This Project Grant award from the National Institute on Drug Abuse (NIDA), under CFDA Program 93.279 "Drug Use and Addiction Research Programs," provides $400,000 in funding to Iontx Inc. to advance the development of a novel small-molecule compound that modulates the FGF13/NAV1.6 protein complex to normalize nucleus accumbens activity for the treatment of Cocaine Use Disorder (CUD). The primary objectives are to conduct structure-activity relationship (SAR) analysis and optimization...
This $441,000 federal Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) supports research to investigate the molecular and cellular mechanisms linking cannabis use disorder (CUD) and major depressive disorder (MDD). The project aims to identify genomic alterations in the CUD brain that contribute to increased risk of developing MDD, and to validate the functional effects of these alterations using a human brain...
This $319,547 project grant awarded on September 15, 2023 by the National Institute on Drug Abuse (NIDA) under the Drug Abuse and Addiction Research Programs (CFDA 93.279) supports Afasci, Inc.'s research and development of a novel treatment for cocaine use disorder (CUD). The project will investigate the effects of Afasci's investigational new drug AFA-281, which inhibits both the T-type Cav3 ion channels and soluble epoxide hydrolase, on reducing cocaine-seeking behavior and hyperlocomotion in...
This Cooperative Agreement award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), aims to support the development of an intravenous CB1 antagonist, ANEB-001, for the treatment of acute cannabinoid intoxication (ACI) and cannabis hyperemesis syndrome (CHS). The $892,290 award to Anebulo Pharmaceuticals, Inc., effective August 1, 2024 through July 31, 2026, will investigate the safety, pharmacokinetics, and therapeutic potential of...
This federal Project Grant award, valued at $334,343.00, was issued on June 15, 2025 by the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279). The grant supports research by Syncanica Bio, Inc., a small disadvantaged business in California, to develop synthetic analogs of 8,9-dihydrocannabidiol (H2CBD) as potential therapeutic agents for substance use disorder (SUD). The key objectives of this award are to: 1) synthesize a series of H2CBD...
This Project Grant award from the National Institute on Drug Abuse (CFDA 93.279 - Drug Use and Addiction Research Programs) provides $445,000.00 to develop and pilot test a novel telehealth and mHealth intervention called MOMENT-V for the treatment of cannabis use disorder (CUD) in young adults aged 18-26 years. The award recipient, The Children's Hospital Corporation (doing business as Boston Children's Hospital), will conduct an open pilot study and a randomized controlled trial to assess...
This federal Project Grant award from the National Institute on Drug Abuse (NIDA), with a CFDA number of 93.279 for the Drug Use and Addiction Research Programs, will provide $2,118,992 to the University of Miami to conduct research on the neural and psychiatric consequences of cannabis use in adolescents. The primary objective is to investigate the effects of cannabis, the most widely used illicit drug among teenagers, on reward and pain neurocircuits in adolescents with depression. The...
Under a $368,673 Project Grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) awarded on September 25, 2023, Artiam Bio Inc., a minority-owned small disadvantaged biotechnology company, is developing and evaluating second-generation partial inverse agonists targeting the type 1 cannabinoid (CB1) receptor as a potential therapy for alcohol use disorder (AUD). Artiam Bio is conducting preclinical efficacy studies of its lead CB1 receptor partial inverse agonist compound in rat...
This Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $541,080 to The Trustees of Columbia University in the City of New York to conduct a human laboratory study examining the effects of repeated cannabidiol (CBD) administration on the abuse-related and analgesic effects of smoked cannabis. The key objectives of this 5-year study are to determine whether daily oral CBD administration alters: 1) the...
This $247,875 Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), aims to examine the potential effectiveness of transcranial direct current stimulation (tDCS) paired with reappraisal training as a treatment for cannabis use disorder (CUD). The researchers at Yale University will recruit 60 participants to receive either real or sham tDCS alongside reappraisal training over 5 weekly sessions, using a double-blind...
DUAL FATTY ACID AMIDE HYDROLASE (FAAH)/MONOACYLGLYCEROL LIPASE (MAGL) INHIBITORS FOR CANNABIS USE DISORDER (CUD). - OTHER PROJECT INFORMATION - UNIT 7 - PROJECT SUMMARY/ABSTRACT THIS PROJECT ADDRESSES THE GROWING NEED FOR MEDICATIONS FOR CANNABIS USE DISORDER (CUD) WHICH, IN THE ABSENCE OF APPROVED MEDICATIONS, IS A MAJOR FOCUS OF NIDA'S MISSION. CURRENTLY AVAILABLE CANNABINERGIC-BASED TREATMENTS FOR CUD INCLUDE THE DIRECTLY ACTING CB1 AGONISTS, E.G., 9-THC OR NABILONE, WHICH HAVE BEEN REPORTED TO REDUCE CANNABIS WITHDRAWAL SYMPTOMS IN HUMANS SUPPORTING THE THERAPEUTIC UTILITY OF AGONIST-BASED MEDICATIONS FOR MANAGEMENT OF CUD. HOWEVER, THE USE OF DIRECTLY ACTING CB1 RECEPTOR AGONISTS IS COMPLICATED BY ADVERSE CANNABIMIMETIC EFFECTS, INCLUDING ERRATIC PHARMACOKINETICS, UNWANTED PHYSIOLOGICAL AND SUBJECTIVE EFFECTS THAT OVERLAP WITH THOSE OF SMOKED MARIJUANA, AND CONSIDERABLE DEPENDENCE LIABILITY. AN ALTERNATE AVENUE FOR DEVELOPING AGONIST-BASED TREATMENTS FOR CUD MAY LIE IN DRUGS THAT INDIRECTLY ENHANCE CANNABINERGIC ACTIVITY, E.G., BY INHIBITING THE METABOLIC ENZYMES FATTY ACID AMIDE HYDROLASE (FAAH) AND MONOACYLGLYCEROL LIPASE (MAGL) TO INCREASE BRAIN LEVELS OF THE ENDOCANNABINOIDS N-ARACHIDONOYLETHANOLAMINE (ANANDAMIDE, AEA) OR 2-ARACHIDONYLGLYCEROL (2-AG), RESPECTIVELY. THIS VIEW IS STRENGTHENED BY OUR PRELIMINARY FINDINGS FROM CB1-DISCRIMINATION STUDIES IN MONKEYS SHOWING THAT COMBINED INHIBITION OF FAAH AND MAGL, BUT NEITHER ACTION ALONE, CAN PRODUCE 9-THC-LIKE INTEROCEPTIVE EFFECTS. MORE RECENTLY, WE IDENTIFIED A SECOND-GENERATION DUAL FAAH-MAGL INHIBITOR MAK2376 WITH IMPROVED DRUGGABILITY PROFILE COMPARED TO THE PARENT DUAL FAAH-MAGL INHIBITOR AM4302, I.E., MAK2376 SHOWED GREATER STABILITY TO HEPATIC MICROSOMES AND HIGHER AQUEOUS SOLUBILITY RELATIVE TO AM4302. ENCOURAGED BY THESE FINDINGS, WE PLAN TO OPTIMIZE PHARMACOKINETIC AND PHARMACOLOGICAL PARAMETERS OF MAK2376 BY DESIGNING, SYNTHESIZING, AND EVALUATING NOVEL DERIVATIVES IN VITRO AND IN VIVO ASSAYS. NOVEL HIGH POTENCY LIGANDS WILL BE TESTED IN MICROSOMAL STABILITY, AQUEOUS SOLUBILITY, AND PHARMACOKINETIC ASSAYS. CRITERIA FOR SELECTING LIGANDS FOR IN VIVO STUDIES INCLUDE: IC5015 (M, R) AND >30 (HUMAN); AQUEOUS SOLUBILITY (PH 7.4) >60 UG/M; ORAL BIOAVAILABILITY >25% AND BRAIN/PLASMA RATIO >50%. SELECT COMPOUNDS WILL BE TESTED IN VIVO TETRAD AND CB1 DISCRIMINATION ASSAYS IN RATS. OUR OVERARCHING GOAL WILL BE TO DISCOVER IMPROVED MIXED-ACTION FAAH-MAGL INHIBITORS THAT PRODUCE 9-THC-LIKE STIMULUS EFFECTS AT DOSES THAT PRODUCE MINIMAL CB1-ASSOCIATED TETRAD SIDE-EFFECTS (E.G., HYPOTHERMIA/CATALEPSY). THE MOST PROMISING 2-4 LIGANDS WILL BE ADVANCED TO PHASE II STUDIES IN NONHUMAN PRIMATES FOR FURTHER OPTIMIZATION. WE ANTICIPATE THAT NOVEL MIXED-ACTION FAAH-MAGL INHIBITORS THAT ARE SUCCESSFUL IN THIS PHASE I AND HIGHLY TRANSLATIONAL PHASE II STUDIES IN NONHUMAN PRIMATES WILL BE 'LEAD' COMPOUNDS THAT WILL BE FURTHER STUDIED IN PRECLINICAL AND CLINICAL TRIALS AS CANDIDATE MEDICATIONS FOR CUD. OUR MULTIDISCIPLINARY TEAM OF SCIENTIFIC AND BUSINESS EXPERTS IS WELL SUITED TO SUCCESSFULLY ADVANCE THIS PROJECT TO COMMERCIALIZATION PHASE II.