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Gabapentin, An Emerging Threat in Today’s Opioid Epidemic

Showing: June 2020

Gabapentin, An Emerging Threat in Today’s Opioid Epidemic

by: Kelly Hack

Gabapentin prescribing increased 64 percent from 39 million prescriptions in 2012 to 64 million by 2016, becoming the 10th most commonly prescribed medication in the United States.1

A recent study from the American Journal of Psychiatry disclosed that the number of Appalachian drug users who reported using gabapentin to get “high” has increased nearly 30-fold from 2008-2014.2 These alarming statistics among other supporting data significantly contributes to the reality that gabapentin is now considered an emerging threat in today’s opioid epidemic.4

What is Gabapentin?

Gabapentin, a gamma-aminobutyric acid (GABA) analog was originally developed as an anticonvulsant and prescribed as an analgesic for neuropathic pain. It is currently sold under the brand names: Neurontin®, Gralise®, Horizant®. The medication is also prescribed as an off-label medication for the treatment of migraines, mental illness, and fibromyalgia. Gabapentin first approved in the United States in 1993 with minimal potential for misuse is now classified as a controlled substance and a current drug of abuse.2 Gabapentin’s effects on the central nervous system including drowsiness and low-level euphoria have been recognized within the addiction community to enhance the euphoric effects of heroin and when consumed exclusively in high doses, produces a marijuana-like high.2 A study from 2016 found that gabapentin misuse was only 1 percent among the general population, however for those that misuse opioids, gabapentin misuse significantly increased to 15-22 percent.3

Side Effects

  • Viral infection
  • Fever
  • Nausea and vomiting
  • Trouble speaking
  • Hostility
  • Jerky Movements4

Gabapentin Overdoses

In 2017, 70,237 drug overdose deaths occurred in the United States, and a vast majority of those fatalities were directly related to opioids.1 In efforts to significantly reduce opioid abuse, providers began to increase their prescribing of gabapentin, with the understanding that the medication was a safer alternative to opioids for the management of acute pain. However, during 2013-2017, 74,175 gabapentin exposures were reported to poison control centers (PCCs) and a clear correlation was documented that the increase of accessibility to gabapentin directly increased toxic exposures.

According to data from the Louisville coroner’s office in Kentucky, gabapentin was found in nearly one-fourth of all overdoses. Throughout the state, the drug is now showing up in about 1 in every 3 overdose deaths.3 Due to the alarming rates of reported overdoses associated with gabapentin, states including Tennessee and Michigan have reclassified the drug as a Schedule V Controlled Substance. Massachusetts, Minnesota, Nebraska, North Dakota, Ohio, Virginia, West Virginia, and Wyoming also require reporting of gabapentin prescriptions through the Prescription Drug Monitoring Program (PDMP) database.

Respiratory Depression and Withdrawal

Drug-induced respiratory depression has been well documented with gabapentin use. The Federal Drug Administration (FDA) now requires new warning labels on all gabapentinoids regarding potential respiratory depressant effects. There is an increased risk for serious breathing difficulties among patients who use gabapentanoids alone or with other drugs that depress the central nervous system (CNS). Patients with a preexisting respiratory impairment such as chronic obstructive pulmonary disease (COPD) also have an augmented risk for experiencing respiratory distress with gabapentanoid usage.6 Additional health complications affiliated with continued gabapentin use occur with abrupt discontinuation of the medication, which has been documented to often mirror symptoms of those withdrawing from alcohol and benzodiazepines.7

Withdrawal Symptoms

  • Anxiety
  • Irritability
  • Agitation
  • Confusion
  • Tachycardia
  • Catatonia7

Co-Prescribing

Since gabapentin and opioids have historically been prescribed for pain, co-prescription of these two medications is quite prevalent. In a population-based nest case-control study among opioid users who were residents of Ontario, Canada between August 1, 1997, and December 31, 2013, it was found that among patients receiving prescription opioids, gabapentin was concomitant with a substantial increase to opioid-related deaths.5 The primary analysis of the study conveyed that the likelihood of opioid-related death was 49 percent higher among individuals exposed to gabapentin and opioids in comparison to those exposed to opioids solely.5 Approximately 8 percent of patients from the study receiving opioids were co-prescribed gabapentin and that co-prescription was directly linked to a 50 percent increase in death probability. Overall, similar studies conducted within the United States and the United Kingdom have drawn parallel conclusions that between 15 and 22 percent of people with opioid use disorder (OUD) are also misusing gabapentin.5

“Misuse of gabapentin is just one more collateral effect of the opioid epidemic. When one drug becomes less available, drug users historically seek out alternatives,” said Caleb Alexander, an epidemiologist at Johns Hopkins University.

In Utero Exposure

Studies are finding a definitive correlation to gabapentin and opioid use among pregnant mothers, as increases in co-exposure, are documented. In a study of 19 infants born to mothers who used opioids and gabapentin during pregnancy, 10 percent of those babies developed Neonatal Abstinence Syndrome (NAS). The failure to control gabapentin withdrawal symptoms with methadone exclusively, lead to gabapentin and methadone being administered congruently. The response from this combined medication-assisted treatment (MAT) showed rapid improvement with newborn withdrawal, indicating that the combined usage of opioid and gabapentin during pregnancy is evident.8

It is imperative that testing for licit drugs such as gabapentin becomes part of a healthcare system’s newborn toxicology testing protocol. It is our goal to continually adapt our offerings to support the systems that are addressing these issues for their population health.

Gabapentin Testing

We offer gabapentin testing in umbilical cord tissue. This specimen type captures substances in the newborn’s system up to approximately 20-weeks prior to birth. We also offer gabapentin testing in hair and nail. Hair offers a window of detection of up to approximately 3-months. Nail offer a windows of detection of up to approximately 3-6 months.

As a leader in forensic toxicology, it is our mission to provide the most comprehensive testing panels to meet the needs of our clients and to proactively address the current trends in today’s substance abuse landscape.


References

  1. Reynolds, K., Kaufman, R., Korenoski, A., Fennimore, L., Shulman, J. and Lynch, M. (2019). Trends in gabapentin and baclofen exposures reported to U.S. poison centers. [online] Taylor & Francis. Available at: https://www.tandfonline.com/doi/full/10.1080/15563650.2019.1687902 [Accessed 14 Feb. 2020].
  2. Vestal, C. (2018). Abuse of Opioid Alternative Gabapentin Is on the Rise. [online] Pewtrusts.org. Available at: https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2018/05/10/abuse-of-opioid-alternative-gabapentin-is-on-the-rise [Accessed 14 Feb. 2020].
  3. Mammoser, G. (2019). Opioid Overdoses and Gabapentin. [online] Healthline. Available at: https://www.healthline.com/health-news/gabapentin-latest-pain-medication-in-opioid-overdoses [Accessed 14 Feb. 2020].
  4. Healthline. (n.d.). Gabapentin: Side Effects, Dosage, Uses, and More. [online] Available at: https://www.healthline.com/health/gabapentin-oral-capsule [Accessed 14 Feb. 2020].
  5. Gomes, T., Juurlink, D., Antoniou, T., Mamdani, M., Paterson, M. and Brink, W. (2017). Gabapentin, opioids, and the risk if opioid-related death: A population-based nested case-control study. [online] Public Library of Science. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626029/ [Accessed 14 Feb. 2020].
  6. U.S. Food and Drug Administration. (2019). FDA requires new respiratory depression risk gabapentinoids warnings. [online] Available at: https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings-gabapentinoids-about-risk-respiratory-depression [Accessed 15 Feb. 2020].
  7. Medscape. (2010). Withdrawal Symptoms After Gabapentin Discontinuation. [online] Available at: https://www.medscape.com/viewarticle/722526 [Accessed 15 Feb. 2020].
  8. Loudin, S., Murray, S., Prunty, L., Davies, T., Evans, J. and Werthammer, J. (2017). An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and Opioids. [online] jpeds.com. Available at: https://www.jpeds.com/article/S0022-3476(16)31232-X/fulltext [Accessed 17 Feb. 2020].

03Jun

What We Know About CBD

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by: Kelly Hack

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].

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