by: Kelly Hack

As a country, we have found ourselves in the abyss of an addiction epidemic. Policymakers, law enforcement, and public health officials analyzing the true magnitude of this American crisis are faced with yet another public health concern—drug “alternatives”.

Kratom, native to the tropical tree Mitragyna speciose, is quickly gaining popularity among those seeking alternative solutions to treating opioid dependency. The plant’s leaves are known to contain compounds that produce psychotropic effects. It is currently listed as a “drug of concern” by The Drug Enforcement Administration (DEA) due to the substance’s similar addictive traits to opioids including risks of abuse, overdose, and fatality.¹

In understanding the heightened concern regarding Kratom, a study published in the Journal of Clinical Toxicology found that calls to U.S. poison control centers increased more than 50-fold from 13 calls in 2011 to 682 calls in 2017 (equivalent from about one call a month to two calls a day).² Of those calls, serious medical outcomes ranged from rapid heartbeat, agitation, irritability, and hypertension to seizures, coma, kidney failure, and death.

The added risk of Kratom in comparison to other substances of abuse is that it’s currently classified as an herbal supplement and not an illicit substance. According to the National Institute on Drug Abuse (NIDA), kratom is sometimes sold as a green powder in packets labeled “not for human consumption”,³ although kratom consumers report that the botanical supplement can be used for many things including minor pain as well as promoting a sense of health and well-being.

Kratom, available as a pill, capsule, or extract can work like an opioid or a stimulant. The two present compounds in its leaves-mitragynine and 7-a-hydroxymitragynine, interact with opioid receptors in the brain, producing sedation and pleasure while also minimizing pain.³ The chemical structure of kratom compounds binds strongly to opioid receptors similar to scheduled opioid drugs.⁴ Through scientific analyzation, kratom compounds are predicted to affect the body just like opioids, producing adverse side effects including seizures and respiratory depression.⁴

Regardless of these findings, kratom in recent years has been used as an herbal alternative for medical treatment in attempts to manage opioid withdrawal symptoms/cravings. In response, the Food and Drug Administration (FDA) in 2017 began issuing a series of warnings about kratom, along with identifying 44 deaths associated with its use.⁴ Supporting studies have found that similar to other drugs that emit opioid-like effects, kratom is subject to dependence and withdrawal symptoms including:

• Muscle aches
• Insomnia
• Irritability
• Hostility
• Aggression
• Emotional changes
• Runny nose
• Jerky movements³

In efforts to prevent new epidemics of abuse, the FDA is working diligently to educate, warn, and fight against how kratom is being misrepresented to the public. According to the FDA, there have been no adequate and well-controlled scientific studies involving the use of kratom as a treatment for opioid withdrawal or other diseases in humans. The substance is currently illegal in Australia, Denmark, Germany, Malaysia, and Thailand and banned in a number of states and municipalities in the U.S.⁵

To combat the use of kratom for treating serious diseases like opioid use disorder (OUD), the FDA has issued additional warning letters to unscrupulous vendors for marketing kratom products with scientifically unsubstantiated claims, which they find a clear violation of federal law. The American Kratom Association claims the contrary, in fact they have stated that kratom is regulated by the FDA as a dietary ingredient/supplement and nearly 5 million Americans safely use the substance.⁶

Understanding the true depth of the opioid epidemic requires a wealth of information regarding the various drugs that are involved and their risk factors. If a drug of concern or an alternative form of the drug is posing a potential health risk to your community, incorporating that drug into your substances of abuse testing efforts can provide a proactive, comprehensive, and advanced approach in addressing the prevalence of opioid use disorder within today’s substance abuse landscape. Kratom detection is available as an add-on to any urine panel and as part of the 18-panel test in hair or fingernail through USDTL.

References:

1. “Poison control calls for kratom have soared in recent years.” (n.d.). Retrieved from https://www.cbsnews.com/news/kratom-poison-control-calls-soared-in-recent-years/
2. “Kratom exposures reported to United States poison control centers”: 2011–2017. (n.d.). Retrieved from https://www.tandfonline.com/doi/full/10.1080/15563650.2019.1569236?scroll=top&needAccess=true
3. National Institute on Drug Abuse. (n.d.). “Kratom.” Retrieved from https://www.drugabuse.gov/publications/drugfacts/kratom
4. Office of the Commissioner. (n.d.). Press Announcements – “Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse.” Retrieved from https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm595622.htm
5. Office of the Commissioner. (n.d.). Press Announcements – “Statement from FDA Commissioner Scott Gottlieb, M.D., on new warning letters FDA is issuing to companies marketing kratom with unproven medical claims; and the agency’s ongoing concerns about kratom.” Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm620106.htm
6. “American Kratom Association.” (n.d.). Retrieved from https://www.americankratom.org/

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