CNR1 cannabinoid receptor 1
ENSG00000118432 · protein coding · Open Targets profile
G protein-coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727, PubMed:35637350). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist- dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a pro- inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta- cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777, ECO:0000250|UniProtKB:P47746, ECO:0000269|PubMed:15620723, ECO:0000269|PubMed:1718258, ECO:0000269|PubMed:17895407, ECO:0000269|PubMed:21895628, ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727, ECO:0000269|PubMed:35637350}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.43406999111175537 (upper bound 0.736270010471344). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against CNR1 (nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, AZD2207, drinabant, nimacimab, surinabant), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Didier Jutras-AswadCentre hospitalier de l'Université de Montréal (CHUM) · 3 of 3 trials Phase 2+
- Godfrey PearlsonFounding Director, Olin Neuropsychiatry Center; Yale University · 2 of 5 trials Phase 2+
- F. Markus LewekeCentral Institute of Mental Health · 2 of 4 trials Phase 2+
- Dennis McNamaraUniversity of Pittsburgh · 2 of 2 trials Phase 2+
- Francisney p NascimentoFederal University of Latin American Integration · 2 of 2 trials Phase 2+
- Giovanni MarottaSunnybrook Health Sciences Centre · 2 of 2 trials Phase 2+
- Jay ConstantinePleoPharma, Inc. · 2 of 2 trials Phase 2+
- Joseph P SchachtUniversity of Colorado, Denver · 2 of 2 trials Phase 2+
- Kent HutchisonUniversity of Colorado, Denver · 2 of 2 trials Phase 2+
- Krista L. LanctotSunnybrook Research Institute · 2 of 2 trials Phase 2+
- Nathaniel M SchusterUniversity of California, San Diego · 2 of 2 trials Phase 2+
- Philip McGuireUniversity of Oxford · 2 of 2 trials Phase 2+
- Susanna CurtisMOUNT SINAI HOSPITAL · 2 of 2 trials Phase 2+
- Virend SomersMayo Clinic · 2 of 2 trials Phase 2+
- Christine A. RabinakWayne State University · 1 of 2 trials Phase 2+
Registry trials of nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, AZD2207, drinabant, nimacimab, surinabant updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 367 of 387 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 13 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
118 trials of drugs against CNR1 were stopped early; 4 give no reason
Terminated, withdrawn and suspended interventional trials of nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, AZD2207, drinabant, nimacimab, surinabant, SAD448, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 118.
- terminated · 2026-10-16 · University Hospital Schleswig-Holstein · matched by the registry's drug synonyms“Given the current recruitment rate and the changes in the treatment landscape, there is no reasonable expectation of achieving the planned sample size.”
- terminated · 2026-10-06 · Medical University of South Carolina · Dronabinol“Funding status change.”
- withdrawn · 2026-09-25 · Foundation for Orthopaedic Research and Education · Cannabidiol Oil“insufficient drug supply at the time.”
- terminated · 2026-09-01 · University of California, San Diego · matched by the registry's drug synonyms“Original funding period ended and a no-cost extension was not granted. Without funding to continue, the study was stopped.”
- withdrawn · 2026-08-19 · Kanako Hayashi · matched by the registry's drug synonyms“We terminated the study. Since the FDA did not approve our study, we could not begin it. I have terminated it.”
- terminated · 2026-07-28 · Simon Ducharme, MD · Nabilone“Terminated due to slow recruitment: only 3 randomized in 2 years. Eligible population overestimated and funding exhausted; PI deemed further recruitment unfeasible. No participants on treatment, no safety concerns. All sites are now closed.”
- suspended · 2026-07-14 · City of Hope Medical Center · matched by the registry's drug synonyms“Accrual goal met”
- terminated · 2026-06-12 · Hôpital le Vinatier · Cannabidiol oral oil“Péremption des unités de traitement prévue début juin 2026. Compte tenu des délais de traitement, aucune administration ne sera plus possible après le 1 février 2026. Ces facteurs ne permettent plus de garantir la poursuite des inclusions.”
- terminated · 2026-05-07 · Eric Hollander · matched by the registry's drug synonyms“Only limited funding was available and the study was never able to be conducted to its natural conclusion.”
- terminated · 2026-04-21 · Cardiol Therapeutics Inc. · Cannabidiol, pharmaceutically produced with < 5 ppm THC“The changing nature of COVID-19 including a more vaccinated population, increasing natural population immunity, milder variants and other related factors has meant that it is no longer realistic to recruit the patients in a reasonable time frame.”
- terminated · 2026-04-09 · Centre for Addiction and Mental Health · Nabilone“Poor tolerability of medication and no preliminary efficacy”
- terminated · 2026-03-27 · Incannex Healthcare Ltd · Cannabidiol“Recruitment challenges”
- terminated · 2026-03-16 · Mclean Hospital · Cannabidiol (CBD)“Study terminated by sponsor due to low enrollment.”
- suspended · 2026-03-16 · University of California, San Diego · matched by the registry's drug synonyms“Inadequate funding”
- withdrawn · 2026-03-13 · Baylor College of Medicine · Dronabinol Capsules“Due to an ongoing national shortage of dronabinol, the study is being discontinued. Given the inability to ensure consistent medication availability, continuation of the study would compromise protocol integrity and participant safety.”
- terminated · 2025-10-31 · Jazz Pharmaceuticals · matched by the registry's drug synonyms“The study was terminated by the Sponsor due to low patient enrollment.”
- terminated · 2025-08-19 · Yale University · matched by the registry's drug synonyms“Insufficient funding”
- terminated · 2025-06-11 · The University of Texas Health Science Center, Houston · Dronabinol“Study concluded because of drug shortage”
- withdrawn · 2025-04-24 · Dr. Paul Lyons · PO BRC-003 (High Cannabidiol Cannabis Extract)“Company decision”
- terminated · 2025-04-04 · Milton S. Hershey Medical Center · Cannabidiol (CBD) Extract“Recruitment has been challenging due to the BMI cutoff, need to take oral progesterone and abstain from cannabis products prior to the study.”
- terminated · 2025-04-02 · University of Sao Paulo · matched by the registry's drug synonyms“The study was prematurely terminated due to the results of the interim analysis conducted, as outlined in the initial project plan.”
- withdrawn · 2025-03-21 · Central Institute of Mental Health, Mannheim · Cannabidiol CR“Lack of funding”
- withdrawn · 2025-03-13 · Central Institute of Mental Health, Mannheim · Cannabidiol“No documents were ever submitted to the Ethics Committee or the competent authority because it was not possible to establish the planned PET measurements in Germany. Therefore, the study never started.”
- terminated · 2025-02-24 · Hospital Israelita Albert Einstein · Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg“an interim analysis to rule out futility was positive, we completed active patients and stopped recruitment with 75 patients enrolled”
- terminated · 2025-02-03 · Jazz Pharmaceuticals · matched by the registry's drug synonyms“The study was terminated due to a business decision.”
Paediatric incentives and obligations for CNR1's drugs
For nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, AZD2207, drinabant, nimacimab, surinabant, SAD448: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · CNR1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001964-PIP02-19 (cannabidiol, Treatment of Rett syndrome): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 18 Mar 2020; EMEA-001964-PIP03-21 (cannabidiol, Epilepsy with myoclonic atonic seizures): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 8 Jul 2022; EMA/PE/0000224912 (cannabidiol, Treatment of seizures associated with Dravet Syndrome (DS);Treatment of seizures associated with Lennox-Gastaut Syndrome (LGS);Treatment of seizures associated with Tuberous Sclerosis Complex (TSC)): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-003176-PIP02-22 (cannabidiol, Treatment of fragile-X syndrome): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 15 Mar 2024; +5 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/23/2800 positive 25 Jul 2023: Treatment of Leigh syndrome; EU/3/22/2600 positive 13 Apr 2022: Treatment of epilepsy with myoclonic-atonic seizures; EU/3/17/1959 positive 17 Jan 2018: Treatment of tuberous sclerosis; EU/3/17/1920 positive 16 Oct 2017: Treatment of West syndrome; +11 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Epidyolex: authorised since 19 Sept 2019, orphan medicineRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Epidyolex, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, azd2207, drinabant, nimacimab, surinabant, sad448Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 98 interventional studies of nabilone, dronabinol, cannabidiol, otenabant, taranabant, ibipinabant, azd2207, drinabant, nimacimab, surinabant, sad448 include patients under 18; 24 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 12 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.