The rapid pace of marijuana legalization across the United States (US) and Canada presents a significant challenge to public health professionals, who are charged with the responsibility to promote health and community well-being.
The field of public health has historically been driven by science. However, the peer-reviewed evidence base on marijuana-related harms – and benefits – is limited. Numerous studies find association between marijuana use and various adverse outcomes. However, in many cases the evidence for causal effects is inconclusive, and it is difficult to completely discount residual confounding or even reverse causality. Some of the phenomena that we are interested in are relatively recent, and the research simply has not caught up. The legal framework around marijuana is evolving rapidly, new and more potent marijuana products have emerged, marijuana use patterns are changing, and new routes of administration have gained popularity. Thus, some of the evidence we rely on today may already be outdated.
The manufacturing, distribution, and use of cannabis are regulated globally by the International Drug Control Conventions. In the United States, it is regulated by the Controlled Substances Act (CSA), which was passed by Congress in 1970. The CSA outlined a scheduling system which placed marijuana in the most restrictive schedule, thereby limiting the opportunity to carry out marijuana research in the United States.
Under the International Drug Control Conventions, the World Health Organization is charged with conducting medical, scientific, and public health evaluation of substances to reflect new knowledge [1]. In 2018, the WHO Expert Committee on Drug Dependence (ECDD) for the first time reviewed cannabis and cannabis-related substances, including cannabidiol (CBD). They recommended that cannabis be moved from the most restrictive schedule (Schedule IV) of the international drug conventions to the second most restrictive schedule (Schedule I), partly due to the potential medical effects of cannabis and partly because cannabis was regarded as less harmful than other drugs in Schedule IV, such as heroin and fentanyl [2]. Furthermore, they recommended that CBD should not be scheduled under the international drug conventions since it is not psychoactive and there is no evidence of abuse or dependence and since CBD also has medical uses [3].
Despite a growing evidence base, the information that we have about cannabis is still somewhat tentative and preliminary. Research points to a number of possible concerns, and new issues may arise as the situation evolves. The surge of vaping-related lung illness in 2019 is a striking case in point. Careful monitoring is needed to identify public health challenges and strengthen the evidence base. Simultaneously, marijuana legalization efforts are accompanied by disparate, and often outspoken, political and social views about its risks and benefits. Anecdotal reports are commonplace.
We are maneuvering through an era of broad marijuana legalization and decriminalization efforts with limited evidence. However, lessons from other fields of public health can provide some guidance. Experiences with alcohol and tobacco suggest that social norms, price, availability, and exposure influence consumption in a population, and that population-level harm is related to consumption levels.
In 1994, the Centers for Disease Control and Environment (CDC) defined the three core functions of public health: assessing, monitoring, and investigating potential health hazards; developing and enforcing policies to regulate, mobilize, and empower groups or individuals; and assuring the effectiveness of programs while linking and educating communities. Public health professionals must respond to new and evolving conditions and events in order to carry out these core functions. The response must be based on the best available evidence and requires monitoring, policy development, community and individual empowerment, as well as continuous evaluation to improve performance.
In this chapter, we present an overview of the most salient topics in the field today, with consideration for the limitations noted above. Many of these topics will be treated at greater length in other chapters of this book. Using the CDC framework as a backdrop, we discuss how marijuana legalization and decriminalization efforts influence public health monitoring, policy, and assurance. Specifically, we review marijuana use and differential risks; health concerns related to accidents and harm associated with acute intoxication, physical health effects, mental health effects and harm to others; and public health response regarding regulations and campaign messaging.
Marijuana Use and Differential Risks
Consumption Rates
While public health is not primarily occupied with the legal status of marijuana, changes in use and usage patterns are relevant to its mission of ensuring community well-being. Insofar as legal status and regulations impact use, public health and safety can be influenced by the rapid increase in legalization and decriminalization.
Historically, most marijuana research has been done in places with relatively low consumption and low rates of heavy, persistent use. Users primarily smoked low potency marijuana, either alone or with tobacco. A look at marijuana today presents a markedly different picture. Consumption rates today are higher; around one in three young adults uses marijuana regularly in states like Colorado, Oregon, Vermont, and Maine, according to the 2017 NSDUH survey [4], and the share of daily or near-daily users has increased [5].
Differential Use Patterns
Differential use patterns have been noted in specific areas and by specific populations. This preliminary finding stands out as an important area to monitor in public health. Several studies indicate that availability influences marijuana use [6–8]. Experience with alcohol and tobacco shows that there are more outlets in less affluent and minority communities [9–11]; a similar trend has been found with marijuana in recent data from Colorado and Washington [12–14]. There is further concern that consumption of marijuana is skewed toward a small minority of heavy users with low socioeconomic status [5]. Recent data from Monitoring the Future shows that the rate of daily marijuana use is twice as high among young adults who do not attend college, compared to their peers in college [15].
Early evidence suggests that legalization affects social norms, which, in turn, may impact consumption rates. Social norms among young college age adults have changed more rapidly in Colorado than in the country as a whole [16]. One study found that the frequency of marijuana use in Colorado college students was much higher than the national average, particularly daily or near-daily use [17]. A review found media coverage, advertising, and social media overwhelmingly favorable to marijuana and positively correlated with the audience’s marijuana-related beliefs and behaviors [18]. Furthermore, a study of adolescents in California found that exposure to marijuana marketing was associated with greater intention to use, higher average use, and more negative consequences over a 7-year period [6].
The NSDUH surveys show that legal states are among the highest consuming states in the United States, with a sharper increase than the rest of the country [19]. Population survey results are supported by other data sources. For example, a recent wastewater analysis from Washington state found a two- to threefold increase in marijuana use since legalization [20].
Potency and Methods of Consumption
Marijuana today is not like marijuana of the past. In the last two decades, tetrahydrocannabinol (THC) potency has risen sharply [21–24], and new products and routes of administration have emerged. Edible products, topical creams, marijuana oils, and various concentrates make up a growing share of the total marijuana market. While the consequences of high THC marijuana are not well documented, studies show that higher potency is associated with a greater severity of dependence [25], an increase in the number of people who seek treatment [26], higher risk of progression to marijuana use disorder [27], and higher rates of psychosis [28–30].
While smoking marijuana remains the most common mode of consumption, vaping and edible use is increasing. Many young people use several modes of administration, which may carry different risks. Most emergency room visits are due to inhaled marijuana; however, edibles seem to carry a greater risk of acute psychiatric visits, intoxication, and cardiovascular symptoms [31]. The shift toward dabbing high concentrate marijuana (such as wax or shatter) carries specific risks, including paranoia, psychosis, burns, and other inhalation injuries [32].
Accidents and Harm Associated with Acute Intoxication
In addition to euphoric effects, marijuana intoxication is associated with impaired thinking and concentration, drowsiness, short-term memory loss, loss of coordination and balance, changes in sensory perception, slower reaction time, and lower ability to perform complex tasks. These acute effects can increase the risk of accidents and harms.
Road Traffic Accidents
Given the temporary physiologic changes that accompany marijuana use, public health is interested in understanding whether the legalization of marijuana increases incidents of impaired driving and accidents. Epidemiological and experimental studies find that marijuana impairs driving performance and increases the risk of crashes. [33] The risk of motor vehicle accidents is 2–3 times higher among marijuana-impaired drivers, with substantially increased risk if the driver also has elevated blood alcohol level [34].
The number of drivers in fatal accidents who tested positive for Delta-9 THC (indicating recent use) in Washington doubled from 2013 to 2017 [35]. Most of these tested above 5 ng/ml and were positive for alcohol or other drugs [36]. Marijuana-related fatalities also increased in Colorado, with a 109% increase in the number of marijuana-related fatalities between 2013 and 2018 [37]. Other studies compared traffic fatalities in neighboring states where marijuana was and was not legalized, finding a temporary increase in Colorado, Washington, and Oregon 1 year after legalization [38].
Survey data suggest that there is an association between people’s perception of risk and their willingness to drive after using [35, 39]. Seven in ten marijuana users in Colorado reported driving within 3 hours after using during the past year; 27% of users said they drove under the influence of marijuana almost daily [40].
Marijuana can stay in a person’s system anywhere from a few hours to up to several weeks, depending on how much is consumed, frequency of use and individual tolerance. The pharmacology of marijuana makes it difficult to assess impairment levels. While there is a close correspondence between blood alcohol content and alcohol intoxication, the relationship between THC levels and intoxication is less consistent and depends on the route of administration.
Workplace Accidents
Based on road accident research, it is plausible that marijuana impairment increases the risk of workplace accidents, injuries, and fatalities [41]. A study of Egyptian construction workers found increased injury severity and more workdays lost among workers who used marijuana [42]. Empirical data in this area are scarce, and effects would likely be dependent on the job sector.
Marijuana use can be of concern in safety sensitive industries. Some business owners report difficulty finding employees who can pass a drug test [43]. National data from the private drug testing company, Quest, reported an increase in positive urine tests for marijuana among nearly all workforce categories from 2004 to 2018 [44].
Violence
The association between marijuana and violence is controversial. Some studies suggest that marijuana is associated with reduced aggression [45]; others find a higher risk of violence [46, 47]. Aggression, increased hostility, and impulsiveness are linked to withdrawal [48, 49], although the risk is relatively modest compared to alcohol.
There is an association between marijuana and psychosis and an association between psychosis and violence in some patients [50]. Marijuana use disorder has been shown to be a risk factor for violence in the early phase of psychosis and in patients with severe mental illness [51–54]. However, given the limited numbers of patients affected, it is unclear if increased risk estimates are large enough to register on the population level.
Hospital and ER Admissions and Overdose
Despite claims that marijuana is a relatively benign and safe drug, marijuana-related emergency room visits and hospital admissions have increased in the United States in recent years [55]. Providers treat a variety of marijuana-related symptoms, including gastrointestinal problems and cardiorespiratory effects, traumatic injuries, and accidental ingestions [56]. Patients may present with varying degrees of mental health symptomology, such as anxiety, paranoia, and psychosis. Studies show high rates of co-occurring mental health diagnoses in marijuana-related ER and hospital visits [57]. In addition to physical and mental health symptomology, patients present with acute injuries including burns from butane hash oil explosions [58] and inhalational injuries [32].
There is growing concern about increased marijuana-related emergencies in children and teens, particularly in newly legal markets [56]. In recent years, there has been increasing awareness of cannabis hyperemesis syndrome (CHS) – uncontrolled and sustained vomiting that subsides when marijuana use ceases [59]. Studies suggest that CHS is frequently undiagnosed and considerably more common than previously thought, potentially impacting more than two million patients a year [60, 61]. The syndrome can be a costly and potentially serious condition, with documented reports of fatalities [62, 63].
Several studies from Colorado found increases in marijuana-related emergency room visits following legalization, perhaps even tripling in frequency [64, 65]. While the majority of emergency room visits were related to inhaled marijuana, edible products accounted for a disproportionate share. Inhaled marijuana was more likely to result in hospitalization, whereas edibles more often result in acute psychiatric symptoms, intoxication, and cardiovascular symptoms [31]. Finn and Salmore found a steep increase in marijuana-related diagnoses at a Colorado hospital between 2009 and 2014, resulting in significant costs to the facility [66]. Other studies found increases in adolescent marijuana-related visits in recent years [67]. Still, the data is not completely consistent. Research looking at inpatient databases found neutral effects on healthcare utilization in the time immediately following legalization compared to two other states [68]. Many of the hospital studies have a low base rate of visits, and the precise clinical relevance is unclear. Further, the study designs often make it difficult to tease out differences between marijuana-related presentations and recent procedural changes which improved marijuana identification.
According to the CDC, direct overdose deaths due to a lethal dose of marijuana are unlikely. Still, this does not mean that ingestion amount is inconsequential. High dosages of marijuana are typically more severe, and effects may include extreme confusion, anxiety, paranoia, panic, rapid heart rate, delusions or hallucinations, increased blood pressure, and severe nausea or vomiting [69].
Physical Health Effects
From a public health perspective, the legalization and decriminalization of marijuana raises concerns about the potential for adverse health effects
Pulmonary Effects
Even though new ways of ingesting marijuana have increased, smoking remains the most common route of administration. In the legal market in Colorado, researchers found that nearly all young people who use marijuana smoke some or most of the time [70]. Decades of research has demonstrated the harmful effects of cigarette smoking; [71] alarmingly, marijuana smoke contains many of the same substances and carcinogens as tobacco smoke, and inhaling burning plant material may harm the lungs. Currently, however, research on the effects of marijuana smoke on lung cancer, emphysema, and chronic obstructive pulmonary disease (COPD) is unclear and inconsistent [34, 72]. Possible explanations include (1) the effect of smoking marijuana may not be as strong as tobacco, (2) marijuana use traditionally has been less intensive than tobacco smoking, or (3) it is hard to disentangle the harms from marijuana from those of tobacco.
Still, other pulmonary problems appear similar to those found in cigarette smokers; marijuana has been linked to chronic bronchitis, coughing, wheezing, and sputum production [34, 73]. Marijuana was identified as a risk factor for bronchial asthma or use of asthma medication in a Norwegian sample, even when controlling for known confounders [74]. Concurrent use of marijuana and tobacco may increase the risk of respiratory harm [75].
Pulmonary Effects from Vaping
In the summer of 2019, there were almost 200 reports of severe lung illness linked to vaping within a couple of weeks. Patients presented with shortness of breath, breathing problems, vomiting, diarrhea, and fever. Some patients were intubated and required treatment in intensive care units [76]. By the end of September 2019, the CDC were investigating 530 cases, and there were at least 8 confirmed fatalities [77].
The cases involved different types of vaping devices and different vaping liquids. Early reports indicate that a majority of the cases were linked to THC oils [78]. While many of the cases involved black market cannabis oil, at least one of the fatalities was an Oregon man who had used a vaping device containing marijuana bought at a licensed dispensary [79].
Many of the patients were quite young. A study from Wisconsin and Illinois shows that the median age was 19 years [78]. However, harms are not limited to young people. The age range in the study was 16–53 years, and at least one of the fatalities was a person over 50 years.
Little is known about the risks of nicotine vaping, and even less is known about vaping cannabis oil. So far it is unclear whether the cases are linked to specific vaping devices, to vaping in general, or to specific vaping products. While black market THC oils are a strong suspect, other vaping liquids have also been involved [76, 79]. Despite regulation, a study found that 50% of THC vaping products in Washington were over the state’s threshold for pesticides [76]. Other possible culprits include harmful substances in commercially available vaping products, such as formaldehyde, tin and lead, as well as certain flavoring and thickening agents.
It is also possible that the phenomenon is not new, but that earlier cases were misclassified or overlooked. Case reports have described similar events before [80, 81].
Further research is needed to understand the mechanisms between vaping and lung illness. However, the recent cases clearly illustrate the need for careful monitoring and evidence-based policy responses.
Cardiovascular Effects
A number of adverse cardiovascular effects are associated with marijuana use, including sudden cardiac death, vascular events, arrhythmias, and stress cardiomyopathy in relatively young users [82–84]. While the most serious cardiovascular events are rare, researchers speculate that they may be underdiagnosed [85]. A population-based study found that marijuana abuse was significantly associated with elevated rates of myocardial infarction in women and young people, even when controlling for known risk factors [86], and that the risk of myocardial infarction increased fourfold for up to an hour after smoking. After controlling for several known confounders, Kalla et al. found that marijuana was an independent predictor of heart failure and cerebrovascular events [87]. Marijuana use has also been shown to produce symptoms of angina in older users [34].
Cancer
Because marijuana contains many of the same carcinogens as tobacco and is often inhaled in the same manner, there may be similar linkages with lung cancer. [88] Research in this area, however, is unclear and often contradictory [34, 89, 90]. A recent meta-analysis [91] finds an association with higher lung cancer rates, although the risk appears to be much lower than with tobacco [92]. Several studies showed an association between marijuana use and testicular cancer [93, 94], particularly among long-term users (>10 years) [91]. There is limited evidence linking marijuana use to other types of cancer [95].
Reproductive Health
Researchers have examined the correlation between marijuana use and infertility in men and women. Smoking marijuana is associated with reduced sperm count, sperm motility, and viability. Evidence from experimental, observational, and animal studies show mixed results concerning fertility among men who use marijuana [96–99]. There is some evidence that cannabinoids can affect the female reproductive system. Studies show that marijuana use can influence ovulation and that exogenous cannabinoids can lower estrogen and progesterone levels [100, 101]. Despite considerable uncertainty, a recent review article concludes that marijuana may reduce the ability to conceive in couples that have difficulties getting pregnant, but not in couples without fertility issues [102].
Mental Health Effects
One of the findings from marijuana research over the past decades is that regular marijuana use is consistently associated with poor psychosocial outcomes and mental health in adulthood [34]. In the absence of randomized trials, it is difficult to tease out causal relationships. However, for some mental health conditions, there is strong evidence for a causal connection and increasing insight into possible biological mechanisms.
Addiction
Despite its reputation as a natural and benign drug, marijuana can be addictive, and those with marijuana dependence may suffer through cycles of use, relapse, and withdrawal, just like any other drug. Earlier studies suggest that around one in nine marijuana users become addicted to marijuana, with risk estimates jumping to one in six among adolescents [34]. Addiction research among recent or current users show even higher rates. NSDUH data indicate that 15% of past month users meet the DSM-IV criteria for a marijuana use disorder [103]; the rate jumps significantly among daily users, with estimates between 30–50% [34, 104].
There is some concern that the rate of marijuana addiction has risen since the most frequently cited studies in the 1990s. THC potency has increased, and new methods of using marijuana have gained popularity. Most sources indicate that marijuana use disorders increased in the United States since 2002 [105], although it is difficult to determine if this is the result of more dependency or better identification of the problem. Analyses show that recent increases were significantly higher in some groups, particularly among men, African Americans, urban residents, and populations who were unmarried or had lower incomes [106]. Somewhat inconsistently, NSDUH data found declining rates of marijuana use disorder among heavy users in the same time period [107, 108]. Changes in addiction rates are not limited to American populations, however. Europe has seen a sharp increase in the number of patients seeking treatment for marijuana use disorders, despite stable use [109]. Marijuana is now the most frequently cited drug among new patients entering treatment in Europe [110]. Marijuana users are significantly more likely to experience addiction than, e.g., psychosis [111].
Marijuana withdrawal is not uncommon. Several studies demonstrate marijuana withdrawal syndrome after cessation of regular use [112]. The symptoms include irritability, anger, aggression, nervousness or anxiety, sleep problems, reduced appetite and weight loss, restlessness, depressed mood, and physical symptoms such as abdominal pain, sweating, fever or chills, and headaches [105, 113]. Symptoms are experienced most during the first week of cessation and can persist up to a month. A study of regular users (>3 times per week) found that 12% reported experiencing withdrawal [114]. Withdrawal increases among heavy users in treatment, with more than half reporting symptoms. Marijuana withdrawal can be debilitating for the user and may present as an obstacle to cessation [105, 114].
Cognitive Effects and the Developing Brain
Acute effects of marijuana use include impaired attention, motor skills, executive functions, and working and episodic memory. Most effects are transitory and cease after less than a month [111, 115–118]. Whereas these short-term effects are well documented, long-term effects are more controversial. It is notoriously difficult to establish causal connections, and even when studies control for known confounders, residual confounding or reverse causality cannot be discounted.
There is strong evidence that marijuana use is associated with poor psychosocial outcomes (e.g., higher risk of dropping out of high school and poorer grades, lower likelihood of enrolling in higher education or attaining a university degree) [119–122]. NSDUH data show that the age of marijuana initiation is associated with unemployment [123]. At least some of these outcomes may be modifiable; research suggests that memory and grades improve upon maintained abstinence [124, 125].
A recent review suggests that long-term cognitive effects have been overstated and that reported deficits can be explained by acute effects or effects of withdrawal [126]. Even if cognitive effects are reversible, persistent marijuana use in formative years can still have long-term effects, because short-term effects could affect educational outcomes or the acquisition of social capital and life skills that are important in adulthood [120].
Growing evidence indicates that the adolescent brain is more vulnerable to marijuana use than the adult brain. The body’s own endocannabinoid system plays a key role in neurodevelopment, and the introduction of exogenous cannabinoids could disrupt the balance of the endocannabinoid system. Such a mechanism is further supported by animal studies [115].
IQ and motivation effects are commonly associated with marijuana use. A study from New Zealand found a persistent drop in IQ among adolescent onset heavy marijuana users over a period of several decades [127]. However, a longitudinal study of teenagers failed to find an effect, and two recent twin studies did not find a long-term impact in the late teens [128, 129]. The results in the later three studies may be partly due to shorter observation period than in the New Zealand study. Since the nineteenth century, marijuana has been linked to “amotivation” – a lack of goal-directed behavior, concentration, and perseverance. This effect is supported by Volkow et al. who demonstrated both preclinical and clinical evidence. An acute amotivational effect has also been found in experimental settings [115, 116].
Long-term effects might indicate a change in one’s physiology. While brain imaging studies found some alterations in brain structure, the differences are generally limited, and causality is not always established. Many of these studies suffer from small sample sizes, and the clinical relevance is often unclear [115, 118, 130, 131].
Psychosis and Schizophrenia
A number of studies have shown a correlation and a dose-response effect between marijuana use and psychosis or schizophrenia [28, 132]. While rare, marijuana-associated psychosis is a serious outcome for the user. Psychosis, particularly with conversion to schizophrenia, is a significant burden on individuals, families and health services.
Although the absence of randomized controlled trials makes it difficult to establish a causal link between marijuana and psychosis, there is strong evidence supporting such a mechanism. Longitudinal studies show that marijuana use precedes psychotic episodes [115]. Current evidence does not support a self-medication theory [133], and the association between marijuana and psychosis remains after controlling for prodromal symptoms, other drugs, and parental psychosis [134]. Furthermore, a Norwegian study found increased risk of psychotic-like symptoms among marijuana using twins compared to their non-using siblings [135].
The risk of psychosis has been linked to THC in marijuana [136]. THC has been found to cause psychotic symptoms in a laboratory setting [137, 138]. A study by Di Forti et al. found that individuals who used high potency marijuana had elevated rates of psychotic disorders [30]. A European multicenter study demonstrated higher incidence of first episode psychosis in cities with high prevalence of high potency marijuana, and estimated that marijuana is involved in 30% of first episode psychosis in London and 50% in Amsterdam [139]. Population-level estimates indicate that the elimination of marijuana could reduce the incidence of schizophrenia by around 10% [140].
Research has identified some biologically plausible mechanisms between marijuana and psychosis [133, 141, 142]. Marijuana use is linked to earlier onset of psychosis [30], and patients who continue using marijuana after their first psychotic episode have poorer prognosis, increased risk of relapse, and worse outcomes [47, 143–145]. Continued use is also associated with increased conversion to schizophrenia [146–149]. There is likely some interaction between marijuana exposure and individual and genetic vulnerability. Marijuana use is neither a necessary nor a sufficient cause for psychosis and schizophrenia, but current evidence suggests that it is a component cause of psychosis [140].
Other Mental Health Outcomes
Marijuana is associated with a number of other mental health problems, including anxiety and depression. However, the association is less consistent than with psychosis, and the link has not been shown to be causal [95].
A recent review found elevated risk for depression and suicidality, but not for anxiety among young adults [150]. For individuals diagnosed with bipolar disorders, near-daily marijuana use may be linked to greater symptom severity. Regular marijuana use may increase the risk of developing social anxiety disorder [95]. Even though individual risk of mental health problems is moderate in most studies, the association is a public health concern. The relatively large number of marijuana users generates a high potential for elevated risk [150].
Suicide risk is an area of particular alarm. Heavy marijuana users are more likely to report thoughts of suicide than non-users [95, 150, 151]. Teens who use marijuana are more likely to make suicide attempts [150, 152], even in low- and middle-income countries [153]. Data from Colorado shows that marijuana is the most frequently noted substance in toxicological screens of young people who die from suicide [37] and heavy marijuana use is associated with higher suicide risk among army veterans [154].
Use of Other Substances (Alcohol, Opioids, Polydrug Use)
Marijuana use is statistically associated with the use of alcohol, tobacco, and other illicit drugs. People who use tobacco or alcohol are more likely to use marijuana [155]. Although the evidence is still limited, there is early evidence that vaping increases the risk of later marijuana use [156, 157]. Similarly, marijuana users frequently use other substances, particularly alcohol and tobacco [158–160]. The association between marijuana and other substances is sometimes interpreted as a “gateway effect” [161], implying that marijuana use increases the risk of using other substances.
Some evidence from animal studies suggests that marijuana use can alter the brain’s susceptibility to other drugs and prime the brain for addiction [92, 162]. This could provide a causal mechanism for a “gateway effect.” However, the evidence is still inconclusive. On the other hand, there is strong evidence to suggest that the use of substances is related to underlying personality traits and vulnerabilities. People who are at risk of using drugs use marijuana first because it is most easily available, and some go on to experiment with other drugs later [92, 162].
In recent years, public health experts have expressed concern about a “reverse gateway effect,” from marijuana to tobacco use [163]. Recent data show that marijuana is increasingly the first substance used by teens [162]. Marijuana is often used together with tobacco, either mixed in joints, spliffs, or blunts, or, sequentially, as a chaser [164–166]. Survey data show that daily marijuana use occurs predominantly among people who also smoke tobacco [158, 160]. Co-use leads to nicotine exposure, which can result in addiction.
Some studies find a higher risk of later daily tobacco smoking among marijuana users and lower odds of quit attempts [75, 167–169]. If marijuana acts as a gateway to tobacco, an increase in marijuana use could have serious public health consequences by increasing tobacco use [170]. Furthermore, co-use is associated with poorer physical and mental health outcomes in young adults [171]. Some people have hypothesized that increased marijuana use will reduce alcohol consumption and therefore reduce the total burden of substance use problems in society. However, the evidence on substitution is contradictory, suggesting that the effect is unclear and perhaps context dependent [172]. The first states to legalize marijuana have not experienced a decrease in alcohol consumption so far, according to industry data [173]. Simultaneous use of alcohol and marijuana is common [174–176]. Mixing alcohol and marijuana is associated with higher consumption, increased risk of negative outcomes, and greater risk of substance use disorders [176–179]. A longitudinal study found that marijuana use is associated with higher risk of alcohol use disorder, marijuana use disorder, nicotine dependence, and any other drug disorder [180]. Marijuana use is also associated with progression to heavier alcohol involvement [181]. Similarly, marijuana use among young people is associated with higher risk of marijuana use disorder and higher risk of use of other illicit drugs [95, 152]. Polysubstance use patterns are more frequent than single-substance use [182].
Molds and Contaminants
While some tout the use of marijuana as a natural and safe substance, the cultivation of many agricultural products presents possible health risks that are relevant to public health tracking and regulation. The primary concerns associated with marijuana surround molds and contaminants.
Mold appears on marijuana for a variety of reasons. On the production side, mold may develop when the plant is exposed to improper humidity levels, watering, ventilation, or drying techniques. On the consumer side, mold may develop if marijuana is exposed to wet conditions, or there is otherwise improper storage in moist conditions [183]. One recent study found that 90% of 20 marijuana samples purchased from California dispensaries tested positive for bacteria and fungi [184]. Exposure to some molds and bacteria can cause illness, particularly among immunocompromised individuals whose risk of opportunistic lung infections may increase from inhaled molds [185, 186]. In a single study, a case of invasive aspergillosis was associated with marijuana use [187]. Others note a risk to even relatively healthy individuals, as exposure to molds and bacteria is associated with increased symptomology in individuals with asthma [188, 189]. Consistent exposure to some molds may further impair the health of the marijuana industry workers [190].
Like all crops, marijuana plants are vulnerable to pests and disease, sometimes requiring the use of agricultural pesticides [189]. According to researchers, the use of pesticides, particularly when used on unlawful grow operations, is severely underestimated. In one study, researchers found evidence of pesticide residue on 65% of the plants tested [191]. In most countries, pesticides use is regulated by a government agency. In the United States, the federal office of the Environmental Protection Agency (EPA) serves in this capacity. Yet, because the federal government considers marijuana a Schedule I drug, no pesticides have been approved for use on marijuana plants, nor has the EPA provided guidance about levels of “safe” pesticide residues on marijuana products. This has led to concern that growers may apply inappropriate levels of pesticide on marijuana plants [189].
Marijuana is susceptible to contamination by chemicals such as lead, ammonia, and formaldehyde, which have been linked to a handful of adverse health events [192–194]. The process used to create marijuana products such as wax and hash oil is another area of concern. Because of this, many localities with legal marijuana now require contaminant testing, as well as labels that list chemicals used during the growing or production process. However, as regulation policies are established by each separate jurisdiction, safety regulations and subsequent monitoring are not ubiquitous. Exposures represent a potential health hazard not only to the individuals purchasing marijuana but to marijuana industry workers. While more research is needed, some question the safety of workers’ exposure to hazards such as dusts, bioaerosols, volatile organic compounds, and ultraviolet radiation during the harvesting and processing phases of marijuana cultivation [195, 196]. While testing requirements and protocols vary between states, evidence suggests that there may be significant shortcomings in this area. An audit by the Oregon Liquor Control Commission determined that the state did not adhere to mandatory inspection schedules, failing to meet even basic standards. In 2018, only 3% of retailers and 32% of growing operations were inspected by regulatory personnel [197].
Harm to Others
Substance use affects not only users, but also the people around them. Secondhand smoke, accidents, fetal effects, and accidental and/or toxic exposure are areas of increased public health concern post-legalization. Further, while we do not expand upon it here, substance use disorders cause considerable stress for children, families, partners, and close friends. Such non-tangible harms are hard to measure, but may have severe emotional, economic, and psychosomatic consequences [198–200].
Secondhand Smoke
Limited evidence on the effects of secondhand smoke from marijuana should not be taken as evidence that it is harmless. Secondhand marijuana smoke shows similar effects to secondhand tobacco smoke in animal studies [82, 201]. Marijuana metabolites can be found in the urine of children who are exposed to marijuana smoke; this risk increases if parents are daily marijuana smokers [202]. Studies found higher likelihood of reporting adverse health outcomes in children who lived in households with marijuana smoking after controlling for cigarette exposure [203] and higher rate of emergency department visits among children who were exposed to a combination of marijuana and tobacco smoke [204].
Social norms surrounding secondhand marijuana smoke have not kept pace with norms surrounding tobacco smoke. The evidence for harmful effects of marijuana smoke is more limited, but inhalation of all kinds of smoke is likely harmful. It may be particularly relevant for cardiovascular effects, which is the main cause of deaths from passive tobacco smoking [205].
Marijuana Use During Pregnancy and Breastfeeding
Several studies have pointed to increasing marijuana use among pregnant women in recent years [206–208]. Volkow et al. documented a twofold increase in marijuana use during pregnancy from 2002/2003 to 2016/2017 [209]. Data from Washington state show a steep increase in marijuana use among pregnant women from 2009 to 2014, accompanied by an increase in the number of maternal inpatients stays related to marijuana use only [210]. Data suggest that marijuana use during pregnancy is more than twice as common among women between 18–25 years than those between 26–44 years [211].
Many women view marijuana as a natural product and therefore believe it is a safer alternative to pharmaceuticals for controlling nausea. However, marijuana use is also increasing among women who do not experience nausea [212–214]. NSDUH data found that 16.2% of pregnant marijuana users report daily or almost daily use, while 18.1% of past year users met the criteria for substance abuse or dependence [212]. National data show an increase in the incidence of marijuana dependence/abuse among pregnant women from 1999 to 2013 [213].
When marijuana is ingested, cannabinoids cross the placental barrier and may affect the endocannabinoid system of the fetus [214]. Marijuana is associated with a number of adverse outcomes, including increased risk of preterm birth and other complications, such as small size for gestational age, longer hospitalization periods, and transfer to neonatal intensive care unit [213, 215, 216]. Marijuana exposure has been linked to child development and behavior, with evidence of psychosocial, behavioral, and cognitive effects [34]. Animal studies suggest that marijuana affects development and impacts the fetus, with some indication that interaction between alcohol and cannabinoids increases the risk of harm [217–219].
Cannabinoids are easily transferred to breast milk and to the baby. THC can be traced in breast milk several days after last reported marijuana use [220]. Some studies have suggested psychomotor deficits in infants exposed to marijuana in breast milk, although the evidence is yet inconclusive [221]. Breastfeeding guidelines warn against marijuana use during breastfeeding [214].
Perceived risk from regular marijuana use has decreased among both pregnant and nonpregnant women in the United States over the past decade [222]. Ko et al. found that a majority of women believe there is no or little risk of harm from marijuana use once or twice during pregnancy. Bayrampour et al. found that women were uncertain about harmful effects and received little counseling from the health services on the topic [212, 223]. Many women seek medical advice from budtenders regarding the safety of using marijuana during pregnancy. While nonmedical employees are advised to refer clients to healthcare practitioners for these types of conversations, one study documented that an alarming 70% of Colorado dispensaries recommended marijuana for treating nausea in the first trimester [224]. Given the multitude of health risks linked to marijuana use, this indicates the need to improve outreach to both dispensaries and the public about the need to discuss marijuana-related questions with medical professionals.
Accidental Exposure
In recent years there have been numerous reports about children accidentally exposed to cannabinoids, particularly high THC products [225]. One study found that the number of children under the age of 6 who ingested marijuana was stable from 2000 to 2008, but later increased by 27% per year. More than 70% of accidental exposure cases occurred in states with legalized marijuana [226]. An increase in accidental exposure in toddlers was also found in Europe [227].
Many edible products can be hard to distinguish from regular food products and candies, and some products have shapes and colors appealing to young children. Legal access to marijuana could cause more people to store marijuana in their homes, which increases the risk that it could get in the hands of children [228]. Data from Colorado show a doubling in exposure in 2 years after legalization and a higher increase than the rest of the country [229]. A study of accidental exposure among children under 6 years found significantly higher rates in states that legalized medical marijuana [230]. Similarly, a study from Massachusetts found an increase in pediatric marijuana exposure after the introduction of medical marijuana [231].
Health Benefits
The use of marijuana for treating various health conditions is not a new concept, although it has gained attention since the global era of legalization and decriminalization. The use of marijuana for medical purposes stretches thousands of years back in China, Egypt, and India. One example of early use in Western medicine is the treatment of rheumatoid pain and convulsions by Irish physician Sir William O’Shaughnessy in the mid-1800s [232].
The international drug control treaties allow the medical use of marijuana as long as certain requirements are fulfilled. Medical use must be based on scientific evidence, supervised by health personnel and dispensed by prescription, and there must be measures in place to prevent diversion [233].
In Europe, market authorization of medicines requires clinical trials for safety and efficacy. Most European countries allow some medical use of cannabinoids for a limited number of diagnoses or in cases where other treatment options have failed or are causing too many side effects. National medicines authorities have approved different cannabinoid products, mostly medicinal products such as dronabinol or nabiximols (Sativex), but in some cases also standardized marijuana products. No EU country recommends smoking as a mode of consumption [234].
Several countries in Europe also have “early access” or “compassionate” programs that make unauthorized medicines available in certain circumstances. “Early access” medicines must be prescribed by a licensed prescriber, and patients often have to cover the costs of the treatment [234].
The US Food and Drug Administration (FDA) has approved individual components of marijuana or similar synthetic substances for certain conditions. In 2018, the agency authorized the use of the CBD-based drug, Epidiolex, for treating seizures associated with two rare, severe forms of epilepsy. Unlike THC, Epidiolex does not give people the sensation of being “high” when consumed. Furthermore, the FDA has approved the synthetic cannabinoids dronabinol and nabilone for nausea associated with chemotherapy when conventional treatment does not work; dronabinol may also be used for the treatment of weight loss associated with AIDS [235].
The FDA has not approved the marijuana plant as medicine. Nevertheless, a majority of US states allow some form of medical marijuana in addition to the FDA-approved cannabinoids. Many of the state laws have been driven by voter initiatives and passed by referenda. Qualifying conditions vary between the states, and the size of the medical marijuana programs varies widely.
Marijuana has been proposed for a wide range of conditions; however, in most cases the evidence is limited, insufficient, or nonexistent. The strongest evidence for an effect of cannabinoids is for chemotherapy-induced nausea, multiple sclerosis-related spasticity, and neuropathic pain. In all these cases, the effect is described as moderate [95]. More recent reviews have questioned the use of cannabinoids for pain due to limited effect and adverse events [236–238].
There is currently great interest in research on cannabinoids. Researchers in the United States and the rest of the world are conducting medical trials with marijuana and marijuana extracts to examine treatment efficacy for other diseases and symptoms such as multiple sclerosis, pain, and substance use disorders [239]. While there are many anecdotal reports about beneficial effects publicized through popular media outlets [95, 240, 241], some providers are reluctant to recommend a drug whose form, contents, dose, and type cannot be specified, as they would be in a typical prescription [242].
Some studies suggest that access to medical or recreational marijuana can reduce the use of opioids and opioid-related deaths, citing state-level differences in opioid mortality [243, 244]. Still others find self-reported reductions in opioid use among people who use marijuana to manage pain, and fewer opioid prescriptions among Medicaid enrollees who have access to medical marijuana [245–248]. However, Shover et al. [249] analyzed state-level data with a longer time series and found that the differences originally observed reversed over time, suggesting that there is no clear link. This conclusion is supported by a study of national survey data that found no effect on opioid use after legalization of medical marijuana [250].
Furthermore, several studies found that marijuana use is associated with higher opioid use in pain patients and greater risk of medical and nonmedical use of prescription drugs [251–253]. A large prospective study from Australia found no evidence that marijuana improved patient outcomes, no evidence that it reduced opioid use, and no evidence that it reduced pain [254]. A recent US study found greater risk of anxiety, depression, and substance abuse issues among medical marijuana users, but not improved pain experience [255]. Patients who receive more opioid prescriptions are also at higher risk of marijuana use disorder [256].
Public Health Response: Regulations and Messaging
Regulations
In 2014, the American Public Health Association issued a position statement which encouraged the development of comprehensive marijuana regulations as a public health priority [257]. The Association aimed to ensure oversight of the burgeoning legalized marijuana market in order to proactively address the unforeseen effects of legalization. Regulations to prevent marijuana access by minors, to protect and inform consumers, and to guard against unintended consequences to others as a result of marijuana use were encouraged.
Local and state governments play a seminal role in this effort health through mechanisms such as setting age limits; developing and monitoring product packaging, labeling, and warning requirements; invoking retail display and access standards; ensuring product testing and quality standards; setting potency and advertising limits, and revoking motor vehicle operation restrictions while impaired.
Response to marijuana legalization varies considerably around the world [258]. The European Federation of Addiction Societies issued a position statement stressing establishment of regulations at European level. The Federation advised the creation of registration and medical indications information, the development of uniform compounds and strength of products, and rules concerning sales and marketing [259].
In the United States, the regulation of these mechanisms varies by locality and may not be uniformly monitored or enforced. Colorado’s regulator, the Marijuana Enforcement Division, updates its policies every year. The public health perspective on regulations is guided by the precautionary principle, which advises that the introduction of a new product whose ultimate effects are disputed or unknown should proceed in such a manner that it serves to protect the community from harm.
Considerations of how regulations will impact the black market are warranted. For example, a legal ban may drive up prices because it introduces inefficiencies in all parts of the supply chain. Taxation of legal products can compensate price drops but may create new incentives for a black market. Furthermore, in legal markets, the marijuana industry is increasingly trying to influence the outcome of policy processes that affect their business interests.
Public Health Messaging
Increasing community knowledge of issues associated with drug use is a key component of public health. Yet, marijuana messaging efforts present a unique challenge, particularly in areas where some form of marijuana legalization or decriminalization has passed. While public health messaging is led by science, it would be ignorant to dismiss the influences of the political and social norms of the time. Public support for marijuana legalization has increased rapidly. According to the Pew Research Center, 62% of Americans believe that marijuana should be legal, compared with about 20% two decades ago [260]. For public health professionals, it can be difficult to provide credible information about known or potential risks to an audience that may be opposed to hearing the message or interpret it as a part of a political debate surrounding legalization.
In the United States, fear tactics have long been used to warn people about the risks associated with tobacco and other drugs [261]. Yet, public health’s approach to community-based messaging is changing, and early mistakes in marijuana media campaigns suggest that a different tactic is needed. In Colorado, one of the first community-level campaigns to rollout after legalization was largely deemed to be a failure after the creators erected human-sized rodent cages around the metro area that prominently displayed the tagline “Don’t be a Lab Rat.” Quickly, the displays became a target of both vandals and skeptics, ultimately backfiring when a school district refused to allow the exhibit on any of their campuses. Simultaneous public outcry focused on the pedantic tone of the campaign, underscoring the evolution of marijuana legalization as a community-backed effort. Within a few short months, the lack of support forced the sponsors to remove the exhibits from public display altogether.
New approaches to public health messaging increasingly focus on teaching the community about personal responsibility and science-based data rather than messages aimed at curtailing use. In alcohol policy, economic operators have tended to favor messaging around “responsible use” – shifting accountability from suppliers to individual consumers – from supply side measures to individual behavior [262]. Critics have described these messages as “strategically ambiguous,” since they fail to define “responsible” and may ultimately promote the product [263–265]. In the case of formerly illegal substances, responsible use messages may have the unintended effect of normalizing use.
Harm reduction is a new paradigm in the field of drug education and treatment. Harm reduction works to minimize the hazards associated with drug use rather than the use itself [266]. Increasingly, public health messaging tailors its messaging efforts toward the needs of the intended audience, attempting to answer questions the audience is likely to ask. Campaign messages provide fact-based information, such as educating expecting mothers about research showing there is no safe level of cannabis use during pregnancy, or about how THC remains in breast milk after using marijuana. Outreach to parents, guardians, and adults who work with children (e.g., teachers, coaches, mentors) provides information about how to talk to young people about marijuana. In Colorado’s Protect What’s Next Campaign, adults were given tips about how to start a conversation about marijuana, how to listen to the concerns of youth, and how to share information about the health and legal consequences of underage use. Colorado took a similar approach to messaging adult users with their Good to Know campaign, which prioritized educating the audience about state laws and potential safety issues [267].
In jurisdictions with greater legal access to marijuana and increased social acceptance of marijuana use, it is important to educate the public about the risks of pediatric exposure and provide clear and strong messaging about safe storage of marijuana products. Regulatory measures, including labeling, childproof packaging, and product designs that are less appealing to children (e.g., candy) should be considered.
Conclusion
The marijuana landscape is changing rapidly, and the research is struggling to keep up. Public attitudes toward marijuana have shifted significantly. Decriminalization, medical marijuana laws, and full legalization have transformed the legal landscape. Changing consumption patterns, new products, and new routes of administration have emerged.
Although the evidence base on marijuana is expanding, there is still limited knowledge about the health and social consequences of marijuana. Based on current knowledge, there are several areas of concern for public health, ranging from physical and mental health to accidents, acute effects, and harm to others. There is also evidence for some medical benefits, although the science is limited. We do not yet know the full impact of these harms and benefits on public health, and careful monitoring is needed.
The changing situation presents public health with new challenges in terms of monitoring, developing adequate regulatory frameworks, responding to new challenges, and communicating effectively about risks and harms. Public health messaging must resonate with shifting public attitudes to marijuana use, and public health policies must be negotiated with consumers as well as economic operators.
While we navigate these unchartered waters, we can draw some lessons from other fields of public health. In the face of uncertainty, public health policy should be based on the best available evidence and guided by the precautionary principle.