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The History of CBD: Ancient Roots, Scientific Breakthroughs, and Future Potential

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In order to understand the future of CBD, the history of cannabis needs to be explored. As we’ll cover in this article, the terms CBD, hemp, cannabis, and marijuana are all related and each part of exploring the same unique plant.

My exposure to medical cannabis came over a decade ago when patients began asking if cannabis could potentially help with the pain they were experiencing. I have been fascinated by the subject ever since, and now know that having an understanding of the medical potential of cannabis and CBD, for many common human conditions, can be of huge benefit to someone.

Here’s a short read on the history and future of CBD. If you would like to understand more about how CBD works in the body, we cover this in an article about the endocannabinoid system.

Let’s start at the beginning.

Ancient Origins: Medical Cannabis in Early Medicine

The relationship between humans and cannabis stretches back millennia, with the earliest documented use appearing in a Chinese pharmacopeia dating to approximately 2900 BCE. Emperor Shen Nung, revered as the father of Chinese medicine, documented the cannabis plant in his compendium of medicinal herbs around 2700 BCE, noting its potential for treating various ailments including gout, rheumatism, and malaria.

“Cannabis is a very important medicine that has been used for thousands of years. The ancients used it to achieve harmony and balance within the body.” - Emperor Shen Nung’s pharmacopeia (as translated by modern scholars)

Archaeological evidence confirms that cannabis played a vital role in many ancient civilizations. The ancient Egyptian Ebers Papyrus (circa 1550 BCE) references cannabis for treating inflammation and pain. In India, cannabis preparations known as “bhang” were used in Ayurvedic medicine and religious ceremonies as early as 1000 BCE. Greek physician Pedanius Dioscorides included cannabis in his seminal work “De Materia Medica” around 70 CE, describing its utility for treating ear pain and inflammation.

Cannabis seeds were also utilized by ancient cultures for various purposes, including the production of cooking oil, highlighting the plant's versatility beyond its psychoactive and medicinal properties.

With a brief glimpse into the ancient historical use of cannabis as a medicine it is surprising, dumbfounding, and difficult to explain the negative stigma cannabis has held over the past century. But interestingly science is countering that stigma and returning cannabis to its long held position as a medicinal herb with many beneficial applications.

The Rise of Medical Cannabis

Early Isolation Efforts

British chemist Robert S. Cahn reported the partial structure of cannabinol (CBN) in 1940, marking the first significant step toward understanding cannabinoids at a molecular level and highlighting the historical significance and medicinal use of cannabis extracts. Shortly thereafter, American chemist Roger Adams made history by isolating cannabidiol (CBD) from wild hemp in 1942. Adams’ pioneering work laid the foundation for cannabinoid research, though he didn’t fully characterize CBD’s structure at the time. “The isolation of these compounds opened entirely new avenues for investigation into plant chemistry and pharmacology.”  -  Roger Adams, in his 1941 paper on cannabis compounds.

In 1963, Israeli scientist Dr. Raphael Mechoulam achieved a landmark breakthrough by identifying CBD’s stereochemistry and exact chemical structure. A year later, he and his team isolated and characterized tetrahydrocannabinol (THC), the compound responsible for cannabis’ psychoactive effects.

The Endocannabinoid System Discovery

Perhaps the most significant discovery came in the late 1980s and early 1990s, when researchers identified the endocannabinoid system (ECS) — a complex cell-signaling system present in all vertebrates. In 1988, Dr. Allyn Howlett and her team discovered cannabinoid receptors in rat brains. By 1990, Dr. Lisa Matsuda and colleagues at the National Institute of Mental Health successfully cloned the CB1 receptor.

"The discovery of the endocannabinoid system has transformed our understanding of human physiology and pathology. It represents one of the most important scientific advances in recent decades." — Dr. Vincenzo Di Marzo, endocannabinoid researcher

I find it fascinating to consider that a system as prevalent as the the endocannabinoid system went undiscovered until a few decades ago. The analogy would be to have not discovered the nervous system until the 80’s.

In 1992, Mechoulam, along with Dr. William Devane and Dr. Lumir Hanuš, discovered anandamide, the first endogenous cannabinoid (endocannabinoid) produced naturally by the human body. This groundbreaking work revealed that humans produce compounds similar to those found in cannabis, which bind to the same receptors.

"Discovering anandamide was like finding a lock and then realizing the body makes its own keys." — Dr. Lumir Hanuš, on the discovery of endocannabinoids

CBD in the Cannabis Plant

CBD, or cannabidiol, is one of the many compounds found in the cannabis plant, specifically in Cannabis sativa. This complex organism contains over 500 identified cannabinoids and terpenes, each contributing to the plant’s unique properties. Among these compounds, CBD stands out for its non-intoxicating nature and wide range of medicinal properties.

CBD is found in higher concentrations in the hemp plant, a variety of Cannabis sativa. This has made hemp-derived CBD products particularly popular, as they are legally distinct from marijuana and more widely accepted. The extraction of CBD from the cannabis plant can now be achieved through various methods, including solvent-based extraction and CO2 extraction. These processes ensure that the final product is pure and potent, free from unwanted contaminants. The extraction and isolation of cannabinoids now allows for the commercial availability of other cannabinoids as well like CBG and CBN.

The quality and potency of CBD products depend heavily on the quality of the cannabis plant used in production. High-quality hemp plants, grown under optimal conditions, yield superior CBD extracts. As the demand for CBD continues to grow, ensuring the quality and consistency of the cannabis plants used in production remains a top priority for reputable manufacturers.

Unlike THC, the compound responsible for the psychoactive effects of cannabis, CBD does not produce a “high.” This makes it an attractive option for those seeking the medicinal benefits of cannabis without the intoxicating effects.

Legal Evolution and Policy Shifts

The legal status of cannabis and CBD has undergone dramatic transformations over the past century, directly impacting research capabilities and medical applications.

Cannabis was classified as a narcotic drug under international treaties like the United Nations Single Convention on Narcotic Drugs in 1961, which significantly influenced global efforts to control its usage and distribution.

Prohibition Era and the Marihuana Tax Act

The 1937 Marijuana Tax Act effectively criminalized cannabis throughout the United States, severely restricting access even for medical research. Dr. William C. Woodward of the American Medical Association opposed the legislation, testifying:

“The American Medical Association knows of no evidence that marijuana is a dangerous drug… To say that further research is necessary before making marihuana available for medical purposes is ignoring the fact that considerable research has already been done.”

William O'Shaughnessy played a pivotal role in introducing cannabis to Western medicine during the 19th century. His research and scientific studies on the plant's medicinal properties led to its acceptance and recognition within Western medical practices, influencing future cannabis research and clinical applications.

Despite his testimony, cannabis prohibition persisted, and the 1970 Controlled Substances Act classified cannabis as a Schedule I substance with “no accepted medical use” - creating nearly insurmountable barriers to research.

Modern Legal Reforms

Medical Research Breakthroughs

The past decade has seen an explosion in clinical research on CBD and other cannabinoids, yielding significant medical advances.

CBD oil, derived from cannabis plants, is often highlighted for its various extraction methods and the importance of purification. The legal implications and lack of regulation concerning its use in dietary supplements and food products are also critical areas of discussion.

FDA-Approved Cannabinoid Medications

In 2018, the FDA approved Epidiolex (cannabidiol) for treating seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, two rare and severe forms of epilepsy. This milestone marked the first FDA-approved drug derived directly from the cannabis plant."

The approval of Epidiolex represents a significant milestone in neurology and pediatric care. For the first time, we have a pharmaceutical-grade CBD medication proven effective for patients with these devastating forms of epilepsy." - Dr. Orrin Devinsky, director of NYU Langone's Comprehensive Epilepsy Center and lead investigator in the Epidiolex trials

In 2023, Epidiolex received expanded approval for treating seizures associated with tuberous sclerosis complex, further validating CBD's therapeutic potential.

Emerging Research Areas

Recent clinical studies have explored CBD's potential in treating anxiety disorders, with a 2023 meta-analysis in the Journal of Psychiatric Research suggesting significant anxiolytic effects in controlled trials. Research published in the Journal of Clinical Investigation has indicated promising results for CBD in treating treatment-resistant PTSD.

"The preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, and post-traumatic stress disorder when administered acutely. However, few clinical studies of CBD for anxiety have been conducted, and those that exist have significant limitations." - Dr. Esther Blessing, assistant professor at NYU Langone Health

Investigations into CBD's anti-inflammatory and neuroprotective properties have also advanced substantially. A 2024 review in Frontiers in Pharmacology highlighted CBD's potential for treating neuroinflammatory conditions, including multiple sclerosis and Alzheimer's disease.

Industry Growth and Trends

The hemp-derived CBD sector is expected to dominate the global CBD market, accounting for over 70% of the total market share by 2025. This dominance stems from the legal distinction between hemp and marijuana, with hemp-derived products enjoying broader acceptance and accessibility worldwide.

The increasing recognition of cannabis's therapeutic benefits, combined with greater product availability, continues to drive the medical cannabis industry forward at an impressive pace.

Marketing and Quality Control

With the CBD market experiencing explosive growth in recent years, a wide array of products are now available for purchase in the US and many other countries around the world. However, this rapid expansion has also highlighted significant concerns regarding quality control and marketing practices within the industry. Many CBD products are marketed with unsubstantiated claims, which can be misleading to consumers seeking reliable and effective treatments.

The FDA has begun to address these issues by cracking down on companies making false or misleading claims about their CBD products. This regulatory oversight is crucial in ensuring that consumers receive accurate information and that products meet safety standards. Quality control is essential in the CBD industry, as products can be contaminated with residual solvents, pesticides, and heavy metals if not properly monitored.

Reputable companies prioritize quality control and transparency, providing consumers with detailed information about their products, including third-party lab test results. This commitment to quality helps build consumer trust and ensures that products are safe and effective. As the global CBD market continues to grow, with projections indicating significant expansion in the coming years, the demand for high-quality CBD products is expected to rise.

To meet this demand, the industry must prioritize quality control and transparency. This includes rigorous testing, clear labeling, and adherence to regulatory standards. By doing so, the CBD market can continue to thrive, offering consumers safe and effective products that harness the therapeutic potential of the cannabis plant.

Regulatory Developments

The regulatory landscape continues to evolve in the US and around the world. In December 2023, the European Food Safety Authority (EFSA) resumed its safety evaluations of CBD as a novel food ingredient after previously pausing assessments due to data gaps. The UK's Food Standards Agency established a regulatory pathway for CBD products, requiring novel food authorization for CBD products to remain on the market.

"The rapid commercialization of CBD has outpaced regulatory frameworks. This creates both opportunities and risks for consumers, highlighting the need for evidence-based regulations that ensure product safety and accurate labeling." — Dr. Ruth Macklin, bioethicist and professor emerita at Albert Einstein College of Medicine

The Future of CBD Science and Applications

The next frontier of CBD research encompasses several promising directions that could significantly expand its therapeutic applications.

Personalized Cannabinoid Medicine

Researchers are investigating how genetic factors influence individual responses to cannabinoids. Dr. Ethan Russo's research on the "entourage effect" — the synergistic interaction between various cannabis compounds — suggests that personalized formulations may be more effective than isolated compounds for certain conditions.

"The future of cannabinoid medicine likely involves tailored combinations of cannabinoids and terpenes optimized for individual patients and specific conditions. This precision approach could revolutionize treatment outcomes." — Dr. Ethan Russo

Pharmaceutical Development

Major pharmaceutical companies are investing in cannabinoid drug development. In 2024, there are over 60 cannabinoid-based drugs in various stages of clinical trials, targeting conditions ranging from chronic pain and epilepsy to neurodegenerative diseases and psychiatric disorders.

"We're just beginning to understand the therapeutic potential of the cannabis plant. With over 100 cannabinoids identified and only a handful studied in depth, we've merely scratched the surface of what cannabinoid medicine may offer." — Dr. Marcel Bonn-Miller, cannabis researcher

Advanced Delivery Systems

Innovations in drug delivery technologies are enhancing CBD's bioavailability and targeting capabilities. Nanoemulsion technology has enabled water-soluble CBD formulations with improved absorption rates, while liposomal encapsulation allows for targeted delivery to specific tissues.

"The challenge with cannabinoids has always been their hydrophobicity and variable absorption. New delivery systems like nanoemulsions and transdermal technologies are revolutionizing how effectively we can deliver precise cannabinoid doses to where they're needed in the body." — Dr. Natalia Reoutova, pharmacologist specializing in cannabinoid pharmacokinetics

Conclusion: CBD's Continuing Evolution

From ancient Chinese medicine to cutting-edge pharmaceutical research, CBD's journey represents an extraordinary convergence of traditional wisdom and modern science. What began as observations of a plant's healing properties has evolved into a sophisticated understanding of a complex biological system that influences nearly every aspect of human physiology.

The story of CBD is far from complete. As research capabilities expand and regulatory barriers diminish, our understanding of this remarkable compound continues to deepen. The coming decades promise further discoveries that may fundamentally transform our approach to treating numerous conditions and enhance our understanding of human health.The evolution of CBD from herbal remedy to pharmaceutical ingredient exemplifies the value of investigating traditional medicines through the lens of modern science. It reminds us that sometimes ancient wisdom contains profound truths awaiting scientific validation.

References

• Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual Review of Psychology, 64, 21-47.
• Devinsky, O., et al. (2018). Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. New England Journal of Medicine, 378(20), 1888-1897.
• Russo, E. B. (2019). The case for the entourage effect and conventional breeding of clinical cannabis: No "strain," no gain. Frontiers in Plant Science, 9, 1969.
• Blessing, E. M., et al. (2015). Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics, 12(4), 825-836.
• Grand View Research. (2024). Cannabidiol Market Size, Share & Trends Analysis Report By Source Type, By Distribution Channel, By End-use, By Region, And Segment Forecasts, 2024 - 2030.
• Di Marzo, V. (2018). New approaches and challenges to targeting the endocannabinoid system. Nature Reviews Drug Discovery, 17(9), 623-639.
• Zuardi, A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Revista Brasileira de Psiquiatria, 30(3), 271-280.
• Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. British Journal of Pharmacology, 153(2), 199-215.
• Bridgeman, M. B., & Abazia, D. T. (2017). Medicinal cannabis: History, pharmacology, and implications for the acute care setting. Pharmacy and Therapeutics, 42(3), 180-188.
• Maccarrone, M., et al. (2015). Endocannabinoid signaling at the periphery: 50 years after THC. Trends in Pharmacological Sciences, 36(5), 277-296.