Full-spectrum cannabidiol (CBD) oil is a hemp extract that contains a myriad of cannabinoids, terpenes, and flavonoids found naturally in whole cannabis and hemp plants. As opposed to pure CBD isolate, a single-molecule extract made from hemp plants, full-spectrum CBD oil contains a wide range of phytochemicals that work in concert to modulate the endocannabinoid system and potentiate therapeutic effects. This paper will provide an overview of the physiological actions, uses, dosing, and safety considerations of full-spectrum CBD oil.
The Endocannabinoid System
The endocannabinoid system is a complex physiological system for maintaining homeostasis that is composed of cannabinoid receptors, endocannabinoids, and enzymes.1,2,3 Cannabinoids are naturally occurring molecules found in hemp and cannabis plants that modulate endocannabinoid function. Over 100 cannabinoids have been isolated from cannabis plants, including CBD, a nonintoxicating cannabinoid, and tetrahydrocannabinol (THC), the compound responsible for the intoxicating effects of cannabis. Other cannabinoids of interest to researchers for potential therapeuticeffects include cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN). In raw or unheated cannabis, precursor cannabinoids in their acidic form can be isolated, including cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA).
Terpenes are naturally occurring aromatic molecules responsible for botanical aromas and flavors present in hemp and cannabis plants, as well as fruits, vegetables, trees, herbs, and flowers. Terpenes are Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA) and other regulatory agencies.4
Organisms use terpenes in innumerable natural processes to communicate with their environment and serve in functions such as protection and reproduction. Terpenes are essential to the entourage effect, which is the synergistic effect of cannabinoids, terpenes, and flavonoids on physiological processes. Terpenes have varying physiological effects that likely contribute to the therapeutic effects of full-spectrum CBD oil.
For example, myrcene may have anxiolytic, antioxidant, anti-aging, anti-inflammatory, and analgesic properties.5 Beta-caryophyllene may modulate inflammation by reducing pro-inflammatory modulators.6 Alpha-bisabolol has been studied for potential benefits, including neuroprotective and antimicrobial effects.7
Flavonoids are a class of naturally occurring molecules that provide pigmentation and protect plants against damage from ultraviolet radiation, pests, and disease. They are of emerging interest to researchers in their potential synergistic action on the endocannabinoid system in concert with cannabinoids and terpenes.8
Potential Therapeutic Uses
The U.S. Drug Enforcement Administration (DEA) classifies cannabis as a federally illegal Schedule 1 controlled substance, a designation that strictly limits research on the potential therapeutic uses. An analysis of research funding between 2000 and 2018 in the United States, Canada, and the United Kingdom found that of the $1.56 billion that was directed to cannabis and cannabinoid research, about half of the money was spent on understanding the potential harms and misuse, rather than the therapeutic benefits.9 As a result of regulatory constraints, the body of research is limited on the possible therapeutic benefits of cannabinoids and hemp- and cannabis-derived products.
Although more rigorously conducted controlled trials are needed to assess the benefits of full-spectrum hemp and cannabinoids, preliminary evidence shows potential for various therapeutic areas of interest. Preliminary studies on full-spectrum hemp and CBD have included investigation of a wide range of therapeutic areas, including but not limited to: addiction,10 anxiety,11 autoimmune diseases,12 cardiovascular disease,13 diabetic complications,14,15 epilepsy,16 gastrointestinal disorders,17 inflammatory bowel disease,18 migraine,19 nausea,20 neurodegenerative diseases,21 pain,22 posttraumatic stress disorder (PTSD),23 psychosis,24 and sleep disorders.25
The following is a brief review of the evidence for selected therapeutic areas of interest.
A limited number of preclinical studies suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction.10 Some preliminary data suggest that it may be beneficial in reducing tobacco addiction.26
Preliminary studies show CBD could potentially be useful for alcohol addiction.27 In animal studies, CBD reduces alcohol intake and motivation to drink. Preliminary evidence suggests that CBD may have therapeutic potential for alcohol-related liver and brain damage.28
Some research shows that CBD may be a potential treatment for opioid use disorder by craving and relapse and through its anxiolytic properties.29,30,31,32 A review of preclinical and clinical reports regarding the effects of CBD as a therapeutic intervention for substance use disorder found that CBD may reduce the consumption, motivation, or relapse of alcohol, opioids, and stimulants. The review also found that CBD may also reduce withdrawal signs of morphine and cocaine.29
According to the National Institute of Mental Health (NIMH), an estimated 19.1% of U.S. adults had any anxiety disorder in the past year.33 Females had a higher past year prevalence for anxiety disorder (23.4%) than males (14.3%). Researchers are investigating the endocannabinoid system as a therapeutic target for new anxiolytic drug development.34 CBD interacts with the cannabinoid type 1 receptor (CB1R), the serotonin 5-HT1A receptor, and other receptors in the brain that regulate fear and anxiety-induced behaviors.11
Studies have found that CBD inhibits the fear of public speaking, one of the main symptoms in patients with generalized social anxiety disorder.35,36 Patients treated with CBD had significantly reduced anxiety, cognitive impairment, and discomfort compared to placebo. In an open-label 4-week trial in 14 patients with moderate-to-severe anxiety, treatment with a full-spectrum high CBD product showed significantly reduced anxiety as well as improvements in mood, sleep, and quality of life.37 Additionally, CBD can offset the common side effect of anxiety caused by THC in cannabis or cannabis products.38
A growing body of evidence shows that endocannabinoid system imbalances are related to metabolic regulation, obesity, and hyperglycemia, leading to an interest in the endocannabinoid system as a pharmaceutical drug development target for the treatment of diabetes.14 The endocannabinoid system plays an important role in pathophysiological processes related to diabetic complications, such as vascular inflammation, oxidative stress, diabetic nephropathy, atherosclerosis, and neuropathy. It is possible that the antioxidant and anti-inflammatory properties of CBD and other cannabinoids may be beneficial in the treatment of cardiovascular and other complications associated with hyperglycemia.15
Various ancient cultures have historically used cannabis to treat epileptic convulsions. CBD has been most thoroughly studied in the treatment of epilepsy compared to other conditions. Several randomized clinical trials have shown the effectiveness of CBD in epilepsy.39,40,41 In June 2018, the FDA approved the first CBD product, Epidiolex®, to treat Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients 1 year of age or older.42
Gastrointestinal tract function and homeostasis is thought to be modulated by the endocannabinoid system, including control of motility, secretion, and epithelial barrier function. Cannabinoids have shown potential for therapeutic uses in gastrointestinal disorders including inflammatory conditions, disorders of motility, abdominal pain, and the prevention of nausea and vomiting.17,20
The endocannabinoid system is known to modulate the formation of migraine headaches through a variety of mechanisms, including glutamine, inflammatory, opiate, and serotonin. A review of studies on cannabinoids for migraine and headaches found several beneficial long-term and short-term effects, including decreased daily analgesic intake, dependence, and level of pain intensity.19
Alzheimer’s disease is the most common neurodegenerative disease, characterized by a progressive decline in memory and cognitive and behavioral functions. Current therapies are limited in effectiveness. The neuroprotective, antioxidant, and anti-inflammatory properties of CBD are of interest to researchers in the treatment of Alzheimer’s disease.43
The endocannabinoid system is also increasing interest to researchers as a potential therapeutic target for Parkinson’s disease, a progressive disorder of the central nervous system that affects movement and the second-most common neurodegenerative disease after Alzheimer's disease.44 CBD has been studied for its potential neuromodulatory and neuroprotective effects in Parkinson’s disease.45
Pain and Inflammation
In the context of the opioid crisis, there is increasing interest in studying the endocannabinoid system as a drug target for pain. Neuronal and immune cell functions play a role in pain, and the endocannabinoid system modulates both cell types. Preclinical evidence suggests the potential for cannabinoids in the treatment of neuropathic pain and acute and chronic inflammatory pain.46
Full-spectrum hemp oil has shown therapeutic potential in chronic neuropathic pain studies in mice.47 Study results are mixed on the potential of CBD to alleviate acute and chronic pain in older adults.48 Cannabinoid receptors are present in immune cells, suggesting that the endocannabinoid system plays an important role in modulating immune function. Therefore, CBD is of increasing interest to researchers due to its potential anti-inflammatory properties.49,50,51
Posttraumatic Stress Disorder
The endocannabinoid system is likely to be involved in posttraumatic disorder (PTSD) symptomology, a mental health disorder that is developed after experiencing traumatic events.23 PTSD can include somatic, cognitive, affective, and behavioral symptoms. Considerable overlap exists between PTSD and other psychiatric conditions, such as anxiety disorders and depression. CBD has been shown to facilitate fear extinction through its action at CB1 receptors. CBD may affect PTSD through action at the amygdala and the hippocampus in the brain.52
According to the Centers for Disease Control and Prevention, an estimated 70 million adults in the U.S. live with chronic sleep disorders.53 Preliminary research suggests that CBD may help regulate sleep, and it may be of potential therapeutic benefit for a number of sleep disorders,25 including insomnia,54 REM sleep behavior disorder,55 and excessive daytime sleepiness.56
Appropriate dosing of full spectrum CBD oil can be difficult to determine because of limited studies, the variable nature of hemp plant composition, and a wide range of results from extraction methods. Inconsistencies in product formulations and labeling accuracy in full-spectrum CBD oil on the market present additional challenges in determining the proper dosage. Optimal doses may depend on individual factors, such as body weight, age, the condition being targeted, and individual physiological differences.
A systematic review of 35 CBD studies found that doses studied spanned a wide range, between less than 1 mg/kg/day to 50 mg/kg/day.57 The review found that studies that used higher doses tended to have better therapeutic outcomes compared to lower doses overall; however, more studies are needed to determine the therapeutic dosing range. Lower cannabinoid doses are less likely to cause drug interactions or side effects.
The most rigorous CBD dosing information available comes from studies on Epidiolex® (CBD oral solution), the only FDA-approved CBD product for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients 1 year of age and older.42 The recommended dosing of Epidiolex® is calculated by the weight.
However, clinicians and patients should be aware that Epidiolex® dosing recommendations cannot be extrapolated to dose full spectrum CBD oil because Epidiolex® is purified CBD and lacks other natural components such as terpenes and cannabinoids. There are currently no FDA guidelines for full-spectrum CBD oil dosing. In the absence of official guidelines or recommendations, experts often recommend a “start low, go slow” approach for cannabinoid dosing, meaning to start at a low dose and then titrate up as tolerated based on individual symptoms and response.58
CBD is generally well tolerated with mild side effects.60,61 The World Health Organization Expert Committee on Drug Dependence found in 2017 that CBD “exhibits no effects indicative of any abuse or dependence potential.”62
The following are some of the potential side effects and risks of CBD:61
- Liver damage
- Changes in appetite
- Mood changes
In large studies of CBD treatment for epileptic patients, adverse effects of CBD included drowsiness, decreased appetite, and diarrhea.63,64,65 Elevated liver function was observed in some patients. Therefore, the FDA recommends liver function tests before beginning Epidiolex® treatment, and at 1 month and 3 months after beginning treatment. Caution should be exercised in prescribing full-spectrum hemp oil or CBD to patients with decreased hepatic function.
Consumers should look for reputable sources of full-spectrum CBD oil with quality control measures including laboratory testing for contaminants, such as heavy metals and phthalates.66 The FDA has issued warnings that CBD products on the market that do not contain the amount of CBD claimed on the label.67
CBD has known drug-drug interactions with many medications, especially those metabolized by cytochrome P450 (CYP450) enzymes in the liver, including but not limited to:68,69,70
- Anti-epileptic drugs
Sedative effects can be compounded when combining CBD with other sedating drugs, such as benzodiazepines or antihistamines.
While preliminary research shows potential benefits, more rigorous studies are needed to determine clinical efficacy, dosing, and safety. Consumers should select full-spectrum CBD oil products from reputable sources with verifiable lab testing and rigorous quality control practices.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. We encourage you to speak with your medical provider to determine if a full-spectrum CBD oil is right for you.
About Blue Gem Hemp
Blue Gem® Hemp proudly makes premium Full-Spectrum CBD Oil. Two simple ingredients: organic, American-grown hemp and medium-chain triglyceride (MCT) oil, designed to elevate your self-care. Your Wellness. Our Passion.
By Simi Burn, PharmD
November 14, 2022
- Pacher, Pál, Sándor Bátkai, and George Kunos. “The Endocannabinoid System as an Emerging Target of Pharmacotherapy.” Pharmacological Reviews 58, no. 3 (September 2006): 389–462. https://doi.org/10.1124/pr.58.3.2.
- Crocq, Marc-Antoine. “History of Cannabis and the Endocannabinoid System.” Dialogues in Clinical Neuroscience 22, no. 3 (September 2020): 223–28. https://doi.org/10.31887/DCNS.2020.22.3/mcrocq.
- Lu, Hui-Chen, and Ken Mackie. “Review of the Endocannabinoid System.” Biological Psychiatry. Cognitive Neuroscience and Neuroimaging 6, no. 6 (June 2021): 607–15. https://doi.org/10.1016/j.bpsc.2020.07.016.
- Adams, T. B., C. Lucas Gavin, M. M. McGowen, W. J. Waddell, S. M. Cohen, V. J. Feron, L. J. Marnett, et al. “The FEMA GRAS Assessment of Aliphatic and Aromatic Terpene Hydrocarbons Used as Flavor Ingredients.” Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 49, no. 10 (October 2011): 2471–94. https://doi.org/10.1016/j.fct.2011.06.011.
- Surendran, Shelini, Fatimah Qassadi, Geyan Surendran, Dash Lilley, and Michael Heinrich. “Myrcene-What Are the Potential Health Benefits of This Flavouring and Aroma Agent?” Frontiers in Nutrition 8 (2021): 699666. https://doi.org/10.3389/fnut.2021.699666.
- Scandiffio, Rosaria, Federica Geddo, Erika Cottone, Giulia Querio, Susanna Antoniotti, Maria Pia Gallo, Massimo E. Maffei, and Patrizia Bovolin. “Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation.” Nutrients 12, no. 11 (October 26, 2020): E3273. https://doi.org/10.3390/nu12113273.
- Eddin, Lujain Bader, Niraj Kumar Jha, Sameer N. Goyal, Yogeeta O. Agrawal, Sandeep B. Subramanya, Salim M. A. Bastaki, and Shreesh Ojha. “Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol.” Nutrients 14, no. 7 (March 25, 2022): 1370. https://doi.org/10.3390/nu14071370.
- Bautista, Johanna L., Shu Yu, and Li Tian. “Flavonoids in Cannabis Sativa: Biosynthesis, Bioactivities, and Biotechnology.” ACS Omega 6, no. 8 (March 2, 2021): 5119–23. https://doi.org/10.1021/acsomega.1c00318.
- O’Grady, Cathleen. “Cannabis Research Database Shows How U.S. Funding Focuses on Harms of the Drug.” Science, August 27, 2020. https://www.science.org/content/article/cannabis-research-database-shows-how-us-funding-focuses-harms-drug.
- Prud’homme, Mélissa, Romulus Cata, and Didier Jutras-Aswad. “Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence.” Substance Abuse: Research and Treatment 9 (2015): 33–38. https://doi.org/10.4137/SART.S25081.
- Blessing, Esther M., Maria M. Steenkamp, Jorge Manzanares, and Charles R. Marmar. “Cannabidiol as a Potential Treatment for Anxiety Disorders.” Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics 12, no. 4 (October 2015): 825–36. https://doi.org/10.1007/s13311-015-0387-1.
- Rodríguez Mesa, Xandy Melissa, Andrés Felipe Moreno Vergara, Leonardo Andrés Contreras Bolaños, Natalia Guevara Moriones, Antonio Luis Mejía Piñeros, and Sandra Paola Santander González. “Therapeutic Prospects of Cannabinoids in the Immunomodulation of Prevalent Autoimmune Diseases.” Cannabis and Cannabinoid Research 6, no. 3 (June 2021): 196–210. https://doi.org/10.1089/can.2020.0183.
- Kicman, Aleksandra, and Marek Toczek. “The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease.” International Journal of Molecular Sciences 21, no. 18 (September 14, 2020): E6740. https://doi.org/10.3390/ijms21186740.
- Rohbeck, Elisabeth, Juergen Eckel, and Tania Romacho. “Cannabinoid Receptors in Metabolic Regulation and Diabetes.” Physiology (Bethesda, Md.) 36, no. 2 (March 1, 2021): 102–13. https://doi.org/10.1152/physiol.00029.2020.
- Horváth, Béla, Partha Mukhopadhyay, György Haskó, and Pál Pacher. “The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications.” The American Journal of Pathology 180, no. 2 (February 2012): 432–42. https://doi.org/10.1016/j.ajpath.2011.11.003.
- Wrede, Randi von, Christoph Helmstaedter, and Rainer Surges. “Cannabidiol in the Treatment of Epilepsy.” Clinical Drug Investigation 41, no. 3 (March 2021): 211–20. https://doi.org/10.1007/s40261-021-01003-y.
- Martínez, Vicente, Amaia Iriondo De-Hond, Francesca Borrelli, Raffaele Capasso, María Dolores Del Castillo, and Raquel Abalo. “Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?” International Journal of Molecular Sciences 21, no. 9 (April 26, 2020): E3067. https://doi.org/10.3390/ijms21093067.
- Swaminath, Arun, Eric P. Berlin, Adam Cheifetz, Ed Hoffenberg, Jami Kinnucan, Laura Wingate, Sarah Buchanan, Nada Zmeter, and David T. Rubin. “The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information.” Inflammatory Bowel Diseases 25, no. 3 (February 21, 2019): 427–35. https://doi.org/10.1093/ibd/izy319.
- Poudel, Sujan, Jonathan Quinonez, Jinal Choudhari, Zachary T. Au, Sylvia Paesani, Armond K. Thiess, Samir Ruxmohan, Mobashir Hosameddin, Gerardo F. Ferrer, and Jack Michel. “Medical Cannabis, Headaches, and Migraines: A Review of the Current Literature.” Cureus 13, no. 8 (August 2021): e17407. https://doi.org/10.7759/cureus.17407.
- Sharkey, Keith A., Nissar A. Darmani, and Linda A. Parker. “Regulation of Nausea and Vomiting by Cannabinoids and the Endocannabinoid System.” European Journal of Pharmacology 722 (January 5, 2014): 134–46. https://doi.org/10.1016/j.ejphar.2013.09.068.
- Cassano, Tommaso, Rosanna Villani, Lorenzo Pace, Antonio Carbone, Vidyasagar Naik Bukke, Stanislaw Orkisz, Carlo Avolio, and Gaetano Serviddio. “From Cannabis Sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases.” Frontiers in Pharmacology 11 (2020): 124. https://doi.org/10.3389/fphar.2020.00124.
- Mlost, Jakub, Marta Bryk, and Katarzyna Starowicz. “Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action.” International Journal of Molecular Sciences 21, no. 22 (November 23, 2020): E8870. https://doi.org/10.3390/ijms21228870.
- Bitencourt, Rafael M., and Reinaldo N. Takahashi. “Cannabidiol as a Therapeutic Alternative for Post-Traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials.” Frontiers in Neuroscience 12 (2018): 502. https://doi.org/10.3389/fnins.2018.00502.
- Schubart, C. D., I. E. C. Sommer, P. Fusar-Poli, L. de Witte, R. S. Kahn, and M. P. M. Boks. “Cannabidiol as a Potential Treatment for Psychosis.” European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology 24, no. 1 (January 2014): 51–64. https://doi.org/10.1016/j.euroneuro.2013.11.002.
- Babson, Kimberly A., James Sottile, and Danielle Morabito. “Cannabis, Cannabinoids, and Sleep: A Review of the Literature.” Current Psychiatry Reports 19, no. 4 (April 2017): 23. https://doi.org/10.1007/s11920-017-0775-9.
- Morgan, Celia J. A., Ravi K. Das, Alyssa Joye, H. Valerie Curran, and Sunjeev K. Kamboj. “Cannabidiol Reduces Cigarette Consumption in Tobacco Smokers: Preliminary Findings.” Addictive Behaviors 38, no. 9 (September 2013): 2433–36. https://doi.org/10.1016/j.addbeh.2013.03.011.
- Nona, Christina N., Christian S. Hendershot, and Bernard Le Foll. “Effects of Cannabidiol on Alcohol-Related Outcomes: A Review of Preclinical and Human Research.” Experimental and Clinical Psychopharmacology 27, no. 4 (August 2019): 359–69. https://doi.org/10.1037/pha0000272.
- De Ternay, Julia, Mickaël Naassila, Mikail Nourredine, Alexandre Louvet, François Bailly, Guillaume Sescousse, Pierre Maurage, Olivier Cottencin, Patrizia Maria Carrieri, and Benjamin Rolland. “Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain.” Frontiers in Pharmacology 10 (2019): 627. https://doi.org/10.3389/fphar.2019.00627.
- Navarrete, Francisco, María Salud García-Gutiérrez, Ani Gasparyan, Amaya Austrich-Olivares, and Jorge Manzanares. “Role of Cannabidiol in the Therapeutic Intervention for Substance Use Disorders.” Frontiers in Pharmacology 12 (2021): 626010. https://doi.org/10.3389/fphar.2021.626010.
- Ren, Yanhua, John Whittard, Alejandro Higuera-Matas, Claudia V. Morris, and Yasmin L. Hurd. “Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 29, no. 47 (November 25, 2009): 14764–69. https://doi.org/10.1523/JNEUROSCI.4291-09.2009.
- Hurd, Yasmin L., Michelle Yoon, Alex F. Manini, Stephanie Hernandez, Ruben Olmedo, Maria Ostman, and Didier Jutras-Aswad. “Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage.” Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics 12, no. 4 (October 2015): 807–15. https://doi.org/10.1007/s13311-015-0373-7.
- Katsidoni, Vicky, Ilektra Anagnostou, and George Panagis. “Cannabidiol Inhibits the Reward-Facilitating Effect of Morphine: Involvement of 5-HT1A Receptors in the Dorsal Raphe Nucleus.” Addiction Biology 18, no. 2 (March 2013): 286–96. https://doi.org/10.1111/j.1369-1600.2012.00483.x.
- Any Anxiety Disorder. National Institute of Mental Health. Accessed November 13, 2022. https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder
- Patel, Sachin, Mathew N. Hill, Joseph F. Cheer, Carsten T. Wotjak, and Andrew Holmes. “The Endocannabinoid System as a Target for Novel Anxiolytic Drugs.” Neuroscience and Biobehavioral Reviews 76, no. Pt A (May 2017): 56–66. https://doi.org/10.1016/j.neubiorev.2016.12.033.
- Bergamaschi, Mateus M., Regina Helena Costa Queiroz, Marcos Hortes Nisihara Chagas, Danielle Chaves Gomes de Oliveira, Bruno Spinosa De Martinis, Flávio Kapczinski, João Quevedo, et al. “Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 36, no. 6 (May 2011): 1219–26. https://doi.org/10.1038/npp.2011.6.
- Zuardi, Antonio W., Natália P. Rodrigues, Angélica L. Silva, Sandra A. Bernardo, Jaime E. C. Hallak, Francisco S. Guimarães, and José A. S. Crippa. “Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life.” Frontiers in Pharmacology 8 (2017): 259. https://doi.org/10.3389/fphar.2017.00259.
- Dahlgren, Mary Kathryn, Ashley M. Lambros, Rosemary T. Smith, Kelly A. Sagar, Celine El-Abboud, and Staci A. Gruber. “Clinical and Cognitive Improvement Following Full-Spectrum, High-Cannabidiol Treatment for Anxiety: Open-Label Data from a Two-Stage, Phase 2 Clinical Trial.” Communications Medicine 2, no. 1 (November 2, 2022): 139. https://doi.org/10.1038/s43856-022-00202-8.
- Zuardi, A. W., I. Shirakawa, E. Finkelfarb, and I. G. Karniol. “Action of Cannabidiol on the Anxiety and Other Effects Produced by Delta 9-THC in Normal Subjects.” Psychopharmacology 76, no. 3 (1982): 245–50. https://doi.org/10.1007/BF00432554.
- Stockings, Emily, Dino Zagic, Gabrielle Campbell, Megan Weier, Wayne D. Hall, Suzanne Nielsen, Geoffrey K. Herkes, Michael Farrell, and Louisa Degenhardt. “Evidence for Cannabis and Cannabinoids for Epilepsy: A Systematic Review of Controlled and Observational Evidence.” Journal of Neurology, Neurosurgery, and Psychiatry 89, no. 7 (July 2018): 741–53. https://doi.org/10.1136/jnnp-2017-317168.
- Silva, Guilherme Diogo, Felipe Borelli Del Guerra, Maira de Oliveira Lelis, and Lécio Figueira Pinto. “Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps.” Frontiers in Neurology 11 (2020): 531939. https://doi.org/10.3389/fneur.2020.531939.
- Sekar, Krithiga, and Alison Pack. “Epidiolex as Adjunct Therapy for Treatment of Refractory Epilepsy: A Comprehensive Review with a Focus on Adverse Effects.” F1000Research 8 (2019): F1000 Faculty Rev-234. https://doi.org/10.12688/f1000research.16515.1.
- Epidiolex [package insert]. Carlsbad, CA: Greenwich Biosciences; 2021.
- Karl, Tim, Brett Garner, and David Cheng. “The Therapeutic Potential of the Phytocannabinoid Cannabidiol for Alzheimer’s Disease.” Behavioural Pharmacology 28, no. 2 and 3-Spec Issue (April 2017): 142–60. https://doi.org/10.1097/FBP.0000000000000247.
- Di Filippo, Massimiliano, Barbara Picconi, Alessandro Tozzi, Veronica Ghiglieri, Aroldo Rossi, and Paolo Calabresi. “The Endocannabinoid System in Parkinson’s Disease.” Current Pharmaceutical Design 14, no. 23 (2008): 2337–47. https://doi.org/10.2174/138161208785740072.
- Patricio, Felipe, Alan Axel Morales-Andrade, Aleidy Patricio-Martínez, and Ilhuicamina Daniel Limón. “Cannabidiol as a Therapeutic Target: Evidence of Its Neuroprotective and Neuromodulatory Function in Parkinson’s Disease.” Frontiers in Pharmacology 11 (2020): 595635. https://doi.org/10.3389/fphar.2020.595635.
- Donvito, Giulia, Sara R. Nass, Jenny L. Wilkerson, Zachary A. Curry, Lesley D. Schurman, Steven G. Kinsey, and Aron H. Lichtman. “The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 43, no. 1 (January 2018): 52–79. https://doi.org/10.1038/npp.2017.204.
- Vigil, Jacob M., Marena A. Montera, Nathan S. Pentkowski, Jegason P. Diviant, Joaquin Orozco, Anthony L. Ortiz, Lawrence J. Rael, and Karin N. Westlund. “The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model.” Life (Basel, Switzerland) 10, no. 5 (May 18, 2020): E69. https://doi.org/10.3390/life10050069.
- Porter, Brooke, Barbara St Marie, Gary Milavetz, and Keela Herr. “Cannabidiol (CBD) Use by Older Adults for Acute and Chronic Pain.” Journal of Gerontological Nursing 47, no. 7 (July 2021): 6–15. https://doi.org/10.3928/00989134-20210610-02.
- Nagarkatti, Prakash, Rupal Pandey, Sadiye Amcaoglu Rieder, Venkatesh L. Hegde, and Mitzi Nagarkatti. “Cannabinoids as Novel Anti-Inflammatory Drugs.” Future Medicinal Chemistry 1, no. 7 (October 2009): 1333–49. https://doi.org/10.4155/fmc.09.93.
- Atalay, Sinemyiz, Iwona Jarocka-Karpowicz, and Elzbieta Skrzydlewska. “Antioxidative and Anti-Inflammatory Properties of Cannabidiol.” Antioxidants (Basel, Switzerland) 9, no. 1 (December 25, 2019): E21. https://doi.org/10.3390/antiox9010021.
- Mecha, M., A. Feliú, P.M. Iñigo, L. Mestre, F.J. Carrillo-Salinas, and C. Guaza. “Cannabidiol Provides Long-Lasting Protection against the Deleterious Effects of Inflammation in a Viral Model of Multiple Sclerosis: A Role for A2A Receptors.” Neurobiology of Disease 59 (November 2013): 141–50. https://doi.org/10.1016/j.nbd.2013.06.016.
- Do Monte, Fabricio H., Rimenez R. Souza, Rafael M. Bitencourt, Juliana A. Kroon, and Reinaldo N. Takahashi. “Infusion of Cannabidiol into Infralimbic Cortex Facilitates Fear Extinction via CB1 Receptors.” Behavioural Brain Research 250 (August 1, 2013): 23–27. https://doi.org/10.1016/j.bbr.2013.04.045.
- About Our Program – Sleep and Sleep Disorders. Centers for Disease Control and Prevention. Updated September 13, 2022. Accessed November 13, 2022. https://www.cdc.gov/sleep/about_us.html
- Shannon, Scott, Nicole Lewis, Heather Lee, and Shannon Hughes. “Cannabidiol in Anxiety and Sleep: A Large Case Series.” The Permanente Journal 23 (2019): 18–041. https://doi.org/10.7812/TPP/18-041.
- Chagas, M. H. N., A. L. Eckeli, A. W. Zuardi, M. A. Pena-Pereira, M. A. Sobreira-Neto, E. T. Sobreira, M. R. Camilo, et al. “Cannabidiol Can Improve Complex Sleep-Related Behaviours Associated with Rapid Eye Movement Sleep Behaviour Disorder in Parkinson’s Disease Patients: A Case Series.” Journal of Clinical Pharmacy and Therapeutics 39, no. 5 (October 2014): 564–66. https://doi.org/10.1111/jcpt.12179.
- Murillo-Rodríguez, Eric, Andrea Sarro-Ramírez, Daniel Sánchez, Stephanie Mijangos-Moreno, Alma Tejeda-Padrón, Alwin Poot-Aké, Khalil Guzmán, Elda Pacheco-Pantoja, and Oscar Arias-Carrión. “Potential Effects of Cannabidiol as a Wake-Promoting Agent.” Current Neuropharmacology 12, no. 3 (May 2014): 269–72. https://doi.org/10.2174/1570159X11666131204235805.
- Millar, S. A., N. L. Stone, Z. D. Bellman, A. S. Yates, T. J. England, and S. E. O’Sullivan. “A Systematic Review of Cannabidiol Dosing in Clinical Populations.” British Journal of Clinical Pharmacology 85, no. 9 (September 2019): 1888–1900. https://doi.org/10.1111/bcp.14038.
- MacCallum, Caroline A., and Ethan B. Russo. “Practical Considerations in Medical Cannabis Administration and Dosing.” European Journal of Internal Medicine 49 (March 2018): 12–19. https://doi.org/10.1016/j.ejim.2018.01.004.
- Larsen, Christian, and Jorida Shahinas. “Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials.” Journal of Clinical Medicine Research 12, no. 3 (March 2020): 129–41. https://doi.org/10.14740/jocmr4090.
- Bergamaschi, Mateus Machado, Regina Helena Costa Queiroz, Antonio Waldo Zuardi, and José Alexandre S. Crippa. “Safety and Side Effects of Cannabidiol, a Cannabis Sativa Constituent.” Current Drug Safety 6, no. 4 (September 1, 2011): 237–49. https://doi.org/10.2174/157488611798280924.
- Iffland, Kerstin, and Franjo Grotenhermen. “An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.” Cannabis and Cannabinoid Research 2, no. 1 (2017): 139–54. https://doi.org/10.1089/can.2016.0034.
- Drugs (psychoactive): Cannabidiol (compound of cannabis). World Health Organization. Updated December 19, 2017. Accessed November 13, 2022. https://www.who.int/news-room/questions-and-answers/item/cannabidiol-(compound-of-cannabis)
- Devinsky, Orrin, J. Helen Cross, Linda Laux, Eric Marsh, Ian Miller, Rima Nabbout, Ingrid E. Scheffer, Elizabeth A. Thiele, and Stephen Wright. “Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.” New England Journal of Medicine 376, no. 21 (May 25, 2017): 2011–20. https://doi.org/10.1056/NEJMoa1611618.
- Devinsky, Orrin, Anup D. Patel, J. Helen Cross, Vicente Villanueva, Elaine C. Wirrell, Michael Privitera, Sam M. Greenwood, et al. “Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome.” New England Journal of Medicine 378, no. 20 (May 17, 2018): 1888–97. https://doi.org/10.1056/NEJMoa1714631.
- Devinsky, Orrin, Anup D. Patel, Elizabeth A. Thiele, Matthew H. Wong, Richard Appleton, Cynthia L. Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville, and GWPCARE1 Part A Study Group. “Randomized, Dose-Ranging Safety Trial of Cannabidiol in Dravet Syndrome.” Neurology 90, no. 14 (April 3, 2018): e1204–11. https://doi.org/10.1212/WNL.0000000000005254.
- Gardener, Hannah, Chela Wallin, and Jaclyn Bowen. “Heavy Metal and Phthalate Contamination and Labeling Integrity in a Large Sample of US Commercially Available Cannabidiol (CBD) Products.” The Science of the Total Environment 851, no. Pt 1 (December 10, 2022): 158110. https://doi.org/10.1016/j.scitotenv.2022.158110.
- Warning Letters and Test Results for Cannabidiol-Related Products. Food and Drug Administration Web site. Accessed November 13, 2022. https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products
- Balachandran, Premalatha, Mahmoud Elsohly, and Kevin P. Hill. “Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: A Comprehensive Review.” Journal of General Internal Medicine 36, no. 7 (July 2021): 2074–84. https://doi.org/10.1007/s11606-020-06504-8.
- Kocis, Paul T., and Kent E. Vrana. “Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions.” Medical Cannabis and Cannabinoids 3, no. 1 (August 2020): 61–73. https://doi.org/10.1159/000507998.
Brown, Joshua D., and Almut G. Winterstein. “Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use.” Journal of Clinical Medicine 8, no. 7 (July 8, 2019): E989. https://doi.org/10.3390/jcm8070989.