Study: Adding a Naturally Occurring Peptide to Cannabinoid-Based Treatment Linked to Longer Survival in Advanced Cancer Patients

A study involving patients with advanced solid tumors found that combining the peptide angiotensin 1-7, a naturally occurring peptide, to a regimen containing cannabinoids and pineal indoles was associated with a 37% three-year survival rate, compared with 19% among those who received the regimen without it.

Researchers examined 100 consecutive patients who received the full regimen and compared their outcomes with 212 patients treated between 2015 and 2019 with pineal indoles and cannabinoids but without angiotensin 1-7. All participants had advanced solid tumors that had progressed following standard treatments or were considered unsuitable for further conventional treatment, with an estimated life expectancy of less than six months.

The study was interventional but nonrandomized, with the earlier group serving as a historical comparator. A separate historical control group received best supportive care alone. Researchers described the analysis as exploratory and intended to identify associations rather than prove that the treatment caused the improved outcomes.

Patients receiving the full regimen were given 0.5 milligrams of angiotensin 1-7 twice daily, 100 milligrams of melatonin at bedtime and 20 milligrams of 5-methoxytryptamine in the early afternoon. They also received 20 milligrams of cannabidiol (CBD) twice daily. Patients with glioblastoma received cannabigerol (CBG) instead of CBD at the same dosage.

Among patients receiving the complete regimen, 23% experienced an objective reduction in tumor size, including five complete responses and 18 partial responses. Another 44 patients had stable disease, producing an overall disease-control rate of 67%.

In comparison, 8% of patients receiving pineal indoles and cannabinoids without angiotensin 1-7 experienced objective tumor regression. The disease-control rate in that group was 52%, a statistically significant difference.

At three years, 37% of patients receiving the angiotensin 1-7 regimen remained alive, compared with 19% of those receiving pineal indoles and cannabinoids alone. Survival in both groups was higher than among patients who received only supportive care.

Both treatment groups experienced increases in their lymphocyte-to-monocyte ratio, a blood-based marker used by the researchers to assess systemic immune status. A low ratio before treatment was associated with a greater likelihood of disease progression.

The treatments were generally well tolerated, with researchers reporting no clinically relevant biological toxicity or significant reductions in blood pressure. Approximately 6% of patients experienced temporary headaches when beginning melatonin treatment. Patients also reported improvements in pain, anxiety, fatigue, mood and sleep, although these outcomes were subjective.

The authors cautioned that the nonrandomized design and use of historical comparison groups created the potential for selection bias, unidentified differences between the groups and changes in supportive care over time. They said prospective randomized clinical trials are needed to determine whether the regimen is responsible for the apparent survival benefit.