*2.4. Cisplatin-Induced Neuropathy*

Peripheral neuropathy was induced by injecting mice with 5 mg/kg of cisplatin intraperitoneally (IP) once weekly for four weeks, as previously described [13,18]. The mice were co-administered 1 mL of 4% sodium bicarbonate solution subcutaneously prior to the cisplatin injection to reduce nephrotoxicity and to minimize compromised renal functions [13,18]. Mechanical allodynia was assessed using an electronic von Frey anesthesiometer equipped with a semi-flexible polypropylene super-tip (IITC Life Science Inc., Woodland Hills, CA, USA), these assessments were made before and after cisplatin treatment to confirm neuropathic pain state, as described below (Data from the pre and post cisplatin assessments are presented in Supplemental Figures S1–S3).

#### *2.5. Von Frey Testing*

Hypersensitivity to mechanical pressure was assessed using an electronic von Frey anesthesiometer (IITC Life Sciences Inc.). For testing, mice were placed in small acrylic chambers on a wire mesh table (IITC Life Sciences Inc.). Animals were allowed to acclimate to the chamber for 20 min prior to testing. The von Frey anesthesiometer was equipped with a semi-flex tip (IITC Life Sciences Inc.), that was applied to the plantar surface of the right hind-paw with increasing force to prompt a withdrawal response. The averages from three tests were calculated with each test being separated by a minimum of 3 min. To measure the effects of test compounds, neuropathic mice were randomly assigned to one of 6 groups and injected intraperitoneally (i.p.) with vehicle (DMSO, Tween 80, saline (1:1:18), i.p.), THC at 6 mg/kg, THC and CBD in combination at 4 mg/kg and 2 mg/kg; 3 mg/kg and 3 mg/kg; 2 mg/kg and 4 mg/kg, respectively, or CBD at 6 mg/kg 1 h prior to tests. These groups represent THC:CBD ratios of 1:0, 2:1, 1:1, 1:2, or 0:1, as shown in Table 1. All von Frey measurements were performed by experimenters blinded to treatments.


**Table 1.** Dose of cannabinoid administered at each ratio for pure compounds.
