by Dr. Bill Rawls
Now that recreational and medical marijuana are legal in some states, it’s become a source of hot debate for people who are both anti- and pro-marijuana, including those who want it outlawed entirely and those who believe it should be legal everywhere. But you may not be aware that marijuana’s close cousin, hemp, is also a hot topic.
This is true despite the fact that unlike marijuana, hemp contains only trace levels of THC (tetrahydrocannabinol), the chemical component that gives marijuana its euphoric qualities. Instead, hemp is primarily known for its fibers, commonly used to make rope, fabrics, auto parts, industrial materials, and a variety of other products. Hemp is also known for its highly-nutritious seeds (a.k.a. hemp hearts), which have been shown to benefit heart health, skin diseases, and more.
These days, however, people are most excited about the properties of a chemical component of hemp called CBD, short for cannabidiol — myself included. This chemical component has been linked with reduction of pain and seizures, improved mood and sleep, protection of the nervous system, and a range of other health benefits.
Unlike marijuana, hemp is legal in all 50 states according to state laws. The federal government, on the other hand, still recognizes the Controlled Substance Act of 1970, which defines agriculture, production, sale, and use of any type of cannabis as illegal — but it’s also not bothering people who purchase and use hemp CBD products. What’s more, the federal legal status of hemp will likely soon be changing.
The 2018 Farm Bill, which has been proposed to replace the 2017 version that expired in September, is presently before Congress. It includes the Hemp Farming Act of 2018, which, if passed (which is highly likely), will make the use and sale of products made from hemp completely legal across the nation. It would not affect the legal status of marijuana.
This is great news for hemp farmers and consumers interested in CBD, an industry that’s predicted to hit $22 billion by 2022. However, the CBD market has all the makings of a wild west show, with many businesses anxious to get in on the action and make a tidy profit. As such, you’re likely to see CBD-infused products with prices all over the map. And with no official system of checks and balances, it will be hard to tell how much CBD is actually present or what quality it is.
Your top CBD questions, answered
Learning how to make informed choices which choosing and using CBD will help you gain the most benefit from this unique and powerful plant extract. If you plan to take advantage of CBD’s benefits — or even if you already are — read on for answers to all your CBD-related questions in this essential guide.
Why did humans start using cannabis?
Cannabis sativa was one of the earliest plants cultivated by humankind. The very first use of cannabis was documented in China around 4000 BC. A very versatile plant, it was used for food, medicine, religious and spiritual rituals, industrial fiber, and, of course, recreation.
From China, cannabis spread to India, the Arabian Peninsula, and then on to Europe with the spice trade. Through European colonization, use of cannabis spread to the Americas, Caribbean, and throughout the world. How the plant was used depended on the variety of cannabis, the parts of the plant, and how the plant was cultivated.
The variety of cannabis known as hemp was traditionally valued primarily for its fibers with high tensile strength, making it ideal for creating rope and textiles. Hemp seeds and sprouts were eaten as a good source of high-quality protein and beneficial omega-3 fatty acids. The variety of cannabis known as marijuana was specifically cultivated for the euphoric properties of THC, which is concentrated mostly in the flower buds of the plant.
Only recently have the unique medicinal properties of both hemp and marijuana been fully recognized.
How are hemp and marijuana different?
Cannabis sativa has several alter egos, but marijuana and hemp are the two best known. Though both plants look the same, their chemical composition is quite different.
The chemical difference has to do with the presence or absence of certain enzymes. Both marijuana and hemp contain a chemical substance called cannabigerol (CBGA), which is concentrated mostly in the flower buds of the plant. Marijuana contains an enzyme that converts CBGA into THC; hemp contains a different enzyme that converts CBGA into CBD (cannabidiol).
Whereas marijuana contains both THC and CBD, hemp contains almost exclusively CBD — THC occurs only in very trace amounts. Remember, though, that there are many varieties of marijuana and hemp plants, and their concentrations of THC and CBD vary. Those with high THC are used primarily for recreational use; plants with low or no THC and high CBD are best for medicinal use. Only cannabis with less than 0.3% THC can be legally classified as hemp.
What’s the difference between THC and CBD?
Both THC (in marijuana) and CBD (in hemp) belong to a class of plant chemical compounds called cannabinoids. There are different receptors for cannabinoid compounds located throughout the body.
For instance, CB1 receptors are found in high concentrations in the brain and nervous system. CB2 receptors are located throughout the body, but predominantly within the lower body and immune system.
THC’s intoxicating powers come from its ability to mimic anandamide, an endocannabinoid or naturally occurring mood-altering substance in the body that binds to CB1 receptors in the brain and is associated with having a rosy disposition. THC binds to anandamide’s CB1 receptors even more tightly than anandamide itself, triggering an exaggerated or euphoric response — in other words, you get high.
Compared to THC, CBD has very different properties. It weakly binds to both CB1 and CB2 receptors in the brain and body, gently stimulating and blocking them at the same time. This not only mildly activates the receptors, but is also thought to trigger the body to create more CB1 and CB2 receptors, a process known as upregulation. It also results in increased natural levels of anandamide.
When the body experiences an increase in CB receptors, it becomes more sensitive to the natural endocannabinoids (anandamide and others) already present in the body. The end result of taking CBD is an uplifted mood and improved pain tolerance without an exaggerated euphoric response, so you don’t get high when you use it.
CBD also modulates other receptors in the body. For instance, modulation of the 5-HT1A receptor (involved with serotonin, a mood hormone) provides mood-balancing properties: It’s calming, but not highly sedating, so it’s considered neutral — though it often results in improved sleep for many people. Another example is modulation of opioid receptors, which provides pain relief and tissue-supporting properties.
Beyond THC and CBD, Cannabis sativa plants contain over a hundred other cannabinoids that have a similar effect as CBD, but milder — THC is the only one known to be intoxicating. Cannabis plants also possess a wide spectrum of different chemical components offering a range of medicinal properties.
What are terpenes, and why are they important?
Aside from cannabinoids, one of the most prominent chemicals in cannabis plants is terpenes, organic and aromatic compounds found in essential oils. Interestingly, it’s the terpenes that give marijuana its distinct “weedy” odor and taste, not the cannabinoids.
Terpenes are beneficial on their own. For instance, research in the British Journal of Pharmacology found that terpenes are gastro-protective, suggesting they may be beneficial to people with ulcers, and that they have anti-inflammatory properties.
Also important is terpenes’ ability to enhance the properties of CBD. This phenomenon, called the “entourage effect,” is considered by many experts in the industry to be essential for gaining the full benefit of the plant. It also points to the importance of using a full-spectrum extract of hemp, which provides a full range of chemical components including terpenes, as opposed to purified CBD or CBD isolate, which contains only CBD.
What are the benefits of taking CBD?
Cannabinoids, including cannabidiol (CBD), work by mimicking natural endocannabinoids like anandamide (described above) in the body. Endocannabinoids are part of a complex messaging system in the body called the endocannabinoid system. The endocannabinoid system oversees or regulates parts of the nervous system, endorphins, immune system functions, hormones, mood and emotions, metabolism, and many other chemical messengers in the body.
My mimicking endocannabinoids, CBD offers a wide range of benefits, including:
- Decreased pain
- Enhanced sense of well-being
- Increased calm
- Improved sleep
- Reduced stress (thanks to CBD’s adaptogenic properties, which make you more resistant to various types of stress)
But because CBD doesn’t cause euphoria or impair motor skills, you can use it any time of the day or evening. Let’s explore in more detail how it works for various health concerns.
Nervous system conditions
Like other cannabinoids, CBD readily crosses the blood brain barrier, making it ideal for affecting central nervous system conditions. CBD helps calm the nervous system, reduces inflammation, and is strongly neuroprotective. Not surprisingly, clinical studies evaluating cannabidiol for treatment of anxiety, post traumatic stress disorder (PTSD), seizure disorders (especially childhood seizures), and even schizophrenia have shown remarkable effectiveness.
Management of chronic pain is another application for which CBD is ideally suited, and it works in a number of ways. It and other non-THC cannabinoids found in hemp flower-bud extracts work to block pain-conducting nerve impulses, which reduces your perception of pain. Stimulation of CB1 in the brain increases dopamine, which counteracts pain. Just as importantly, these same chemical substances reduce inflammation, the driving force behind pain, which allows healing to occur.
CBD and other cannabinoids also reduce pain by affecting endorphins, the feel-good chemicals we naturally produce to suppress pain. Unlike opioids (heroin, narcotics), which mimic endorphins and ultimately suppress natural endorphins, cannabinoids modulate endorphins.
This means, in effect, that CBD and cannabinoids increase natural endorphins. So instead of causing dependence and addiction like opioids, CBD and cannabinoids do the opposite — so much so that CBD has proven valuable for countering narcotic and cocaine addiction. From a medicinal standpoint, the fact that CBD has the potential to relieve pain without causing euphoria, intoxication, or addiction makes it an intriguing therapeutic option — it has high potential for being at least a partial solution to the current opioid epidemic.
Immune dysfunction + chronic illness
CBD and other chemical substances in hemp flower-bud extracts are strong immune system modulators. This means they control inflammation throughout the body, and also fine-tune the immune system for optimal performance. This combined with CBD’s ability to ease pain and anxiety make it an ideal consideration for illnesses associated with immune dysfunction, including fibromyalgia, chronic fatigue syndrome, chronic Lyme disease, and autoimmune illnesses.
The immunomodulation benefits of CBD and cannabinoids extend to the GI tract. CBD may have value in treating inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, but that value is still being defined by clinical studies.
The wide range of benefits associated with cannabis have garnered interest for use in cancer therapy. Research suggests that cannabinoids, including CBD, may have anti-tumor effects. While this is not enough to define cannabis as a treatment for cancer, it does make it attractive as a complement to other therapies, for both reducing symptoms and possibly enhancing the effects of anticancer drugs.
Additional health concerns
The benefits of CBD and other non-THC cannabinoids don’t stop there. Terpenes and the wide spectrum of other chemical compounds found in hemp flower-bud extracts provide potent anti-inflammatory and antioxidant properties. And like most other herbs, hemp flower-bud extracts have been associated with antimicrobial properties, though cannabis doesn’t appear to be as strong an antimicrobial as many other herbs.
What’s the difference between hemp oil and hemp oil with CBD?
This is a common source of confusion. Many people see hemp oil on grocery store shelves and assume or wonder if it contains CBD and other cannabinoids. Adding to the confusion, CBD products are often sold as hemp oil, and CBD oil is often mixed with hemp oil.
But make no mistake, hemp oil and hemp oil with CBD (or CBD oil) are not the same. The hemp oil you might see on grocery store shelves is made by cold pressing hemp seeds. It’s high in omega-3 fatty acids and other beneficial fatty acids, but hemp oil found in the grocery store does not contain significant amounts of cannabinoids including THC or CBD. While hemp oil is a healthful option for a salad dressing, it has no medicinal value by itself.
Cannabinoids, including CBD in hemp and THC in marijuana, are most highly concentrated in the flower buds, not the seeds. These chemical components of the plant must be extracted from the flower buds to be useful.
What is the best CBD extraction method?
For medicinal use, cannabinoids are extracted from hemp and concentrated into a thick oil that, when ingested, elevates blood levels of cannabinoids for a more sustained period of time. (That’s compared to inhaling vaporized marijuana, where THC dissipates from blood quickly, making it ideal for recreational use.)
CBD oil from hemp contains CBD and other cannabinoids, along with terpenes and other chemical components. It contains only trace amounts of THC (<0.3%).
The four main methods of CBD extraction
- Chemical extraction: The most common method, chemical extraction uses alcohol or hexane as solvents. The solvent is dried off, leaving the dense oil — and possibly harmful residual solvents — behind.
- CO2 extraction: A newer method, CO2 extraction is done without using chemical solvents. Instead, it uses carbon dioxide to extract the full range of chemical components from the flower buds and then distill them into dense CBD oil.
- Vapor Distillation™: Also sometimes called thermal extraction, vapor distillation uses hot air to safely vaporize the full spectrum of chemical components at high concentration from the buds, and then the vapor is distilled into CBD oil. This method also activates the cannabinoids by removing an extra carboxyl ring from their molecular chain (a chemical reaction called decarboxylation), enabling them to interact directly with CB receptors for maximal medicinal value.
I believe vapor distillation is the best method for obtaining the full range of activated chemical compounds from the cannabis plant. This method preserves the terpenes, which are beneficial on their own, and also enhance the properties of CBD via the entourage effect.
- Lipid-based extraction: This method uses fats such as organic coconut oil to absorb and encapsulate the plant’s chemical compounds. The upsides of lipid-based extraction are that the fat helps make the CBD more bioavailable (easy to absorb), and there are no harsh solvents used. The downside: you won’t get a full spectrum of compounds like you would with vapor distillation or CO2 extraction.
What’s the best way to take hemp oil with CBD?
Condensed CBD oil can be taken as a thick paste, but this is the least pleasant option. More commonly, the CBD oil is mixed with a carrier oil, such as hemp oil or coconut oil, to a specific concentration of CBD. The distinctive taste — which comes from the terpenes and not the cannabinoids — is often masked with chocolate, mint, or other flavorings. It typically comes in a small bottle with a dropper to administer the oil mixture.
The best way to take CBD oil mixed with a carrier oil to a specific concentration is to place a few drops or dropperfuls under your tongue for 15 seconds to access the sublingual gland. There, the CBD is absorbed directly into the bloodstream (called sublingual consumption or administration) for the fastest acting effects.
Another method is to take a few drops or dropperfuls orally, swish the liquid around in your mouth, and then swallow it. With this method, CBD’s chemical components are absorbed through mucous membranes of the mouth and intestinal tract directly into the bloodstream.
CBD oil mixed with a carrier oil can also be taken as soft-gel capsules to avoid any taste, but absorption is only through the intestinal tract. This decreases the oil’s potential benefits, because some of the chemical components may be broken down by digestion before being absorbed.
What’s the correct dose of CBD?
The average dose range is 10-50 mg of CBD, one to three times per day, though much higher doses of 100-200 mg (sometimes required to control pain) are equally well tolerated. Some people will notice benefit at the lower end of the dose range, but most people will need 15-30 mg to notice any effects. Because different products provide different concentrations of CBD, the packaging usually states how much CBD is in the entire bottle as opposed to the amount in a certain number of drops or dropperfuls, so measuring can be a little tricky.
If you’re taking the oil in liquid form, one dropperful of a low concentration product (100 mg CBD per fluid ounce) will provide about 3 mg of CBD per dropperful — not enough to notice any significant effects. A dropperful of the medium grade product (500 mg of CBD per fluid ounce) will deliver about 15 mg of CBD — a good starting dose. And a dropperful of a high concentration product (1500 mg CBD per fluid ounce) will provide about 50 mg of CBD per dropperful.
CBD oil is also available as soft gel capsules. With these, the mg quantity of CBD should be designated per capsule. Because some of the chemical compounds in capsules are lost during digestion, you may find you need to take a little more to experience the benefits.
As with any medicinal herb, start at a low dose and gradually build up to a higher dose as you get used to the effects of the substance. Most people notice benefits almost immediately, but some experts suggest that full benefit does not occur until after a couple of weeks of consecutive use.
What’s the difference between CBD isolate and full-spectrum CBD oil?
A lot. CBD isolate (which is CBD alone) acts very differently in the body than a spectrum of hemp chemical components. Here are some quick definitions:
- CBD isolate is purified cannabidiol (CBD) without any other chemical components of hemp. Usually purity is a good thing, but in this case, purified CBD is missing all of the other beneficial compounds the hemp plant has to offer.
- Full-spectrum CBD oil contains cannabidiol, plus the full spectrum of other components of the whole plant, including trace amounts of THC (at less than 0.3%), other cannabinoids, and terpenes.
- Broad-spectrum CBD oil is full-spectrum CBD with the THC removed. It’s not as effective as full-spectrum CBD oil with trace THC.
The cannabis plant naturally generates cannabinoids, terpenes, and other chemical compounds to serve different functions in the plant. These functions include regulatory properties, potent antioxidants, and protection from microbes and insects. Any creature that consumes the chemicals from the plant gains these same benefits.
You can think of the full spectrum of all the chemical compounds found in cannabis as the “language” of the plant. It’s not one chemical, but all the chemicals combined working together that cause a response (again, the entourage effect). When you consume CBD oil, you gain the benefits of all those chemical substances in natural synergy. For that reason, you get full benefit at a dose range of 25-50 mg.
CBD isolate is limited to that single chemical messenger. The synergy provided by the full spectrum of chemicals in CBD oil is lost. This is likely why clinical studies using purified CBD require very high doses, in the range of 750-1500 mg of CBD several times daily, to see a benefit.
When CBD is formally legalized at the national level, prescription drugs providing high doses of purified CBD will become available (several are already in the pipeline). CBD drugs will likely be very costly, require very high doses of CBD isolate, and will likely not provide the same benefits as full-spectrum CBD oil.
What are the potential side effects of CBD oil?
Reported side effects of hemp oil with CBD are generally mild and uncommon and can include tiredness, loose stools, and mild changes in appetite and weight (either increased or decreased). Both hemp oil with CBD (hemp flower-bud extracts) and purified CBD (CBD isolate) have been shown in both animal and human clinical trials to be remarkably safe and well tolerated.
Prolonged use is not associated with an increased risk of side effects. In research studies, up to 1500 mg of purified CBD per day has been used to address various medical illnesses without reported harmful effects including changes in heart rate, blood pressure, temperature, oxygen and carbon dioxide levels, electrolyte balance, gastrointestinal function, psychomotor functions, or sleep cycles.
Prolonged use at high doses has not shown potential for abuse of CBD. In fact, a clinical study published in 2018 found that recreational polydrug users did not show abuse potential with use of CBD. Long-term studies have not evaluated potential changes in hormonal balance or long-term adverse changes in liver function, though prolonged use of CBD enhances metabolism of certain drugs. Stopping CBD oil suddenly has not been associated with withdrawal effects.
How do you know you’re getting your money’s worth?
While the cost of CBD oil products is presently high, it will likely come down dramatically after CBD and hemp are legal by federal standards — but prices will still vary widely. A high price for a CBD product does not always imply high quality, though a low price generally indicates you’re not getting enough CBD to see a benefit, so it’s important to know what to look for when buying or using a product.
Reputable companies selling CBD oil products will state the CBD concentration and extraction methods on the bottle or website. Typically, the concentration is stated as milligrams (mg) of CBD per fluid ounce (though some products standardize mg of CBD to milliliters (ml). The benefit comes from the amount of CBD consumed, not the amount of oil.
To calculate the cost per milligram of CBD, simply divide the dollar amount of the product by the total milligrams of CBD in the bottle. So for instance, a product with 600 mg CBD in a 1 fluid-ounce bottle costing $80 is equal to about 13 cents per mg of CBD; a product with 100 mg of CBD in the same size bottle selling for $40 works out to 40 cents per mg of CBD. In this case, it pays to splurge on the $80 bottle.
As for extraction methods, remember that vapor distillation and CO2 extraction are preferred. These methods yield a full-spectrum CBD product, which will likely be more costly than a CBD isolate because it’s significantly more beneficial. Alcohol extraction is a cheaper method that pulls a more narrow spectrum of plant chemicals and higher levels of chlorophyll, which doesn’t taste great and also takes up space where more CBD could be. Lipid-based extractions will likely fall in the middle price-wise.
The highest quality cannabis is grown indoors, so quality standards can be controlled. Use of clean water and organic methods of farming that are free of pesticide use and unnatural fertilizers are, of course, preferred. With outdoor-farmed cannabis, quality standards and potency are not as easily controlled.
Taste can be a sign of value, too. Poor quality oils will have a very unpleasant chemical taste, and they can cause significant burning to mouth tissues. A good quality product should be smooth and not cause significant burning. Interestingly, the best quality products are associated with a distinct cannabis taste, indicating that the full spectrum of chemical components (with trace levels of THC) are present.
Will I get high from using CBD?
No. Even in high doses, CBD oil will not cause euphoria or impair coordination, balance, or motor functions. Psychoactive effects start at 3-5% THC; CBD products contain less than 0.3% THC. Use of CBD oil is associated with improved sense of well-being, but not an exaggerated feeling of well-being. Use of CBD oil has never been associated with hallucinations or abnormal mental activity.
Will using CBD make me fail a drug test?
The trace amount of THC in CBD oil (<0.3%) is not enough to trigger most drug tests as being positive for THC. You would need to consume about 1000-2000 mg per day of CBD to fail a drug test for THC if the employer is testing to SAMHSA guidelines (Substance Abuse and Mental Health Services Administration). If you are tested regularly and taking high doses of CBD, and you are concerned about the very low risk of a positive drug test for THC associated with using hemp-derived products, you could opt to use purified CBD, which does not contain anything but CBD. Just know that purified CBD doesn’t provide the same spectrum of benefits as CBD oil.
How effective are topical CBD products?
Creams and salves for musculoskeletal discomfort generally contain very small amounts of CBD that are absorbed through the skin. Many of these products do provide significant benefit, however, but the benefit is likely derived from other aspects of CBD — especially terpenes from cannabis and essential oils, thanks to their anti-inflammatory properties.
Though CBD will likely become a highly promoted ingredient in beauty products, it is unclear whether the concentration of CBD present in these products will provide a benefit.
Can you get hooked on hemp CBD products?
There is near zero potential of becoming habituated to hemp CBD products. In other words, if you take it for a long time and then stop it suddenly, you won’t experience withdrawal symptoms.
It should be noted that recreational use of marijuana (high THC, low CBD cannabis) does result in dependence (but different from narcotics or alcohol, and not as debilitating). Chronic use of THC may be associated with atrophy in certain areas of the brain and reduction of certain cognitive functions (at this point, studies are not conclusive). Interestingly, studies have shown that taking CBD oil regularly can restore areas of the brain that have become atrophied in marijuana abusers.
Can you overdose on cannabis?
There have been no reports of anyone overdosing on cannabis. One of the unique properties of the chemical components of cannabis, including both hemp and marijuana, is that they don’t cause respiratory or cardiac depression. This sets even recreational use of cannabis widely apart from narcotics and alcohol, both of which can cause severe respiratory depression and death at excessive doses. Excessive doses of hemp, and more especially, marijuana, may make you very agitated and feel terrible, but there are no known deaths from cannabis overdose.
Are foods and beverages with purified CBD safe?
Many food and beverage companies are already taking advantage of the growing CBD trend and adding CBD to food and beverage products, though the practice is not approved by the FDA. They are mostly using purified CBD (CBD isolate) instead of CBD oil, because purified CBD has no significant taste and comes from poorer quality hemp, which is cheaper to produce. Whether it’s completely safe is totally unknown.
Using CBD in defined doses for medicinal purposes is one thing, but putting it in food and beverages is something entirely different. Someone may wind up getting CBD from multiple products, and so their daily dose could vary significantly. Taking a standardized dose of CBD oil daily as a recognized medicinal is a very different thing from taking uncontrolled doses of CBD isolate daily infused artificially into food and beverage products, and the long term risk may be very different — no one really knows for sure.
Can hemp oil with CBD treat Lyme disease, fibromyalgia, and other chronic illness?
Like most herbs, cannabis does have some antimicrobial and immune-boosting properties, but it is not as strong an antimicrobial as many other herbs. There are many better herbal choices for overcoming chronic Lyme disease and similar conditions related to chronic infections with stealth microbes such as fibromyalgia and chronic fatigue syndrome. (Top ones include andrographis, berberine, cat’s claw, Japanese knotweed, sarsaparilla, and garlic.)
There’s also the cost factor: Chronic use of CBD oil can be costly and less effective against microbes compared to alternative antimicrobial herbs like Japanese knotweed, cat’s claw, andrographis, garlic, sarsaparilla, and berberine. The bottom line is, CBD oil is a good option for controlling symptoms associated with Lyme disease, fibromyalgia, and other chronic illnesses, but it should be combined with other antimicrobial and immunomodulating herbs for optimal benefit. CBD oil is best used intermittently to treat symptoms of pain or anxiety, or used chronically only until symptoms gradually resolve, and then discontinued.
The story around CBD will continue to change and evolve once hemp is legalized and as the industry continues to grow and advance. I’ll be keeping a close eye on it and addressing related issues as needed — stay tuned!
1. Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg Med Chem. 2015 Apr 1;23(7):1377-85.
2. Blessing EM et al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015 Oct;12(4):825-36.
3. Devinsky O et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014 Jun;55(6):791-802.
4. Prud’homme M, Cata R, Jutras-Aswad D. Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence. Subst Abuse. 2015 May 21;9:33-8.
5. Massi P et al. Cannabidiol as potential anticancer drug. Br J Clin Pharmacol. 2013 Feb;75(2):303-12.
6. Bergamaschi MM et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49. Review.
7. Hurd YL et al. Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. Neurotherapeutics. 2015 Oct;12(4):807-15.
8. Crippa JA et al. Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age. Front Immunol. 2018 Sep 21;9:2009.
9. Bruni N et al. Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules. 2018 Sep 27;23(10). pii: E2478.
10. Schoedel KA et al. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial. Epilepsy Behav. 2018 Oct 1;88:162-171.
11. Leweke FM et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar 20;2:e94.
12. Iffland K, Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017 Jun 1;2(1):139-154.
13. Katsuyama S et al. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Eur J Pain. 2013 May;17(5):664-75.
14. Hasenoehrl C, Storr M, Schicho R. Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go? Expert Rev Gastroenterol Hepatol. 2017 Apr 3; 11(4): 329–337.
15. Russo EB, Marcu J. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Adv Pharmacol. 2017;80:67-134.
16. Bitencourt RM, Takahashi RN. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials. Front Neurosci. 2018 Jul 24;12:502.
17. Kerstin Iffland, et. al. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Research. 2017; 2(1): 139–154.
18. Bergamaschi MM, et. al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Current Drug Safety. 2011 Sep 1;6(4):237-49.
19. Schoedel KA, et. al. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial. Epilepsy & Behavior. 2018 Nov;88:162-171.
20. Esther M. Blessing, et. al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015 Oct; 12(4): 825–836.
21. F M Leweke, et. al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry. 2012 Mar; 2(3): e94.
22. Orrin Devinsky, et. al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014 Jun; 55(6): 791–802.
23. Mélissa Prud’homme, et. al. Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence. Substance Abuse. 2015; 9: 33–38.
24. Yasmin L. Hurd, et. al. Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. Neurotherapeutics. 2015 Oct; 12(4): 807–815.
25. José A. Crippa, et. al. Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age. Frontiers in Immunology. 2018; 9: 2009.
26. Russo EB.Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016 Jul 1;1(1):154-165.
27. Ethan B Russo. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug; 163(7): 1344–1364.