significant reduction in GC compared to control∗
Contraction response, in vitro:
|
GC was calculated as Σ (%beads per segment x segment number)/100 LPS ↓ geometric center (GC) CBD had no effect on GC of control mice CBD further reduced the GC of LPS treated mice CBD failed to induce contractions in mouse jejunal segments LPS significantly increased FAAH expression CBD significantly reduced FAAH expression in LPS treated mice |
| Chester et al., 1973 [69] |
in vivo |
|
N/A |
6–30 mg/kg, oral gavage |
|
|
| Anderson et al., 1974 [71] |
in vivo |
|
THC
Cannabinol |
0–50 mg/kg, oral gavage |
Passage rate (distance traveled % of control):
Control: 100 ± 2.9 CBD 10 mg/kg: 82.8 ± 2.4∗ significantly less than control CBD + THC (10 mg/kg each): 48.5 ± 2.4∗ significantly less than CBD + cannabinol (10 mg/kg each) and THC + cannabinol (10 mg/kg each), significantly more than THC + CBD (10 mg/kg and 40 mg/kg respectively)
|
CBD ↓ the % transit of a charcoal meal CBD followed a bell-shaped activity curve Additional cannabinoid interactions were identified such as those between THC, cannabinol, and cannabidiol on % transit. |
| Sabo et al., 2013 [72] |
in vivo |
|
N/A |
Unknown, oral in water |
Charcoal meal distance from cecum (cm):
|
|
| Pagano et al., 2016 [73] |
in vivo |
|
Croton oil (CO) |
5–60 mg/kg, oral gavage
1–10 mg/kg, i.p. |
Passage rate (transit %) CBD Botanical Drug Substance (CBD BDS):
CBD BDS (10∗ mg/kg, IP): significant reduction in transit % of healthy mice CO: Increased transit %∗ CBD BDS (1∗, 2.5∗∗∗, 5∗∗∗, 10∗∗∗ mg/kg, IP) + CO: significant reduction in transit % compared to CO alone CBD BDS (5∗∗ & 10∗∗∗ mg/kg, IP) + CO: significant reduction compared to control (no CO) CBD BDS (10∗∗∗, 30∗, 60∗∗ mg/kg, oral): significant reduction in transit % of healthy mice CBD BDS (5∗∗, 10∗∗∗, 30∗∗∗, 60∗∗∗ mg/kg, oral) + CO: significant reduction in transit % compared to CO alone CBD BDS (10∗∗, 30∗∗, 60∗∗∗ mg/kg, oral) + CO: significant reduction in transit % compared to control (no CO)
Passage rate (transit %) CBD:
CBD (5∗∗ & 10∗ mg/kg, IP) + CO: significant reduction in transit % (data reported in figure) CBD (5∗∗ mg/kg, oral) + CO: significant reduction in transit % (data reported in figure)
|
% Transit was calculated by the distance the charcoal traveled in the small intestine The CBD BDS was 63.9% CBD Croton oil (CO) ↑ transit % CBD BDS (i.p. and oral) ↓ transit % in both control mice and CO treated mice CBD (i.p. and oral) ↓ % transit in CO treated mice but not of healthy controls |
| Shook and Burks, 1989 [70] |
in vivo |
|
N/A |
Dose not reported, i.v. |
% inhibition of small intestine (SI) transit
|
|
| Lin et al., 2011 [77] |
in vitro/ex vivo
& in vivo
|
Charcoal meal passage (C57/BL mice, % transit of SI) SI myoelectrical activity (frequency and amplitude, Sprague-Dawley rat jejunum) Spontaneous contraction response (% control, Sprague-Dawley rat ileum and colon) Membrane potential (mouse jejunum) |
LPS |
In vivo: 1 mg/kg, i.p.
In vitro: 0.001–0.1 μM |
SI myoelectrical spiking activity (SA) (% of control frequency & amplitude), in vivo:
Passage rate (SI transit % of control), in vivo:
Spontaneous Contraction response (% of control), in vitro:
LPS (ileum): 59.6 ± 7.4∗∗ Significantly decreased compared to control LPS (colon): 151.1 ± 27.6∗ Significantly increased compared to control LPS + CBD (0.001 μM∗, 0.01 μM∗∗, 0.1 μM∗∗ mol/L): Significantly increased % contraction compared to LPS group in both the ileum and colon tissue
Membrane potential (MP), in vitro:
|
LPS ↓ frequency and amplitude of SA CBD pretreatment ↑ frequency and amplitude of SA in LPS treated rats LPS ↓ charcoal meal transit % CBD pretreatment ↑ meal transit % in LPS treated mice CBD normalized spontaneous contraction response in mouse ileum and colon segments CBD did not affect membrane potential |
| Capasso et al., 2008 [74] |
In vitro
& in vivo
|
Rhodamine-B-labeled dextran (geometric center of SI, ICR mice) Contractile response (ICR mouse terminal ileum) |
In vivo: Croton oil, SR144528, naloxone, yohimbine, AA-5-HT, loperamide
In vitro: ACh |
In vivo:
1–10 mg/kg, i.p.
In vitro:
0.01–100 μM |
Geometric center (GC) score of 1-10, in vivo:
Control (no croton oil): 4.91 ± 0.43 Croton oil (CO): 6.65 ± 0.41 (P < 0.05 vs control) CO + CBD (5 mg/kg): 5.01 ± 0.36∗ CO + CBD (5 mg/kg) + CB2 antagonist: 4.99 ± 0.38∗ CO + CBD (5 mg/kg) + naloxone: 4.98 ± 0.44∗ CO + CBD (5 mg/kg) + yohimbine: 4.97 ± 0.43∗ CO + CBD (5 mg/kg) + AA-5-HT: significantly decreased GC (values not shown) CO + CBD (10 mg/kg): significantly decreased the GC
Contractile response (% inhibition), in vitro:
|
GC was calculated as Σ (fraction of fluorescence per segment x segment number) Croton oil ↑ the geometric center CBD ↓ the GC of croton oil treated mice A CB2 antagonist, opioid receptor antagonist, and ⍺2-adrenoceptor antagonist did not modify the effect of CBD CBD did not have an additive effect when administered with a FAAH inhibitor CBD reduced ACh induced contractions in control and croton oil treated mouse ileum segments, however, the control and croton oil tissue % inhibition did not significantly differ from one another. CBD effected only croton oil treated mice in vivo but both control and treated mice in vitro |
| Wei et al., 2020 [78] |
in vitro/ex vivo
& in vivo
|
Charcoal passage (% of control, Sprague-Dawley rat) Disease activity index score (C57/BL mice) Contraction response to EFS (% if control, Sprague-Dawley rat colon) Membrane potential (colon, Sprague-Dawley rat colon) |
TNBS |
In vivo: 1 mg/kg, i.p.
In vitro: 0.1 μM |
Charcoal passage (% of control), in vivo:
Disease activity index (DAI) score, in vivo:
EFS contraction response (% of control), in vitro:
TNBS significantly increased contraction∗∗ CBD alone increased contraction∗ CBD decreased contraction compared to TNBS∗∗
Membrane potential, in vitro:
|
TNBS ↓ charcoal meal passage % CBD had no effect on control mice charcoal meal passage % CBD ↑ the charcoal meal passage % in TNBS treated mice DAI score included weight loss, diarrhea, & bleeding. TNBS ↑ the DAI CBD ↓ the DAI of TNBS treated rats TNBS ↑ contraction response in vitro CBD blocked the effect of TNBS on EFS induced contractions CBD exerted an effect on EFS contractions of control tissue |
| Schicho et al., 2012 [81] |
in vivo |
Macroscopic assessment (change in score, CD1 mice, in vivo) |
TNBS |
10 mg/kg, i.p.
20 mg/kg, i.g. (intragastric) & i.r. (intrarectal) |
Macroscopic scoring:
TBNS + CBD, i.p.: significant reduction∗ TNBS + CBD, i.g.: not significant TNBS + CBD, i.r.: significant reduction∗
|
|
| Becker et al., 2021 [82] |
in vivo |
Murine endoscopic index of colitis severity (change in score, C57BL/6 mice) Stool score (change in score, C57BL/6 mice) |
DSS
TNBS |
10 mg/kg, oral gavage |
Murine endoscopic index of colitis severity (MEICS):
Stool Score:
DSS: increased stool score DSS + CBD: no significant change DSS + CBD + THC (10 mg/kg): significant reduction∗∗∗∗
|
Stool consistency was one for the four variables of the MEICS TNBS ↑ MEICS score CBD did not attenuate TNBS or DSS induced colitis scores CBD + THC ↓ MEICS and Stool Score THC was as effective alone as in combination with CBD |
| Yekhtin et al., 2022 [79] |
in vivo |
|
DSS
THC
THC-extract |
CBD, 5 mg/kg, i.p. every other day for 10 days
CBD-extract (36% CBD, 1.3% THC), 5 mg/kg, i.p. every other day for 10 days |
Difference between DSS group and all cannabinoid treatment groups∗∗∗ Difference between purified CBD and extract∗∗∗ Difference between purified CBD and purified THC∗ |
Clinical score was calculated from: stool score, rectal score, and general clinical parameters Significant reduction in clinical score with both purified CBD and CBD-extract CBD-extract decreased the clinical score more significantly than the purified CBD Purified THC decreased the score more significantly than purified CBD |
| Silvestri et al., 2020 [83] |
in vivo |
|
DSS
Fish oil (FO) |
0.3–10 mg/kg, oral gavage |
Disease Activity Index (DAI):
|
The DAI score was assessed by stool consistency and blood in stool CBD alone did not affect the DAI CBD + fish oil ↓ DAI CBD activity followed a bell-shaped curve |
| Fride et al., 2005 [80] |
in vivo |
|
NA |
20 mg/kg, i.p. |
|
|
| Naftali et al., 2017 [85] |
Human parallel group RCT |
|
N/A |
20 mg/day for 8 weeks, sublingual (olive oil) |
Crohn’s disease activity index (CDAI) Score:
|
CDAI score had 2 of 8 variables relating to defecation patterns Reduction in CDAI score was not significant Side effects/adverse effects did not differ between CBD and placebo group |
| Irving et al., 2018 [84] |
Human parallel group RCT |
|
N/A |
Up to 500 mg/day for 10 weeks (2 weeks escalation, 8 weeks maintenance), oral (gelatin capsule) |
Total Mayo score:
Partial Mayo Score:
|
Total mayo score includes stool frequency, rectal bleeding, endoscopy assessment, physician rating of disease activity; partial mayo score does not include endoscopy assessment The mean daily dose the CBD botanical extract was approximately 300 mg/day The CBD botanical extract group took fewer capsules and had more protocol compliance deviations than the placebo group The CBD botanical extract group had a ↑ % of AEs compared to the placebo group, the majority were mild to moderate CBD botanical extract ↓ partial mayo score significantly CBD botanical extract ↑ IBD quality of life assessment but was not statistically significant |
| Naftali et al., 2021 [86] |
Human parallel group RCT |
|
N/A |
80 mg/day for 8 weeks, sublingual (cannabis oil) |
Bowel movements per day:
|
The CBD extract contained 16% CBD and 4% THC CBD did not significantly alter bowel movements per day compared to the placebo group No significant adverse effects were found in the CBD group compared to the placebo group |
| Van Orten-Luiten et al., 2021 [87] |
Human crossover RCT |
|
N/A |
Up to 300 mg/day for 3 weeks, oral (chewing gum) |
QOL survey score:
|
Two 2 weeks intervention periods Chewing gum was associated with adverse effects CBD was not associated with any significant changes to Quality-of-Life score or defecation patterns |
