Mechanism and optimization of CBD-mediated analgesic effects (Diversity Supplement)

CBD介导的镇痛作用的机制和优化（多样性补充）

• 批准号: 10714331
• 负责人: ZHIGANG HE
• 金额: $ 2.82万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10714331
• 关键词: Absence of pain sensation; Affective; Affinity; Analgesics; Animal Model; Animals; Binding; Brain; CNR1 gene; CNR2 gene; Calcium; Calcium Signaling; Cannabidiol; Cannabinoids; Cannabis; Cannabis sativa plant; Cells; Characteristics; Clinical Research; Clinical Trials; Coupling; Development; Endocannabinoids; Enzymes; Feedback; Future; Hyperactivity; In Vitro; Ion Channel; Label; Maps; Mediating; Medical; Minor; Modeling; Molecular Target; Moods; Mus; Nervous System; Neurons; Pain; Pain management; Parents; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Production; Productivity; Quality of life; Regulation; Reporting; Research; Role; Sativex; Somatosensory Cortex; Spinal; Synaptic Transmission; System; Techniques; Testing; Tetrahydrocannabinol; Therapeutic; Vertebral column; Work; allodynia; behavioral response; cell type; chronic pain management; dosage; endocannabinoid signaling; endogenous cannabinoid system; improved; in vivo; innovation; insight; mouse model; nerve injury; neural; neural circuit; neuromechanism; pain model; pain reduction; pain relief; painful neuropathy; parent project; preclinical study; prevent; receptor; response; sensor; side effect; somatosensory; spared nerve; synergism; therapeutic target; treatment strategy

Project Summary Neuropathic pain is caused by damage to the somatosensory nervous system and the resulting pain has serious consequences to productivity, mood, and overall quality of life. Cannabis sativa has been used for thousands of years as a potent analgesic. However, its main cannabinoid component, delta-9-tetrahydrocannabinol (THC), has strong psychotropic side effects which restrict its usage for pain treatment. The second abundant constituent of cannabis, cannabidiol (CBD), can provide pain relief without major psychotropic effects, but its analgesic effects are not as potent as THC or cannabis. Interestingly, both clinical and preclinical studies suggest that administration of THC and CBD in a fixed ratio results in superior analgesic effects and avoids unwanted side effects. However, the mechanisms underlying the synergistic actions of THC and CBD remain unknown. The parent project to this research supplement aims to identify the neural mechanisms and provide optimization of CBD-mediated analgesic effects. The overall objective for this supplement is to investigate the neural mechanisms underlying the synergistic actions of THC and CBD in order to optimize analgesic potency and minimize psychotropic side effects. In Aim 1, we will determine if THC:CBD engages distinct neural circuit activation patterns compared to single drugs in a neuropathic pain mouse model. In Aim 2, we will determine if THC:CBD engages distinct dynamic coupling between calcium activities and endocannabinoid (eCB) signaling compared to single drugs. These proposed studies will contribute to the parent project’s overall premise of identifying the analgesic mechanisms and improving the therapeutical potentials of cannabinoids by adding an innovative and understudied research component. Revealing specific neural activation and eCB signaling changes induced by THC:CBD will advance not only mechanistic understanding of cannabis synergy, but also therapeutic target identification and optimization.

项目总结