CB2 receptor drug AM1710 relieved chemo-induced pain and delayed morphine tolerance in mice
The CB2 agonist AM1710 sustainably reduced chemotherapy-induced nerve pain without tolerance and delayed the development of morphine tolerance, but did not work for inflammatory or surgical nerve pain.
Quick Facts
What This Study Found
AM1710 produced sustained relief from paclitaxel-induced nerve pain without tolerance. Prior AM1710 treatment delayed morphine tolerance development and attenuated morphine physical dependence. However, AM1710 failed to reduce pain from inflammatory (CFA) or surgical nerve injury (PSNL) models, showing it is not a broad-spectrum pain treatment.
Key Numbers
AM1710 at 5 mg/kg/day for 12 days delayed morphine tolerance; 10 mg/kg was ineffective in CFA and PSNL models; the drug did not precipitate withdrawal in THC-tolerant mice, confirming it does not block CB1 receptors.
How They Did This
In vitro signaling studies in HEK cells expressing CB2 receptors, plus in vivo testing in mice across three pain models (paclitaxel neuropathy, CFA inflammation, and partial sciatic nerve ligation), with additional morphine tolerance and dependence assessments.
Why This Research Matters
A pain treatment that works through CB2 receptors (not CB1) avoids the psychoactive effects of THC. The added benefit of delaying opioid tolerance could make it valuable as combination therapy.
The Bigger Picture
CB2-selective drugs have long been a goal of pain research because they could provide pain relief without the high. This study maps exactly where AM1710 works (chemo neuropathy) and where it does not (inflammatory and surgical pain), which is critical for clinical development.
What This Study Doesn't Tell Us
Mouse study only. The selective efficacy for chemo neuropathy but not other pain types limits clinical applicability. Signaling profile differences between human and mouse CB2 receptors noted but described as modest.
Questions This Raises
- ?Why does AM1710 only work for chemotherapy-induced pain?
- ?Could combination with other analgesics extend its efficacy to other pain types?
Trust & Context
- Key Stat:
- Pain-type-specific efficacy
- Evidence Grade:
- Preliminary: animal study, though with comprehensive in vitro and in vivo characterization.
- Study Age:
- Published in 2019.
- Original Title:
- Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.
- Published In:
- Molecular pharmacology, 95(2), 155-168 (2019)
- Authors:
- Li, Ai-Ling, Lin, Xiaoyan(3), Dhopeshwarkar, Amey S(2), Thomaz, Ana Carla, Carey, Lawrence M, Liu, Yingpeng, Nikas, Spyros P, Makriyannis, Alexandros, Mackie, Ken, Hohmann, Andrea G
- Database ID:
- RTHC-02136
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is a CB2 agonist?
It is a drug that activates the CB2 cannabinoid receptor, which is involved in pain and inflammation without the psychoactive effects associated with the CB1 receptor that THC primarily targets.
Could this drug reduce opioid dependence?
In mice, prior AM1710 treatment delayed morphine tolerance and reduced physical dependence, suggesting potential as an opioid-sparing combination therapy.
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Cite This Study
https://rethinkthc.com/research/RTHC-02136APA
Li, Ai-Ling; Lin, Xiaoyan; Dhopeshwarkar, Amey S; Thomaz, Ana Carla; Carey, Lawrence M; Liu, Yingpeng; Nikas, Spyros P; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G. (2019). Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.. Molecular pharmacology, 95(2), 155-168. https://doi.org/10.1124/mol.118.113233
MLA
Li, Ai-Ling, et al. "Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.." Molecular pharmacology, 2019. https://doi.org/10.1124/mol.118.113233
RethinkTHC
RethinkTHC Research Database. "Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Dis..." RTHC-02136. Retrieved from https://rethinkthc.com/research/li-2019-cannabinoid-cb2-agonist-am1710
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.