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Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.
Singh, Simar; Ellioff, Kaylin J; Bruchas, Michael R; Land, Benjamin B; Stella, Nephi.
Afiliación
  • Singh S; Departments of Pharmacology (S.S., K.J.E., M.R.B., B.B.L., N.S.), Anesthesiology and Pain Medicine (M.R.B.), and Psychiatry and Behavioral Sciences (N.S.), and Center of Excellence in Neuroscience of Addiction, Pain, and Emotion (S.S., K.J.E., M.R.B., B.B.L., N.S.), University of Washington, Seattle
  • Ellioff KJ; Departments of Pharmacology (S.S., K.J.E., M.R.B., B.B.L., N.S.), Anesthesiology and Pain Medicine (M.R.B.), and Psychiatry and Behavioral Sciences (N.S.), and Center of Excellence in Neuroscience of Addiction, Pain, and Emotion (S.S., K.J.E., M.R.B., B.B.L., N.S.), University of Washington, Seattle
  • Bruchas MR; Departments of Pharmacology (S.S., K.J.E., M.R.B., B.B.L., N.S.), Anesthesiology and Pain Medicine (M.R.B.), and Psychiatry and Behavioral Sciences (N.S.), and Center of Excellence in Neuroscience of Addiction, Pain, and Emotion (S.S., K.J.E., M.R.B., B.B.L., N.S.), University of Washington, Seattle
  • Land BB; Departments of Pharmacology (S.S., K.J.E., M.R.B., B.B.L., N.S.), Anesthesiology and Pain Medicine (M.R.B.), and Psychiatry and Behavioral Sciences (N.S.), and Center of Excellence in Neuroscience of Addiction, Pain, and Emotion (S.S., K.J.E., M.R.B., B.B.L., N.S.), University of Washington, Seattle
  • Stella N; Departments of Pharmacology (S.S., K.J.E., M.R.B., B.B.L., N.S.), Anesthesiology and Pain Medicine (M.R.B.), and Psychiatry and Behavioral Sciences (N.S.), and Center of Excellence in Neuroscience of Addiction, Pain, and Emotion (S.S., K.J.E., M.R.B., B.B.L., N.S.), University of Washington, Seattle
J Pharmacol Exp Ther ; 391(2): 162-173, 2024 Oct 18.
Article en En | MEDLINE | ID: mdl-39060165
ABSTRACT
Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/ß-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRABeCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level. SIGNIFICANCE STATEMENT Cannabis has been used by humans as an effective medicine for millennia, including for pain management. Recent evidence emphasizes the therapeutic potential of compounds that modulate endocannabinoid signaling. Specifically, cannabidiol and inhibitors of the enzyme ABHD6 represent promising strategies to achieve pain relief by modulating endocannabinoid signaling in pain pathways via distinct, nonintoxicating mechanisms of action.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor / Transducción de Señal / Endocannabinoides / Analgésicos Límite: Animals / Humans Idioma: En Revista: J Pharmacol Exp Ther Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor / Transducción de Señal / Endocannabinoides / Analgésicos Límite: Animals / Humans Idioma: En Revista: J Pharmacol Exp Ther Año: 2024 Tipo del documento: Article