PrNMI’s Two-Week Rat Result Was a Compound-Specific Cannabinoid Tolerance Finding
PrNMI maintained pain-related efficacy during two weeks of treatment in a rat chemotherapy-neuropathy model. That finding concerns one experimental cannabinoid and regimen, rather than proving that cannabis analgesia generally remains unchanged with repeated use.
The study targeted peripheral CB1 receptors
Researchers tested the synthetic, peripherally restricted agonist PrNMI in cisplatin-treated rats. Local, systemic and oral administration reduced mechanical and cold hypersensitivity. Receptor-blocking experiments supported CB1 involvement. Tissue assays examined sensory-ganglion receptor expression.
The positive result had defined boundaries
Daily treatment did not produce appreciable loss of anti-allodynic effect over the observed two weeks. Oral dosing showed similar potency and efficacy between males and females. The study also included an operant pain-related task, extending its observations beyond withdrawal reflexes alone.
Absence of detected tolerance was not lifelong stability
Two weeks of repeated dosing cannot establish that tolerance never develops, or that longer exposure would have the same profile. The investigators also noted that effectiveness in other chemotherapy-neuropathy models required investigation. A cisplatin model is not interchangeable with every source of neuropathic pain.
Keep chemistry, function and species separate
The selected central-effect assessments were favorable at the tested conditions, but they were not human driving or cognitive examinations. PrNMI is not THC and was not a retail cannabis preparation. The paper provides evidence for further development of a particular peripheral-cannabinoid strategy; it does not establish a safe human dose, an impairment-free interval or a general exemption from cannabis tolerance.
Related analysis: Cannabis Tolerance Claims: Questions to Ask Before Relying on Expert Testimony.
Primary research
Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation. Neuropharmacology (2018). DOI: 10.1016/j.neuropharm.2018.07.002.
