Acomplia (rimonabant) / Sanofi - LARVOL DELTA

Cannabinoids Shape Synaptic Activity and Adult Neurogenesis in the Zebrafish Pallium. (PubMed, J Neurochem) - "This effect was reverted by the CB1R antagonist rimonabant. These results indicate that cannabinoid signaling modulates synaptic activity and neuronal integration, highlighting a conserved control of neurogenesis by the endocannabinoid system across vertebrates."

Journal • CNS Disorders

Cannabinoid 1 receptor occupancy and neurovascular responses induced by agonist, antagonist/inverse-agonist, and potential modulator in non-human primate brains: PET/fMRI study. (PubMed, J Cereb Blood Flow Metab) - "This study investigated CB1R occupancy and neuronal activation in non-human primate brains following acute administration of a CB1R agonist (CP55,940), an antagonist/inverse-agonist (rimonabant), an MOR agonist (morphine) using simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Morphine administration (1 mg/kg, n = 2) reduced CBV in MOR-rich areas and modestly increased [11C]OMAR VT, suggesting a potential indirect modulation of CB1R availability. Given the small sample size and variability close to test-retest levels, these preliminary findings should be interpreted with caution."

Journal

Brain Hsp90 Inhibition Mitigates Facial Allodynia in a Rat Model of CSD Headache and Upregulates Endocannabinoid Signaling in the PAG. (PubMed, Pharmaceuticals (Basel)) - "This effect was blocked by injection of the CB1R antagonist rimonabant (1 mg/kg, ip)...This effect was accompanied by reduced expression of FAAH and increased expression of NAPE-PLD in the same nuclei. These results suggest that Hsp90 inhibition positively modulates the endocannabinoid system, causing pain relief through descending pain modulation in PAG post-CSD."

Journal • Preclinical • CNS Disorders • Depression • Migraine • Pain • Psychiatry • CDC37 • HSP90AA1

Topical WIN 55 212-2 Confers Long-Term Intraocular Pressure-Independent Neuroprotection in the DBA/2J Mouse Model of Glaucoma. (PubMed, Ophthalmol Sci) - "Ninety 6-month-old DBA/2J mice (180 eyes) grouped in Untreated (UN), WIN 1%, or WIN 1% + rimonabant (RIM)...Topical WIN 1% transiently lowers IOP, preserves retinal ganglion cell function, and attenuates structural and molecular degeneration in a seemingly cannabinoid receptor 1-dependent and IOP-independent fashion, thus representing a promising neuroprotective strategy for glaucoma. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Journal • Preclinical • Glaucoma • Ophthalmology • OPTN • RBPMS

Development of PROTAC-Based Strategies for Cannabinoid Receptor Type 1 (CB1R) Degradation in Cancer. (PubMed, ACS Pharmacol Transl Sci) - "These compounds were specifically engineered to avoid central nervous system (CNS) penetration, thereby minimizing adverse effects linked to the parent compound, Rimonabant...Consistent with its design, in vivo evaluation confirmed that the compound does not significantly penetrate the blood-brain barrier, supporting its peripheral selectivity. Overall, our findings establish targeted CB1R degradation via PROTACs as a viable and innovative strategy for cancer therapy, paving the way for the development of next-generation, precision-targeted therapeutics."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

BI-5756 Reduces Graft-Versus-Host Disease Through CB1-Mediated Treg Upregulation. (PubMed, Molecules) - "The ability of BI-5756 to increase Tregs was significantly abrogated by rimonabant, a potent and selective CB1 antagonist, suggesting that the immunomodulatory effect of BI-5756 is mediated via CB1. In summary, BI-5756, a potent CB1 agonist, increases Tregs while preserving anti-tumor responses in vitro and effectively reduces GvHD in vivo."

Journal • Graft versus Host Disease • Immunology • Oncology • Transplantation • CD80

Cannabis Medicine 2.0: Nanotechnology-Based Delivery Systems for Synthetic and Chemically Modified Cannabinoids for Enhanced Therapeutic Performance. (PubMed, Nanomaterials (Basel)) - "This comprehensive review explores the advancements in nanoformulation strategies to enhance the therapeutic efficacy and safety of synthetic cannabinoids and related compounds, such as CB13, rimonabant, and HU-211, which have been studied in a range of preclinical models addressing conditions such as neuropathic pain, depression, and cancer. The provided summary of research concerning either chemical modifications of existing cannabinoids or the creation of new compounds that interact with cannabinoid receptors, followed by the development of nanoformulations for these agents, allows for the identification of new research directions and future perspectives for Cannabis-based medicine. In conclusion, the combination of nanotechnology and cannabinoid pharmacology holds promise for delivering more effective and safer therapeutic solutions for a broad spectrum of medical conditions, making this an exciting area of research with profound implications for the healthcare and..."

Journal • Review • CNS Disorders • Depression • Neuralgia • Oncology • Pain • Psychiatry

THC and CBD in insomnia associated to neuropathic pain: effect on sleep architecture and descending anti-nociceptive pathways (WSS 2025) - "To investigate the involvement of CB1 and 5-HT1A receptors in the pro-hypnotic effect of THC and CBD, rimonabant (1 mg/kg) and WAY 100635 (2 mg/kg) were injected 10 min before an effective dose of THC (5 mg/kg) and CBD (20 mg/kg), respectively... The findings suggest that THC and CBD have a moderate acute analgesic effect, but significantly recovered the sleep disruption in NP rats by modulating the neural nociceptive pathway. Therefore, THC and CBD have potential in the treatment of neuropathic pain and comorbid insomnia."

CNS Disorders • Insomnia • Neuralgia • Pain • Sleep Disorder

Rimonabant treatment partly attenuates skeletal muscle loss following immobilization in young and in old, sarcopenic male mice. (PubMed, J Gerontol A Biol Sci Med Sci) - "Immobilization decreased the expression of the enzyme NAPE-PLD, responsible for synthesis of the endocannabinoid anandamide, whereas its degrading enzyme FAAH was higher expressed. More research is needed to unravel the mechanisms underlying the muscle sparing effect of Rimonabant, and anandamide's role in muscle degeneration."

Journal • Preclinical • Sarcopenia • EIF4EBP1

Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons. (PubMed, iScience) - "In this study, we show that rimonabant (Rim), a selective non-restricted CB1 antagonist, induces substantial weight loss across multiple diet groups, although reduced food intake occurred only in the high-fat (HF) diet group. Mice lacking CB1 in sensory neurons (Nav1.8Cre/CB1flox/flox) showed reduced diet-induced weight gain and diminished metabolic response to JD5037, a peripherally restricted CB1 antagonist. These findings emphasize the importance of CB1 signaling in sensory neurons as a key mechanism regulating energy homeostasis."

Journal • NAV1

"Modulatory role of baseline impulsivity on the acute and persistent effects of CB1 agonism on impulsive choice". (PubMed, J Psychopharmacol) - "Our results suggest a potential benefit of CB1/2 agonism in vulnerable subpopulations with high levels of impulsivity. To maximize therapeutic benefits and minimize potential iatrogenic effects, assessing choice impulsivity and other variables is essential, aligning with personalized medicine principles to effectively tailor interventions."

Journal • Substance Abuse

Cannabinoid Receptor Modulation in Focal Ischemic Stroke: A Systematic Review and Meta-Analysis of Infarct Volume and Behavioral Deficits in Animal Models. (PubMed, Med Princ Pract) - "These results highlight the potential of cannabinoid receptor modulation as a neuroprotective strategy in ischemic strokes and underscore the need for further research to elucidate the underlying mechanisms and optimize therapeutic approaches."

Journal • Preclinical • Retrospective data • Review • Cardiovascular • Ischemic stroke

PHARMACOLOGICAL CHARACTERIZATION OF A NEW SYNTHESIS COMPOUND WITH ANTAGONISTIC ACTION ON CB1 RECEPTORS: EVIDENCE FROM THE ANIMAL EXPERIMENTAL MODEL. (PubMed, Eur J Pharmacol) - "However, the adverse effects of CB1 antagonists like rimonabant have spurred the development of new compounds with improved safety profiles...Its modulation of CB1 effects in the tetrad task and gastrointestinal assays suggests potential therapy for neuropsychiatric disorders, obesity, and addiction. Further studies are needed to clarify QD13's safety and efficacy."

Journal • CNS Disorders • Genetic Disorders • Mental Retardation • Obesity • Psychiatry

A Tourette Syndrome/ADHD-like Phenotype Results from Postnatal Disruption of CB1 and CB2 Receptor Signalling. (PubMed, Int J Mol Sci) - "Here, ADHD/TS-like behaviours were studied from postnatal to adulthood by exposing postnatal wild-type CB1 and Cannabinoid receptor 2 (CB2) knockout mouse pups to SR141716A (rimonabant), a CB1 receptor antagonist/inverse agonist...Inhibition of CB1 receptor signalling together with CB2 receptor stimulation underlie ADHD/TS-like behaviours in males. This study suggests that the ADHD/TS phenotype may be a single clinical entity resulting from incorrect cannabinoid signalling after birth."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Movement Disorders • Psychiatry • Tourette Syndrome

Assessment of Abuse Potential of Three Indazole-Carboxamide Synthetic Cannabinoids 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA. (PubMed, Int J Mol Sci) - "A significant increase in paw tremors and head twitches was observed in the rimonabant-precipitated withdrawal assay, indicating that the repeated administration of these SCs can lead to potential physical dependence...These findings strongly suggested that the three SCs exhibited similar but stronger cannabinoid-specific tetrad effects, rewarding effect and physical dependence compared with Δ9-THC, indicating their high abuse potential and possible threats to human health. The rank order of abuse potential for these drugs was 5F-ADB > MDMB-4en-PINACA > ADB-4en-PINACA > Δ9-THC."

Journal • Movement Disorders

Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans. (PubMed, Geroscience) - "It promotes longevity of C. elegans by enhancing antioxidant defense and detoxification pathways. Our findings position both quinacrine and rimonabant as promising anti-aging candidates, offering novel mechanistic insights for developing interventions against age-related disorders."

Journal • Inflammation • SOD3

CB1 receptor antagonism reverses social and cognitive deficits induced by repeated exposure to distressed conspecifics in rats. (PubMed, Neurosci Lett) - "Furthermore, hippocampal levels of brain-derived neurotrophic factor (BDNF) decreased in both demonstrator and observer rats, whereas rimonabant administration resulted in an increase in BDNF levels in the hippocampus, in contrast to WIN. These results suggest that the CB1R may be intricately involved in prosocial behavior and emotional contagion, potentially through the modulation of BDNF levels in the hippocampus."

Journal • Preclinical • Cognitive Disorders • Pain • BDNF

Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression (CINP-AsCNP 2025) - "In conclusion, our study demonstrated that S-KET regulates the tone of the ECS in the PFC of FSL animals. This effect potentially occurs through the regulation of gene expression of some ECS catabolizing enzymes, such as FAAH, as well as through its (and its metabolites') direct interactions with ECS targets. The inability of rimonabant to block the antidepressant effect of S-KET highlights the complexity of its interaction with the ECS, warranting further investigation into the molecular pathways."

Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • GPR55

CB1 Receptor Positive Allosteric MODULATORS: Assessment of Cannabimimetic Side EFFECTS, Misuse POTENTIAL, and Dependence Liability (CPDD 2025) - "These findings indicate that CB1 PAMs possess efficacy in a mouse neuropathic pain model without cannabimimetic side effects associated with THC. Because rimonabant precipitated withdrawal signs in mice given repeated injections of CB1 PAMs, an ongoing study is examining whether discontinuation following prolonged administration of CB1 PAMs results in spontaneous withdrawal signs. In sum, CB1 PAMs show promise as potential therapeutics with fewer side effects than THC, but nonetheless may possess dependence liability."

Adverse events • Neuralgia • Pain

CB1 Receptor Agonist ACEA Resists ER Stress-Mediated Apoptosis via CB1R-Independent Mechanism. (PubMed, Biol Pharm Bull) - "These findings indicate that rimonabant and AM251 induce neurotoxicity independently of CB1R under serum-free conditions and that ER stress is likely to be a key target of CB1R-independent neuroprotection by ACEA. Our study highlights the complexity of CB1R ligand-associated neurotoxicity and neuroprotection."

Journal • Neuroblastoma • Oncology • Solid Tumor • TRPV1

Acetaminophen attenuates pathological pain through a mechanism that requires CB1 cannabinoid receptors and the enzyme diacylglycerol lipase in mice. (PubMed, bioRxiv) - "Pharmacological specificity was assessed using global (Rimonabant, AM251) and peripherally restricted (AM6545) CB1 antagonists. Our studies demonstrate that the analgesic effects of APAP observed in mouse models of pathological pain require both DAGL and CB1 activation. Our findings support a potential mechanism of APAP-induced analgesic action involving the enzyme DAGL and CB1 receptors."

Journal • Preclinical • Immunology • Inflammation • Pain

Demonstrating the sufficiency of peripheral CB1 inhibition to promote weight loss using clinical pharmacokinetic (PK) and pharmacodynamic (PD) models (ECO 2025) - " We compared clinical PK profiles of rimonabant, monlunabant, and nimacimab using PK/PD modeling to analyze their target engagement and distribution in the brain and periphery. Our findings suggest that peripheral CB1 inhibition, rather than central CB1 inhibition, is sufficient to drive weight loss, minimizing the potential for neuropsychiatric AEs associated with central CB1 inhibition. This work supports further development of novel mAb-based CB1 inhibitors with superior peripheral restriction to promote weight loss with reduced centrally mediated neuropsychiatric effects which continues to be a hurdle for the less restricted small molecule inhibitors. Conflict of Interest: The author is a consultant for Skye Bioscience, a biopharmaceutical company developing therapies for obesity and metabolic diseases."

Clinical • PK/PD data • Genetic Disorders • Metabolic Disorders • Obesity • Psychiatry

Targeting the CB1 Receptor for Enhanced Obesity Management: Efficacy Comparison of Rimonabant and GLP-1 Receptor Agonist in Diet-Induced Obesity (ECO 2025) - "This study shows Rimonabant's significant potential as an obesity treatment. It outperformed Semaglutide in reducing body weight and fat, with both treatments causing similar lean body mass loss. Rimonabant also improved metabolic parameters, such as food intake, fasting blood glucose, liver triglycerides, adipose tissue weight, and NAFLD activity."

Clinical • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Comparing Effects of Edible or Vaping Cannabinoid Exposure to Lungs Inducing Proinflammatory Lung Microenvironment (ATS 2025) - "This led to significant increases in IFN-γ, IL-6, CCL2, and CCL1 in bronchoalveolar lavage fluid (BALF) and lung tissue Importantly, systemic CB1R antagonist rimonabant administration attenuated these inflammatory changes, reinforcing the role of CB1R activation in cannabinoid induced lung inflammation. These findings indicate that THC vaping leads to localized proinflammatory alterations in the lungs, potentially mediated through CB1R. These findings indicate that THC vaping leads to localized proinflammatory alterations in the lungs, potentially mediated through CB1R. CB1R antagonism may be a therapeutic target for mitigating cannabis-related pulmonary toxicity. Further studies are warranted to elucidate the long-term consequences of chronic THC inhalation and its implications for public health."

Late-breaking abstract • Inflammation • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases • CCL2 • CNR1 • IFNG • IL17A • IL6

Skye Bioscience Clinical Model Demonstrating Necessity of Peripheral CB1 Inhibition for Weight Loss Presented at European Congress on Obesity (Skye Bioscience Press Release) - "Skye Bioscience, Inc...presented a clinical pharmacokinetic ('PK') and pharmacodynamic ('PD') model that underscores the fundamental relationship between biodistribution and efficacy of CB1 inhibitors...Published clinical PK and potency data coupled with Phase 2 ('P2') and Phase 3 efficacy data from Novo Nordisk’s monlunabant and Sanofi’s rimonabant, respectively, as well as Phase 1 data from nimacimab were used to develop a model to determine whether peripheral CB1 inhibition alone is sufficient for weight loss, or if central inhibition is also required for optimal efficacy. The results showed that central inhibition of CB1 alone was not sufficient for weight loss with P2 data for monlunabant, and demonstrated that increasing drug levels in the brain did not improve efficacy."

Clinical data • PK/PD data • Obesity