The modulation of the endocannabinoid system in the treatment of cancer and other systemic human diseases

  title={The modulation of the endocannabinoid system in the treatment of cancer and other systemic human diseases},
  author={Paolo Lissoni and Giusy Messina and Giorgio L. Porro and Roberto Trampetti and Arianna Lissoni and Franco Rovelli and Vezika Cenay and Enrica Porta and Giuseppe Di Fede},
It is known that the endocannabinoid system exerts a fundamental role in the regulation of most biological functions by inducing metabolic, immunomodulatory and psychochemical effects, and in particular it has been shown that brain cannabinoid system plays an essential role in both pleasure perception and pain control [1]. Moreover, the recent discoveries in the area of the Psycho-neuro-endocrino-immunology (PNEI) have demonstrated that immune system-mediated systemic human diseases, including… 

SunText Review of Pediatric Care

The most frequent systemic disease-associated endocrine alteration is represented by an increased adrenal activity concomitantly to a decline in the pineal function, with the following evidence of high cortisol levels in association with a diminished secretion of melatonin (MLT), the main pineal hormone.

A Randomized Study of High-Dose Pineal Hormone Melatonin Alone Versus High-Dose Melatonin Plus Low-Dose Angiotensin-(1-7) in Untreatable Advanced Cancer Patients

The cannabinoid agonists may counteract cancer growth by either exerting a cytotoxic anticancer and anti-angiogenic actions or inhibiting IL-17 secretion, which in contrast stimulates cancer cell proliferation and macrophage release of inflammatory suppressive cytokines, including IL-1beta, IL-6 and TNF-alpha.

Coronavirus-induced severe acute respiratory syndrome (sars) as a possibile expression of fatty acid amide hydrolase (faah) hyper-activation and possible therapeutic role of faah inhibitors in covid19

  • P. Lissoni
  • Biology
    Journal of Clinical Research and Reports
  • 2020
COVID 19-related cannabinoid reduced activity would be due to a virus-induced activation of the enzyme responsible for cannabinoid degradation, the fatty acid amide hydrolase (FAAH), and FAAH inhibitors could exert a therapeutic role in COVID 19 infection.



The psychoneuroimmunotherapy of human immune-mediated systemic diseases, including cancer and autoimmune diseases

The immune responses are inhibited by the opioid system, mainly by acting on mu-opioid receptors, whereas they are stimulated by the pineal-cannabinergic system functional axis, and IL-17-induced immunoinflammatory response occurring in the autoimmune diseases may be counteracted by cannabinoid agonists, which may inhibit IL- 17 secretion.

Pharmacology of cannabinoids.

There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptorSubtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection.

The pineal gland as a central regulator of cytokine network.

  • P. Lissoni
  • Biology, Medicine
    Neuro endocrinology letters
  • 1999
A further knowledge of pineal-cytokine interactions, as well as of other endocrine-immune circuits, will allow a better definition of the physiopathology of human chronic immunoinflammatory diseases, whose clinical course has appeared to be influenced by psychoemotional factors.

Progesterone Up-Regulates Anandamide Hydrolase in Human Lymphocytes: Role of Cytokines and Implications for Fertility1

A clinical study performed on 100 healthy women showed that a low FAAH activity in lymphocytes correlates with spontaneous abortion, whereas anandamide transporter and cannabinoid receptors in these cells remain unchanged, adding the endocannabinoids to the hormone-cytokine array involved in the control of human pregnancy.

Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders

This review highlights advances in the development of FAAH inhibitors of different mechanistic classes and their in vivo efficacy, selectivity and drug-like pharmacokinetic properties.

Expression and function of fatty acid amide hydrolase in prostate cancer

It is demonstrated that fatty acid amide hydrolase (FAAH) was differentially expressed in normal and prostate carcinoma cells and is potentially involved in prostate tumorigenesis.

Structure of neprilysin in complex with the active metabolite of sacubitril

Three-dimensional structure of LBQ657 in complex with human NEP at 2 Å resolution unravels the binding mode of the compound occupying the S1, S1’ and S2’ sub-pockets of the active site, consistent with a competitive inhibition mode.

The role of IL-17 secretion in mediartingtyheinfluebnceiof stress n cabncer and otgherhuansystemicduiseases

  • MOJ Lymphol Phlebol
  • 2018