Discovered in 1940, cannabidiol (CBD) has remained the subject of intensive scientific research over the past eight decades. Amid the rapidly changing landscape of drug policy in the United States, intrepid cannabinoid researchers have done their best to unveil and explore all the potential benefits that CBD might have to offer.
While research into CBD was slow-going until the early 2000s, recent changes in federal drug legislation have opened up a whole new world of preclinical and clinical studies into cannabidiol and its potential medical uses. CBD research has reached a fever pitch over the last decade or so, and it’s unlikely that the ongoing scientific examination of this cannabinoid will slow down any time soon.
In this detailed guide, we will explore 25 of the most important CBD studies and scholarly articles in the order in which they were published. You’ll see for yourself as we progress just how much cannabidiol research has evolved in recent years, and you’ll gain critical insights into what CBD is, how it works, and why so many scientists and laymen around the world have unanimously concluded that this cannabinoid is profoundly beneficial to human health.
1980-2000: Foundational studies and scientific reviews
We start our foray into the world of cannabidiol studies and scholarly articles with one of the earliest portions of CBD’s research history: the 1980s. While CBD had been researched before this decade, it was only in the ‘80s and ‘90s that significant numbers of CBD studies started making their way into prestigious publications. By the turn of the millennium, however, it had already become clear that CBD was very different from THC and that this fascinating cannabinoid would inevitably become a force to be reckoned with.
Initially, CBD researchers were mainly interested in how this cannabinoid interacted with THC. In this landmark 1980 study, the scientific community received its first clue that CBD might change or reduce the effects of THC.
Researchers still didn’t know how these effects came about, but this clinical study showed that “CBD was efficient in blocking most of the effects of Δ9-THC when both drugs were given together.” The participants in this preliminary research reported that using CBD also made the effects of THC “more pleasurable.”
Even as early as 1980, researchers already suspected that there might be a link between cannabidiol and epilepsy. This clinical study involved eight epileptic subjects who received cannabidiol and eight epileptic subjects who received a placebo over the course of nearly five months.
At the end of the study, four out of the eight patients who had been given cannabidiol showed an improvement, but only one member of the placebo group showed any improvement. This study is considered foundational for further research into the potential relationship between CBD and epilepsy.
Huntington’s disease is a rare neurological condition that causes rapid breakdown of central nervous system functions starting in a patient’s 30s or 40s. Due to initial research into CBD that had shown promising results, this 1991 study sought to establish whether CBD could also be useful for Huntington’s disease.
At the end of the clinical study, CBD failed to provide the results that the researchers had anticipated. Regardless, this study provided important data and served as a foundation for further research into the neuroprotective potential of this cannabinoid. It was established, for instance, that CBD remained non-toxic even when administered in quantities as great as 700mg per day over the course of six weeks, emboldening scientists to use this cannabinoid in future clinical trials.
A single case study published in 1995 served as the basis for an ensuing slew of research into the potential benefits of CBD for schizophrenia and other forms of psychosis. In this case study, a 19-year-old female suffering from typical schizophrenia symptoms were treated with cannabidiol, and the researchers conducting the study noted improvements across the board.
In particular, improvements were noted in categories such as “thought disturbance and hostility–suspiciousness,” which are typically associated with schizophrenia. In the 25 years since this study was published, dozens of other researchers have been emboldened to research the potential relationship between CBD and psychosis based on these preliminary results.
By the end of the ‘90s, there was already an amassing body of evidence that CBD offered a surprising array of benefits. Scientists were still puzzled, however, regarding the underlying mechanisms that were causing these apparent benefits, which is part of why this landmark 1998 study has proven so pivotal over the ensuing years.
In this study, scientists noted that CBD appeared to prevent the neurotoxicity caused by glutamate better than either vitamin C or vitamin E, leading them to believe that CBD might have potent antioxidant properties. Ever since, the potential antioxidant power of CBD has remained a critical focus of study within the international scientific community.
2000-2005: Cannabidiol research evolves
Medical marijuana became legal in California in 1996, and this event marked a turning point in the history of CBD more important than perhaps any other. While the rest of the nation was slow to adopt California’s progressive views on Cannabis sativa, the new legal status of marijuana in this state proved that cannabis was on its way into the mainstream. As a result, CBD research became more common, and it became more informative.
6. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis
By the year 2000, scientists had become thoroughly suspicious that CBD might exert anti-inflammatory and antioxidant functions. As a result, researchers decided to perform an animal study into the potential relationship between CBD and rheumatoid arthritis, which has both inflammatory and immune underpinnings.
In the context of this animal model, the researchers found that CBD had “combined immunosuppressive and anti-inflammatory actions” that caused a “potent anti-arthritic effect.” While further research has seemingly confirmed these results, this incredibly important 2000 study was almost single-handedly responsible for popularizing the idea that CBD might have a relationship with rheumatoid arthritis.
Research into the potential beneficial effects of CBD continued to gradually gain momentum throughout the early 2000s, and by 2002, scientists believed that they had accumulated enough evidence to make some conclusions regarding the methods by which CBD affected the body. In this review of the available evidence, researchers reiterated that CBD did not appear to affect any of the traditional cannabinoid receptors but that it seemed to provide “anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties” within the context of the currently available studies.
In 2005, cannabinoid scientists performed a study using the latest neural imaging technologies in an attempt to determine the exact mechanisms by which CBD exerted its observed anxiolytic qualities. Compared to placebo, cannabidiol provided the results the scientists were looking for, and by performing brain scans, it was determined that cannabidiol caused increased blood flow in the “left amygdala–hippocampal complex” and in “a second cluster in the left posterior cingulate gyrus.” This study marked the first time that researchers had attempted to determine the effects of CBD via brain scan, and it indicated that the potential benefits of cannabidiol may be caused by increased cerebral blood flow.
9. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation
Between 2000 and 2005, researchers also started taking a close look at the potential relationship between CBD and pain reduction. There are two main types of pain, neuropathic and inflammatory, and in this 2001 study, scientists sought to establish whether CBD could impact inflammatory pain.
The sensation of inflammatory pain is governed mainly by the TRP family of neuroreceptors with TRPV1 and TRPV2 being the most important. In this study, researchers found that the “TRPV1 receptor could be a molecular target” of CBD, which helped answer questions that had lingered ever since the discovery that CBD does not significantly interact with conventional cannabinoid receptors. This landmark research also raised new questions regarding the ability of CBD to fight pain.
With the results of the above study in mind, prominent cannabis researchers decided to determine the potential effects of CBD on neuropathic pain in 2005. Neuropathic pain is mainly governed by serotonin, and the 5-HT1a receptors are the body’s most abundant serotonin neuroreceptors.
This study further confirmed that CBD’s main actions lay beyond the conventional cannabinoid receptors, and it found that CBD may act as a “modest affinity agonist at the human 5-HT1a receptor.” Based on these results, scientists around the world started taking the potential relationship between CBD and pain much more seriously.
2005-2010: The dawn of the CBD industry
This period in CBD research history can be likened to the faint glow in the sky indicating that dawn will soon arrive. While the CBD industry was still nonexistent outside of medical marijuana states until the following decade, savvy entrepreneurs began looking to the horizon, and cannabis scholars redoubled their efforts to lend a scientific perspective to the inevitable rise of THC, CBD, and other cannabinoids. As a result, we learned more about CBD between 2005 and 2010 than during any previous five-year period.
Building on previous research, this 2006 review of the available evidence sought to more fully establish the antipsychotic and anti-schizophrenia potential of cannabidiol. Citing the fact that CBD appears to reduce the psychosis-inducing effects of THC in multiple animal studies and even in clinical studies involving ketamine-induced psychosis, this scholarly article makes a compelling case for continued research into cannabidiol’s antipsychotic potential.
12. Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing
By 2009, scientists had known for decades that CBD and THC affect the brain in widely different ways. This study, however, sought to determine the differences between the emotional effects these two cannabinoids induce. While the researchers who conducted this study found that THC “increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms,” they did not note any negative emotional effects after administering CBD.
Among other factors, diabetes can be caused by a faulty autoimmune response that produces unreasonable numbers of cytokines, which can cause oxidative stress. In this preclinical study, researchers noted a significant difference between the number of animal subjects that developed diabetes after being treated with CBD versus those that did not receive CBD treatment. The researchers postulate that a potential immunomodulatory function of CBD may be responsible.
14. Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol in Experimental Diabetes
This study took a different route toward uncovering the potential anti-diabetes effects of CBD. Diabetic retinopathy is an ocular condition that can occur in conjunction with type 2 diabetes, and the authors of this 2006 study sought to better understand the relationship between CBD and neurotoxicity. In the end, the researchers found sufficient grounds for further studies into CBD’s potential neurotoxicity and inflammation benefits.
Building off earlier research suggesting a connection between CBD and the 5-HT1a receptors, this study sought to better understand the relationship between CBD and depression. It was found that WAY-100635, a research drug that blocks the 5-HT1a receptors, prevented certain psychological effects of CBD in animals, providing further evidence that CBD may share a deep connection with serotonin. In addition to affecting your state of mind, serotonin is also used in dozens of other critical biological processes.
2010-2015: CBD becomes a global phenomenon
2014 marked a pivotal moment in the history of the CBD industry. Hundreds of entrepreneurs took the passage of the 2014 Farm Bill as the green light to establish general-market CBD brands, and this cannabinoid quickly became the talk of the nation. Taking note that CBD was about to profoundly alter the mainstream of American society, cannabis researchers around the world redoubled their efforts to understand this cannabinoid and its unique effects.
This review of the available evidence marked the first major inquiry into the toxicity and overall safety of cannabidiol. Citing research that had been conducted over the past three decades, this 2011 scholarly article confirmed that CBD has remarkably low toxicity and that this cannabinoid does not cause any serious side effects. Most importantly, this review established that doses of up to 1,500mg of CBD per day were well-tolerated, indicating that it’s practically impossible to overdose on this cannabinoid.
Building off earlier research, this study sought to identify the exact mechanisms responsible for the observed impact of CBD on types of psychosis such as schizophrenia. The researchers who conducted this study ultimately found that CBD modulated concentrations of anandamide in the brain, which is an important neurotransmitter that is associated with feelings of happiness or bliss. The relationship with CBD and anandamide may also be important in areas of psychology beyond schizophrenia treatment.
In this review of the evidence, researchers took a look at the potential usefulness of CBD for cancer treatment. The authors of this review point out that while THC has been used to treat cancer and relieve the symptoms of chemotherapy, this cannabinoid has unwanted psychoactive effects. Since CBD does not have any significant psychotropic effects, this cannabinoid is an obvious target for cannabinoid-based cancer therapy. This review concludes that further investigation into the anti-cancer potential of CBD is certainly warranted.
19. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy
By 2013, public awareness of the potential benefits of CBD for epilepsy had spread like wildfire, and pioneering parents around the country had started giving this cannabinoid to their epileptic children in the hope that it would work miracles. This study surveyed 19 parents of children with intractable forms of epilepsy, and the vast majority of the parents surveyed reported that cannabidiol had exerted beneficial effects.
The most-reported side effects were drowsiness and fatigue. On average, the parents surveyed had tried 12 antiepileptic drugs before resorting to cannabidiol.
This 2015 review summarized the findings of every study that had been conducted into the potential benefits of CBD for anxiety so far. It pointed out that most of the research into CBD for anxiety had been based on acute instead of chronic dosing, which made it hard to determine the potential long-term benefits of using CBD for anxiety. In conclusion, however, the authors of this review reported that there is a pressing “need for further study of chronic and therapeutic effects in relevant clinical populations.”
2015-2020: CBD is now a target of mainstream scientific inquiry
Every year since 2014 has marked monumental changes to the CBD industry. The passage of the 2018 Farm Bill legitimized CBD in America even further, and with the FDA approval of Epidiolex, the first federally sanctioned CBD drug entered the market. The period since 2015 has been the most prolific era of CBD research to date, and here is a small sampling of the data we’ve gleaned during this critical time:
A variety of clinical trials were conducted in the leadup to the approval of Epidiolex as the first CBD-based prescription drug. These trials used larger sample sizes and stricter methodologies than any previous studies, and they delivered some of the most authoritative results to date. This drug trial involved 120 children and young adults with Dravet syndrome, and the results that were reported were highly influential in the Epidiolex approval process.
Over the last few years, scientists have become increasingly interested in the potential interaction between CBD and addictive behaviors. CBD is known to reduce the intensity of the effects of THC, and in this review of the evidence, researchers investigated the potential usefulness of CBD for tobacco and cannabis addiction. This review concludes by suggesting that there’s enough evidence on this subject to merit further studies.
23. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol
In the early days of the CBD industry, researchers and manufacturers didn’t think that isolated cannabidiol and CBD combined with the other constituents of Cannabis sativa flower provided significantly different effects. This 2015 Israeli study, however, pointed out for the first time that CBD appears to be more effective at higher doses when combined with the trace cannabinoids and terpenes that are also present in hemp flower.
This 2019 review of the available evidence compiled 16 studies that had previously been conducted into the potential benefits of CBD for mood disorders such as depression and anxiety. While the researchers determined that not enough studies had been conducted to definitively determine the effectiveness of CBD for mood disorders, they also reported that the research conducted so far has led to an “urgent need for well-designed clinical trials” into this potential application of cannabidiol.
Building on the widespread popularity of the prescription drug Epidiolex and the increasing acceptance of CBD among the general public, this evidentiary review sought to determine the immunomodulatory effects of CBD. The researchers who conducted this review found that CBD interacts both with your nervous system and your immune system, adding to the importance of studying the effects of this cannabinoid on conditions that are improved by immunomodulatory and neuroprotective substances.
Examine the evidence to draw your own conclusions
At this point, so much research has been conducted into the potential benefits of CBD that it’s no longer possible to dismiss this cannabinoid as snake oil or a fad. While we still aren’t exactly sure what these benefits are or how potent they may be, CBD clearly has impressive benefits that merit deep consideration and further research.
Even though the 25 studies we’ve listed above contain a mountain of evidence on their own, we’ve only scratched the surface of the available research on the benefits of CBD. After you’ve taken a close look at the studies we’ve linked, we encourage you to do your own research.While dangerous substances that breed false hope show their true colors in the light of day, substances with true benefits only look better the more that illumination is shed upon them. CBD has nothing to hide, so we strongly encourage you to explore everything this unique cannabinoid has to offer. Visit our blog for more in-depth articles, and contact us if you have any feedback or questions.