CB2 receptor drug AM1710 relieved chemo-induced pain and delayed morphine tolerance in mice | Research

The takeaway

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.

Pain researchers, oncologists managing chemo neuropathy, and pharmacologists developing CB2-targeted therapies.

Pain-type-specific efficacy

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Preliminary: animal study, though with comprehensive in vitro and in vivo characterization.

When this study was published

Published in 2019.

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.

Questions still open

Why does AM1710 only work for chemotherapy-induced pain? Could combination with other analgesics extend its efficacy to other pain types?

Common 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.

Read the original research

Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.

Molecular pharmacology, 95(2), 155-168

View on PubMed ↗Publisher’s paper ↗

Citation

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