It is undeniable that the market for Cannabidiol (CBD) is booming, profits are generating at $2 billion in sales and projected to reach $16 billion by 2025.¹

Seven percent of Americans are using CBD. That percentage is estimated to increase 10% by 2025, according to investment research firm Cowen & Co.¹ Additional research published in the JAMA Network Open also documented that in April 2019, 6.4 million CBD Google searches were conducted.¹

The ABCs of CBD

CBD and tetrahydrocannabinol (THC) are the primary natural compounds found within the cannabis plant, also known as phytocannabinoids.² CBD is one of more than 80 active phytocannabinoids identified in marijuana and hemp.³

CBD’s chemical structure is very similar to THC (21 carbon atoms, 30 hydrogen atoms, and two oxygen atoms). However, the slight yet significant difference in the atom arrangement between these two compounds produce differing physiological effects.⁴

Both CBD and THC work with receptors that release neurotransmitters in the brain. These compounds interact with CB1 and CB2 receptors, which are located within the endocannabinoid system –an essential component to the human nervous system. CB1 receptors are located in the cerebellum of the brain that influences functions including memory processing, pain regulation, and motor control.⁵ The CB1 receptors are what also activate the euphoric effects from THC, whereas CBD has a very low effectiveness when it binds to CB1 receptors, producing insignificant to non-existent euphoric effects.⁶ CB2 receptors found on white blood cells, in the tonsils, and in the spleen also produce no euphoric effects. However, CB2 receptors have become increasingly popular due to their potential anti-inflammatory properties.⁵

Fact from Fiction

Both THC and CBD derive from the cannabis plant. Marijuana is defined as any cannabis sativa plant that has greater than 0.3 percent THC, which classifies the substance as a federally illegal, Schedule 1 drug by the Drug Enforcement Administration (DEA).⁷ Hemp plants are defined as any cannabis plant that has 0.3 percent or less THC and legal CBD originates from the hemp plant.⁷ The 2014 Farm Bill, national legislation permitting hemp research, began the process of hemp legalization. Within four years, the 2018 Farm Bill was enacted, fully legalizing the production and sale of hemp and its extracts.⁸ Agriculture of the hemp plant is primarily utilized for its CBD content, seeds, and fibers. Whereas, marijuana is usually grown for its psychoactive THC content.² A single hemp plant can produce an estimated half kilogram of plant material for CBD extraction and farmers can legally grow up to 4,000 hemp plants in an acre. A single acre of hemp can generate about 1.4 million bottles of CBD lotion.⁸

Medicinal Benefits and Side Effects

According to the National Institute on Drug Abuse (NIDA), preclinical and clinical studies in animal models have shown potential therapeutic properties in CBD for the following: anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti–psychotic, anti-anxiety, and substance use disorders.³ Despite several studies eluding to CBD health benefits, currently, the only Food and Drug Administration (FDA) approved medicine containing CBD is Epidiolex. Within a series of scientific studies, CBD intake among those affected by childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS) resulted in significant effectiveness compared to other unresponsive anti-seizure medication.⁹ Although CBD has revealed medical benefits, research has also documented possible side effects of CBD including nausea, diarrhea, upset stomach, tiredness, lightheadedness, crankiness, low blood pressure, and drowsiness.⁵

Safety

Aside from side effects, a significant concern regarding CBD is it’s primarily marketed and sold as a supplement, not a medication. The FDA does not regulate the safety or purity of dietary supplements; therefore unidentified elements may be found in products labeled as “pure” CBD.⁸ The FDA strictly prohibits the sale of CBD in any unapproved health products, dietary supplements or food.⁸ The FDA has issued warning letters to companies marketing products containing cannabis and cannabis-derived compounds as a treatment of any disease or condition. Firms making unsubstantiated claims regarding CBD are breaking the law. It is a direct violation to the Federal Food, Drug and Cosmetic Act (FD&C Act) and may put the health and safety of consumers at risk.¹⁰ 

Cultivation

Hemp, which is the only current legal plant for extracting CBD can accidentally cause breeding of marijuana by pollination of female and male plants. Due to this biological process, the University of Connecticut is adamant in maintaining all-female greenhouses.⁸ However, hemp grown outside of a controlled environment is much more susceptible to marijuana conversion. Pharmaceutical-grade extraction is imperative. The method for extracting CBD or THC is very similar, therefore if a supplier incorrectly extracts from the hemp plant, a CBD product may contain an illegal dose of THC.⁸ In efforts to prevent CBD products from being unknowingly contaminated with higher levels of THC, a process known as fractional distillation can be implemented, which isolates cannabinoids through temperature variation. With added heat, the evaporation of carbon dioxide and ethanol occurs, resulting in either pure CBD or THC.⁸

“What many consumers don’t realize is that the FDA, who’s charged with protecting our safety with respect to food and medicine in the U.S., is not on top of policing those CBD products that you see in the gas station or at the grocery store,” says Rino Ferrarese, COO of the medical marijuana extractor CT pharma.⁸

Pregnancy & Breastfeeding

According to a recent warning issued by the FDA, using products with CBD or THC is prohibited by women who are breastfeeding or pregnant. There is no comprehensive research studying the effects of CBD on the developing fetus, expectant mother, or breastfed baby.¹¹ Studies have been conducted on pregnant animals and have shown complications with the reproductive system of developing male fetuses.¹² Despite warnings, researchers who surveyed anesthesiologists, certified nurse-midwives, and doulas found the following:

• 7% of physician anesthesiologists would consider using CBD to reduce anxiety in women during pregnancy and labor.
• 12% would consider it to reduce nausea during pregnancy and 8% during labor.
• 13% would consider it to reduce pain during pregnancy and 12% during labor.
• 42% of certified nurse-midwives would consider using CBD to reduce anxiety in women during pregnancy, and 33% would consider it during labor.
• 54% of doulas would consider using CBD to reduce anxiety in women during pregnancy, and 44% would consider it during labor.¹³

Mark Zakowski M.D., FASA, senior author of the study and chief obstetrical anesthesiologist at Cedars-Sinai Medical Center, Los Angeles says, “That’s concerning because CBD may interact with commonly used anesthetics that might be needed during labor and delivery. And ongoing CBD use has shown the potential to act like a common class of antidepressants, SSRI inhibitors, which can adversely interact with other drugs.”¹³

Buyer Beware

Due to the abundance of unsubstantiated claims regarding CBD and the inconclusive research pertaining to the safety of its use, health experts and federal authorities are urging consumers to approach their use with extreme caution. Much of the CBD studies that have been conducted are preliminary research. Therefore, until further concrete evidence regarding the safety and complexity of CBD is concluded, it’s highly advised that all CBD or cannabis products be examined by an FDA review process.¹⁴  

References:

1. Usatoday.com. (2019). [online] Available at: https://www.usatoday.com/story/news/health/2019/10/23/cbd-google-searches-cannabidiol-skyrocket-do-products-works/4062879002/ [Accessed 14 Nov. 2019].
2. Usatoday.com. (2019). [online] Available at: https://www.usatoday.com/story/sponsor-story/medterra/2019/10/01/what-cbd-oil-separate-facts-fiction-learn-truth-cbd/3786588002/ [Accessed 14 Nov. 2019].
3. Drugabuse.gov. (2019). The Biology and Potential Therapeutic Effects of Cannabidiol. [online] Available at: https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2015/biology-potential-therapeutic-effects-cannabidiol [Accessed 14 Nov. 2019].
4. WebMD. (2019). CBD vs. THC: What’s the Difference?. [online] Available at: https://www.webmd.com/pain-management/cbd-thc-difference#1 [Accessed 14 Nov. 2019].
5. Dr. Ananya Mandal, M. (2019). Cannabinoid Receptors. [online] News-Medical.net. Available at: https://www.news-medical.net/health/Cannabinoid-Receptors.aspx [Accessed 22 Nov. 2019].
6. Analytical Cannabis. (2019). CBD vs THC – What are the Main Differences?. [online] Available at: https://www.analyticalcannabis.com/articles/cbd-vs-thc-what-are-the-main-differences-297486 [Accessed 14 Nov. 2019].
7. Analytical Cannabis. (2019). Hemp vs Marijuana: Is There a Difference?. [online] Available at: https://www.analyticalcannabis.com/articles/hemp-vs-marijuana-is-there-a-difference-311880 [Accessed 22 Nov. 2019].
8. PBS NewsHour. (2019). Is CBD legal? Here’s what you need to know, according to science. [online] Available at: https://www.pbs.org/newshour/science/is-cbd-legal-heres-what-you-need-to-know-according-to-science [Accessed 14 Nov. 2019].
9. Peter Grinspoon, M. (2019). Cannabidiol (CBD) — what we know and what we don’t – Harvard Health Blog. [online] Harvard Health Blog. Available at: https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476 [Accessed 15 Nov. 2019].
10. U.S. Food and Drug Administration. (2019). FDA Regulation of Cannabis and Cannabis-Derived Products: Q&A. [online] Available at: https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#statesallowing [Accessed 22 Nov. 2019].
11. U.S. Food and Drug Administration. (2019). What You Should Know About Using CBD When Pregnant or Breastfeeding. [online] Available at: https://www.fda.gov/consumers/consumer-updates/what-you-should-know-about-using-cannabis-including-cbd-when-pregnant-or-breastfeeding [Accessed 16 Nov. 2019].
12. DG, D. (2019). Maternal cannabinoid exposure. Effects on spermatogenesis in male offspring. – PubMed – NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3026968 [Accessed 16 Nov. 2019].
13. Medicalxpress.com. (2019). Many women and health care providers assume CBD safe during pregnancy despite lack of research. [online] Available at: https://medicalxpress.com/news/2019-10-women-health-assume-cbd-safe.html [Accessed 16 Nov. 2019].
14. NIH MedlinePlus Magazine. (2019). The ABCs of CBD: Separating fact from fiction | NIH MedlinePlus Magazine. [online] Available at: https://magazine.medlineplus.gov/article/the-abcs-of-cbd-separating-fact-from-fiction [Accessed 16 Nov. 2019].

In 1996, California became the first state to pass legislation condoning the use of marijuana for medicinal purposes, and since the onset of that law, a powerful trend was set. Over 33 other states, including the District of Columbia, have now adopted various statutes for the permittance of recreational and medicinal marijuana. Although many government entities have sided that the benefits of the cannabis plant outweigh the risks, others are anxious that the ease of accessibility may cause an influx of misleading notions regarding the plant. Its exposure to vulnerable populations, including adolescents, those pregnant, or individuals suffering from preexisting psychiatric disorders continues to be a significant concern among communities.   

The Impact of Legalization on Local Communities

In a cross-sectional marijuana dispensary density study from 2001-2012 in California, associations between marijuana abuse/dependence hospitalizations disclosed that an additional one dispensary per square mile was associated with a 6.8% increase in the number of marijuana hospitalizations. The study’s findings concluded that increased availability of marijuana in zip codes with a higher density of dispensaries continues to be a probable correlation to the increased hospitalizations in dispensary-dense areas.¹

Despite this study and others, a recent CBS News Poll found that support for marijuana legalization has risen among groups that have historically opposed it. More than half of Republicans (56 percent) now think marijuana use should be legal due to reasons such as marijuana being less harmful than alcohol and believing it is less harmful than other drugs.² However, increases in marijuana potency is triggering a valid fear that the levels of THC in today’s plants are more toxic than therapeutic.

Increased Potency, Increased Risks

As highly potent cannabis increases in availability, scientists who study marijuana and the effects it has to the human body are becoming disturbed with the increasingly high rates of potency in delta-9-tetrahydrocannabinol (THC)–the main compound responsible for the drug’s psychoactive effects. According to a U.S. Drug Enforcement Administration seize, the potency of marijuana has increased from about 4% THC in 1995 to about 12% in 2014. By 2017 marijuana samples were up to 17.1% THC, totaling an increase of more than 300% from 1995-2017. Concentrated cannabis products known as hash and hash oil are also reaching potency levels as high as 80-90% THC.³

Nora Volkow, Director of the National Institute on Drug Abuse (NIDA) states, “The notion that it is a completely safe drug is incorrect when you start to address the consequences of this very high content of Delta-9-THC.”

The levels of THC within cannabis is imperative when factoring the effects it can have on the body when consumed. Low THC levels have been known to have less adverse effects compared to high THC levels.  

Low THC Content:

• Decreases Anxiety
• Treats Nausea
• Relaxation³

High THC Content:

• Panic Attacks
• Psychosis
• Paranoia
• Cannabinoid Hyperemesis Syndrome³

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) of the American Psychiatric Association now includes Cannabis Use Disorder (CUD) as a substance use disorder (SUD) diagnosis. Not all cannabis users develop CUD, however it is becoming more common than we think and can be serious. Normalizing use and reducing perception of harm can increase the development of CUD.⁴

DSM-5 Cannabis Withdrawal Symptoms:

• Anxiety, restlessness
• Depression, irritability
• Insomnia/odd dreams
• Physical symptoms, e.g.Tremors
• Decreased appetite⁴

In a longitudinal study published in Addiction, CUD was found to be significantly associated with psychotic and depressive symptoms.⁵

The Association Between Cannabis Use and Psychiatric Comorbidity

Cannabis use is recognized as a contributing factor for developing a psychotic disorder, children and teens with a family history of psychosis are most vulnerable.⁴

In a long-term prospective study, 1265 children born in Christchurch, New Zealand in 1977 were assessed repeatedly for psychosis symptoms due to daily exposure of cannabis in utero, which contributed to psychotic symptoms portrayed in these children at between the ages of 18-25. There was a significant correlation between cannabis use and later development of psychosis.⁴

A study conducted by Lancet Psychiatry found that three European cities­­–London, Paris, and Amsterdam, where high-potency weed is most prevalent, also have the highest rates of new cases of psychosis. The study indicates that daily pot users are three times more likely to endure a psychotic episode compared to an individual who has abstained from the substance.⁴

High potency forms of marijuana known as wax, butane hash oil, dabs, or shatter are growing in popularity and are more likely to induce psychotic states. The principal psychoactive component of cannabis is THC, which binds to cannabinoid-1 (CB-1) receptors found throughout the central nervous system. Studies specify that pure THC and CB1 agonists can produce psychotic symptoms including suspiciousness, paranoia, thought disorganization, and derealization.⁷

Marta Di Forti, lead author from the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London says, “As the legal status of cannabis change in many countries and states, and as we consider the medicinal properties of some types of cannabis, it is of vital public health importance that we also consider the potential adverse effects that are associated with daily cannabis use, especially high potency varieties.”⁶

Maternal Marijuana Use

The adverse effects of marijuana can become extremely dangerous when the substance is used among those pregnant. According to the National Survey on Drug Use and Health, nearly 4% of pregnant women in 2007 and 2012 used marijuana in the past 30 days. Long-term neurobehavioral studies have shown that negative consequences have been found in children exposed to marijuana in utero such as altered neural functioning, behavioral deficits, emotional deficits, low academic achievement, and increased risk of adolescent substance use initiation.⁸ 

The uptick of marijuana legalization has generated a significant concern among obstetricians, gynecologists, and neonatal practitioners who are combating misleading claims that marijuana use during pregnancy is safe. According to the Center for Disease Control and Prevention (CDC), about 1 in 25 women in the U.S. report using marijuana while pregnant, despite the fact that marijuana use during pregnancy may increase the baby’s risk of developmental problems and low birth weight.⁹ The American College of Obstetricians and Gynecologists (ACOG) recommends that obstetrician-gynecologists counsel women against using marijuana while trying to get pregnant, during pregnancy, and while breastfeeding.¹⁰ Studies have found that cannabinoid receptors appear in the fetal brain around the 14^th week of gestation and are located in areas where cognitive and behavioral functioning develop.¹¹

According to a qualitative study, women reported that although they were consistently seeking prenatal care throughout their pregnancy, information and resources regarding maternal marijuana use was either not helpful or non-existent, resulting in the assumption that marijuana did not pose a significant threat to a developing fetus.¹² The study concludes that absenteeism of perinatal marijuana education can lead to an increase of use among pregnant women.¹²

Testing for Abuse

Cannabis is not a harmless substance. It has been found to have addictive properties, which can lead to impairments and cause serious health risks. Our tests are designed to identify the detection of short-term and long-term marijuana usage. Each available specimen type provides a unique window of detection.

• Hair: Up to approximately 3 months prior to collection.
• Nail: Up to approximately 3-6 months prior to collection.
• Umbilical Cord: Up to approximately 20 weeks prior to birth.
• Meconium: Up to approximately 20 weeks prior to birth.
• Urine: Up to approximately 2-3 days prior to collection.

We believe that to remain at the forefront of toxicology, it is imperative to offer testing services for all substances that may pose an increased risk for abuse and dependence. Our continued investment in developing and implementing testing for drug ingestion and exposure helps us address substances that most concern you.

References:

1. Mair, C., Freisthler, B., Ponicki, W. R., & Gaidus, A. (2015, September 01). “The impacts of marijuana dispensary density and neighborhood ecology on marijuana abuse and dependence.” Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536157/
2. “Support for marijuana legalization hits new high, CBS News poll finds.” (n.d.). Retrieved from https://www.cbsnews.com/news/support-for-marijuana-legalization-hits-new-high-cbs-news-poll-finds/
3. Chatterjee, R. (2019, May 15). “Highly Potent Weed Has Swept The Market, Raising Concerns About Health Risks.” Retrieved from https://www.npr.org/sections/health-shots/2019/05/15/723656629/highly-potent-weed-has-swept-the-market-raising-concerns-about-health-risks
4. Hasin, D. S. (2018, January). “US Epidemiology of Cannabis Use and Associated Problems.” Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719106/
5. Pond, E. (2019, January 28). “Cannabis Use, Cannabis Use Disorder Linked to Psychotic, Depressive Symptoms.” Retrieved from https://www.psychiatryadvisor.com/home/topics/addiction/cannabis-use-cannabis-use-disorder-linked-to-psychotic-depressive-symptoms/
6. Robinson, J. (2019, March 20). “Daily use of high-potency cannabis increases risk of psychosis by four times, study finds.” Retrieved from https://www.pharmaceutical-journal.com/news-and-analysis/news/daily-use-of-high-potency-cannabis-increases-risk-of-psychosis-by-four-times-study-finds/20206308.article?firstPass=false
7. Corey J. Keller, Evan C. Chen, Kimberly Brodsky & Jong H. Yoon(2016)“A case of butane hash oil (marijuana wax)–induced psychosis, Substance Abuse”, 37:3, 384-386, DOI: 10.1080/08897077.2016.1141153
8. Jones, J. (2018).“Medical Marijuana Laws and Maternal Marijuana Use.” Des Plaines, IL: Archives of Women Health and Care.
9. “What You Need to Know About Marijuana Use and Pregnancy” | Fact Sheets | CDC. (n.d.). Retrieved from https://www.cdc.gov/marijuana/factsheets/pregnancy.htm
10. National Institute on Drug Abuse. (n.d.).“Can marijuana use during and after pregnancy harm the baby?” Retrieved from https://www.drugabuse.gov/publications/research-reports/marijuana/can-marijuana-use-during-pregnancy-harm-baby
11. Day, N. L., Goldschmidt, L., Day, R., Larkby, C., & Richardson, G. A. (2015, June). “Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults.” Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25534593
12. Jarlenski, M., Tarr, J. A., Holland, C. L., Farrell, D., & Chang, J. C. (2016). “Pregnant Women’s Access to Information About Perinatal Marijuana Use: A Qualitative Study.” Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27131908