Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

Background: Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer’s disease, and cannabinoid-based therapy appears to be a feasible possibility. Case presentation: This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer’s disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-Cognitive Subscale were performed. Conclusions: Here we provide original evidence that cannabinoid microdosing could be effective as an Alzheimer’s disease treatment while preventing major side effects. This is an important step toward dissociating cannabinoids’ health-improving effects from potential narcotic-related limitations.

Background: Preclinical and clinical evidence suggest that low-dose cannabinoids could ameliorate Alzheimer's disease (AD) signs and symptoms. We designed this trial to evaluate the safety and efficacy of low-dose THC-CBD balanced cannabinoid extract in the treatment of patients with AD-associated dementia. Objective: The objective of this phase 2 trial was to evaluate the safety and efficacy of a balanced THC-CBD cannabinoid extract for symptomatic patients with AD. Methods: A Phase 2, randomized, double-blind, placebo-controlled, clinical trial including patients between 60 and 80 years-old diagnosed with AD-associated dementia. For 26 weeks, participants orally received either placebo or THC-CBD extract (0.350 mg/THC and 0.245 mg/CBD), daily. Results: At week 26, Mini-Mental State Exam total score was significantly higher in cannabis- when compared to placebo-treated patients, which was assessed using the mixed model analysis. No significant difference was detected between placebo and cannabis groups in terms of secondary outcomes and adverse events incidence. Conclusions: To this date, this is the longest clinical trial evaluating cannabinoids effects on AD patients. We initially demonstrate that low-dose THC-CBD potentially can be an effective and safe therapeutic option for AD-related dementia. Nonetheless, larger and longer trials are necessary to confirm this finding and establish cannabinoid administration as therapy for AD dementia. Trial Registration: The Brazilian Registry of Clinical Trials (ReBEC) registration #U1111-1258-2058 - REBEC (ensaiosclinicos.gov.br).

Introduction: Canine osteoarthritis (OA) is a prevalent disease characterized by progressive joint degeneration, pain, and impaired mobility. In older dogs, OA affects approximately 80% of the population. Current pharmacological treatments are often limited in efficacy and may cause significant adverse effects. In this context, cannabinoids have emerged as a promising therapeutic alternative. Methods: This double-blind, randomized study aimed to evaluate the efficacy and safety of a full-spectrum cannabis extract in managing OA-related pain and dysfunction in dogs. Seventeen dogs with OA were randomly assigned to receive either the cannabis extract (containing measured amounts of CBD, THC, CBG, CBC, and other cannabinoids) or a placebo for 90 days. Results: Although the cannabis treatment did not significantly reduce pain levels according to the Helsinki Chronic Pain Index (HCPI) [F(1,14) = 0.001, p = 0.981, η ² = 0.000], a reduction of 2.4 points in HCPI scores compared to the placebo was observed at 90 days. Additionally, the treatment proved to be entirely safe, with no significant adverse effects reported. The few mild side effects observed resolved spontaneously within 24 h. Biomarker analysis revealed no significant differences between the cannabis and placebo groups. Conclusion: Our findings suggest that full-spectrum cannabis extract containing CBD and THC is safe for use in dogs for up to 90 days. However, further research is needed to determine the optimal doses and formulations required to effectively alleviate OA-induced pain.

Introduction: Parkinson’s disease (PD) is mainly characterized by motor symptoms including muscle rigidity, resting tremor and bradykinesia. However, the management of the non-motor symptoms represent a relevant clinical challenger in PD. These non-motor symptoms include cognitive and sleep disturbance and there is evidence that cannabinoids may represent alternative and effective treatments for non-motor symptoms of PD.Methods: Therefore, this study addressed the effects of oral treatment with cannabis extract on cognition, insomnia, and daytime sleepiness in six patients with moderate PD. The patients were randomized to receive two different doses of a cannabis extract: THC:CBD 250:28 μg/day (n = 3) or 1000:112 μg/day (n = 3). The assessment of cannabis administration related to the cognitive field was measured by the Montreal Cognitive Assessment test (MoCA test), the insomnia was assessed by the Insomnia Severity Index (ISI), and daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). All clinical evaluations were performed before treatment and at 15, 30, 60, and 90 days of treatment.Results: The statistical analysis indicated a significant benefit of the cannabis extract treatment, at dose of 1000:112 μg/day after 60 days of treatment, on insomnia assessed by ISI. Moreover, the statistical analysis of data from ISI and MoCA tests showed a trend toward improvement over time, while no significant effect was observed in the ESS. There were no reports of significant adverse effects during the cannabis extract treatment.Discussion: These results demonstrate benefits of short-time treatment (60 days) with low doses of cannabis extract on insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.