Table 1.
Summary of Evidence: Preclinical Studies of Cannabinoid Drug Effect on Body Weight.
| Study Reference | Animal Model (Species) | Cannabinoid Administered | Cannabinoid Type | Drug Administration | Population Size | Duration | Effect on Body Weight, Compared to Vehicle (If Applicable) | Other Notes |
|---|---|---|---|---|---|---|---|---|
| Rusznák et al., 2018 [33] | Chronic mild stress (male NMRI mice) | Cannabis | Cannabis | Whole body smoke, 30 min, twice per day | n = 36 | 8 weeks | Increase | |
| Colombo et al., 1998 [25] | Lean (male Wistar rats) | Rimonabant | Inverse Agonist | IP injection, once daily (2.5, 10 mg/kg) | n = 19 | 2 weeks | Decrease | |
| Kunz et al., 2008 [34] | Lean (male Sprague–Dawley rats) and CB1R deficient mice) | Rimonabant | Inverse Agonist | Oral micro-suspension, once daily (2 mL/kg, 4 mL/kg) | n = 20 | 2 weeks | Decrease | |
| Richey et al., 2009 [35] | Lean (mongrel dogs) | Rimonabant | Inverse Agonist | Oral, once daily (1.25 mg/kg) | n = 20 | 16 weeks | Decrease | |
| Herling et al., 2008 [36] | DIO (female Wistar rats) | Rimonabant | Inverse Agonist | Oral, once daily (10 mg/kg) | n = 16 | 6 weeks | Decrease | |
| Gobshtis et al., 2007 [37] | Antidepressant-treated (female Sabra mice) | Rimonabant | Inverse Agonist | IP injection, 5 weekly (2, 5 mg/kg) | n = 16 | Acute and up to 22 weeks | Decrease | |
| Dore et al., 2014 [38] | High-sucrose diet (male Wistar rats) | Rimonabant | Inverse Agonist | IP injection, once daily (0.3, 1, 3 mg/kg) | n = 44 | 24 days | Decrease | |
| Bajzer et al., 2011 [39] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | IP injection, once daily (10 mg/kg) | n = 33 | 7 weeks | Decrease | |
| Boon et al., 2014 [40] | DIO (E3L.CETP male mice) | Rimonabant | Inverse Agonist | IP injection, once daily (10 mg/kg) | n = 18 | 4 weeks | Decrease | |
| AM6545 | Neutral Antagonist | IP injection, once daily (10 mg/kg) | Decrease | |||||
| Karlsson et al., 2015 [41] | DIO and diet-resistant (male Sprague–Dawley rats) | Rimonabant | Inverse Agonist | Gavage, once daily (5 mL/kg) | n = 30 | 2 weeks | Decrease | |
| Lazzari et al., 2017 [42] | Antipsychotic-treated (female Wistar rats) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | n = 40 | 5 weeks | Decrease | |
| NESS06SM | Neutral Antagonist | Gavage, once daily (10 mg/kg) | Decrease | |||||
| Muller et al., 2020 [43] | Cultured adipocytes (male Wistar rats) | Rimonabant | Inverse Agonist | Bolus, single administration (30 mg/kg) | unknown | Acute | Not assessed | |
| Chang et al., 2018 [44] | Severely uncontrolled diabetes (LETO rats) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | n = 20 | 6 weeks | No change | |
| Mehrpouya-Bahrami, 2017 [45] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | n ~ 50 | 4 weeks | Decrease | |
| Zhang et al., 2012 [46] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | n = 23 | 30 days | Decrease | |
| Wei et al., 2018 [47] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | n = 70 | 3 weeks | Decrease | |
| Mehrpouya-Bahrami, 2018 [48] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | unknown | 4 weeks | Decrease | |
| Chen and Hu, 2017 [49] | DIO (male C57BL/6 J mice) | Rimonabant | Inverse Agonist | Gavage, once daily (30 mg/kg) | n = 39 | 5 weeks | Decrease | |
| Fong et al., 2007 [50] | Wild-type and CB1 knockout (male C57BL/6 J mice), and DIO (male Sprague–Dawley rats) | Taranabant | Inverse Agonist | Gavage, once daily (0.3, 1, 3 mg/kg) | n = 36 mice; n = 23 rats | 2 weeks | Decrease | |
| Martín-García et al., 2010 [51] | DIO and lean (female Wistar rats) | Taranabant | Inverse Agonist | Sublingual, once daily (3 mg/kg) | n = 48 | 13 weeks | Decrease | Rimonabant and taranabant were more effective in obese mice |
| Rimonabant | Inverse Agonist | Sublingual, once daily (10 mg/kg) | Decrease | |||||
| Hildebrandt et al., 2003 [52] | DIO (male C57BL/6 J mice) | AM 251 | Inverse Agonist | Gavage, once daily (3, 30 mg/kg) | n = 30 | 6 weeks | Decrease | |
| Chambers et al., 2004 [53] | DIO (Lewis rats) | AM 251 | Inverse Agonist | IP injection, once daily (1.25, 2.5, 5 mg/kg) | n = 8 | 10 days | Decrease | |
| Riedel et al., 2009 [54] | Wild-type (male C57BL/6 J mice) | AM 251 | Inverse Agonist | IP injection, once daily (10 mg/kg) | n = 16 | 4 days | Decrease | |
| THCV | Neutral Antagonist | IP injection, once daily (3, 10, 30 mg/kg) | n = 28 | 2 days | Decrease | |||
| Judge et al., 2009 [55] | Wild-type and DIO (male Fisher 344X Brown Norway rats) | AM 251 | Inverse Agonist | IP injection, once daily (0.83, 2.78 mg/kg) | n = 61 | 6 days | Decrease | |
| Merroun et al., 2013 [56] | Lean and DIO (male Zucker rats) | AM 251 | Inverse Agonist | IP injection, once daily (3 mg/kg) | n = 32 | 3 weeks | Decrease | |
| Wierucka-Rybak et al., 2014 [57] | DIO (male Wistar rats) | AM 251 | Inverse Agonist | IP injection, once daily (1 mg/kg) | n = 34 | 6 days | Decrease | AM 251 and Leptin coadministration augmented weight loss |
| Wierucka-Rybak et al., 2016 [58] | DIO (male Wistar rats) | AM 251 | Inverse Agonist | IP injection, once daily (1 mg/kg) | n = 40 | 6 days | Decrease | Serotonin receptor antagonism abolished anorectic effects |
| Bowles et al., 2014 [59] | Wild-type and CB1R knockout (C57BL/6 J mice) | AM 251 | Inverse Agonist | IP injection, once daily (2 mg/kg) | n ~ 20 | 4 weeks | Decrease | |
| AM6545 | Neutral Antagonist | IP injection, once daily (10 mg/kg) | Decrease | |||||
| Merroun et al., 2015 [60] | Wild-type (male Wistar rats) | AM 251 | Inverse Agonist | Sub-chronic IP injection, once daily (1, 2, 5 mg/kg) | n = 40 | 8 days | Decrease | |
| Jenkin et al., 2015 [61] | DIO (male Sprague–Dawley rats) | AM 251 | Inverse Agonist | IP injection, once daily (3 mg/kg) | n = 18 | 6 weeks | Decrease | |
| Miranda et al., 2019 [62] | DIO (C57BL/6 J mice) | AM 251 | Inverse Agonist | Gavage, once daily (10 mg/kg) | n = 20 | 4 weeks | Decrease | |
| Takano et al., 2014 [63] | Wild-type (cynomolgus monkeys) | TM38837 | Inverse Agonist | Intravenous (0.3–4 mg/kg) | n = 3 | Acute | Not assessed | |
| Micale et al., 2019 [64] | Wild-type (male C57BL/6 J mice) | TM38837 | Inverse Agonist | Oral, once daily (10, 30, 100 mg/kg) | n = 45 | 10 days | Not assessed | Study of fear-promoting effects in mice |
| Han et al., 2019 [65] | DIO and leptin-receptor deficient (male and female C57BL/6 J mice) | AJ5012 | Inverse Agonist | IP injection, once daily (20 mg/kg) | n = 20 | 4 weeks | Decrease | |
| AJ5018 | Inverse Agonist | Not assessed | Not assessed | |||||
| Han et al., 2018 [66] | DIO (C57BL/6 J mice) | AJ5018 | Inverse Agonist | IP injection, once daily (10 mg/kg) | n ~ 16 | 4 weeks | Decrease | |
| Tam et al., 2012 [67] | DIO (male C57BL/6 J mice) | JD5037 | Inverse Agonist | Gavage, once daily (3 mg/kg) | n = 28 | 4 weeks | Decrease | |
| Udi et al., 2020 [68] | DIO (male C57BL/6 J mice) | JD5037 | Inverse Agonist | Oral, once daily (3 mg/kg) | n = 58 | 4 weeks | Decrease | |
| MRI-1867 | Inverse Agonist | Oral, once daily (3 mg/kg) | Decrease | |||||
| Kale et al., 2019 [69] | Wild-type (Sprague–Dawley rats and Beagle dogs) | JD5037 | Inverse Agonist | Rats: Gavage, once daily (10, 40, 150 mg/kg); dogs: Gavage, once daily (5, 20, 75 mg/kg) | Rats: n = 140; dogs: n = 44 | 34 days | Decrease in rats; no change in dogs | |
| Hsiao et al., 2015 [70] | DIO (male C57BL/6 J mice) | BPR0912 | Inverse Agonist | Gavage, once daily (3, 10 mg/kg) | n = 24 | 19 days | Decrease | |
| Chen et al., 2017 [71] | DIO (male C57BL/6 J mice) | TXX-522 | Inverse Agonist | Gavage, once daily (5, 10 mg/kg) | n = 32 | 4 weeks | Decrease | |
| Méndez-Díaz et al., 2015 [72] | Wild-type (male Wistar rats) | ENP11 | Inverse Agonist | IP injection, once daily (0.5, 1, 3 mg/kg) | n = 40 | Acute | Not assessed | |
| Zhang et al., 2018 [73] | DIO (mice) | Compound 6a | Inverse Agonist | Oral, once daily (30 mg/kg) | unknown | 5 days | Decrease | |
| Aceto et al., 2001 [74] | Wild-type (male Sprague–Dawley rats) | WIN 55,212-2 | Agonist | IP injection, once daily (1, 2, 4, 8, 16, mg/kg) | n = 82 | 4 days | Decrease | |
| Abalo et al., 2009 [75] | Wild-type (male Wistar rats) | WIN 55,212-2 | Agonist | IP injection, once daily (0.5, 5 mg/kg) | n = 56 | 14 days | Decrease | |
| Abalo et al., 2013 [76] | Wild-type (male Wistar rats) | WIN 55,212-2 | Agonist | IP injection, once weekly (0.5, 1 mg/kg) | n = 54 | 4 weeks | Decrease | Intensified weight loss from cisplatin |
| Radziszewska et al., 2014 [77] | Wild-type (male Wistar rats) | WIN 55,212-2 | Agonist | IP injection, once daily (1 mg/kg) | n ~ 32 | 3 days | Decrease | |
| AM 251 | Inverse Agonist | IP injection, once daily (1 mg/kg) | Decrease | |||||
| Radziszewska et al., 2013 [78] | Wild-type (male Wistar rats) | WIN 55,212-2 | Agonist | IP injection, once daily (0.5, 1, 2, 4 mg/kg) | unknown | Acute | Decrease | |
| Segev et al., 2014 [79] | Chronic mild stress (male Sprague–Dawley rats) | WIN 55,212-2 | Agonist | IP injection, once daily (0.5 mg/kg) | unknown | 3 days | No change | WIN 55,212-2 and AM 251 were coadministered |
| AM 251 | Inverse Agonist | IP injection, once daily (0.3 mg/kg) | ||||||
| Jahanabadi et al., 2016 [80] | Diabetes (male Wistar albino rats) | WIN 55,212-2 | Agonist | Intrathecal injection (1, 10, 100 µg/10 µL) | n ~ 28 | Acute | No change | |
| Argueta et al., 2019 [81] | Wild-type (C57BL/6 J mice) | WIN 55,212-2 | Agonist | IP injection, once daily (3 mg/kg) | n ~ 20 | 60 days | Not assessed | Study of satiation peptide response |
| AM6545 | Neutral Antagonist | IP injection, once daily (10 mg/kg) | ||||||
| de Sousa Cavalcante et al., 2020 [82] | Cachexia (male Wistar rats) | WIN 55,212-2 | Agonist | Subcutaneous injection, once daily (2 mg/kg) | n ~ 64 | 1 week | Decrease | No change in body weight in cachexia induced rats |
| Dalton et al., 2009 [83] | Wild-type (male Wistar rats) | HU-210 | Agonist | IP injection, once daily (25, 50, 100 µg/kg) | n = 40 | 2 weeks | Decrease | |
| Giuliani et al., 2000 [84] | Wild-type (male Wistar rats) | HU-210 | Agonist | IP injection, once daily (25, 50, 100 µg/kg) | n = 32 | 4 days | Decrease | |
| del Arco et al., 2000 [85] | Pregnancy (female Wistar rats) | HU-210 | Agonist | IP injection, once daily (1, 5, 25 µg/kg) | unknown | >70 days | Decrease | |
| Scherma et al., 2017 [86] | Activity-based anorexia (female Sprague–Dawley rats) | CP-55,940 | Agonist | IP injection, once daily (0.03, 0.06 mg/kg) | n = 168 | 6 days | Increase | Both caused decrease in body weight loss compared to vehicle |
| THC | Partial Agonist | IP injection, once daily (0.5, 0.75 mg/kg) | Increase | |||||
| Takeda et al., 2015 [87] | Wild-type and Apo-E deficient (male BALB/c mice) | CBDD | Agonist | Oral, once daily (0.025, 0.25 mg/kg) | n = 12 | ~24 weeks | Increase | |
| Järbe et al., 2005 [24] | Wild-type (male Sprague–Dawley rats) | THC | Partial Agonist | IP injection, once daily (0.1-1.8 mg/kg) | n = 32 | 6 days | Decrease | THC and rimonabant administered separately and together |
| Rimonabant | Inverse Agonist | IP injection, once daily (0.03-0.3 mg/kg) | ||||||
| Lewis et al., 2010 [88] | Activity-based anorexia (male C57BL/6 J mice) | THC | Partial Agonist | IP injection, once daily (0.5 mg/kg) | n = 32 | 8 days | Increase | |
| Verty et al., 2011 [89] | Activity-based anorexia (female Sprague–Dawley rats) | THC | Partial Agonist | IP injection, once daily (0.1, 0.5, 2 mg/kg) | n = 28 | 6 days | Increase | |
| Wong et al., 2012 [90] | Wild-type (Australian Albino Wistar rats) | THC | Partial Agonist | IP injection, once daily (10 mg/kg) | n = 10 | 10 days | Decrease | |
| Coskun and Bolkent, 2014 [91] | Diabetes (rats) | THC | Partial Agonist | IP injection, once daily (3 mg/kg) | n = 29 | 7 days | Increase | |
| Keeley et al., 2015 [92] | Puberty (male and female Long–Evans and Wistar rats) | THC | Partial Agonist | IP injection, once daily (5 mg/kg) | n = 335 | 2 weeks | Decrease | |
| Cluny et al., 2015 [93] | DIO and lean (male C57BL/6N mice) | THC | Partial Agonist | IP injection, once daily (2 mg/kg for 3 weeks, 4 mg/kg for 1 week) | n = 32 | 4 weeks | Decrease in DIO mice | No effect on body weight in lean mice |
| Marcus et al., 2016 [94] | Hyper-sensitive CB1 (male S426A/S430A mice) | THC | Partial Agonist | IP injection (1, 3, 10 mg/kg) | unknown | Acute | No change | |
| Beydogan et al., 2019 [95] | High-fructose diet (male Sprague–Dawley rats) | THC | Partial Agonist | IP injection, once daily (1.5 mg/kg) | n = 32 | 12 weeks (THC administration for final 4 weeks) | Decrease | |
| Nguyen et al., 2020 [96] | Adolescence (female and male Wistar rats) | THC | Partial Agonist | Vapour inhalation (30 mins, twice daily, 5 days/week) | n = 88 | 2 weeks | Decrease in males | |
| Ogden et al., 2019 [97] | Wild-type (female Long–Evans rats) | AM11101 | Partial Agonist | IP injection, (0.1 mg/kg) | n = 21 | 1 week | No change | |
| THC | Partial Agonist | IP injection, (1 mg/kg) | No change | |||||
| Pavon et al., 2006 [98] | DIO (Zucker rats) and Wild-type (male Wistar rats) | LH-21 | Neutral Antagonist | IP injection, once daily (0.03, 0.3, 3 mg/kg) | unknown | 8 days | Decrease in DIO rats | |
| Alonso et al., 2012 [99] | DIO (male Wistar rats) | LH-21 | Neutral Antagonist | IP injection, once daily (3 mg/kg) | n = 32 | 10 days | Decrease | |
| Chen et al., 2008 [100] | Wild-type (C57BL/6 J mice) | LH-21 | Neutral Antagonist | IP injection (10, 30, 60 mg/kg) | n = 45 | Acute | Decrease | |
| Romero-Zerbo et al., 2017 [101] | DIO, pre-diabetes (C57BL/6 J mice) | LH-21 | Neutral Antagonist | IP injection (3 mg/kg) | n ~ 30 | 2 weeks | No change | |
| Dong et al., 2018 [102] | DIO, hypertension (female C57BL/6 J mice) | LH-21 | Neutral Antagonist | IP injection (1, 3 mg/kg) | n = 8 | 3 weeks | Decrease | |
| Cluny et al., 2010 [103] | Wild-type (male Sprague–Dawley rats) | AM6545 | Neutral Antagonist | IP injection (10 mg/kg) | n = 8 | 1 week | Decrease | |
| Tam et al., 2010 [104] | DIO (male C57BL/6 J mice) | AM6545 | Neutral Antagonist | IP injection (10 mg/kg) | n = 40 | 4 weeks | Decrease | |
| Rimonabant | Inverse Agonist | IP injection (10 mg/kg) | Decrease | |||||
| Ma et al., 2018 [105] | DIO (ICR mice) | AM6545 | Neutral Antagonist | IP injection (3, 10 mg/kg) | n = 32 | 3 weeks | Decrease | |
| Chambers et al., 2007 [106] | Wild-type (male Sprague–Dawley rats) | AM4113 | Neutral Antagonist | IP injection (1, 5, 10, 20 mg/kg) | n = 39 | 5 days | Decrease | |
| AM 251 | Inverse Agonist | IP injection (5 mg/kg) | Decrease | |||||
| Sink et al., 2008 [107] | Wild-type (male Sprague–Dawley rats) | AM4113 | Neutral Antagonist | IP injection (2, 4, 8 mg/kg) | n = 30 | Acute | Not assessed | |
| Cluny et al., 2011 [108] | Wild-type (male Sprague–Dawley rats) | AM4113 | Neutral Antagonist | IP injection (2, 10 mg/kg) | n = 17 | 2 weeks | Decrease | |
| Gueye et al., 2016 [109] | Nicotine Dependence (male Long–Evans and Wistar rats) | AM4113 | Neutral Antagonist | IP injection (1, 3, 10 mg/kg) | n = 149 | 3 weeks | Decrease | |
| Rimonabant | Inverse Agonist | IP injection (1, 3, 10 mg/kg) | Decrease | |||||
| Balla et al., 2018 [110] | Alcoholism (male C57BL/6 J mice) | AM4113 | Neutral Antagonist | IP injection (1, 3 mg/kg) | n = 31 | 4 days | No change | |
| Wargent et al., 2013 [111] | DIO (female C5BL/6 J mice) | THCV | Neutral Antagonist | Gavage, once or twice daily (0.1–12.5 mg/kg) | n = 63 | 45 days | No change | |
| AM 251 | Inverse Agonist | Gavage, twice daily (10 mg/kg) | 45 days | Decrease | ||||
| Mastinu et al., 2013 [112] | DIO (male C57BL/6 N mice) | NESS06SM | Neutral Antagonist | Gavage, once daily (10, 30 mg/kg) | n = 60 | 30 days | Decrease | |
| Rimonabant | Inverse Agonist | Gavage, once daily (10 mg/kg) | Decrease | |||||
| Fois et al., 2016 [113] | Wild-type (male Sprague–Dawley rats) | SM-11 | Neutral Antagonist | IP injection (0.05, 0.125, 0.25 mg/kg) | n = 32 | 10 days | Decrease | |
| Seltzman et al., 2017 [114] | DIO (male C57BL/6 J mice) | PIMSR | Neutral Antagonist | IP injection (10 mg/kg) | n = 12 | 4 weeks | Decrease |