Stockholm Medical Cannabis Conference

Adverse Effects of Too Much Cannabis

I. Introduction

Cannabis has been used for both recreational and medicinal purposes for centuries. Medical cannabis has shown potential therapeutic benefits for a large and growing number of medical conditions, and responsible consumption practices can promote safe and effective use. However, it is important to be aware of the potential risks associated with excessive cannabis use. With the increasing legalization and acceptance of cannabis worldwide, it is crucial to educate the public on the potential risks of excessive cannabis use and to discuss strategies for harm reduction. This article provides a focused comprehensive overview of the potential adverse effects from excessive cannabis use and discusses strategies for reducing said risks.

We will begin by examining the short-term and long-term effects of cannabis use, followed by an exploration of specific conditions such as Cannabis Hyperemesis Syndrome. The article then highlights the risks associated with large oral doses or edibles, interactions with medications and other substances, and offers practical advice for reducing the risk of adverse effects through responsible use and education.

Ultimately, the goal of this article is to promote an increased understanding of the potential risks of cannabis, while promoting safe and informed consumption practices. Although this article mainly discusses potential adverse health effects of recreational cannabis use, it is important to note that the risks and benefits may differ when considering medical cannabis use, as the context, dosage, and specific cannabinoid formulations may vary.

II. Short-term adverse effects of cannabis use

Cannabis contains various cannabinoids, with THC (tetrahydrocannabinol) being the primary psychoactive component responsible for many of the effects discussed in this section, while CBD is a non-intoxicating compound with potential therapeutic effects and significantly less prominent adverse effects. Different chemovars of cannabis contain varying concentrations of cannabinoids, such as THC and CBD, which influences the potential health effects of a specific cannabis chemovar.

Cannabis consumption, particularly in excessive amounts or for inexperienced users, can lead to a variety of short-term effects, that may impact an individual’s daily functioning and overall well-being, with the severity and occurrence of these effects varying based on factors such as individual tolerance, dosage, and the specific strain or type of cannabis used. Individual factors, such as genetics, previous cannabis exposure, and overall health, also play a significant role in the severity and occurrence of these effects [1]. The onset and intensity of these short-term effects can also vary depending on the mode of consumption, such as smoking, vaping, or consuming edibles. One of the most prevalent reported effects is a transient impairment in memory and cognitive function, though the severity of these effects can vary significantly between individuals [2]. Research has shown that acute cannabis use can interfere with the encoding, storage, and retrieval of information, leading to potential difficulties in remembering events and performing complex cognitive tasks [3].

Another short-term effect of cannabis use is altered judgment and coordination, which can result in an increased risk of accidents and injuries. Cannabis impairs motor coordination and reaction time, and studies have found that cannabis users under the influence might be more likely to be involved in motor vehicle accidents [4]. Other studies have found that the risk of a fatal crashes is not significantly increased in cannabis-positive drivers when properly adjusted for other factors such as alcohol and other drug use [5]. Nonetheless, it is crucial for individuals to be aware of these risks and avoid engaging in activities that require precise motor skills, such as driving or operating heavy machinery, while under the influence of cannabis. 

Cannabis use may also induce feelings of anxiety and paranoia in some individuals, especially at higher doses of THC, with these psychological effects thought to be related to the dose of cannabis and the individual’s pre-existing susceptibility to anxiety disorders [6]. While many people use cannabis for its calming and relaxing effects, excessive consumption can exacerbate anxiety and trigger panic attacks in susceptible individuals.

Additionally, cannabis use can result in an increased heart rate, which may be particularly concerning for individuals with pre-existing cardiovascular conditions. Studies have shown that cannabis can cause a temporary increase in heart rate and blood pressure, potentially leading to a temporary increased risk of heart attack or stroke in vulnerable predisposed populations during the period of cannabis use [7].

Lastly, common physical side effects of cannabis use include dry mouth and red eyes. These symptoms are typically mild and short-lived but can cause discomfort for users. They result from the activation of cannabinoid receptors in the salivary glands and ocular tissues, leading to reduced saliva production and vasodilation of ocular blood vessels [8].

Given these short-term effects of cannabis use, individuals should approach cannabis consumption cautiously and with awareness. Although many people may use cannabis recreationally or medicinally without any problems whatsoever, it is important to recognize that individual responses vary significantly, and excessive use may result in undesirable outcomes in some people. To minimize the risk of these short-term effects, users should always start with a low dose of cannabis and gradually increase it as needed, while closely monitoring their own reactions. This approach, often referred to as “start low and go slow,” allows individuals to find the optimal balance between the desired effects of cannabis and the potential for adverse reactions [9]. It is also important to note that the severity of some of these effects may decrease with regular use as individuals develop tolerance to certain effects of THC; however, this may not be applicable to all individuals or all potential side effects. 

Interestingly, preclinical research suggests that CBD (cannabidiol) has been found to act as a negative allosteric modulator (NAM) at the CB1 receptor, providing a mechanistic rationale for the ability of CBD to reduce some of the adverse effects of THC, thus potentially helping to mitigate some of the negative consequences associated with excessive cannabis use [10]. Despite the strong preclinical evidence combined with a large body of anecdotal evidence, so far, clinical research in human healthy volunteers has not been able to replicate any THC-alleviating effects from CBD in controlled clinical settings [11]. Nonetheless, selecting a cannabis chemovar with higher CBD content automatically translates into a chemovar with lower THC content, thus lowering any potential adverse effects from THC.

In summary, excessive cannabis use can lead to a range of short-term effects, including impaired memory and altered cognition, judgment, coordination, anxiety, heart rate, paranoia, and physical symptoms such as dry mouth and red eyes. Far from all users will experience such effects, as both dosage, genetics, and life-style choices play a large role in determining the severity of these outcomes. It is however important for individuals to be aware of these potential risks and consume cannabis responsibly to minimize potential adverse outcomes. Further research is needed to better understand the full range of effects of cannabis use and to develop more targeted strategies for reducing the risk of adverse outcomes.

III. Long-term adverse effects of cannabis use

Research suggests that chronic cannabis use can have several potential long-term effects on mental and physical health, such as cognitive decline, respiratory issues, and addiction [1]. However, it is important to note that not all users will experience these effects, and individual factors, such as genetic predisposition and the frequency and duration of use, play a role in determining the severity of these outcomes.

Although the risk of developing an addiction to cannabis is lower than that of other substances, such as alcohol or opioids, research indicates that approximately 9% of people who use cannabis will develop a substance use disorder (SUD) [12]. This risk increases among those who start using cannabis in their teenage years or consume it daily, but it is important to note that individual susceptibility to addiction can vary significantly.

Respiratory issues may arise from smoking cannabis regularly, similar to those associated with tobacco smoking. Chronic cannabis smokers may experience symptoms like chronic bronchitis, lung inflammation, and impaired lung function [13]. To reduce the risk of respiratory problems, alternative methods of consumption, such as vaporizing or using edibles, should be considered.

Long-term cannabis use may also have a significant impact on mental health. Studies have linked heavy cannabis use to an increased risk of developing depression, anxiety, and psychosis, particularly among individuals with a genetic predisposition to these disorders [14,15]. However, more research is needed to establish a causal relationship between cannabis use and the development of these disorders, as well as to understand the individual factors that may contribute to the risk. It is essential for users to monitor their mental health and seek professional help if they notice any concerning changes.

Furthermore, long-term cannabis use, especially during adolescence, can adversely affect brain development. The human brain continues to develop until the mid-20s, and early exposure to cannabis may lead to alterations in brain structure and function, resulting in impaired cognitive abilities, memory, and executive functioning [16].

Lastly, chronic cannabis use has been associated with decreased motivation and productivity, often referred to as the “amotivational syndrome” [17]. This condition is characterized by a lack of interest in pursuing personal, social, and professional goals, which may lead to significant difficulties in various aspects of an individual’s life. 

Interestingly, long-term cannabis use is associated with CB1 receptor downregulation, which also has some potential benefits. For instance, chronic cannabis users with downregulated CB1 receptors have been found to have a lower body mass index (BMI) compared to non-users, suggesting a potential protective effect against obesity [18]. Additionally, CB1 receptor downregulation may also contribute to improved insulin sensitivity, which could have positive implications for managing diabetes [19]. However, further research is needed to fully understand the mechanisms behind these effects and to determine their clinical significance.

In conclusion, effects of excessive cannabis use can have a potential lasting impact on an individual’s physical and mental health, as well as their overall quality of life. It is crucial for users to be aware of these potential risks and consume cannabis responsibly to minimize the likelihood of adverse outcomes.

IV. Cannabis Hyperemesis Syndrome (CHS)

Chronic cannabis use may lead to a rare but serious condition known as Cannabis Hyperemesis Syndrome (CHS). CHS is characterized by recurrent episodes of severe nausea, vomiting, and abdominal pain. The exact cause of CHS is not well understood, but it is believed to be related to the dysregulation of the endocannabinoid system. Patients suffering from CHS often find relief from their symptoms by taking hot showers or baths, and the only definitive treatment is cessation of cannabis use [20-22].

V. Risks associated with large oral doses/edibles

While edibles can offer certain benefits, such as a discreet and smoke-free method of consumption, they also introduce new risks associated with excessive cannabis consumption. One notable issue with edibles is the delayed onset of effects, which can range from 30 minutes to several hours after ingestion [23]. This delayed onset can lead to overconsumption, as users may be tempted to consume more of the product to achieve the desired effects more quickly, ultimately resulting in an excessive dose that may cause much stronger effects than intended.

The prolonged effects of oral cannabinoids, which can last for several hours or even into the next day in high enough doses together with fatty foods, further contribute to the risks associated with large oral doses. These long-lasting effects, which can vary in duration and intensity between users, can be particularly concerning for sporadic heavy users, who need to engage in activities requiring alertness, such as driving or operating machinery, as their cognitive and motor skills may still be impaired the following day.

Accidental ingestion of cannabis edibles is another significant concern, particularly for vulnerable populations such as children and older adults. The appearance and flavors of edibles can lead to unintentional consumption, potentially resulting in severe adverse reactions. To minimize this risk, it is crucial for individuals to store cannabis edibles securely, out of reach of children and pets, and to label them clearly to prevent confusion.

In conclusion, the risks associated with large oral doses and edibles include delayed onset and prolonged effects, overconsumption, and accidental ingestion, particularly among vulnerable populations. It is essential for cannabis users to be aware of these risks, consume edibles responsibly, and educate others about the potential dangers to prevent unintended consumption.

VI. Interactions with medications and other substances

It is important to note that the vast majority of adverse effects are directly related to the amount of THC consumed, with the exception of cases involving very large doses of CBD [24]. For instance, in pediatric epilepsy patients, high doses of CBD can cause adverse effects through drug-drug interactions with other anti-epileptic medications.

Another important aspect to consider when discussing the adverse effects of excessive cannabis use is the potential for interactions with medications and other substances. Cannabis can interact with various prescription drugs, leading to alterations in their effectiveness or causing unintended side effects. For instance, cannabis may interact with medications metabolized by the cytochrome P450 enzyme system, such as anticoagulants like warfarin, antidepressants like fluoxetine, and antiepileptic drugs like valproate, potentially affecting drug levels in the body and increasing the risk of adverse reactions [25].

In addition to prescription drug interactions, combining cannabis with other substances, such as alcohol or illicit drugs, can lead to synergistic effects, exacerbating the potential for negative outcomes. For example, consuming cannabis and alcohol together may increase the risk of impaired coordination, cognitive function, and driving ability more than using either substance alone [26]. Moreover, combining cannabis with other central nervous system depressants, such as opioids or benzodiazepines, may further increase the risk of respiratory depression and other severe side effects [27]. Individuals should always consult with a healthcare professional before combining cannabis with prescription medications or other substances to avoid potential harmful interactions.

VII. Reducing the risk of adverse effects

In light of the potential adverse effects associated with excessive cannabis use, it is crucial for individuals to take proactive steps to reduce these risks. By understanding appropriate dosages and frequency of use, choosing safer methods of consumption, monitoring mental and physical health, and recognizing signs of problematic use, users can minimize the likelihood of negative outcomes. It is worth noting that chronic medical cannabis users tend to consume significantly lower amounts of THC and higher amounts of CBD than chronic recreational users, indicating that the warnings regarding excessive use apply particularly to recreational users [28]. 

First, understanding appropriate dosages and frequency of use is essential for reducing the risk of adverse effects. It is crucial for individuals to start with low doses, particularly when trying new products or consuming edibles, and gradually increase the dosage until they achieve the desired effects without experiencing negative side effects [29]. The majority of adverse effects from medical cannabis are directly related to the THC dose, suggesting that daily or heavy cannabis use, especially with high THC content, increases the likelihood of adverse effects. This pattern of consumption has been linked to a higher risk of dependence, mental health issues, and other long-term consequences [1]. 

Choosing medical cannabis product with lower amounts of THC and/or products with safer routes of administration can also play a significant role in reducing the risks associated with cannabis use. To be clear, these suggestions apply to all cannabis users, not just medical users. For example, vaporizing cannabis, as opposed to smoking it, has been shown to produce fewer respiratory symptoms and harmful byproducts [30]. Additionally, vaporizing allows users to more accurately control the dose and onset of effects, further minimizing the potential for negative outcomes.

Monitoring one’s mental and physical health is another important aspect of responsible cannabis use. Users should be aware of any changes in mood, cognitive function, or overall well-being that may be related to their cannabis consumption. By keeping track of these changes, individuals can more effectively identify potential issues and adjust their usage patterns or seek professional help if necessary. To minimize the risks associated with cannabis use, it is crucial to employ harm reduction strategies tailored to specific populations or situations. For instance, pregnant or breastfeeding individuals should avoid cannabis use, as THC can cross the placenta and enter breast milk, potentially impacting the developing fetus and newborn [31]. Additionally, individuals with a history of psychosis or other mental health conditions should exercise caution when using cannabis, as it may exacerbate their symptoms [32].

Finally, recognizing the signs of problematic use and seeking support from family, friends, or support groups is crucial for minimizing the risk of long-term harm. Signs of problematic use may include neglecting personal, social, or professional responsibilities, using cannabis as a primary coping mechanism, or experiencing withdrawal symptoms when attempting to reduce or discontinue use [33]. If any of these signs are present, individuals should consult with a healthcare professional or a substance abuse specialist to discuss their concerns and explore other treatment options.

Preliminary research on the adverse effect profiles of most “minor” phytocannabinoids, such as CBG and CBC, appears promising, though admittedly most evidence is currently based on preclinical in-vivo data [34]. The combination of specific phytocannabinoids in addition to THC and CBD has the potential to fine-tune the biological responses further and reduce CB1-receptor-specific side effects. Further research is needed to ensure that the safety profiles and potential benefits of these lesser-known cannabinoids are also applicable in humans.

In conclusion, by understanding appropriate dosages and frequency of use, choosing safer methods of consumption, monitoring mental and physical health, and recognizing signs of problematic use, individuals can reduce the risk of adverse effects associated with excessive cannabis use, particularly for recreational users who tend to consume higher amounts of THC.

VIII. Conclusion

This article has highlighted the potential adverse effects of excessive cannabis use, including short-term effects such as impaired memory and cognitive function, anxiety, and altered judgment; long-term effects like addiction, respiratory issues, and impact on mental health; as well as specific conditions such as Cannabis Hyperemesis Syndrome. We have also discussed the risks associated with large oral doses or edibles, interactions with medications and other substances, and the importance of reducing the risk of adverse effects through responsible use and education.

In addition to the discussed health risks, cannabis and its various components show enormous potential therapeutic applications for treating a staggering number of different indications, due to the cannabinoids’ ability of interacting and modulating the human ECS.

As cannabis becomes increasingly legalized and accepted, it is crucial to educate the public on both the potential risks and benefits of cannabis use and to promote balanced and informed consumption practices. This involves understanding appropriate dosages, selecting safer methods of consumption, monitoring one’s mental and physical health, and seeking professional help if necessary. Further research on the topic is highly encouraged to better understand the risks associated with heavy long-term cannabis consumption and to develop evidence-based guidelines to promote safe consumption.

Stefan Broselid, Ph.D.
Editor-In-Chief, Aurea Care Medical Science Journal

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