Nociplastic Pain (NP) represents a fundamental shift in our understanding of chronic pain mechanisms. This term describes pain arising from altered pain modulation within the central nervous system, without clear evidence of tissue damage or inflammation. Advances in neuroimaging have revealed that patients with NP exhibit altered resting-state connectivity in the brain, with abnormal functional connectivity in the brain’s pain-processing networks, even in the absence of external or internal painful stimuli. When exposed to pain stimuli, these patients demonstrate exaggerated responses in these networks, indicating an overactive pain-processing system. The pharmacological treatment of NP remains a challenge in clinical practice. Most traditional treatments are not effective at controlling symptoms and often cause poor adherence or even treatment interruption due to undesirable adverse effects. The Endocannabinoid System (ECS) is a homeostasis system considered a neuromodulatory system. The ECS has the capacity of retrograde neuromodulation, balancing this overactive pain processing. The Clinical Endocannabinoid Deficiency theory proposes an underactive ECS in conditions like migraine, fibromyalgia, and irritable bowel syndrome, which are classical examples of NP. This theory posits that low levels of endocannabinoids are responsible for these and other disorders recognized as NP syndromes. This concept is supported by research showing shared symptoms, comorbidity, and the potential benefits of cannabinoid treatments for these specific conditions. This presentation aims to demonstrate the validity of the ECS as an important target for the multimodal treatment of NP, attract the attention of researchers to demonstrate the efficacy and safety of cannabis-based medicines through randomized controlled trials, and promote the development of new therapeutic options that can act on this system to improve the body’s endocannabinoid levels for treating pain and other symptoms associated with this disorder.

Maria Teresa R. J. Jacob is a Medical Doctor and Anesthesiologist specializing in Pain Medicine at Clinique de la Toussaint, Strasbourg, France. She holds the title of Pain Specialist from the Brazilian Medical Association and the Brazilian Society of Anesthesiology. She completed her postgraduate studies in Endocannabinology, Cannabis, and Cannabinoids at the National University of Rosario, Argentina, and obtained a Certificate in Endocannabinology, Cannabis, and Cannabinoids from the Ministry of Education and Culture of Uruguay. She is a speaker at international conferences and has published articles in national and international medical journals. She has been practicing in a private pain clinic since 1992.