Over the last few decades, numerous weight-loss drugs have been sanctioned. Orlistat, sibutramine and rimonabant are some examples. None of these, however, have delivered as expected. In this article, we are going to have a look one of these drugs – rimonabant.
Notwithstanding the promising modes of action of rimonabant (and other CB1 receptor antagonists like taranabant), research shows that weight-loss achieved with rimonabant isn’t greater than that achieved using other safer weight-loss drugs (Akbas, Gasteyger, Sjodin, Astrup, & Larsen, 2009). Also, the very realistic risk of developing psychiatric adverse effects rules against the use of rimonabant for weight-loss.
Over the last few decades, numerous such drugs for causing weight-loss have been sanctioned. Orlistat, sibutramine and rimonabant are some examples. None of these, however, have delivered as expected.
In this article, we are going to have a look at one of these drugs – rimonabant.
Rimonabant – How Does it Work?
Rimonabant (like sibutramine) is a centrally-acting weight-reducing agent; meaning, it works by exerting its effects on receptors in the brain.
To be more specific, rimonabant, is a cannabinoid receptor-1 (CB1) antagonist (Heppenstall, Bunce, & Smith, 2012; Pagotto & Pasquali, 2005; Akbas et al., 2009). That is to say, it blocks the actions carried out through the cannabinoid receptors-1 (CB1). (Important to note here that stimulation of CB1 in the brain causes increase in appetite (Matsuda, Lolait, Brownstein, Young, & Bonner, 1990) – hence, it makes sense that blocking these CB1s – as is done by rimonabant – will result in suppression of appetite).
Furthermore, it has also been theorized that inhibition of these receptors in adipose tissues may cause oxidation of fat.
Rimonabant’s alleged mechanism of weight-loss – as shown in human clinical trials – involves (Pagotto & Pasquali, 2005; Akbas et al., 2009):
- Reduced appetite (or increased satiety), and therefore
- Decreased intake of calories
Additionally, animal data suggests that rimonabant also causes (Herling, Kilp, Elvert, Haschke, & Kramer, 2008; Heppenstall et al., 2012; Akbas et al., 2009):
- Increased energy expenditure
- Increased fat oxidation in the adipose tissue
- Increased compliance towards healthy food*
*When it comes to weight-loss, there is another interesting aspect to the use of rimonabant and other CB1 receptor antagonists – they preferentially reduce the use of palatable fatty and sugary foods (Heppenstall et al., 2012; Simiand, Keane, Keane, & Soubrie, 1998; Gessa et al., 2006; Mathes, Ferrara, & Rowland, 2008; Kirkham, 2005)!
The downside is that these animal findings have not yet been proved in human studies (Heppenstall et al., 2012).
Recommended Dosage of Rimonabant
The standardized licensed dose of rimonabant is 20mg/day (Heppenstall et al., 2012). However, to maximize weight-loss, it is recommended that this dose of rimonabant be combined with reduced calorie consumption (by 600-800 calories/day) and lifestyle modification interventions (Heppenstall et al., 2012).
This therapy can be used for as long as 6 months.
Adverse Effects Profiling of Rimonabant
Rimonabant was withdrawn from the market in 2008 (Akbas et al., 2009). This was mainly owing to some serious adverse effects associated with its use (Heppenstall et al., 2012; Akbas et al., 2009):
- Depression and
- Suicidal ideation
Conditions under which rimonabant is strictly contraindicated are:
- Psychiatric disorders,
- Left ventricular pathologies,
- Peripheral vascular disease, and
- Kidney disease (renal clearance, GFR** < 30ml/min)
**glomerular filtration rate
Does Scientific Literature Support the Use of Rimonabant for Weight-loss?
There is ample evidence to suggest rimonabant causes loss of body weight:
- Rimonabant has been shown to reduce in excess of 5% of body weight over a duration of 6 months. Additionally, it also causes a reduction in waist circumference and improves blood glucose and blood lipid profiles (Heppenstall et al., 2012).
- Also, as opposed to other fat-reducing agents, rimonabant needs to be combined with a minimal decrease in calorie intake (600 calories/day) (Scheen, Finer, Hollander, Jensen, & Van Gaal, 2006).
- In addition to suppressing appetite, animal studies suggest that rimonabant also increases energy expenditure, induces fat oxidation and improves compliance towards healthy food (Heppenstall et al., 2012; Simiand et al., 1998; Gessa et al., 2006). However, these findings have not been replicated in human clinical studies as yet (Heppenstall et al., 2012).
- There is some suggestion that rimonabant may also improve the macronutrient content (carbohydrate, proteins and fats) of food (Heppenstall et al., 2012; Mathes et al., 2008). However, despite large clinical studies conducted to investigate the mechanism of action of rimonabant, how rimonabant affects macronutrient content is not known (Heppenstall et al., 2012).
Although rimonabant causes fat loss, the fact that it is also associated with severe adverse effects – especially psychiatric ones – makes its use quite tricky.
Our Verdict on rimonabant
Notwithstanding the promising modes of action of rimonabant (and other CB1 receptor antagonists like taranabant), research shows that weight-loss achieved with rimonabant isn’t greater than that achieved using other safer weight-loss agents (Akbas et al., 2009).
Also, the very realistic risk of developing psychiatric adverse effects rules against its use.
Thus, rimonabant fails to score with the Diet Pills Watchdog team!
- Akbas, F., Gasteyger, C., Sjodin, A., Astrup, A., & Larsen, T. M. (2009). A critical review of the cannabinoid receptor as a drug target for obesity management. Obes Rev, 10, 58-67. Online Resource
- Gessa, G. L., Orru, A., Lai, P., Maccioni, P., Lecca, R., Lobina, C. et al. (2006). Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats. Psychopharmacology (Berl), 185, 248-254. Online Resource
- Heppenstall, C., Bunce, S., & Smith, J. C. (2012). Relationships between glucose, energy intake and dietary composition in obese adults with type 2 diabetes receiving the cannabinoid 1 (CB1) receptor antagonist, rimonabant. Nutr.J, 11, 50.
- Herling, A. W., Kilp, S., Elvert, R., Haschke, G., & Kramer, W. (2008). Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats. Endocrinology, 149, 2557-2566. Online Resource
- Kirkham, T. C. (2005). Endocannabinoids in the regulation of appetite and body weight. Behav.Pharmacol., 16, 297-313. Online Resource
- Mathes, C. M., Ferrara, M., & Rowland, N. E. (2008). Cannabinoid-1 receptor antagonists reduce caloric intake by decreasing palatable diet selection in a novel dessert protocol in female rats. Am J Physiol Regul.Integr.Comp Physiol, 295, R67-R75. Online Resource
- Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346, 561-564. Online Resource
- Pagotto, U. & Pasquali, R. (2005). Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors. Lancet, 365, 1363-1364. Online Resource
- Scheen, A. J., Finer, N., Hollander, P., Jensen, M. D., & Van Gaal, L. F. (2006). RIO-Diabetes Study Group: Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet, 368, 1660-1672. Online Resource
- Simiand, J., Keane, M., Keane, P. E., & Soubrie, P. (1998). SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav.Pharmacol., 9, 179-181.
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