Renato Leonardo de Freitas

Individuals with Autism Spectrum Disorder (ASD) present a high prevalence of neuropsychiatric comorbidities, particularly anxiety disorders, depression, and Attention-Deficit/Hyperactivity Disorder (ADHD). These conditions substantially intensify the clinical, functional, and psychosocial challenges associated with the autism spectrum across the lifespan. This study aimed to analyze, through a narrative review of the literature, the association between ASD and these comorbidities, as well as their impacts on mental health, daily functioning, and overall quality of life. The literature search was conducted in the PubMed, Scopus, and Web of Science databases, prioritizing recent and methodologically relevant studies addressing this topic. The findings indicate that symptomatic overlap between core ASD features and co-occurring psychiatric disorders complicates early identification, differential diagnosis, and clinical management. This overlap often leads to delayed treatment and suboptimal outcomes, underscoring the need for integrated, developmentally sensitive, and personalized diagnostic and therapeutic approaches. In addition, the literature highlights significant structural barriers, including a shortage of trained specialists, limited access to multidisciplinary services, and the lack of targeted public policies, all of which hinder the provision of adequate care for this population. In conclusion, multidisciplinary interventions, combined with social inclusion strategies, community-based support, family and caregiver guidance, and the promotion of neurodiversity, are essential to improve emotional well-being, functional autonomy, and quality of life for individuals with ASD. Such efforts also have a positive impact on families and caregivers, contributing to more equitable and effective mental health care.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior. Although increasing evidence suggests that cannabidiol (CBD) may represent a promising therapeutic strategy for ASD, the preclinical literature remains fragmented, with substantial variability in experimental models, treatment protocols, CBD formulations, and reported outcomes. This systematic review (PROSPERO registration: CRD420251177933) aimed to critically evaluate the psychopharmacological effects of CBD in rodent models of ASD, with an emphasis on behavioral outcomes, underlying neurobiological mechanisms, and methodological quality. A systematic search was conducted in PubMed, Embase, Web of Science, Scopus, and ProQuest Dissertations & Theses, with a final sample of 14 articles. Due to the substantial heterogeneity across studies, a qualitative synthesis of results was performed using the Synthesis Without Meta-analysis (SWiM) approach. Overall, CBD and CBD-based preparations produced beneficial effects across multiple ASD-relevant behavioral domains. Enhanced social interaction, reductions in repetitive behaviors, anxiety-like responses, and cognitive impairments were observed in specific models. Neurobiological analyses revealed modulation of the endocannabinoid system, restoration of excitation/inhibition balance, anti-inflammatory and antioxidant effects, and transcriptional regulation. Positive outcomes were observed across pharmacological, genetic, and maternal immune activation models, suggesting that CBD acts on convergent neurobiological pathways implicated in ASD pathophysiology. Despite these promising findings, important limitations were identified, including substantial heterogeneity in experimental protocols and methodological limitations, such as insufficient reporting of randomization, blinding, and allocation concealment procedures, as well as the underrepresentation of female animals. This review synthesizes behavioral, neurobiological, and methodological evidence on CBD and CBD-based preparations in rodent models of ASD, highlighting its therapeutic potential and the need for more rigorous, standardized preclinical investigations that directly compare isolated CBD with its formulations and combinations.

Background: Chronic neuropathic pain (NP) is frequently accompanied by anxiety- and depression‑like symptoms, reflecting maladaptive interactions between nociceptive and affective brain networks. The anterior insular cortex (AIC) integrates sensory and emotional dimensions of pain and represents a potential target for pharmacological modulation. Cannabidiol (CBD) exhibits analgesic and anxiolytic/antidepressant‑like properties through interactions with endocannabinoid and serotonergic systems. Objectives: We investigated whether CBD microinjection into the AIC modulates NP and its affective comorbidities, and whether these effects depend on CB ₁ and 5‑HT _1A receptors. Methods: Male Wistar rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. Fourteen days later, guide cannulae were implanted into the AIC. On day 21 post‑CCI, animals received intra‑AIC microinjections of CBD (15, 30, or 60 nmol/200 nL) or vehicle. Mechanical (von Frey test) and cold (acetone test) allodynia, anxiety‑like behavior (open field and elevated plus maze tests), and depression‑like behavior (forced swim and sucrose spray tests) were assessed by different psychobiological tests. The role of cannabinoid and serotonergic receptors was addressed by intra‑AIC pretreatment with either the CB ₁ receptor antagonist AM251 or the 5‑HT _1A receptor antagonist WAY-100,635 in independent groups. Results: AIC pretreatment with CBD dose‑dependently reduced mechanical and cold allodynia and anxiety‑ and depression‑like behaviors, with the most robust effects observed at 60 nmol. AIC Pretreatment with either AM251 or WAY-100,635 abolished the antinociceptive and affective effects of CBD. Conclusion: CBD administration within the AIC produces integrated analgesic, anxiolytic, and antidepressant-like effects in a model of neuropathic pain. These effects are consistent with the involvement of CB ₁ and 5-HT _1A receptor signaling. The findings identify the AIC as a relevant cortical substrate linking nociceptive and affective processes and support CBD as a promising psychopharmacological strategy for NP associated with emotional comorbidities.

Neuropathic pain (NP) represents a complex disorder with sensory, cognitive, and emotional symptoms. The medial prefrontal cortex (mPFC) takes critical regulatory roles and may change functionally and morphologically during chronic NP. There needs to be a complete understanding of the neurophysiological and psychopharmacological bases of the NP phenomenon. This study aimed to investigate the participation of the infralimbic division (IFL) of the mPFC in chronic NP, as well as the role of the N-methyl-D-aspartic acid receptor (NMDAr) in the elaboration of chronic NP. Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham-procedure (“false operated”). Electrical neurostimulation of the IFL/mPFC was performed by low-frequency stimuli (20 μA, 100 Hz) applied for 15 s by deep brain stimulation (DBS) device 21 days after CCI. Either cobalt chloride (CoCl₂ at 1.0 mM/200 nL), NMDAr agonist (at 0.25, 1.0, and 2.0 nmol/200 nL) or physiological saline (200 nL) was administered into the IFL/mPFC. CoCl₂ administration in the IFL cortex did not alter either mechanical or cold allodynia. DBS stimulation of the IFL cortex decreased mechanical allodynia in CCI rats. Chemical stimulation of the IFL cortex by an NMDA agonist (at 2.0 nmol) decreased mechanical allodynia. NMDA at any dose (0.25, 1.0, and 2.0 nmol) reduced the flicking/licking duration in the cold test. These findings suggest that the IFL/mPFC and the NMDAr of the neocortex are involved in attenuating chronic NP in rats.