CRA13 / Novartis - LARVOL DELTA

Cannabidiol and cocaine induce heterogenous and donor-dependent inflammatory responses in primary human peripheral immune cells (Neuroscience 2025) - "Interestingly, CB-13 suppressed LPS-induced cytokines, reflecting CBD's anti-inflammatory potential during immune perturbation. In the future, evaluating the direct impact of CBD and COC on immune cell recruitment at the BBB may reveal trends in neuroimmune interactions that mechanistically contribute to heterogenous immune responses during substance abuse."

Immune cell • CNS Disorders • Psychiatry • Substance Abuse

Peripherally restricted cannabinoid and mu-opioid receptor agonists synergistically attenuate neuropathic mechanical hypersensitivity in mice. (PubMed, Pain) - "We also find that CB-13 (a peripherally restricted dual CB1R and cannabinoid receptor type 2 agonist) and DALDA (a peripherally restricted MOR agonist) both attenuate mechanical hypersensitivity in a murine model of neuropathic pain...However, repeated dosing of these agents is associated with the development of tolerance to these drugs. Collectively, these findings suggest that leveraging synergistic pain inhibition between cannabinoid receptor and MOR agonists in peripheral sensory neurons may be worth examining in patients with neuropathic pain."

Journal • Preclinical • Anesthesia • Fatigue • Immunology • Neuralgia • Pain • CNR1 • OPRM1

Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice. (PubMed, Biomed Pharmacother) - "Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to..."

Journal • Preclinical

Effect of Reproductive Stage-Waterlogging on the Growth and Yield of Upland Cotton (Gossypium hirsutum). (PubMed, Plants (Basel)) - "Moreover, extensive multivariate analyses like Spearman correlation and the principle component analysis revealed that CB-12 and Rupali-1 had greater coefficients in yield and physiological attributes at 9-day waterlogging, whereas CB-13 and DM-3 were sensitive cultivars in response to the same levels of waterlogging. Thus, CB-12 and Rupali-1 might be well adapted to the low-lying waterlogging-prone areas for high and sustained yield."

Journal

The cannabinoid agonist CB-13 produces peripherally mediated analgesia in mice but elicits tolerance and signs of CNS activity with repeated dosing. (PubMed, Pain) - "Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB1 receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development."

Journal • Preclinical • Immunology • Inflammation • Pain

Role of primary sensory neurone cannabinoid type-1 receptors in pain and the analgesic effects of the peripherally acting agonist CB-13 in mice. (PubMed, Br J Anaesth) - "CBR signalling in primary sensory neurones did not inhibit nociceptive or inflammatory pain, or the intrinsic excitability of nociceptive neurones. However, peripheral CBRs are important for the analgesic effects of systemically administered CB-13. In addition, HVA-I inhibition appears to be a key ionic mechanism for CB-13-induced pain inhibition. Thus, peripherally restricted CBR agonists could have utility for pain treatment."

Journal • Preclinical • Immunology • Inflammation • Pain

[VIRTUAL] The Role of Peripheral Cannabinoid (CB)-1 Receptors in Inflammatory Pain (IASP 2021) - "CB-13 (10 nM) significantly inhibited high-voltage activated (HVA) calcium currents (ICa) in small-diameter WT DRG neurons, which was attenuated by CB1R antagonist, AM6545 (10 nM), and was unaffected by peripheral MOR knockout...Morphine (5 mg/kg, s.c.) analgesia was unaffected in CB1R cKO mice. The present results suggest that endogenous CB1R signaling in DRG neurons does not contribute to a tonic inhibition of nociceptive pain thresholds... The present results suggest that endogenous CB1R signaling in DRG neurons does not contribute to a tonic inhibition of nociceptive pain thresholds. However, pain inhibition produced by systemic CB-13 administration in vivo is mediated by CB1Rs on DRG neurons, and is not affected by peripheral MOR signaling. Additionally, CB1R signaling initiated by CB-13 application produced significant HVA-ICa reductions in small DRG neurons, which potentially reduces overall nociceptive signal input to the spinal cord and represents a key ionic..."

Pain

Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22. (PubMed, Biomol Ther (Seoul)) - "The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential."

Journal

Activation of Cannabinoid Receptors Attenuates Endothelin-1-induced Mitochondrial Dysfunction in Rat Ventricular Myocytes. (PubMed, J Cardiovasc Pharmacol) - "In fact, the ability of CB-13 to rescue fatty acid oxidation-related bioenergetics, as well as expression of PGC-1α and CPT-1β, was abolished by pharmacological inhibition of AMPK using compound C and shRNA knockdown of AMPKα1/α2, respectively. Interventions that target CB/AMPK signaling might represent a novel therapeutic approach to address the multi-factorial problem of cardiovascular disease."

Journal • Preclinical • Cardiovascular • Metabolic Disorders

Fluorinated CRA13 analogues: Synthesis, in vitro evaluation, radiosynthesis, in silico and in vivo PET study. (PubMed, Bioorg Chem) - "While most of previous efforts aimed to develop central cannabinoid PET imaging agents, F-labeled compound 7c might be a promising agent serving as a universal CBR/CBR PET imaging agents for diagnosis and therapy of various diseases correlated with peripheral cannabinoid system. It might also serve as a lead compound for development of PET imaging of peripheral and central cannabinoid systems."

Journal • Preclinical

Effects of cannabinoid agonist on human sensory neurons (Neuroscience 2019) - "Patch clamp recordings of human sensory neurons were performed to test changes in membrane properties by cannabinoid receptor activation by CB-13. In these experiments, CB-13 suppressed action potential discharge relative to PGE2 alone supporting the concept that peripherally acting cannabinoid receptors may have the capacity to reduce sensory neuron nociceptive responses."