The topics of this book are the endocannabinoid system and cannabis as a therapeutic agent. Unlike all other physiological systems, the endocannabinoid system does no include any organs, and thus does not resemble other bodily systems; besides, the cannabis plant and its products do not fit the prevailing pharmaceutical model. The conceptual paradigm of both these interrelated fields needs some amendment to promote broader acceptance and practical application.
This book is the result of systematized knowledge acquired during a challenging but immensely fulfilling journey of study and self-education. The author chose self-study out of necessity: despite the fact that the endocannabinoid system is possibly the oldest and most fundamental system in most animals, it is not considered significant enough to be formally taught in institutions of formal education. Its name—historically associated with a once "disreputable" plant—may partly explain this oversight. However, the endocannabinoid system predates both the plant and Homo sapiens by millions of years.
As a physician, I was once cautious, even dismissive, about the therapeutic applications of cannabis. My transformation into an open-minded scholar is owed to exhaustive research into scientific data from the sources, which convinced me that there is something important here that prejudice has long obscured. This book is not merely a collection of medical knowledge—it embodies the transformation of my perspective on a subject that fluctuates between undue stigma and inflated expectations.
The endocannabinoid system—a complex and pervasive network of receptors, endogenous substances, and enzymes—has recently become a focus of research for the scientific community, particularly outside of medicine. Publications largely come from chemists, biochemists, physiologists, pharmacologists, biologists, and botanists, with only a few from physicians. The system’s central role in maintaining health has earned it the title of "orchestra conductor" of our body’s organs. In medical terms, it could be called the homeostatic regulator of bodily functions, though it remains hidden at the molecular level, invisible to clinicians. The intricate role it plays in physiological processes and the relatively short time it has been under systematic study have left many gaps in our understanding, and even more areas of contradictory research findings. It is likely that, with more organized research — better-designed studies that systematically utilize previous findings, follow standardized reporting, and include more clinical practitioners — these issues will gradually be resolved, with answers geared more toward clinical application and less toward theoretical research, which, though abundant, has yet to translate into clinically usable knowledge.
Cannabis and its products have therapeutic applications dating back to antiquity [Clarke & Merlin (2013), Wikipedia: History Of Medical Cannabis]. The lack of detailed records from those times makes it challenging to pinpoint the "first" medical use, but evidence shows that hemp fiber was used in China around 10,000 B.C., likely including its seeds as food, and possibly its flowers for other uses (religious, medicinal, recreational). In the late Neolithic period, cannabis was possibly used as an analgesic in the Netherland area. In Egypt’s 23rd century B.C., we see the first probable record of medicinal use through unclear metaphors, which are difficult to interpret due to cultural distance. However, records from 15th-century B.C. Egyptian papyri are much clearer and more descriptive (Russo, 2007).
Herodotus mentions the medical and veterinary use of cannabis in Greece before the 5th century B.C. (Butrica, 2002). Humanity’s long history with cannabis implies a high safety profile, particularly when used judiciously and under medical supervision for therapeutic purposes. The modern era of scientific cannabis therapy began in California in 1996, with legal approval for the management of symptoms, mainly from adverse effects of chemotherapy (Malhotra, Casari, & Falasca, 2021). Gradually, other states and many countries worldwide followed suit. In 1975, the psychoactive component THC was recognized as a potential antineoplastic agent (Munson, Harris, Friedman, Dewey & Carchman, 1975). Yet, cannabinoids have only been extensively studied over the past two decades. Many are quick to take a stance for or against medicinal cannabis, but it is still too early to draw conclusions. We are at the beginning of a new path, just now being paved. While we already know a lot, only a few of these insights are currently applicable in clinical practice: Ας αν indicative εχαμπλε, οf the 144 known phytocannabinoids, we are familiar with the clinical handling of just five or six. The other compounds and synthetic molecules are not yet well understood.
The medical community must stay informed and take responsibility by engaging in serious education on this subject to avoid falling behind. Currently, activists far outnumber medical professionals, who have the essential training needed to guide patients effectively and safely. With the audacity characteristic of the semi-literate, some activists often impose themselves on the erudite, in whom modesty — and an acute awareness of their own limitations—prevail1 (Kruger & Dunning, 1999).
Typically, medical books are written by researchers with substantial investigative support from large teams. That is not the case here. This book is mainly the product of my own intensive literature review, motivated by the intellectual satisfaction of understanding complex mechanisms and functions in largely "uncharted waters." To a lesser extent, it is supplemented by my own clinical experience gained over time. The goal of this work is to pass on comprehensive and distilled knowledge to healthcare providers interested in exploring the potential of cannabis. Understandably, writing this book required considerable time; therefore, the risk of the information becoming outdated was—and remains—high. However, recording the knowledge, while keeping the possibility of future updates, represents a significant step, realized through this publication.
The endocannabinoid system and the therapeutic use of cannabis do not belong to any specific medical specialty; rather, they are relevant to all physicians and healthcare professionals, albeit with varying requirements in terms of the depth of understanding. Physicians from various specialties generally lack familiarity with essential knowledge, such as Molecular Biology or Biochemistry, necessary for understanding cannabinoids. Therefore, key foundational knowledge is included as footnotes, sparing readers the need to consult other manuals and making prerequisite knowledge readily available. Additionally, each chapter’s extensive bibliography reflects the vast scope of these topics, which cannot be exhaustively covered within the book’s constraints. It is worth noting that the literature on cannabis and cannabinoids is rapidly expanding, necessitating active tracking by any serious scholar.
The messages this book aims to convey are as follows: • The complexity of the endocannabinoid system and the pharmacology of cannabis is great. It is not acceptable to treat cannabinoids "lightly", and in a de-medicalised way. • Cannabis and its products have other uses besides medicine, such as health supplements - not food supplements- lifestyle, euphorics, etc. These uses are fundamentally different from therapeutic use, and the behaviour of medical users is different from that of recreational users (Gruber et al., 2018).The therapeutic use of cannabis should be solely the responsibility of physicians, as should the management of its misuse and abuse. • The medical profession should take its fair share in research and participation in government regulatory committees; nearly all research and regulatory work to date has been carried out by other disciplines. As a result, (a) cannabis is primarily treated as a drug of abuse rather than as a medicine, (b) urgent clinical questions remain unanswered, and (c) financial resources are wasted on unproductive areas of basic research. • It is imperative to remove both stigma and excessive expectations from cannabis. Anything outside the scientific mainstream is harmful. • We need to overcome the conceptual limitations imposed by the dominant pharmaceutical paradigm: Cannabis does not 'fit' into this framework. Insisting on regulating its medical applications based on the prevailing pharmaceutical paradigm—and excessive conservatism—ultimately deprives patients of a valuable medicine; it also complicates its commercial regulation by classifying cannabinoids as novel foods(!)2.
This book has been written as a guide for healthcare professionals—primarily physicians—seeking a deeper understanding and systematization of knowledge related to the endocannabinoid system and the therapeutic use of cannabis. It is also intended as a foundation for further cognitive immersion in the subject. In a context where empirical guidance from well-meaning counselors and activists still predominates, I hope this book will provide a basis for making sound and scientifically grounded therapeutic decisions for patients.
Athens, May 2026
Aias-Theodoros Papastavrou, MD, PhD
Butrica, J. L. (2002). The Medical Use of Cannabis Among the Greeks and Romans. J Cann Therap, 2(2), 51–70. Gruber, S. A., Sagar, K. A., Dahlgren, M. K., Gonenc, A., Smith, R. T., Lambros, A. M., Cabrera, K. B., et al. (2018). The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment. Front Pharmacol, 8. Malhotra, P., Casari, I., & Falasca, M. (2021). Therapeutic potential of cannabinoids in combination cancer therapy. Adv Biol Reg, 79, 100774. Munson, A. E., Harris, L. S., Friedman, M. A., Dewey, W. L., & Carchman, R. A. (1975). Antineoplastic Activity of Cannabinoids2. J Nat Cancer Inst, 55(3), 597–602. Wikipedia: History Of Medical Cannabis. Wikipedia https://en.wikipedia.org/wiki/History_of_medical_cannabis