MICHAEL M. KRINSKY, MD, AND MYRON GENEL, MD
From the Editors’ Desk, April 2019, Connecticut Medicine
There is a notion that marijuana is innocuous, and being relatively harmless, it should be legal for recreational use – that it is not really any more dangerous than, say, hula hoops. This idea is rampant, embraced by many physicians, lawyers, teachers, judges, policemen, clergy, butchers, bakers, and candlestick makers. And many of the political class. Especially certain politicians. In the case of the latter, legalizing it and taxing it offers an easy way to expunge years of governmental mismanagement which has lead to financial instability. Connecticut is a prime example of this, but is certainly not alone among the states. For some it is a way to influence votes. This year it is seen in some quarters as a litmus test of a politician’s convictions of what constitutes social justice. But, before we jointly pursue the rush of pot for all and all for pot, it is worthwhile pausing, inhaling deeply, and spending at least a toke[n] amount of time-consuming marijuana basics.
First of all, we don’t know enough about marijuana because it has not been researched in enough scientific studies to conclude convincingly regarding its safety profile for recreational use. There is plenty of folklore. But, in order to permissively and affirmatively promote a substance which has a potential darker side broadly into a population, prudence requires more than ignorance of its risks. We already have enough trouble with opioids and alcohol. Some of what is known follows.
The main psychoactive chemical substrate in marijuana is delta-9-tetrahydrocannabinol (THC).1 It is to be distinguished from cannabidiol (CBD), which has been mildly effective in, and FDA approved for, two “conventional drug” resistant, but rare genetic seizure disorders in children (Lennox-Gastaut Syndrome and Dravet Syndrome). That signal event occurred in June, 2018 when Epidiolex was approved.2 CBD is that substance which doesn’t yield a buzz like its sister, THC, and is being incessantly hyped by lifestyle experts for almost incalculable uses in ointments, creams, cosmetics, sexual aids, pet products, and oils for every purpose.3 THC is just one of approximately 100 compounds (cannabinoids) that are chemically similar. There are over 500 other compounds found in the female cannabis plant.1 Most have been identified, but never fully studied. Marijuana is a Schedule 1 drug, defined by the DEA as having “no currently accepted medical use and a high potential for abuse.” Clearly CBD is an exception. THC is another matter.2
The potency of today’s plant strains is at a minimum 20 to 30 times as strong as the weed familiar to the Woodstock Generation. By the 1990s the THC content averaged 3.8%. In 2014, that rose to 12.2%.1 The average marijuana extract is 50% THC, but can exceed 80% in some strains. It is this potency which harbors extreme risks for today’s user, casual and habitual alike. A THC level of greater than or equal to 5 nanograms is thought to be the level consistent with intoxication, but there is no reliable way to routinely evaluate for this in a standardized fashion in the field. When multiple drugs are onboard, the intoxication level could conceivably be lower via potentiation or other mechanisms.
Marijuana currently is in widespread use by some who the proposed legislation efforts would not authorize for use. One study found that in 2016, 9.4% of 8th graders, 23.9% of 10th graders, and 35.6% of 12th graders used it during the study year. Six percent of those used it daily or nearly so.4
Problem use of marijuana can lead to Marijuana Use Disorder (MUD) which is considered an addiction in severe cases.5 People who start the use of pot before the age of 18 are four to seven times more likely to develop MUD.6 In 2015, circa four million people met criteria for this diagnosis.7
Nine percent of people who use pot will become dependent on it.8,9 But, that rises to 17% in those who begin usage in their teen years.10 To be precise, dependency is to be distinguished from addiction. Dependency, with all of its attendant effects, occurs when the brain adapts to large amounts of THC presented to it by reducing the native production of intrinsic endocannabinoid neurotransmitters and, also, its sensitivity to those substances.
Evidence of exposure of developing brain in animal studies reveals long-term and probably permanent structural changes, particularly in the hippocampus, the memory formation center of the brain.11,12 Contradictory findings in studies of adult animal brains have yet to be resolved – meaning it is not yet known what, if any, danger there is to the adult brain.13
But, it is known that there is an altered reward system in dopamine-containing centers of the brain after repeated marijuana exposure.14 The import of this is the suggestion of an increased risk of the subject to self- administer other drugs of habituation/reward when given the opportunity to do so. This is akin to current theories concerning gambling predisposition, smartphone use, and gamers’ habituation.
Alarmingly, pot impairs short-term memory, judgment (especially as to gauging the passage of time), and it distorts perception.15 The implication is that use at any age imposes a competitive disadvantage in the employment arena and academically.16
Though marijuana may not automatically lead to the often discussed gateway phenomenon, it most certainly does lead to an enhanced behavioral response to THC re-exposure and to other addictive type substances.17 Morphine is an example. This is known as the phenomenon of cross-sensitization. This may explain how simultaneous drug use or experimentation could expedite the slippery slope to use of more potent and more addictive substances.18,19
Adults who use marijuana have an increased percentage likelihood of developing Alcohol Use Disorder with- in three years of starting with marijuana.20 Several studies link heavy marijuana use to lower income, lesser educational attainment, and diminished life satisfaction.21,22 Of course, we must bear in mind that correlation is not causation. An increase in automobile accidents does meet the causation standard, however.23 (There is some controversy whether this is so once case control factors of age, gender, race, and alcohol are factored in, however.) So do increased risk of worker HR problems including industrial accidents and absenteeism in people who test positive on pre-employment urine screens.24
On the psychiatric front a recent European study published in Lancet25 confirms a link to schizophrenia in users. Symptoms associated with usage include an increased incidence of anxiety, depression, and substance use disorders. Acute psychotic reactions are well-known in non-schizophrenic users with high usage of higher potency marijuana. Luckily this is usually reversible. It does lead to an increase in emergency room visits with their attendant costs and documentation of the event which cannot be expunged thanks to electronic medical records (EMR). More ominously, users with specific (but unknown to the user at time of use) gene variations such as the AKT 1 gene which modulates dopamine signalling in the striatum, are at increased risk of psychosis.26 This is estimated at up to seven times higher occurrence in those who are daily marijuana users vs those who rarely or never use it. The same phenomenon occurs in people who carry a variant catechol-O-methyltransferase [COMT] gene if they are exposed in young adulthood after using it in adolescence.27 This is a “ticking timebomb effect.” Most worrisome, marijuana use can worsen the course of the illness in those suffering pre-existing schizophrenia.
Let us add the following to the list of undesirable cannabis effects: Amotivational Syndrome, impaired balance, and coordination, Hyperemesis Syndrome, irritation of throat and lungs, myocardial infarction after in- gestion, a 26% increase in stroke risk in young and middle-aged users, 10% increase in risk of developing heart failure, an obesity link, a hypertension link, and definite increased risks of tobacco and alcohol usage. We would be remiss to avoid mentioning marijuana’s association with decreased sperm counts. No one can currently state with certainty the full risks of second hand exposure to marijuana smoke, vaping risks, or lung cancer. But it is known that the risk of fatality rises with oral intake. Gastrointestinal uptake is slower than inhalation, leading to disappointed expectations in the novice (and others) followed by binge eating, followed by possibly serious and overwhelming results. So, don’t enjoy the brownies too much. And, no, it is not a substitute for your opioid habit. There is more, but there is no reason to bore the reader.
As if the natural substance weren’t enough of a challenge there is synthetic cannabinoid which was recently associated with a very dangerous coagulopathy.28
Until more research is done to qualify and quantify this substance as well as what research has already shown, it should not be considered for legalized recreational use. Let’s be forthright. Many want this legalization to legitimize their personal habits and to reduce the risk of legal exposure. Many just see an opportunity to enrich themselves by exploiting the vulnerabilities of others. While our capital markets can survive without a questionable new investment vehicle, there is real risk as to the individual user’s health and that of all our children and grandchildren. Once upon a time we didn’t know it was ignorant to drive without a seatbelt, to ski without a helmet, to invite disease and death by smoking and chewing tobacco, by polluting land, air, and water with chemicals, and that repeated trauma to the head and torso from contact sports can lead to progressive and irreversible brain damage. Now that we do, we are impelled to make choices that benefit ourselves and our society in order to lead more fruitful and healthy lives.
In time, it may be possible to know precisely whether marijuana use will undermine our society in ways our enemies hope it will, a self-inflicted wound that will reverberate and degrade all of us. Those who extol marijuana’s societal virtues are deluding themselves and hope to delude the rest of us.
The bottom line is that tax revenues will not reach projected levels, taxation will simply spur the black market, addictive behavior will rise, and human potential will be squandered. Corporate interests will dominate the market because there is the insatiable need to recoup the loss of revenue from falling tobacco use. Spiking alcohol will inevitably drive up the numbers of the habituated. The inevitable consumer branding outcome will not likely respond pliably to regulators, but instead, primarily to the principle of market equilibrium; that is, supply demanded equals quantity supplied.
Once upon a time in this country government foisted an experiment upon unwitting citizens to our everlasting dishonor. We should not permit a Tuskegee-like experiment upon the citizens of Connecticut promoted by the ethically challenged. Some folks just want to get high. Our goal should be to lift everyone up, not to drag everyone down. A people cannot effect social justice by mandating social injustice.
The state medical societies of Connecticut, New York, New Jersey, and Delaware, representing more than 40,000 physicians together have said “No, No, No, No” to legalizing recreational marijuana. Patients and politicians should listen to their doctors.
- Mehmedic Z, Chandra S, Slade D, et Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci. 2010;55(5):1209–17.
- Samson More research is underway for cannabinoids for neurologic disorders: but it’s on-again, off-again legal status presents barriers. Neurol Today. 2019;19(6):1,20–1.
- Holson Martha Stewart will advise cannabis grower on products for humans and pets. New York Times. https://www.nytimes.com/2019/03/01/ business/martha-stewart-cannabis-pot.html. Published March 2, 2019.
- Johnston LD, Miech RA, O’Malley PM, et Monitoring the future: national survey results on drug use. 1975-2018. 2018 overview: key findings on adolescent drug use. Ann Arbor, MI: Institute of Social Research, University of Michigan. Published January 2019
- Center for Behavioral Health Statistics and Quality (CBHSQ). Treatment episode data set (TEDS):2003-2013. National admission to substance abuse treatment Rockville, MD: Substance Abuse and Mental Health Services Administration. BHSIS Series S-75, HHS Publication No. (SMA)15-4934. Published December 2015.
- Winters KC, Lee Likelihood of developing an alcohol and cannabis use disorder during youth: association with recent use and age. Drug Alcohol Depend. 2008;92(1–3):239–47.
- Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Results from the 2015 National Survey on Drug Use and Health: detailed tables. https://www.samhsa.gov/data/report/results-2015-national-survey-drug-use-and- health-detailed-tables. Published September 8, 2016.
- Anthony JC, Warner LA, Kessler Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbility Survey. Exp Clin Psychopharmacol. 1994;2(3):244–86.
- Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, et Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 2011;115(1–2):120–30.
- Anthony The epidemiology of cannabis dependence. In: Hoffman RA, Stephens RS, eds. Cannabis Dependence: Its Nature, Consequences and Treatment. Cambridge, UK: Cambridge University Press, 2006: 58–105.
- Verrico CD, Gu H, Peterson, ML, et Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory. Am J Psychiatry. 2014;171(4):416–25.
- Rubino T, Realini N, Braida D, et Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are as- sociated with cognitive impairment in adulthood. Hippocampus. 2009;19(8):763–72.
- Pagliaccio D, Barch DM, Bogdan R, et Shared predisposition in the association between cannabis use and subcortical brain structure. JAMA Psychiatry. 2015;72(10):994–1001.
- Pistis M, Perra S, Pillolla G, et Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry. 2004;56(2):86–94.
- Volkow ND, Swanson JM, Evins AE, et Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review. JAMA Psychiatry. 2016;73(3):292–7.
- McCaffrey DF1, Pacula RL, Han B, et Marijuana use and high school dropout: the influence of unobservables. Health Econ. 2010;19(11):1281–99.
- Agrawal A1, Neale MC, Prescott CA, et A twin study of early cannabis use and subsequent use and abuse/dependence of other illicit drugs. Psychol Med. 2004;34(7):1227–37.
- Panlilio LV, Zanettini C, Barnes C, et Prior exposure to THC increases the addictive effects of nicotine in rats. Neuropsychopharmacology. 2013;38(7):1198–208.
- Cadoni C, Pisanu A, Solinas M, et Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology (Berl). 2001;158(3):259–66.
- Elvik Risk of road accident associated with the use of drugs: a systematic review and meta-analysis of evidence from epidemiological studies. Accid Anal Prev. 2013;60:254–67.
- Macleod J, Oakes R, Copello A, et Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet. 2004;363(9421):1579–88.
- Gruber AJ, Pope HG, Hudson JI, et Attributes of long-term heavy cannabis users: a case-control study. Psychol Med. 2003;33(8):1415–22.
- Li MC, Brady JE, DiMaggio CJ, et Marijuana use and motor vehicle crashes. Epidemiol Rev. 2012;34:65–72.
- Zwerling C, Ryan J, Orav The efficacy of preemployment drug screening for marijuana and cocaine in predicting employment outcome. JAMA. 1990;264(20):2639–43.
- Di Forti M, Quattrone D, Freeman TP, et The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. Lancet Psychiatry. 2019 Mar 19.
- Di Forti M, Iyegbe C, Sallis H, et Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol Psychiatry. 2012 Nov;72(10):811–6.
- CaspiA1, Moffitt TE, Cannon M, et Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57(10):1117–27.
KelkarAH, Smith NA, MartialA, et al.An outbreak of synthetic cannabinoid-associated coagulopathy in Illinois. NEngl J Med. 2018;379(13):1216