Neuroimmune treatment of advanced solid tumors: 3-year survival after angiotensin 1-7, pineal indoles, and cannabinoids

In a recent study, the exogenous administration of angiotensin 1-7 (Ang 1,7) together with melatonin, 5-methoxytryptamine, and cannabidiol increased 1-year survival in advanced cancer patients, underlining the utility of neuromodulation in oncology. We now report a single-arm interventional study to evaluate the effectiveness of introducing Ang 1-7 in the neuroimmune regime, including pineal indoles and cannabinoids. Two cohorts of patients with advanced solid tumors refractory to standard oncologic treatments and with an estimated life expectancy of less than six months were studied. The full neuroimmune regimen cohort consisted of 100 consecutive patients treated over the last three years with Ang 1-7, pineal indoles, and cannabinoids, while the comparator cohort included 212 consecutive patients treated between 2015 and 2019 with pineal indoles and cannabinoids alone. Gastroprotected capsules of Ang 1-7 coupled with cyclodextrin were administered at 0.5 mg p.o. twice/day. Melatonin (100 mg) and 5-methoxytryptamine (20 mg) were given p.o. at bedtime and in the early afternoon, respectively. Cannabidiol or cannabigerol (in the case of glioblastoma) was given at 20 mg p.o. twice/day. Clinical response, disease control, and overall survival, along with the lymphocyte-to-monocyte ratio, were evaluated. In the full regimen cohort, disease control was achieved in 67 of 100 patients, with objective tumor regression observed in 23%. In the comparator cohort, disease control was obtained in 111 of 212 patients, with objective regression in 8%. Three-year overall survival was significantly higher in the full regimen cohort (37%) compared with the comparator cohort (19%). Both treatments were associated with a significant increase in the lymphocyte-to-monocyte ratio, suggesting an improvement in systemic immune status. The addition of Ang 1-7 to a neuroimmune regimen combining pineal indoles and cannabinoids was associated with improved disease control and long-term survival in patients with end-stage solid tumors lacking effective therapeutic options.