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The effects of 20 mg/kg fluoxetine and different doses of CBD (3, 10 and 30 mg/kg) were evaluated in rats with sciatic nerve injury. The single dose of fluoxetine, the researcher reports, is the amount validated in studies by her own research group for reducing depressive symptoms in rodents. The doses of CBD administered evaluated the rodents’ responses to different dosages.

The animal model was chosen to “promote sciatic nerve constriction with a biodegradable thread while maintaining the sensory effects of pain in the animals.” This model reproduces characteristics common to human neuropathies, such as allodynia, a type of pain caused by normally non-painful stimuli, and hyperalgesia, an increased response to pain, in addition to behaviors related to cognitive impairments and depressive and anxious types, “common comorbidities found in patients with chronic pain,” she adds.

The researchers performed different tests evaluating the animals’ pain perception and response (mechanical stimuli), behavioral depression or despair (cessation of active escape efforts), and anhedonia (inability to feel pleasure in previously enjoyable activities). Among the results, they observed that fluoxetine, as well as the lowest dose of CBD (3 mg/kg), managed to reduce depression. Meanwhile, the other doses of CBD (10 and 30 mg/kg) were more effective in reducing pain sensitivity. “The most consistent analgesic effects were obtained with the highest dose, 30 mg/kg,” the researcher emphasizes.

According to Priscila, the study’s findings “reinforce the potential of CBD, particularly given the therapeutic effects it has demonstrated in various behavioral tests.” She notes that CBD should not yet be considered a replacement for existing treatments, but that “it may represent an additional option within the current pharmacological arsenal.”

Even in the preclinical phase, animal experiments, such as those conducted by the USP group, “are essential to support mechanisms of action and the design of more robust clinical trials that evaluate efficacy, safety, dosage, and routes of administration in humans,” Priscila continues. From these, it will be possible to advance therapeutic validation and, in the future, “incorporate CBD as a viable alternative in medical practice for patients with chronic pain and psychiatric comorbidities, and, thus, its translational application in human populations.”

She also adds that some clinical studies (in humans) already suggest the benefits of CBD in patients with chronic pain and associated depression, involving analgesic, anti-inflammatory and neuromodulatory properties, however “more clinical studies are needed”. Regarding depression, clinical studies have shown potential effects of CBD, especially in people with anxiety comorbidities or in cases of depression resistant to conventional treatment. 

The project was developed as part of physiotherapist Débora Thais Pereira Brito’s undergraduate research at the Laboratory of Neurosciences of Pain and Emotions – Multiuser Center for Neuroelectrophysiology, coordinated by professor Renato Leonardo de Freitas from the Ribeirão Preto Medical School (FMRP). The research team also included professor Christie Ramos Leite-Panissi from FFCLRP; Professor Evelin Capellari Cárnio from the Ribeirão Preto School of Nursing (EERP); Professors Norberto Cysne Coimbra and Hélio Rubens Machado; and doctoral student Ana Carolina Medeiros (FMRP) – all affiliated with USP in Ribeirão Preto.

The article Comparison between Cannabidiol and Fluoxetine effects on chronic neuropathic pain and comorbid depression in rats is available online and can be read here.

More information: priscila.neuro@usp.br, with Priscila Medeiros de Freitas

 *Intern under the supervision of Rita Stella

**Intern under the supervision of Moisés Dorado

English version: Nexus Traduções, edited by Denis Pacheco