Table 1.
Synergistic effects on opioid analgesia induced by endocannabinoids.
| Pain Model | Animal | eCB enhancer | Interaction with morphine | Reference | ||
|---|---|---|---|---|---|---|
| AEA | 2-AG | |||||
| FAAH inhibitor | MAGL inhibitor | Acute morphinea (Dose) | Repeated morphineb (Dose, days) | |||
| Inflammatory pain (formalin test) | SD rat | ABD-1970 | Synergistic analgesia (2.49 mg kg−1, s.c.) | Clapper et al., 2018 | ||
| Neuropathic pain (CCI) | C57BL/6J mouse | MJN110 | Synergistic analgesia (0.82 mg kg−1, i.p.) | Reduced tolerance (0.82 mg kg−1, 2× day−1, 6 days) | Wilkerson et al., 2016 | |
| Acute pain (tail-flick) | Wistar rat | URB597 | Reduce tolerance (10 mg kg−1, 2× day−1, 7 days) | Hasanein and Ghafari-Vahed, 2016 | ||
| Neuropathic pain (chemotherapy) | C57BL/6J mouse | URB597 URB937 | Reduction of morphine ED50 | Slivicki et al., 2018a | ||
| Neuropathic pain (CCI) | C57BL/6J mouse | SA-57 (dual inhibitor) | Reduction of morphine ED50 | Without tolerance (1.12 mg kg−1, 2× day−1, 5 days) | Wilkerson et al., 2017 | |
| Acute pain (tail-immersion) | CD1 mouse | URB597 | No interaction (15 mg kg−1, s.c.) | Reduced tolerance (15–30 mg kg−1, 2× day−1, 7 days) | Fotio et al., 2020 | |
| URB937 | No interaction (15 mg kg−1, s.c.) | No interaction (15–30 mg kg−1, 2× day−1, 7 days) | ||||
| Neuropathic pain (chemotherapy) | C57BL/6J mouse | GAT211 (CB1R PAM) | Reduction of morphine ED50 | Without tolerance (10 mg kg−1, 1× day−1, 20 days) | Slivicki et al., 2020 | |
a
The acute dose of morphine when co-administrated with the eCB enhancer.
b
The repeated doses of morphine and treatment duration when co-administrated with the eCB enhancer. URB597 is a BBB-permeable and URB937 is a BBB-impermeable FAAH inhibitors. SA-57 is an FAAH and MAGL dual inhibitor. 2-AG: 2-arachidonoylglycerol; AEA: anandamide; CB1R PAM: CB1 receptor positive allosteric modulator; CCI, chronic constriction injury; eCB, endocannabinoid; FAAH, fatty acid amide hydrolase; i.p., intraperitoneal injection; MAGL, monoacylglycerol lipase; s.c., subcutaneous injection; SD rat, Sprague Dawley rat.