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Rimonabant The first CB1 cannabinoid-receptor blocker; a withdrawn anti-obesity drug (Acomplia) that curbed appetite and cleaned up metabolic markers, but was pulled worldwide for serious psychiatric risk.
- Reduced appetite and the reward value of food
- Meaningful weight and waist loss, about 5 to 7 kg over placebo at 20 mg over a year
- Higher HDL cholesterol and lower triglycerides
- Lower HbA1c in type 2 diabetes
- Raised adiponectin and lower high-sensitivity CRP
- Studied as an aid for smoking cessation
- Depression and mood alteration, up to about 10 percent
- Anxiety, irritability, and insomnia
- Nausea, diarrhea, and vomiting
- Dizziness and hot flushes
Overview
Rimonabant is basically the anti-cannabis molecule; where THC switches CB1 on and gives you the munchies, rimonabant switches CB1 off, so appetite and food reward drop. It genuinely worked, real weight loss plus better lipids and blood sugar, but blocking CB1 in the brain also strips away a buffer on mood, and depression, anxiety, and suicidal thoughts climbed enough that regulators pulled it in 2008. It lives on as a research tool and a cautionary tale, not as something to take.
- Rimonabant does the exact opposite of cannabis: THC activates CB1 to trigger appetite and reward, while rimonabant blocks CB1, so appetite and food reward drop.
- Its half-life is huge for a small molecule, roughly 6 to 9 days in lean people and up to about 16 days in people with obesity, because it stores in body fat.
- Nearly half of its metabolic benefit (higher HDL, lower triglycerides, lower HbA1c) could not be explained by weight loss alone; CB1 blockade acts directly on liver, fat, and muscle.
- It was the first-in-class CB1 inverse agonist, and every follow-up drug (taranabant, otenabant, surinabant, ibipinabant) was abandoned for the same psychiatric side effects.
Mechanism
Rimonabant (SR141716A) is a selective inverse and at the CB1 cannabinoid receptor, with a binding affinity around Ki 1.8 nM and roughly 1000-fold selectivity over CB2. The endocannabinoid system (anandamide and 2-AG acting on CB1) normally drives appetite, the rewarding pull of food, and fat and glucose handling in the liver, fat, muscle, and pancreas.
By blocking CB1 in the and the mesolimbic reward pathway, rimonabant lowers food intake and the reward value of eating; by blocking CB1 in peripheral metabolic tissue it raises HDL and adiponectin and lowers triglycerides and HbA1c, and trials showed that roughly 45 to 57 percent of that metabolic benefit could not be explained by weight loss alone. It also has weak antagonism at the mu-opioid receptor. The catch is mechanistic: CB1 signaling also dampens anxiety and supports mood, so blocking it centrally removes that brake, which is why depressed mood and anxiety track the drug rather than appearing at random.
receptor fingerprint
CB1 receptorinverse agonist / antagonist
CB2 receptorminimal activity
mu-opioid receptorantagonist
Evidencehow good the literature is
Withdrawn worldwide; large trial base, no current clinical use
Safetyrisks and cautions, not medical advice
This is a withdrawn drug and is not for human use. The defining problem is psychiatric: pooled trial data showed depressed mood or mood alteration in up to about 10 percent of users and suicidal ideation in roughly 1 percent, and post-marketing data suggested the risk of psychiatric disorders was roughly doubled. It was contraindicated in anyone with a psychiatric history, and depressed mood was an exclusion criterion in the trials yet still emerged. Common side effects included nausea, anxiety, irritability, insomnia and other sleep problems, dizziness, diarrhea, vomiting, and hot flushes. The therapeutic window looked narrow. The European Medicines Agency suspended it in October 2008 and withdrawal followed in early 2009; the FDA had already declined it as not approvable in 2007. Treat it as a reference compound only.
History
SR141716A was synthesised at Sanofi and reported by Rinaldi-Carmona and colleagues in 1994 as the first potent, selective, orally active antagonist of the brain cannabinoid receptor. Sanofi-Aventis developed it as Acomplia and Zimulti for obesity, cardiometabolic risk, and smoking cessation, tested in the large Rimonabant in Obesity (RIO) program of about 6,600 patients across RIO-Europe, RIO-Lipids, RIO-North America, and RIO-Diabetes. The European Commission approved it on 21 June 2006, but the US FDA declined it as not approvable on 30 June 2007 over psychiatric safety.
In October 2008 the EMA recommended suspension because the risks outweighed the benefits, Sanofi-Aventis suspended sales worldwide that November, and the European approval was withdrawn in January 2009. It was the first-in-class CB1 inverse agonist and spawned a whole class, taranabant, otenabant, surinabant, ibipinabant, drinabant, and rosonabant, all abandoned for the same psychiatric problem; the idea later resurfaced with peripherally restricted CB1 blockers designed to stay out of the brain.
Reputation
In the research and nootropics community rimonabant is remembered as the anti-munchies drug and as the textbook example of a mechanism that worked on paper but backfired in the brain. It occasionally circulates as a grey-market research chemical for its appetite and metabolic effects, but the mood risk is widely known and it carries a heavy caution.
Subjective profileweighing the evidence above
A beautiful mechanism wrecked by its own biology. The metabolic benefits were real and partly independent of weight loss, but the mood crash is baked into central CB1 blockade, not a fluke; every follow-up drug hit the same wall. Firmly a research chemical and a history lesson now; do not use it to lose weight.
Resources
This entry is here for reference.
Research
- 1994first citedSR141716A, a potent and selective antagonist of the brain cannabinoid receptor.
- 2015most recentEnhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as…
- 1.SR141716A, a potent and selective antagonist of the brain cannabinoid receptor.
- 2.Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.
- 3.Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program.
- 4.Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.
- 5.The role of endocannabinoid system blockade in the treatment of the metabolic syndrome.
- 6.Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward.
6 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What is rimonabant?
It is the first CB1 cannabinoid-receptor blocker, sold briefly as Acomplia by Sanofi for weight loss; it was withdrawn worldwide in 2008 over serious psychiatric side effects.
How does rimonabant work?
It blocks and inverse-agonises the CB1 receptor, the same receptor THC activates. That lowers appetite and food reward and improves lipids and blood sugar, partly independent of the weight lost.
Why was rimonabant banned?
Blocking CB1 in the brain also removes a buffer on mood, so it roughly doubled the risk of depression and anxiety and raised suicidal ideation; regulators judged the risks to outweigh the benefits.
Does rimonabant work for weight loss?
Yes; in trials, 20 mg daily produced roughly 5 to 7 kg more weight loss than placebo over a year, plus better HDL and triglycerides. The psychiatric risk is what makes it unsafe to actually use.
Is rimonabant legal or available?
No; it is withdrawn and not approved anywhere. It survives only as a research tool and reference compound, and any grey-market supply is unregulated.
Adverse effects
- Depression and mood alteration, up to about 10 percent
- Anxiety, irritability, and insomnia
- Nausea, diarrhea, and vomiting
- Dizziness and hot flushes
Notes and cautions
- Suicidal ideation, around 1 percent
- Contraindicated in any psychiatric illness; withdrawn worldwide for psychiatric risk