A Complete Guide To CBD

Today, CBD (cannabidiol) is one of the most prevalent and extensively studied cannabinoid molecules in the cannabis plant. It has become an extremely popular topic among scientific communities, politicians, and the media. This is due to its strong potential for easing the symptoms of various medical conditions without serious side effects, abuse, or dependency. Unlike THC (tetrahydrocannabinol), it does not produce intoxicating effects. Patients can achieve symptom relief without feeling “high.”

Thanks to recent changes in legislation, consumers now benefit from an increasingly saturated market with thousands of CBD products. While this broad array of options makes it easier to access CBD, many people are unsure about what exactly this substance is, the therapeutic benefits it provides, and whether it can help them with their unique medical concerns. Unfortunately, the FDA has yet to approve any nonprescription CBD products, so it is the responsibility of the consumer to determine the quality of these products before making an informed purchase. Informed decision making, of course, starts with understanding the cannabis compound.

What is CBD? How Does CBD Work in the Human Body?

The cannabis sativa plant produces hundreds of compounds called cannabinoids that interact with the body’s endocannabinoid system (ECS). Discovered in the early 1990s, this complex neuromodulatory system consists of a vast network of chemical signals and cellular receptors throughout the brain and body and plays several vital roles in the development of the central nervous system and synaptic plasticity.

The ECS is comprised of three main parts: messenger molecules called endogenous cannabinoids (endocannabinoids), cannabinoid receptors that are stimulated by endocannabinoids and control the activity of other neurotransmitters, and enzymes responsible for synthesizing and degrading these endocannabinoids. This system works by gathering feedback about the body, such as appetite, temperature, or alertness, enabling communication between cells, and adjusting their activity to maintain homeostasis.

The receptors in the brain are sensitive to chemical messengers generated outside the body as well as the neurotransmitters produced naturally within the body. When you inhale or ingest cannabis, the plant-based compounds enter your body, travel through your bloodstream, and reach your brain. Because cannabinoids produced by the cannabis plant show a structural similarity to endocannabinoids, they interact with the receptors of the endocannabinoid system to mimic the endocannabinoids and influence brain activity. The two primary cannabinoid receptors are CB1 and CB2. CB1 receptors are abundant in the central nervous system (particularly in the cortex, cerebellum, hippocampus, and basal ganglia). CB2 receptors are expressed at lower levels in the brain and are mainly found in the peripheral nervous system, immune system, and gastrointestinal system.

CBD and THC are the two most common and widely studied cannabinoids and interact with these receptors to produce distinct effects. THC binds to CB1 and CB2 receptors as an agonist, meaning it mimics the body’s endocannabinoids and activates these receptors. In contrast, CBD binds to these receptors as an antagonist, which blocks the receptors and limits their activity.

THC stimulates both receptors but has a stronger influence on CB1 receptors. Activation of CB1 receptors creates feelings of bliss, euphoria, and relaxation, but can also cause short-term memory impairment, anxiety, and paranoia. CBD has a lower binding affinity for these receptors and does not act directly to activate or suppress them. Instead, it suppresses the CB1-activating qualities of THC, helping to modulate some of its potentially negative psychoactive effects.

Evidence indicates that CBD may have neuroprotective, anti-inflammatory, and pain-relieving properties, enabling it to treat the symptoms of mental health disorders and neurological diseases. The basis for CBD’s therapeutic use lies in this molecule’s ability to influence a wide range of receptor systems in the brain and body. Along with exerting an indirect influence on CB1 and CB2 receptors, CBD can increase levels of endocannabinoids by inhibiting the enzymes that degrade them.

It can also influence multiple non-cannabinoid receptor systems, including opioid, dopamine, and serotonin systems. Opioid and dopamine receptors regulate numerous aspects of cognition and behavior, including pain, motivation, reward-seeking, and aversion to negative stimuli. Serotonin is a neurotransmitter implicated in pain, anxiety, and depression, and the impact of CBD on the serotonin system has been demonstrated in robust clinical studies.

Is CBD Legal?

Cannabis has a long history of medical use in the US - in fact, American physicians prescribed cannabis sativa to patients until the federal government passed the Controlled Substances Act in 1970. This legislation classified cannabis as an illegal Schedule I substance, a designation reserved for drugs with no accepted medical value and a high risk for abuse.

Cannabis remained illegal on a federal level, but California challenged the federal ban to legalize medical cannabis in 1996. As of January 2022, 36 states now permit medical cannabis use, 18 permit recreational use, and several more states are set to follow. Change is also impacting the nation on a federal level. Introduced in 2021, the proposed MORE (Marijuana Opportunity Reinvestment and Expungement) Act aims to end the criminalization of cannabis by removing it from the DEA’s controlled substances list, eliminating past cannabis-related convictions and penalties, creating a diverse and inclusive cannabis industry, and taxing cannabis products to fund social reform projects. The committees assigned to this bill have sent it to Congress for consideration.

It is important to note that CBD is only legal on the federal level if it is derived from hemp, contains less than 0.3% THC, is cultivated by licensed growers, and adheres to shared state-federal regulations. Because CBD derived from marijuana is still a Schedule I substance, it remains illegal. Furthermore, federal legality of hemp-derived CBD does not translate to legality in all fifty states. Each state has its own version of the Controlled Substances Act that mirrors federal law and has the ultimate say in which products are legal. Certain states have fully legalized hemp CBD products, while others have legalized it with restrictions (such as doctor’s approval and a state medical cannabis license). It is illegal to transport marijuana-derived CBD products from states with legal cannabis across state lines, regardless if cannabis is legal in the state you are traveling to.

What’s The Difference Between Hemp CBD And Cannabis CBD?

Marijuana and hemp are both varieties of cannabis, but they differ significantly in THC content, causing different effects for users. Cannabis provides a richer source of cannabinoids and other therapeutic substances than industrial hemp because it contains more resin, a sticky sap-like substance found on the trichomes of female cannabis flowers that delivers the majority of THC. Cannabis-derived hemp is prized for the entourage effect, a proposed mechanism by which multiple cannabis compounds act synergistically to enhance the overall effects of the substance. Due to the entourage effect, most cannabis experts believe that whole plant extracts offer greater therapeutic power.

While hemp also contains cannabinoids and terpenes, it does not provide the same range or concentration of these substances that are present in cannabis. Because it produces only trace amounts of THC, hemp-derived CBD is appealing for consumers who want to avoid the high altogether. Still, hemp-derived CBD can be made into full-spectrum or broad-spectrum extracts for consumers who want the full scope of health benefits. Full-spectrum CBD products contain all the cannabinoids in the plant used to make the CBD product, while broad-spectrum CBD products contain most plant compounds, but not all. CBD isolate is the purest form of CBD in which all other compounds in the cannabis or hemp plant are extracted, creating a tasteless, odorless crystal or powder that can be consumed sublingually (under the tongue) or mixed with other products.

Aside from the differences in concentration and effectiveness, hemp-derived CBD and cannabis-derived CBD also differ in terms of regulations and safety. Hemp is a bioaccumulator, meaning it absorbs toxins such as pesticides, heavy metals, microbes, mold, bacteria, and other harmful substances from the soil, as well as solvents used for the extraction process. When manufacturers extract CBD from large quantities of industrial hemp cultivated under non-organic conditions, there is a possibility that these contaminants will be present in the final product, compromising safety and efficacy. Unlike cannabis-derived CBD products that are strictly tested and regulated according to state laws, hemp products are currently unregulated, allowing companies to sell products with unreliable ingredients or make dubious claims about their effects.

Does CBD Cause Psychoactive Effects?

As we’ve previously mentioned, CBD does not interact with receptors in the brain and endocannabinoid system the same way as THC. Since that direct interaction is what causes the “high” associated with THC-heavy strains of cannabis, it is safe to say that CBD does not cause a psychoactive high or a sense of euphoria. In other words, CBD is not an intoxicating substance like THC, and is not psychoactive in that regard.

But the definition of a “psychoactive substance” is a substance that affects the way the central nervous system—particularly the brain—works. This can include any substance that alters the way the brain’s neurotransmitters function. As noted, CBD interacts with the body’s endocannabinoid system to exert multiple, desired, therapeutic outcomes. The effects CBD is best known for, including appetite promotion, pain relief, relaxation, stress relief, improved sleep, and more, are by definition psychoactive effects. Thus, it is correct to state that CBD is psychoactive but does not produce a high or alter your state of mind.

How Is CBD Used?

Extensive research has proven that CBD may offer therapeutic potential for a diverse array of conditions, from neuropathic, inflammatory, and osteoarthritis pain sleep disturbances caused by insomnia, restless leg syndrome, and PTSD-related nightmares:

Decrease Epileptic Seizures

In 1980, a small clinical trial of eight epileptic patients found that four of them remained nearly free of convulsive crisis during the experiment, and three others showed partial improvement in their condition. Other studies exploring CBD followed for several decades that decisively show CBD can benefit patients with epileptic disorders. In 2017, a controlled trial that determined CBD resulted in reduced frequency of convulsive seizures among adults and children with Dravet syndrome. In 2018, researchers found that CBD also significantly reduced seizures in patients with Lennox-Gastaut syndrome, a form of epilepsy, when accompanied by a traditional antiepileptic treatment regimen. The same year, the FDA approved a CBD-based medication called Epidiolex for treating both forms of epilepsy, and over 15,000 people have been treated with it since.

Reduce Psychosis

Animal studies, anecdotal evidence, and clinical trials have suggested that CBD may help with many more medical conditions and interest in CBD continues to skyrocket. A quick search of “cannabidiol” on PubMed, a comprehensive online database for biomedical and life sciences research, generates over 4,600 results. One particularly promising area of research focuses on reducing psychosis among individuals with schizophrenia. In 2019, CBD administered along with antipsychotic treatment resulted in significant improvement of positive psychotic symptoms and their clinician’s impressions of improvement.

Alleviate Anxiety

While many studies are currently investigating CBD, a recent cross-sectional study of 387 CBD users found that two of the most common reasons for taking this drug are to manage self-perceived anxiety and stress. 92.2% of this group stated that they felt less stressed after using CBD. Pharmacological research indicates that CBD’s anxiolytic and stress-reducing properties may result from its role as a partial agonist of the 5-HT1 serotonin receptor, whose activation has shown to provide anti-anxiety, anti-depressant, and anti-psychosis benefits. Researchers believe CBD can be helpful in treating social anxiety disorder, anxiety related to PTSD, performance anxiety, and anxiety associated with the onset of tics in patients with Tourette’s syndrome.

Pain Relief

Many people around the globe report using CBD to alleviate pain. These individuals often use CBD for pain associated with surgery, inflammatory conditions like arthritis and gastrointestinal disorders, cancer pain, and fibromyalgia. Encouragingly, many of these individuals report not only a reduction in pain, but improved sleep that may help the body recuperate as well as heal from the pain-inducing event. Though anecdotal evidence abounds, due to the limitations of testing CBD on human subjects, there is currently limited research to demonstrate CBD’s pain-relieving effects.

In addition, many of the existing studies were performed with CBD in combination with THC. Still, a study of fibromyalgia patients revealed that many individuals chose to replace prescription pain medications—particularly opioids and benzodiazepines—with CBD. Over 94% of these individuals completely stopped use of prescription pain medications. They reported positive changes in their experience of pain and improved symptom management. Best of all, subjects reported far fewer side effects than those that continued taking prescription pharmaceuticals, and researchers note that increased availability of CBD could help stem opioid overdose or addiction.

What Are The Different Types Of CBD Products?

CBD products are available in many different forms, including:

A quick, convenient, and discreet way to consume CBD, edibles are available in a wide variety of products such as chocolates, cookies, tablets, gummies, mints, honey sticks, tea, soda, coffee, and so much more. Depending on the product, these can include only CBD or a ratio of THC to CBD. Dosing is easy because these products are pre-dosed and can often be broken down into smaller amounts for even more precise doses. Because the CBD is partially broken down by the digestive tract and liver, it can take up to two hours after consumption to notice the effects, and you will absorb 20-30% of the total CBD content listed on the packaging.

Oral Products

CBD oils, tinctures, and sprays are designed for absorption via the mucous membranes under the tongue (sublingually) rather than through digestion. This preserves more of the CBD, meaning the effects will occur quicker, typically within 15 to 45 minutes. Most tinctures are packaged in bottles with a dropper built into the lid for dosing individual drops. Following the recommended dosing on the bottle, place the product beneath your tongue, and wait for 30 to 90 seconds before swallowing. CBD oil can also be found in tablet or gel caps that you swallow like a supplement. Though with edibles, this method doesn’t take effect as quickly because it must pass through the digestive system.

Topicals

CBD-infused topical products are often used to treat localized joint pain, muscle soreness, headaches, and skin conditions such as eczema and psoriasis. Topicals include creams, lotions, balms, serums, and transdermal patches.

These products provide concentrated pain relief to the affected area without the waiting time associated with edibles. Skin is less permeable than the mucous membranes, so it’s best to choose a topical with a high concentration of CBD but use sparingly. Expect to feel the effects in 45 to 60 minutes. Water-based topicals absorb faster, while oil-based products absorb more deeply. Transdermal patches deliver CBD to your bloodstream through the skin, providing steady relief for hours or even days without the need to reapply.

Vapes And Concentrates

Inhaling vaporized CBD oil provides a highly concentrated dose with the quickest effects, as compounds are absorbed directly from the lungs into the bloodstream. You can attach a pre-filled CBD cartridge to a vape pen, use a vape pen with a specific chamber for concentrates, or “dab” solid concentrates with a specially designed rig. CBD concentrates come in many forms with various compounds and moisture contents. Some popular CBD extracts include RSO, sugar, shatter and budder, though RSO should never be inhaled.

Flower

Similar to vaping, smoking dried flower allows the CBD to enter your bloodstream directly, with the same onset time and absorption percentage. While most cannabis strains have been cultivated for high THC levels, there are many high-CBD strains of flower for consumers who want the therapeutic benefits without feeling high. CBD strains come in two primary forms – CBD-dominant and balanced. CBD-dominant strains contain high levels of CBD and little to no THC, meaning they rarely offer a high. Balanced strains contain equal or nearly equal levels of CBD and THC and can produce a high when consumed. The combustion that occurs during smoking may be irritating, so if you’re sensitive to smoke, you may want to try a dry herb vaporizer instead, which vaporizes the beneficial cannabinoids to a vapor to be inhaled.

How Do I Find High-Quality CBD Products?

After determining the type of product that you want, it is crucial to purchase CBD products only from a licensed, reputable dispensary to ensure you know exactly what you’re purchasing. A recent study performed by the FDA analyzed 102 products with specific CBD contents on their label. It found that only 45% of them contained CBD levels within 20% of the amount indicated on the label.

Reputable CBD products from a certified dispensary will feature a certificate of analysis (COA). COAs show that the product has been third-party tested by an accredited, independent laboratory with no interest in the product. They also confirm that industry-approved techniques were used to verify the content of the product. Some product packages display QR codes you can scan with your phone, and most retailers have COAs available on their websites.

When looking at the CBD facts presented in the COA, keep these tips in mind:

• Carefully review the ingredient list to make sure the product contains CBD. Some products only list cannabis sativa seed oil, hemp seeds, or hemp seed oil, and these are not the same as CBD.
• Look for a detailed list of all detectable cannabinoids, including CBD, CBDV, CBG, and THC. Any cannabinoids marked with “ND” were not detected in the lab testing.
• Double-check that the CBD and THC concentrations on the COA match the label. Concentration is measured in milligrams per gram. For example, if you purchase a product that weighs 50 grams and advertises it contains 600 mg of CBD, it should have a concentration of 12 mg of CBD per gram, found by dividing the total CBD in milligrams by the total weight in grams of the product.
• The COA should include heavy metal and pesticide analyses, indicating whether these contaminants are detected and if they occur within safe limits for ingestion. The heavy metal analysis will show the tested concentration level of each heavy metal, how much of each was found during testing, and the maximum amount that is safe to consume. The concentration should be significantly lower than the ingestion use limit. The pesticide analysis will show the name of the pesticides tested, the level of concentration detected, the acceptable limits, and whether the results pass.

Additionally, look for products with a USDA organic certification to reduce the chances of consuming pesticides and other harmful substances. This ensures that you are consuming CBD extracted from US-grown hemp cultivated under conditions that meet the official USDA organic standards. It also confirms that the hemp extraction process did not involve any synthetic chemical additives.

How Do I Choose The Right Dose Of CBD?

Cannabis experts claim that the medicinal efficacy of CBD requires a particular dose range, referred to as the Goldilocks Zone. Just like taking too little CBD can fail to produce the desired effects, taking too much for a specific condition can also reduce the effectiveness. This “inverted-U” phenomenon is fairly common among drugs that influence multiple brain receptors, and differences in sensitivity for different receptors may underlie this response.

The effect of a CBD product depends on many factors, including the type of product, the specific dosage, your body weight, metabolism, and tolerance to CBD. This means two different people can take the same dose of the same product and have very different responses. CBD is generally well-tolerated, even at high doses, but taking too much can result in side effects such as fatigue, diarrhea, and changes in appetite or weight. The higher the dose, the higher the chance of experiencing negative symptoms. Ultimately, it’s best to start at the lowest dosage to determine how your body reacts, give yourself sufficient time to feel the effects, and gradually increase the dose over time as you assess the best dose for your symptom management. Be sure to track your progress in a notebook, recording the dose, how long it took to take effect, and how it made you feel to build an optimized cannabis regimen.

Does CBD Interact With Medications?

It is possible for CBD to interact with certain medications based on how the body metabolizes different substances. CYP3A4 is an enzyme that metabolizes CBD as well as many other prescription medications. CBD can interfere with this enzyme by preventing it from effectively breaking down the medications in your system. When a medication metabolizes too slowly, you can accumulate a higher level in your system than intended. When it metabolizes too quickly, you may not have enough in your system. Researchers are still determining the interactions between CBD and specific medications, but a good rule to follow is to avoid consuming CBD if you take any medications that feature a grapefruit warning on the label - this is because the enzyme in grapefruits that may produce a negative drug interaction with medications is very similar to CBD in how it behaves with your body.

Happy CBD Shopping!

Hopefully, our comprehensive guide to CBD has taught you everything you need to know about this valuable compound -  what CBD is, how it’s produced, what it’s used for, the types of products that are available, and the most important features to look for when selecting a product. Now, you can shop with confidence and find the right CBD product for your needs.

References:

1. Crocq M. A. (2020). History of cannabis and the endocannabinoid system. Dialogues in clinical neuroscience, 22(3), 223–228.
2. Lu, H. C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological psychiatry, 79(7), 516–525.
3. Ferber, S. G., Namdar, D., Hen-Shoval, D., Eger, G., Koltai, H., Shoval, G., Shbiro, L., & Weller, A. (2020). The "Entourage Effect": Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Current neuropharmacology, 18(2), 87–96.
4. Mlost, J., Bryk, M., & Starowicz, K. (2020). Cannabidiol for pain treatment: Focus on pharmacology and mechanism of action. International Journal of Molecular Sciences, 21(22), 8870.
5. Kaul, M., Zee, P.C. & Sahni, A.S. (2021). Effects of cannabinoids on sleep and their therapeutic potential for sleep disorders. Neurotherapeutics 18, 217–227.
6. Cunha, J. M., Carlini, E. A., Pereira, A. E., Ramos, O. L., Pimentel, C., Gagliardi, R., Sanvito, W. L., Lander, N., & Mechoulam, R. (1980). Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology, 21(3), 175–185.
7. Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., Scheffer, I. E., Thiele, E. A., & Wright, S. (2017). Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. New England Journal of Medicine, 376(21), 2011–2020.
8. Devinsky, O., Patel, A. D., Cross, J. H., Villanueva, V., Wirrell, E. C., Privitera, M., Greenwood, S. M., Roberts, C., Checketts, D., VanLandingham, K. E., & Zuberi, S. M. (2018). Effect of cannabidiol on drop seizures in the lennox–gastaut syndrome. New England Journal of Medicine, 378(20), 1888–1897.
9. Leweke, F., Piomelli, D., Pahlisch, F. et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2, e94.
10. Larsen, C., & Shahinas, J. (2020). Dosage, efficacy, and safety of cannabidiol administration in adults: A systematic review of human trials. Journal of clinical medicine research, 12(3), 129–141.
11. Moltke, J., Hindocha, C. J (2021) Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. Cannabis Res 3, 5.
12. Khan, R., Naveed, S., Mian, N. et al. (2020). The therapeutic role of cannabidiol in mental health: a systematic review. J Cannabis Res 2, 2.
13. Boehnke, K. F., Gagnier, J. J., Matallana, L., & Williams, D. A. (2021). Substituting cannabidiol for opioids and pain medications among individuals with fibromyalgia: a large online survey. The journal of pain, 22(11), 1418-1428.
14. US Food and Drug Administration. (2020). Report to the U.S. House Committee on Appropriations and the U.S. Senate Committee on Appropriations: Sampling Study of the Current Cannabidiol Marketplace to Determine the Extent That Products are Mislabeled or Adulterated. Retrieved March 21, 2022
15. Zlebnik, N. E., & Cheer, J. F. (2016). Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?. Annual review of neuroscience, 39, 1–17.
16. Silva, G. D., Del Guerra, F. B., de Oliveira Lelis, M., & Pinto, L. F. (2020). Cannabidiol in the treatment of epilepsy: A focused review of evidence and gaps. Frontiers in Neurology, 11, 531939.
17. Iffland, K., Grotenhermen, F. Cannabis and Cannabinoid Research. 139-154.