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%Start What Is the Endocannabinoid System? Cannabinoids, Receptors, Research and More Everyday Health MenuNewslettersSearch Neurology
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In the course of this work, scientists discovered that the human body has cannabinoid receptors — cell proteins that respond to chemicals — distributed throughout the body. They also discovered that the human body makes a class of chemicals known as endocannabinoids that interact with these receptors to affect health. Two of the main active compounds in cannabis, THC (tetrahydrocannabinol) and CBD (cannabidiol) — called plant or phytocannabinoids — are chemically similar to the natural endocannabinoids produced by the human body.
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The discovery of the ECS, coupled with the awareness of plant cannabinoids and the opportunity to make synthetic (or human-made) versions has generated a substantial amount of scientific interest in understanding how cannabinoids might be used to maintain health and alleviate symptoms of disease.
Common Questions & Answers
What does the endocannabinoid system do?Endocannabinoids are molecules produced by the body to maintain homeostasis (stability) in response to changes in the environment.
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The endocannabinoid system interacts with all of the major systems and organs in the body to enable and restore optimal functioning.What’s the difference between plant cannabinoids and endocannabinoids?The word “cannabinoid” usually refers to a chemical found in the cannabis (marijuana or hemp) plant. "Endo," in this context, refers to substances produced inside the body.
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Endocannabinoids are, in effect, the body’s own source of cannabis-like substances.How do CBD and THC interact with the endocannabinoid system? CBD and THC are plant cannabinoids, which operate much as endocannabinoids do, by attaching to certain receptors on the outsides of cells and altering the behavior of those cells or the bodily systems they are a part of.How do cannabinoids affect the body? Cannabinoids and endocannabinoids can affect pain perception, memory, mood, appetite, and many other bodily systems.
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The endocannabinoid system regulates the release of other neurotransmitters — that’s how it maintains homeostasis — and helps the body heal from any damage it sustains. Plant cannabinoids can similarly enhance feelings of well-being, but they can have undesirable side effects as well, particularly in young people.Are there ways to enhance your endocannabinoid system? Research suggests that endocannabinoids can be boosted by certain foods, such as those containing essential fatty acids, chocolate, herbs, spices, and teas, as well as by stress-reducing activities.
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See all in NeurologyWhat Is the Endocannabinoid System Made Of
The endocannabinoid system is primarily made up of three parts.Endocannabinoids
Endocannabinoids are neurotransmitters derived from fat (lipids). The body makes endocannabinoids naturally (“endo” means originating in the body).
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Researchers have extensively studied two major endocannabinoids, each of which plays a distinct role within the ECS:Arachidonoyl ethanolamide (anandamide, AEA), also known as the “bliss” molecule2-arachidonoyl glycerol (2-AG)
These endocannabinoids are synthesized on demand, meaning the body makes them when needed rather than producing them in advance.
Endocannabinoid Receptors
Endocannabinoids bind with endocannabinoid receptors, which reside on the surface of a variety of types of cells throughout the body, to trigger a physiological response. Researchers have focused on two endocannabinoid receptors in particular:Cannabinoid 1 (CB1) Receptors Most of these are in the central nervous system, especially neurons (nerve cells) in the brain.
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Both anandamide and THC (the compound in cannabis that makes people feel high or stoned) bind with CD1 receptors.Cannabinoid 2 (CB2) Receptors These are located mainly on immune cells but are also found in the central nervous system. The endocannabinoid 2-AG binds with CB2 receptors.
Enzymes
Enzymes are responsible for both producing endocannabinoids and breaking them down when they are no longer needed.
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There are two major enzymes that break down endocannabinoids:
Fatty acid amide hydrolase (FAAH), which breaks down anandamideMonoacylglycerol (MAG-L), which breaks down 2-AG
Condition Kitchen Bites Cacao Smoothie
What Does the Endocannabinoid System Do
Scientists believe the main purpose of the ECS is to maintain homeostasis — biological harmony — in response to changes in the body’s external and internal environment. While scientists initially believed that the ECS only affected the brain and nerves, they now agree that it exerts an influence on almost every part of the body: skin, bone, fat tissue, liver, pancreas, skeletal muscle, heart, blood vessels, kidneys, the gastrointestinal tract, and more. Researchers are continuing to investigate the many complex ways in which the ECS interacts with the central nervous system, the peripheral nervous system, the immune system, the digestive system, the reproductive system, virtually all the major organs, and many other parts of the human body.
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Since their discovery, endocannabinoids have been found to play a role in:Pain sensation
ThermoregulationMemoryMoodAppetiteStressSleepMetabolismImmune functionReproduction
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The discovery of the ECS and studies investigating how it works have pointed to a number of ways to use both natural and laboratory-made forms of the cannabinoids THC and CBD therapeutically.Currently, two drugs (Marinol, Syndros) containing the synthetic form of THC — called dronabinol — are approved by the U.S. Food and Drug Administration (FDA) for nausea and vomiting caused by chemotherapy regimens used to treat many cancers, as well as loss of appetite and weight loss related to HIV/AIDS.
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The drug nabilone (Cesamet) has a chemical structure similar to THC and is approved to treat nausea associated with cancer chemotherapy. Synthetic cannabidiol (Epidiolex) was approved by the FDA in 2018 to treat certain rare pediatric seizure disorders, including:Dravet syndromeInfantile spasmsLennox-Gastaut syndromeTuberous sclerosis complex
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Research in Other Issues Potentially Helped by the ECS
A landmark study published in 2017 by the U.S. National Academy of Sciences, Engineering, and Medicine stated that there is “substantial” evidence that cannabinoids are effective for:Chronic painNausea and vomiting during chemotherapySpasticity (tightness and involuntary muscle spasms) in multiple sclerosisThe study cited “moderate" evidence that cannabinoids are effective for: Improving sleep in people with conditions such as chronic pain, obstructive sleep apnea, and fibromyalgia The study concluded that the evidence is “limited but promising” for the use of cannabinoids as treatment for:Post-traumatic stress disorder (PTSD)Tourette’s syndromeSocial anxietyTraumatic brain injury Since the study was first published, numerous clinical trials and reviews also suggest a potential role for cannabinoids for:Palliative careSkin disordersLupusDiabetesBacterial infectionsAutism Everyday HealthThe Endocannabinoid System CBD and THC How They Interact
CBD binds only weakly with CB1 and CB2 receptors, exerting its influence on the ECS in a number of more indirect ways.For instance, CBD can block the enzymes that break down anandamide, boosting levels of this feel-good endocannabinoid.
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Researchers have launched preliminary studies looking at the therapeutic potential of CBD as a treatment for a wide variety of disorders ranging from anxiety
to opioid addiction. Compared with CBD, THC binds strongly with CB1 and CB2 receptors to influence pain, spasticity, sedation, appetite, and mood.
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It also has 20 times the anti-inflammatory power of aspirin, and twice that of steroids like hydrocortisone. In addition, THC interacts with a variety of other receptors and enzymes in the body, with research suggesting a variety of potential benefits in terms of treating addiction, and even helping to reduce complications during organ transplant surgery.
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The Role of Minor Cannabinoids
Although CBD and THC garner most of the attention, the cannabis plant actually contains numerous other cannabinoids that researchers are starting to look at more closely. These minor cannabinoids (called “minor” because they occur in lower amounts than CBD and THC), include cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN), as well as others. The cannabis plant also contains metabolites called “terpenes” that are responsible for its color and smell and for promoting its therapeutic properties.Together, the major and minor cannabinoids and terpenes work together to provide therapeutic benefits; this complementary action is called the “entourage effect.”Are There Ways to Enhance the ECS
As scientists unravel the numerous mysteries of the ECS, they are also learning that certain spices such as black pepper and oregano — and foods such as truffles and dark chocolate — may enhance the activity of the ECS.
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For example, the essential oils of black pepper and oregano contain a dietary cannabinoid called beta-carophyllene (BCP), a substance that is well known for its anti-inflammatory and pain-relieving effects due to its ability to stimulate the CB2 receptors. Beta-carophyllene is also widespread in lemon balm, cloves, and hops. Truffles are not only highly prized by chefs across the globe, but research also suggests that they inexplicably contain high concentrations of AEA — amounts that are sufficient enough to activate the CB1 and CB2 receptors.
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Dark chocolate is also a food cannabinoid and one that lives up to its reputation as the food of the gods. Cacao beans possess two compounds, N-oleoyl ethanolamine and N-linoleoyl ethanolamine, that inhibit FAAH so that the blissful effects of anandamide are prolonged.
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But these examples are just the tip of the iceberg. Dietary intake of specific plants and vegetables that contain prebiotic dietary fiber like inulin or fructans — types of fiber that help stimulate the growth of healthy bacteria in the gut — are also believed to stimulate the ECS in beneficial ways.
Discovery of the Endocannabinoid System A Timeline
Mid-1960s The Israeli researcher Raphael Mechoulam, PhD, and his colleagues identify CBD and THC as active compounds in cannabis.
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In the following decades scientists will study the pharmacology, biochemistry, and clinical effects of these cannabinoids, but will struggle to understand how they exert their effects. The prevailing theory was that THC worked by disturbing cell membranes and changing cellular behavior. The idea that there are cannabinoid receptors located throughout the body would not gain traction until much later.
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1988 The researcher Allyn Howlett, PhD, and her lab at St. Louis University in Missouri, use a new technique called radiolabeling to identify “high-affinity binding sites” — cannabinoid receptors — in rat brains.
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1990 Scientists succeed in cloning the CB1 receptor in rats and humans. 1992 Dr.
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Mechoulam’s lab identifies anandamine. 1993 A researcher at Cambridge University in England becomes the first to clone the CB2 receptor. 1995 Mechoulam’s lab discovers 2-AG.
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Clinical Endocannabinoid Deficiency A Hypothesis
One theory about how the endocannabinoid system contributes to certain illnesses is that there is such a thing as clinical endocannabinoid deficiency (CED or CCED), a lack of balance in endocannabinoid levels, density of receptors, and enzyme activity. Some researchers suspect that CED, whether genetic or caused by injury or disease, can lead to a variety of medical conditions, including:MigraineIrritable bowel syndrome (IBS)Fibromyalgia, a chronic disorder marked by pain and tenderness throughout the body as well as fatigue Supporting the CED hypothesis are clinical data showing that, for people with the above conditions, cannabinoid treatment (medicinal cannabis, pharmaceutical cannabinoids, and their synthetic derivatives) and other changes aimed at the ECS may decrease pain and improve sleep, among other benefits.Glossary of the Endocannabinoid System
The ECS system is complex and, for nonscientists, so is the vocabulary used to describe it.
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Still, familiarizing yourself with the key terms will make it easier to understand current research aimed at utilizing the power of the ECS to prevent illness, treat disease, and maximize health and well-being. Learn More About the Language of the ECS
Resources We Love
The endocannabinoid system plays a vital role in helping your body perform many daily functions.
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If you’re searching for more information on how this complex system operates or to enhance your knowledge about the health benefits of cannabis, look no further. Here are Everyday Health’s most recommended resources for understanding the endocannabinoid system.
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Favorite Orgs for the Endocannabinoid System
Society of Cannabis Clinicians This educational and scientific society is composed of physicians and healthcare professionals who are dedicated to the support of cannabis for medical use. We like their research library, which lets you browse through different studies covering the use of cannabis for specific health conditions.
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Project CBD
This nonprofit educational organization is dedicated to promoting and publicizing research about the medical use of cannabis. Additionally, their site provides in-depth information about the endocannabinoid system and its many functions.
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District of Columbia Department of Health
The DC Department of Health’s online slide show "An Introduction to the Biochemistry & Pharmacology of Medical Cannabis" provides a wealth of information about the history of cannabis, its use in medicine, and the endocannabinoid system as a whole. ProCon.org
This nonprofit offers resources for critical thinking and ways to educate the public without bias.
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As its name implies, the site presents both pros and cons about many controversial issues, including medical marijuana use. United Patients Group
The United Patients Group is a trusted resource for medical cannabis information.
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The organization offers continuing medical education (CME) courses and one-on-one consulting for physicians and medical institutions. Don’t miss their Medical Directory, which provides a list of professionals that embrace the use of medical cannabis and other integrative health practices. The Medical Cannabis Institute
When it comes to education, this group has got you covered.
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The Medical Cannabis Institute provides online, science-based continuing education for healthcare professionals. Their goal is to better prepare those who treat patients who might benefit from or are already using medical cannabis.
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They also aim to educate researchers seeking to gain a broader understanding of the endocannabinoid system.
Favorite Online Support and Advocacy Networks
Weed for Black Women Weed for Black Women is a new organization dedicated to destigmatizing, educating, and supporting Black women and other women of color who are interested in all things related to medicinal and recreational cannabis. Ellementa Ellementa is a global, women-centric wellness company that is well-entrenched in the cannabis, CBD, and other plant medicine space.
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Offerings include education, robust community engagement, and a weekly live-broadcast exploring various plant-centric topics on women’s health. Marijuana Policy Project
The mission of this group is to increase public support for nonpunitive, noncoercive marijuana policies; identify and activate supporters; change state laws to reduce or eliminate penalties for use of marijuana; and gain influence in Congress. On their site, you’ll find information about newsworthy issues and policies.
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You can take action to support their work by visiting the Federal Policy page. Americans for Safe Access
If you’re looking to become an advocate, the ASA is ready for you. The organization provides resources and training opportunities for activists.
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Their mission is to ensure safe and legal access to cannabis for therapeutic use and research. You’ll find resources and brochures on how to talk to your doctor about medical cannabis, ways to become a state-authorized patient, and information about your legal rights.
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NORML
NORML’s mission is to sway public opinion to legalize the responsible use of marijuana by adults. The group also aims to serve as an advocate for consumers, so they have access to high-quality marijuana that’s safe, convenient, and affordable.
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Favorite Apps
WeedMaps This app is your ultimate guide to cannabis. You can learn about different products and locate dispensaries, deliveries, deals, and doctors near you. WeedMaps also provides community reviews on thousands of cannabis products and brands.
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Releaf
This app allows you to anonymously log real-time experiences with specific cannabis and CBD products. You can easily track the product you’re using, where you purchased it from, and what symptoms you experienced to help guide your next treatment decision.
Favorite Product Sites
Leafly From CBD oil to edibles to apparel, we like that Leafly offers a variety of cannabis products.
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You’ll find customer reviews and FAQs about the different items listed on the site.
Favorite Blogs
MedicalMarijuana.com The Medical Marijuana Blog features informative entries about different medical cannabis topics.
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From tips on how to grow your hemp to info on legalization, you’ll find a wide range of subjects covered on this site.
Favorite Patient-Centered Annual Meetings
CannMed CannMed is the leading scientific conference covering the latest in cannabis science, medicine, cultivation, and safety. International Cannabinoid Research Society Symposium on the Cannabinoids The International Cannabinoid Research Society is a scientific association with more than 500 international members, who are researchers in the field of cannabinoids and related bioactive lipids.
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Their annual symposium covers the latest breakthroughs in cannabinoid science.
Favorite Retreats or Experiences
Cannabliss Retreats Looking for a cannabis-inspired getaway?
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Cannabliss helps educate its retreatgoers on how to strengthen the body, expand the mind, and awaken the spirit with cannabis. Guests travel to locations such as Jamaica and interact with different cultures. Cannabis Food Experiences
Enthusiasts and chefs are just starting to explore the role of food cannabinoids in the ECS.
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Participants can partake in communal dining experiences, grab a CBD smoothie, or discover new recipes for home dinners and parties. Additional reporting by Liz Scherer.
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Editorial Sources and Fact-Checking
Human Endocannabinoid System. UCLA Health Cannabis Research Initiative.Alger BE.
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Getting High on the Endocannabinoid System. Cerebrum.
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November–December 2013.FDA and Cannabis: Research and Drug Approval Process. U.S.
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Food and Drug Administration. October 1, 2020.Russo EB.
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Beyond Cannabis: Plants and the Endocannabinoid System. Trends in Pharmacological Sciences.
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July 2016.Walsh KB, McKinney AE, Holmes AE. Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses. Frontiers in Pharmacology. November 2021.Lu HC, Mackie K.
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Review of the Endocannabinoid System. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. June 2021.Bie B, Wu J, Foss JF, Naguib M.
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An Overview of the Cannabinoid Type 2 Receptor System and Its Therapeutic Potential. Current Opinion in Anaesthesiology. August 2018.Barrie N, Manolios N.
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Endocannabinoid System in Pain and Inflammation: Its Relevance to Rheumatic Disease. European Journal of Neurology. September 2017.Fride E.
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Multiple Roles for the Endocannabinoid System During the Earliest Stages of Life: Pre- and Postnatal Development. Journal of Neuroendocrinology. April 17, 2008.Therapeutic Potential.
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UCLA Health Cannabis Research Initiative.Elmes MW, Kaczocha M, Berger WT, et al. Fatty Acid-Binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).
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Journal of Biological Chemistry. April 2015.Hurd YL, Spriggs S, Alishayev J, et al. Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial.
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The American Journal of Psychiatry. May 2019.Shannon S, Lewis N, Lee H, Hughes S.
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Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente Journal.
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2019.Russo EB, Marcu J. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.
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In: Advances in Pharmacology, Volume 80. 2017.Ferber SG, Namdar D, Hen-Shoval D, et al.
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‘The Entourage Effect’: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Current Neuropharmacology. 2020.Gertsch J, Leonti M, Raduner S, et al.
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Beta-Caryophyllene Is a Dietary Cannabinoid. Proceedings of the National Academy of Sciences. July 1, 2008.Hiding in Plain Sight: The Discovery of the Endocannabinoid System.
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Epigraph. Winter 2019.Pertwee RG.
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Cannabinoid Pharmacology: The First 66 Years. British Journal of Pharmacology.
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January 2006.Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.
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Cannabis and Cannabinoid Research. 2016.National Academies of Sciences, Engineering, and Medicine.
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The Health Effects of Cannabis and Cannabinoids. 2017.Show LessNEWSLETTERS
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