Table 1.
Use of Cannabinoids in Obesity
| References in chronological order | Substance | Dose route of administration | Object of study | Results |
|---|---|---|---|---|
| Van Gaal et al., 2005132 | Rimonabant | 5 and 20 mg daily for 12 months | Obese humans with comorbidities | There was weight loss, reduced waist circumference, increased HDL cholesterol, and the insulin resistance marker (mainly on 20 mg). But the adverse effects were also greater. |
| Després et al., 2005133 | Rimonabant | 5 and 20 mg daily for 12 months | Obese humans with comorbidities | There was weight loss, reduced waist circumference, increased HDL cholesterol, reduction in triglycerides, and increase in plasma adiponectin levels (mainly on 20 mg). |
| Järbe and DiPatrizio, 2005155 | THC e Rimonabant | Study 1: 0.1, 0.3, 0.56, 1.8 mg/kg THC I.P., twice weekly. 0.03, 0.3 mg/kg Rimonabant. I.P. Study 2: 0.56, 1.0, 1.8 mg/kg of THC I.P. |
Male Sprague-Dawley rats | There was a dose-related increase in high-fat diet intake, peaking at 0.56–1 mg/kg D9-THC. SR-141716 alone suppressed the high-fat diet intake below control levels. A combination of 0.3 mg/kg SR 141716 and 0.56 mg/kg D9-THC counteracted the effects on consumption of either drug alone. In study 2, attenuation of the hyperphagia (high-fat diet) was evident after the second injection Increasing doses of D9-THC (1 and 1.8 mg/kg, for two and three consecutive days, respectively) did not reinstate the initial hyperphagia. |
| Weiss et al., 2006122 | CBD | 5 mg/kg per day. 10 to 20 injections (five times a week). | Female nonobese diabetic NOD/LtJ mice | Reduction in diabetes incidence from 86% to 30%. Reduction of plasma levels of proinflammatory cytokines (INF-g and TNF-a) and production of T cells associated with the TH1 profile. Increase in cytokines associated with the th2 profile and reduced insulitis. |
| Durst et al., 2007124 | CBD | 5 mg/kg per day, I.P. | Male Sprague-Dawley rats | In vivo studies showed preservation of shortening fraction in CBD-treated animals. Infarct size was reduced by 66% in CBD-treated animals. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels. |
| Nissen et al., 2008136 | Rimonabant | 20 mg daily for 3, 6, 12, and 18 months | Obese humans with comorbidities | In the rimonabant vs. placebo groups, increase in percent atheroma volume and decrease in total atheroma volume. There was weight loss, reduced waist circumference, increased HDL cholesterol, and reduction in triglycerides. Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein. Psychiatric adverse effects were more common in the rimonabant group. |
| Weiss et al., 2008123 | CBD | Dose of 5 mg/kg per day, in 0.1 mL, I.P. | Nonobese female NOD/LtJ mice and BALB/c female mice | It softened the manifestation of diabetes mellitus from 86 to 100% in untreated groups with CBD to 32% in treated groups. In addition, it reduced IL-12 (proinflammatory) and increased IL-10 (anti-inflammatory). Pancreatic islets were much more intact in animals treated with CBD. |
| Riedel et al., 2009101 | AM251 and THCV | 10 mg/kg AM251; 0.48, 0.96, 1, 1.44, 3, 10, 30 mg/kg THCV; 10 mg/kg CBD, I.P. | Male C57 BL6 mice | AM251 suppressed food intake and weight gain in fasted and nonfasted animals. Pure THCV also induced hypophagia and weight reduction at doses as low as 3 mg/kg. However, a THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual THC. This THC effect was overcome by the co-administration of CBD. |
| Gallant et al., 2009168 | THC and a lipophilic cannabis extract | Cannabis extract containing THC levels ranging from 2.5–10 mg/mL | In vitro | Insulin-induced glucose uptake increased, whereas the rate of adipogenesis decreased with increasing THC concentration. Insulin resistance was induced using TNF-a, exposed to the extract and insulin-induced glucose uptake measured. Insulin-induced glucose was increased in these cell safer exposures to the extract. There was a significant increase in IRS-1, IRS-2, and GLUT-4 genes expression for THC. |
| Klein et al., 2011172 | CBD and THC | 1, 3, and 10 mg/kg THC I.P.; 1, 3, and 10 mg/kg CBD I.P. for 21 days | Male Australian Albino Wistar rats | CBD potentiated an inhibition of body weight gain caused by chronic THC. |
| Ignatowska-Jankowska et al., 2011147 | CBD and AM630 | Study 1: 2.5 and 5 mg/kg per day CBD I.P. for 14 consecutive days. Study 2: CBD+vehicle (5 mg/kg) and vehicle+vehicle, vehicle+AM630, CBD+AM630 (1 mg/kg) |
Male Wistar rats | Both doses of CBD produced significant decrease in body weight gain, with the effect produced by 5 mg/kg being more pronounced. The CB2 receptor selective antagonist, AM630, blocked the decrease in body weight gain. AM630 alone did not affect body weight gain. The results suggest that CBD has the ability to alter body weight gain, possibly through the CB2 receptor. |
| Meye et al., 2013140 | DNQX; Bicuculline; Tetrodotoxin, WIN55,212–2; URB597; URB602; O-2050; AM251; NESS0327; Rimonabant | 1 mL/kg−1 I.P. | Electrophysiological exp.: C57Bl/6 mice. Behavioral exp.: Wistar rats | NESS0327 does not suppress CB1R constitutive activity, unlike Rimonabant. Therefore, it promotes the reduction of body weight and food intake with safer effects than Rimonabant. |
| Wargent et al., 2013143 | THCV | Study 1: 0.3, 1, 2.5, 5 and 12.5 mg/kg, orally twice a day for 30 days. Study 2: 0.1, 0.5, 2.5 and 12.5 mg/kg, orally once a day for 45 days. Study 3: 0.3 and 3 mg/kg, orally once daily. Study 4: 0.1, 0.5, 2.5 and 12.5 mg/kg, oral once daily in ob/ob for 30 days. |
For studies 1 and 2, female C57Bl/6 mice DIO. For studies 3 and 4, C57Bl/6 female ob/ob mice. |
THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. It dose dependently reduced glucose intolerance in ob/ob mice and improved glucose tolerance and increased insulin sensitivity in DIO mice, without consistently affecting plasma lipids. THCV also restored insulin signalling in insulin-resistant hepatocytes and myotubes. |
| Cluny et al., 2015163 | THC | 2 mg/kg for 3 weeks and 4 mg/kg for 1 additional week | Adult male DIO and lean mice | THC reduced weight gain, fat mass gain, and energy intake in DIO but not lean mice. DIO induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. |
| Jadoon et al., 2016144 | THCV and CBD | 100 mg CBD; 5 mg THCV; 1:1 ratio (5 mg/5 mg) of CBD and THCV; 20:1 ratio (100 mg/5 mg) of CBD and THCV, twice daily for 13 weeks. | Humans with type 2 diabetes | THCV significantly reduced fasting glycemia with parallel improvement in β cell function, as well as increased APO A, and adiponectin. CBD decreased resistin and increased levels of glucose-dependent insulinotropic peptide. CBD and THCV were well tolerated. |
| Parray and Yun, 2016184 | CBD | 1, 5, and 10 μm for 72 h | In vitro | CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cited1, Tmem26, Prdm16, Cidea, Tbx1, Fgf21, and Pgc-1a) and proteins (UCP1, PRDM16, and PGC-1a). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly through activation of PPARc and PI3K. In addition, CBD increased protein expression levels of CPT1, ACSL, SIRT1, and PLIN, whereas downregulating JNK2, SREBP1, and LPL. These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. |
AM251, CB1 receptor antagonist drug; AM630, selective CB2 agonist drug; APO A, apolipoprotein A; BDS, botanical drug substance; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; CBC, cannabichromene; CBDA, cannabidiolic acid; CBDV, cannabidivarin; CBDVA, cannabidivarinic acid; CBG, cannabigerol; CBGA, cannabigerolic acid; CBGV, cannabigerivarin; CBN, cannabinol; DIO, diet-induced obesity; DPCPX, cyclopentyl-1,3-dipropylxanthine; HDL, high-density lipoprotein; IL, interleukin; I.P., intraperitoneally; IRS-1, insulin receptor substrate 1; IRS-2, insulin receptor substrate 2; PPAR, peroxisome proliferation-activated receptor; Rimonabant, CB1 receptor antagonist drug; THCA, tetrahydrocannabinolic acid; THCV, Δ9-tetrahydrocannabivarin; TNF, tumor necrosis factor.