Background and Aims Neuropathic pain is produced by an injury or a disease that affects the somatosensory system, responsible for the sense of touch, pressure, pain, temperature, movement, and vibration, and is still difficult to treat with the pharmacological agents currently available on the pharmaceutical market. The endocannabinoid system appears to be a good target for the treatment of chronic neuropathic pain. A series of scientific reports published in the last 20 years showed the efficacy of some synthetic cannabinoids in various types of pain, especially by acting on CB2 receptors, which supports the hypothesis.

Methods In this study we conducted an acute toxicity assessment for three synthetic cannabinoids selected based on their affinity for CB1 and CB2 receptors, following the recommendations of the OECD Guidelines for Acute Toxicity Testing, this being the first phase of an efficacy study“in vivo”on animal models of chronic neuropathic pain.

Results Our study showed that only one of the substances had toxic effects on the central nervous system, observable in the monitoring stage. Studied substances didn’t have a lethal effect, up to a maximum tested dose of 300 mg orally and 50 mg intraperitoneally.

Conclusions These findings are very important for the next phase of our study as they suggest that at least two of these compounds have low oral and intraperitoneal toxicity.

Funding This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2020–1247, within PNCDI III.