The Psychoactive Drug 5-Methoxy-2-aminoindane (MEAI) Ameliorates Obesity and its Metabolic Complications

Joseph (Yossi) Tam, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel (yossi.tam@mail.huji.ac.il)
Saja Baraghithy, Institute For Drug Research, School Of Pharmacy, The Hebrew University Of Jerusalem, Jerusalem, Israel

Obesity and its associated comorbidities represent a growing health challenge worldwide. Currently, there are relatively few effective pharmacological treatments for obesity, and those that do exist have limiting side effects. 5-Methoxy-2-aminoindane (MEAI) is a novel psychoactive aminoindane derivative that exerts a euphoric, alcohol-like tipsy experience, and importantly, reduces the desire to consume alcoholic beverages. Considering these observations, it is also of a great interest to investigate the effects of MEAI on food addictive behaviors. To that end, we tested the metabolic efficacy of MEAI on appetite regulation and obesity.

To generate diet-induced obesity (DIO), C57Bl6/J adult male mice were fed either a high-fat diet (HFD) or a standard laboratory diet (STD) for 18 weeks. HFD-fed obese mice received vehicle (Saline) or MEAI (40 mg/kg p.o.) daily for 28 days. Age-matched control mice on STD received vehicle daily. At the end of the treatment, body composition, metabolic profiling, glucose and insulin tolerance tests, and various biochemical parameters were assessed.

Treatment with MEAI significantly attenuated the overweight and adiposity associated with obesity in the DIO mouse model, by dually preserving the lean mass, and reducing the overall fat mass. Moreover, HFD-induced hyperglycemia, glucose intolerance, and hyperinsulinemia were reversed by MEAI administration, indicating specific positive effects on glucose metabolism. Additionally, MEAI ameliorated DIO-induced hepatic steatosis by reducing hepatic lipid accumulation and lowering liver triglyceride and cholesterol levels. Metabolic phenotyping revealed that MEAI increased energy expenditure and fat utilization, with a comparable food consumption to that observed in the vehicle-treated group. Lastly, analysis of locomotion patterns indicated that MEAI normalized the reduction in voluntary locomotion actions observed in the vehicle-treated group without having an over-stimulatory effect.

Collectively, these data provide strong evidence for the anti-obesity effects of MEAI treatment, warranting further preclinical testing.

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Short Biography of Presenting Author

Prof. Yossi Tam received his B.Med.Sc., M.Sc., Ph.D. and D.M.D. from the Hebrew University of Jerusalem. He did his postdoctoral training at the National Institutes of Health (NIH), and in 2014 he moved to the Hebrew University to head the Obesity and Metabolism Laboratory at the Institute for Drug Research, where he focuses on targeting the endocannabinoid system for Obesity, Diabetes and the metabolic syndrome. Prof. Tam won major national and international grants (ERC, ISF, JDRF, BARD, GIF, EFSD, FPWR, TOS). He authored over 80 peer-reviewed papers in leading journals (such as Science, Nature Medicine, Cell Metabolism, JCI, PNAS, Hepatology, Gastroenterology, Molecular Metabolism, to name a few), and three book chapters.

Prof. Tam also serves as the Director of the Hebrew University’s Multidisciplinary Center for Cannabinoid Research and a Scientific Advisory Board Member of several biotech companies, which develop a portfolio of non-psychoactive cannabinoid and cannabinoid-modulating medicines for unmet market needs.

Prof. Tam's research projects over the past twenty years has crossed subjects, disciplines and methodologies, yet the main research interests remain focused on the different pathophysiological aspects of the endocannabinoid system. Having a clinical background with basic science training, he has always been interested in how science can directly improve people’s everyday lives. Thus, he has strived unceasingly to integrate his clinical curiosity and experimental knowledge, in order to deepen the understanding of clinically relevant research questions.