By FEDERICO MARIONA, MD
The Michigan voters recently approved Proposal 1 by a margin of 56 to 44 percent. Retail for-profit sales of marijuana and related products is now the law in Michigan. Our state is the first state in the Midwest to take this step. Our neighbor Canada already has this in place. There are no neighboring states that have approved the use of marijuana for retail sales, yet.
Marijuana is a product from the flowers, stems, leaves and seeds of the plant (Phyto cannabinoids), and is the most common illicit drug used in the United States. Phyto active elements have been described for centuries. Marijuana’s history as a source of these elements described as having “medical effects” dates to biblical times. The main psychoactive component is the delta-9-tetrahydrocannabinol (THC). Marijuana “extracts” are rich in this element. Industrial “hemp” contains low levels of d-9-THC. Emerging in the United States, specifically in the Midwest, are the “synthetic cannabinoids” that replicate the effects of the natural product, but they induce more severe adverse health effects. In addition, marijuana contains a number of other phytocannabinoids, such as Canabidiol (CBD) without psychoactive effects and, arguably, with some medicinal properties.
Pediatricians and healthcare workers, especially those providing care to women planning a pregnancy, who are pregnant or breast feeding, have the ethical duty to educate themselves about cannabis and to inform the public and state elected and appointed officials about the science behind marijuana (cannabis sativa or Indica) and related products. That education should include information on potential side effects—negative, positive or still under investigation.
We recognize and understand that cannabis human clinical research performed in the last century produced information regarding its use during adolescence or while pregnant; its potential side effects on pregnancy outcome lack clarity, are somewhat confusing, contradictory, inaccurate and incomplete. There is poor or no definitive data regarding its absolute effects during lactation.
Medical marijuana has been available in Michigan and its use is associated with reported clinical diagnosis where some benefits from THC have been described, including but not limited to multiple sclerosis, Parkinson’s disease, certain types of resistant childhood epilepsy, persistent nausea and vomiting associated with certain chemotherapeutic agents, anxiety, chronic pain in osteoarthritis and more.
Almost on a daily basis we are requested to “consult” on possible health issues associated with the recreational use of cannabis by pregnant women. Currently, in our clinics and our offices more than 10 percent of pregnant women of all ages, when prompted, refer to the the use of marijuana, usually smoking, on frequent basis, from daily to periodic with no identifiable medical necessity or clinical indication. These consultations only add time, redundant visits and expense to caregivers to what should be a simple dialog. Voluntary self-reporting of cannabis use is approximately 4 percent. Toxicology testing provides a clearer picture. More than 60 percent of these patients believe that the use of cannabis while pregnant presents “no risk” and that it may be beneficial.
Counseling pregnant patients regarding the use of cannabis presents a challenge. Any practitioner involved in maternity care in today’s environment must be fully equipped, educated and informed to discuss the subject with their clients. Marijuana is the most common illicit drug used by pregnant women and use during pregnancy continues to increase. It must be clearly understood that today’s cannabis products are 20 to 25 percent more powerful than the previous generation. The newer “synthetic cannabinoids” are almost 100 percent more powerful.
The ubiquitous Cannabis contains more than 400 different natural chemical elements many of them Phyto cannabinoids. The THC is the main psychoactive drug present in cannabis; it acts on type 1 and type 2 (CB1, CB2) receptor agonists that are present in the central nervous system and peripheral tissues. Both delta-9-THC and cannabidiol (CBD, FDA approved Epidiolex™ ) the non-psychoactive component have demonstrated therapeutic effects in some studies as mentioned above. Cannabinoids cross the placenta and compete with the naturally occurring endocannabinoids that have known properties for embryo implantation, placental development and pregnancy maintenance. Repeated exposure to extra cannabis disrupts endocannabinoid signaling, especially on the CB1 receptors resulting in a phenomenon called “rewiring” of the fetal cerebral cortex. These “manipulations” of the system by exogenous cannabis could have unknown, but significant, effects on the fetus.
Further evidence shows that the repeated or long term use of cannabis by adolescents (young mothers to be or mothers amongst them), is associated with their increased risk of addiction and loss of up to eight IQ points. Pregnant women age 15 are reported to use THC in 21 percent, even when the use decreases in the last three months of pregnancy. High school juniors, 26 percent, are reported to be using THC. The rate for seniors is 28 percent. An increasing number of teens believe that the use of THC is benign and inconsequential. The approved Michigan law allows the retail sale for persons over 21.
Almost 40 percent of cannabis users partake for “recreational” purposes. Recreation is defined as “refreshment in body or mind, as after work, by some form of play, amusement or relaxation.” There is no medical necessity or clinical indication. Many of the other users can be counseled to use an alternative medication (for which there is accurate information) while pregnant to alleviate the condition for which they use cannabis, namely nausea, vomiting or anxiety.
Several practical points are available to use while counseling pregnant women using cannabis; we currently have insufficient evidence to associate the use of cannabis with fetal structural anomalies; there is some evidence that THC is associated with low birth weight in newborns with increasing maternal use. The association with prematurity (delivery before 37 completed weeks of gestation) is confusing and further studies are needed to clearly relate the effect of THC (if any) on prematurity with or without known causes—a very critical issue in infant morbidity and mortality in the state. THC metabolites in umbilical cord were statistically significant higher (3.9 percent) in association with intrauterine fetal deaths versus live births (1.7 percent). There is an increased risk of neonatal morbidity associated with respiratory, neurologic and hematologic pictures and perinatal death. The National Academy of Sciences reported insufficient evidence to support or refute an association between prenatal use of THC and long-term effects on cognition and academic performance, without adjusting for the potential environmental factors present. The use of THC is confounded by the use of tobacco and other risk factors such as maternal sociodemographic conditions that make definitive counseling difficult. However, abstinence from THC while pregnant and during lactation is the approach that we should use in our daily practice. In addition, in spite of the legalization, a positive test for THC in pregnancy may prompt a social worker consultation and a visit from child protective services. Marijuana is still considered illicit by the federal government.
Pregnant women must be warned against the use of synthetic cannabinoids, known as “designer drugs,” and growing in popularity. Information regarding their effects (agitation, irritability, confusion, hallucinations, delusions, psychosis and death) and toxicity is scarce; the number of medical emergencies created by their use is reportedly increasing. Rigorous research is urgently needed to understand the pharmacology of these compounds and guide clinicians to manage adverse events.
That THC is now legal in Michigan along with eight other states and the District of Columbia, does not make it safer. Our neighbors in Canada have retail for-profit cannabis available. Additional states had “recreational” marijuana on the ballot this November, however none of our surrounding states have approved such measures.
The Michigan Department of Health and Human Services and other national organizations offer easy online access information to use in counseling pregnant women to avoid using THC. Frequent use, defined as once a week opens the door for undefined deleterious effects, short term and long term. Burning marijuana, as in smoking, which is the most common reported method of use (83 percent) adds all the additional components of tar combustion, may affect others in a confined household with repeated exposure or in a closed vehicle by prolonged second-hand contact, including house pets. Other products that are available on retail like candy, chewing gum or cookies infused with THC failed to provide the desired “high” rapidly (may take 30 minutes), so there is potential for overdose to reach the desired gratification. Children in that scenario are at increased risk of serious side effects sometimes due to unintentional ingestion. None of these products are currently regulated in Michigan regarding the approved amount of THC-CBD contained per serving or per package and should be safely stored. For example, under different scenarios, firearms are also to be kept under lock and key, however we know that distractions and failures occur and minors get hurt or killed. Driving a vehicle during the “high” increases the risk of an accident and injury or death to unaware innocent passengers or other drivers, as in the case of carpooling with children involved. Vaping (heating below the combustion point) and dabbing (use of THC extracts) are additional means utilized by frequent users. Teens gravitate toward creative USB-looking portable devices.
Patient testing for the presence and/or amount of cannabis components in a given person, has no standard methodology. Detecting the cannabinoid’s concentration and the presence of contaminants is important for public health and epidemiologic monitoring. Testing for THC needs to be provided within the limits of the state of Michigan due to federal restrictions. A toxicity threshold must be promptly established based on available evidence, as is the case with alcohol. These tests are expensive, somewhat difficult to interpret and not available in all laboratories. Levels of cannabinoids in biologic samples and standard methods for their determination and confirmation are an imperative. Certain countries have reported frequencies from 1 to 18 percent for cannabis (psychoactive drugs) in drivers involved in traffic accidents. Progress in the science of cannabis must be periodically and swiftly reviewed to adjust the state policies and regulations. The state would be well served if a reference laboratory utilizing sanctioned technology for the determination of THC, CBD, THC/CBD ratios and other potential contaminants is established. A clear, consistent policy and definition to evaluate a person’s “impairment” or driving under the influence (DUI) second to cannabis use must be established, clearly explained and widely distributed for the public, emergency medical services and law enforcement information. Currently, the synthetic cannabinoids, such as SF-ADB, Spice and K2 mostly elude detection. These drugs are inexpensive to make, may be cut into other illegal drugs, and are more available than cannabis. Indeed, the for-profit drug trade in the United States moves faster than science, regulation and legislation.
Only recently, CBD was changed to Schedule V (Federal Register September 28, 2018); this important step may facilitate the performance of well designed, well conducted research with real world data collection and clinical outcomes monitoring in relatively short time.
There is an additional aspect of marijuana legalization that has not been discussed or included in the new law: the impact on marijuana industry workers of cultivating, harvesting, processing, transporting and storing marijuana plants. Those anxious to actively participate in the manipulation of cannabis must be informed and periodically tested.
The state legislators must work expeditiously with the health care teams, clinical laboratories, diagnostic testing producers and vendors and the department of public health to avoid any real or perceived regulatory discrepancies associated with the use of prescription “medical” with that of “recreational” cannabis and avoid any potential confusion. An active cannabis regulation enforcement division may be a useful step for the state to contemplate as the details of the new legislation are being developed.
Additional social and economic or financial issues may be beyond the scope of our essay, however it merits mentioning. The Michigan current tax levied on for profit retail cannabis as proposed by the law is shamefully meager. It compares poorly with other states with more experience. It opens the door for the “big cannabis business” to set foot in Michigan sooner or later. “Biggest Marijuana Works” will give a brand new meaning to BMW, in spite of the current limitations placed by the Michigan law. A few years from now, in the same fashion that the big tobacco executives denied the addictive properties of their product, we may have a similar scenario in Michigan associated with the use of cannabis. Cannabis tourism will soon find the way to travel from neighboring states, since no other state in the area offers the opportunity to “recreate” using cannabis.
As we understand, it appears that the legalization of cannabis will soon be OR is now the law in Michigan; an intelligent comprehensive and proactive approach to the implementation is essential. Now we have the trifecta for the legal use of human behavior modifiers: alcohol, tobacco and cannabis. Legislators must act proactively to expeditiously, properly, systematically and uniformly regulate the production, use and price of cannabis and related compounds, create evidence-based standards, and limit the advertising of these products in the open market. May future generations look at us and wonder.
References
NORML. Medical marijuana: information for each state. http://norml.org/legal/medical-marijuana-2
National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017.
The National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. http://nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx.
Marijuana use in pregnancy and while breast feeding. Metz TD, Borgelt LM. Obstetrics and Gynecol. 2018. 132. 1198-1210
Lessons learned after three years of legal recreational marijuana: the Colorado experience. Ghosh, TS, Vigil DL, Maffey A et al. Preventive Medicine. 2017 Elsevier Inc.
Synthetic and non-synthetic cannabinoid drugs and their adverse effects – A review from public health perspective. Cohen K, Weinstein AM. Frontiers in public health. 2018.