Cannabis knowledge and implications for health: Considerations regarding the legalization of non-medical cannabis

Abstract

Cannabis contains over a hundred of different cannabinoids, of which Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well studied. The use of high-potency cannabis, containing high concentrations of THC and low concentrations of CBD, has been linked to adverse health outcomes, particularly for adolescents and young adults. Recently, an increase in cannabis potency has been observed in jurisdictions that legalized the sale of cannabis for non-medical purposes. Moreover, an increase of cannabis use and cannabis-related emergency treatment have also been observed in these jurisdictions. At the same time, risk perception regarding cannabis use has decreased in these populations. Trivializing language and an increased appearance of commercial cannabis in the public space may lead to a generalized underestimation of the risks of cannabis use. New regulation models principally focus on the creation of a legal cannabis market economy, the diversion of profits from illegal markets, and the reduction of costs associated with prohibition. However, an approach that specifically focuses on the rights to the health and safety of the individual should be considered in order to reduce the risks associated with cannabis legalization. Such an approach should promote and protect individual and social health and safety, establish a strict quality control of legal cannabis products regulated according to THC and CBD content, and eliminate all sorts of incentives to use, thus providing a more consistent, sustainable, and ethical framework for the legalization of non-medical cannabis use.

Keywords

Non-medical cannabis legalization young people risk perception health outcomes

Cannabis and the endocannabinoid system

Cannabis is a genus of a plant containing hundreds of different (psycho)active ingredients (cannabinoids) in variable concentrations. However, only a few cannabinoids are being studied for their effects on the human body.¹ Cannabis is the source of the psychoactive drug ‘cannabis’, also known as marihuana or hashish among other names. How the (psycho)active ingredients in cannabis interact with the human endocannabinoid system (ECS) – a delicate system implicated in the regulation of a multitude of physiological processes – is of utmost importance in the context of changing cannabis regulations around the world.

When Δ⁹-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, activates cannabinoid receptors (CB1 and CB2), it does so in a non-selective way, affecting receptors throughout the brain and the body.² With repeated exposure to THC, the endocannabinoid system may undergo plastic changes in an attempt to adapt to a chronically increased cannabinoid level.² This maladaptive process typically involves reductions in the number of CB1 receptors, which leads to the ECS becoming less sensitive to endogenous cannabinoids and/or natural stimulations. Users may experience this as tolerance, or a decrease in cannabis’ effects, which could lead to more frequent use or the use of more potent cannabis strains.²

Cannabis potency

The natural biological variability of cannabinoids in Cannabis plants determines different patterns of concentrations of the active ingredients involved in the (psychoactive) effects on the human body. Therefore, the same amount of cannabis may have different biological effects. In recent years, an increasing trend has been observed worldwide in the THC concentration (potency) of cannabis products. For example, the potency of cannabis has been steadily increasing in the USA, from approximately 4% in the 1995 to 17% in 2017.^3,4

Systematic crossbreeding of Cannabis plants has led to a market dominance of high-potency plants: novel ways of extraction have produced cannabis concentrates with 70% THC content or above.⁵ In Washington State, where non-medical cannabis was legalized in 2012, there has been a notable increase in sales of the most potent products (cannabis concentrates), which rose to over 20% of all sales within two years.⁶

Similar trends have been observed in other countries.^7–9 For example, cannabis resin (hashish) has increased substantially in THC concentrations across Europe, rising from 8% in 2006 to 17% in 2016.¹⁰

Along with the increase of THC concentration, a decrease in the average concentration of the cannabinoid cannabidiol (CBD) has been observed.¹ This is particularly relevant because CBD may moderate the effects of THC. Therefore, variations in the relative proportions of THC and CBD may have implications for the health effects of cannabis. High doses of THC may induce several psychological changes, including transient psychotic symptoms and memory impairment, while co-administration of CBD may offset these negative effects of THC.¹

High-potency cannabis and health effects

The use of cannabis containing high concentrations of THC and low concentrations of CBD has been linked to adverse health outcomes. People using high-potency cannabis on a daily basis were found to be five times more likely than non-users to suffer from a psychotic disorder.^11,12 High-THC/low-CBD products have also been found to be associated with an increased severity of dependence on cannabis.^13,14 THC concentrations in cannabis have been found to correlate with rates of treatment for cannabis disorders¹⁵ and the incidence of psychosis¹⁶ in Europe. This suggests that variations in cannabis products may influence the burden or morbidity related to cannabis at the population level.

Decades of experimental research with cannabinoids have shown that administration is safe in controlled settings to participants who have been screened for potential risk factors.¹ However, repeated and heavy use of cannabis products may have harmful consequences to the individual. This calls for attention in legalizing non-medical (adult) use of cannabis. In Colorado, where legal sales of non-medical cannabis started in 2014, a significant increase in adolescent marijuana-associated emergency department (ED) and urgent cares visits has been observed,¹⁷ along with incidents of accidental cannabis ingestion among young children.¹⁸ Among ED visits and hospitalizations with cannabis-related billing codes, the overall prevalence of mental illness was found to be a fivefold and a ninefold higher, compared to the prevalence of mental illness without cannabis-related billing codes in ED visits and hospitalizations, respectively.¹⁷ These data are not conclusive but show preliminary trends which should be considered when discussing outcomes of different legalization models, especially to prevent additional exposure for young people.

Cannabis use in vulnerable groups

Adolescence and young adulthood are characterized by critical and delicate transitions in human brain development. Risky behaviours occur especially during these periods, and growth processes may be disrupted by substance use and the development of substance use disorders.¹⁹ Approximately 1 in 11 people (9%) who ever use cannabis will become dependent at some point in their lifetime. However, this risk is almost doubled (1 in 6) if use starts in adolescence, and it is between 25% and 50% for people who use cannabis daily.^1,20 It is estimated that, worldwide, 22 million people are dependent on cannabis, making it one of the most prevalent illicit drug use disorders, with a similar prevalence to opioid dependence (27 million).²¹ Moreover, cannabis accounts for more first-time admissions to drug treatment in Europe than any other illicit drug.²² However, even though cannabis use has increased in the USA in recent years, rates of cannabis dependence have not increased.²³

There is epidemiological evidence supporting a link between cannabis exposure during adolescence and psychosis,^5,24 as well as the development of acute amotivational and other acute and chronic adverse effects (e.g. short-term memory impairment and cognitive deficiencies), mostly related to cannabis potency and persistence of use.^1,2,11,12 A growing body of neuroimaging research also suggests that early cannabis use may negatively impact the structure and function of developing brain circuits.²⁰ Consequently, the adolescent and young adult brain is particularly vulnerable.^2,24

The adverse effects of cannabis on the developing brain are particularly relevant because cannabis use is most prevalent among young people. In 2018, 22.1% of the US population in the age range 18–25 were current cannabis users (use in the past month); this prevalence was 6.7% in the age range 12–17 and 8.6% for the ages 26 and older.²⁵ In 2016–2017, Colorado had one of the highest past-month prevalences of cannabis use among young people: 31.74% in the age range 18–25 (the sixth highest prevalence nationally, after Vermont, District of Columbia, Maine, Oregon and Rhode Island; national average: 21.45%) and 9.02% in the age range 12–17 (the sixth highest prevalence nationally, after Vermont, Oregon, Maine, New Mexico and Rhode Island; national average: 6.46%).²⁶ Moreover, the prevalence of past-month cannabis use in 18–25 year olds was significantly higher (p=0.004) in 2016–2017 than the prevalence of 24.18% measured in 2008–2009, while the prevalence of past-month cannabis use in minors (12–17 years) was (non-significantly) lower in 2016–2017 than the prevalence of 10.17% measured in 2008–2009.²⁶ This is consistent with cannabis use trends in all US states that legalized non-medical cannabis before July 2016 and supports preliminary evidence that non-medical cannabis legalization may particularly increase the prevalence of use among adults, who suddenly gain legal access to cannabis, but not among minors.²⁷

Another group that may be more vulnerable to cannabis harms is older adults. There is limited research on the effects of cannabis use on the aging brain, but evidence from the United States suggests that increases in the prevalence of cannabis use have been driven by changes in adults rather than adolescents^27,28 and that increases are especially pronounced in older adults.²⁹ In the case of Colorado, for example, the prevalence of past-month cannabis use in the age group of 26 years and older more than doubled from 7.31% in 2008–2009 to 14.81% in 2016–2017.²⁶

Individual risks also have social reverberations. For example, impairment due to cannabis may increase risks of accidents, especially while driving.³⁰ There is substantial evidence of a statistical association between cannabis use and increased risk of motor vehicle crashes and fatal collisions, especially in combination with alcohol.^31–33 According to the 2018 Washington State Healthy Youth Survey, 53% of the 12th graders who had used marijuana during the 30 days prior to the survey reported driving within three hours of using marijuana, and one in four reported riding with a driver who had used marijuana.^34,35

Risk perception

The risks associated with cannabis use tend to be underestimated and understanding why may help avoiding adverse consequences.^36,37 Language, especially in public debates, may have an important role. ‘Recreational use’, for example, may be ambiguously interpreted by young people. According to McNeely et al.,³⁸ who interviewed adult primary care patients about prescription drug use, the term ‘recreational’, in comparison with ‘non-medical’, has a unilateral connotation of producing positive effects: ‘to have fun, get high, party with’ (p. 17). Likewise, since cannabis is also used in medical settings, the term ‘recreational cannabis use’ should be replaced by ‘non-medical cannabis use’, for the former term may trivialize the risks associated with cannabis use.

Referring to cannabis as a ‘soft drug’, as opposed to ‘hard drugs’, should also be avoided. The concept is misleading and generic and conveys a clear qualitative indication about the supposed potency of the drug, indirectly referring to lower risks associated to its use. The use of this concept has mostly historic origins, but the chemical composition – and, therefore, the psychoactive potential – of the current cannabis strains has radically changed over time, as well as patterns of use and, consequently, the corresponding risks. Because of such changes, the Expert Committee on the List System of the Opium Act³⁹ recommended to the Dutch government in 2011 that cannabis products with a THC content of over 15% be legally regarded as a hard drug, rather than a soft drug – a legal concept that allows the retail of limited amounts of cannabis in the Netherlands. Even though the Dutch government has not adopted the committee’s advice, it does convey two important messages: it warns about the current potency of cannabis products, and it challenges the stereotypical perception that cannabis is ‘soft’. Janik et al.⁴⁰ argue that the terms ‘hard drug’ and ‘soft drug’ should be avoided altogether, because a scientific basis for this distinction is currently missing. Moreover, they warn that such an imprecise definition might negatively affect risk perception regarding drug use. Language may thus play a critical role in the construction of the public’s attitudes towards cannabis that should not be underestimated, for it may contribute to trivializing the fact that cannabis is not an innocuous substance. Consequently, any message suggesting a simple division between what is dangerous and what is not should be avoided.

Changing cannabis policies

To date, the main institutional approach to non-medical use of cannabis has been prohibition (at different levels of implementation). Nevertheless, the percentage of global cannabis users has remained almost stable: about 4% of the world population.⁴¹ Moreover, an analysis of data collected by the European Monitoring Centre for Drugs and Drug Addiction found no relationship between changes in statutory penalties for cannabis and prevalence of use.⁴² Recently, the use of cannabis for medical purposes has become legal in many countries, but legal use of cannabis for non-medical purposes is still rare. Most of the governments that have legalized non-medical use of cannabis are US state governments (e.g. Colorado,⁴³ Oregon⁴⁴ and Nevada⁴⁵), with regulation models that principally focus on the creation of a legal cannabis market economy, the diversion of profits from illegal markets and the reduction of costs associated with prohibition. The overall process environment is the market economy typical of modern Western societies, based on the interplay of supply, demand and competition, which determines the prices of goods and services. In this model, cannabis is the product to be marketed and the individual is safeguarded in his rights as a consumer.

The increased appearance of commercial cannabis in the public space may lead to an underestimation of the risks associated with its use. Although specific regulations may restrict advertising, the cannabis market will still respond to basic factors such as competition, supply and demand. For example, as of June 2017 – three-and-a-half years after legal sales started – there were 491 marijuana retail stores in the state of Colorado, compared to 392 Starbucks and 208 McDonald’s.³² As a consequence, urban scenarios, social habits and risk perception may change along with the legalization processes.⁴¹ There is some evidence that the perceived risks of cannabis use decreased in US adolescents following the passing of state recreational cannabis laws in the United States.³⁷ Moreover, risk perception of cannabis use has demonstrated a significant decrease among young people in Colorado during the years after cannabis legalization.⁴⁶ A generalized underestimation of the risks associated with cannabis use may lead to a growing consumer population, and an increase in acute intoxications, hospitalizations and cannabis-related car accidents, as well as additional exposure for young people.^34,41,47 However, the real implications of changing risk perceptions are not clear yet.^2,48,49

Concluding remarks

In order to reduce the risks associated with cannabis legalization, an approach that specifically focuses on the rights to health and safety of the individual should be considered. Such an approach should aim to increase awareness and responsibility in individuals in order to become a sustainable process in the long term. In that sense, cannabis legalization should be carried out under a strictly controlled health-based policy, whose primary objectives should be: (a) to promote and protect individual and social health and safety through the implementation of continuing education and prevention programs, by adopting use-reduction policies directed at young people, by empowering adults to make informed decisions, by increasing risk awareness at the individual and social levels through unambiguous information campaigns and by enhancing access to treatment; (b) to increase safety by establishing a strict quality control of legal cannabis products, by taxing or setting maximum THC and minimum CBD contents,¹ by limiting edible dosages/serving units, by developing the concept of standard cannabis units⁵⁰ and guidelines for safer use, by adopting child-proof packaging and by improving product information and staff training; (c) to decrease use by eliminating all sorts of incentives to use, by prohibiting marketing and promotional advertising, by creating a strict regulated government monopoly on sales and balancing tax rates to substitute the black market, and by setting a minimum age, retail density and limited hours of sales. A similar health-based approach has been recently recommended by Chief Medical Officers of Health of Canada and Urban Public Health Network⁵¹ and some measures have also been implemented in countries that have already legalized non-medical cannabis use.⁴⁶ Such an approach may balance the contradictions of the currently prevailing model, providing a more consistent, sustainable and ethical framework for the legalization of non-medical use of cannabis.

Footnotes

Declaration of conflicting interests

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors received no specific funding or sponsorship for this work.

ORCID iD

Guus Zwitser

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