Over the last few years, public and medical opinion towards marijuana has shifted, and it has gained wider acceptance across the board.
What was once demonized and ridiculed, is now as mainstream as caffeine and protein. But when it comes to athletic performance, there's plenty of marketing that says it helps, but today we're going to look at the science.
Marijuana is an herb that contains molecules called cannabinoids. While Δ9-tetrahydrocannabinol (THC) is considered the main psychoactive constituent, cannabis contains hundreds of potentially biologically active chemicals, some of which may provide synergistic effects, and some revealed less potent psychotropic effects, including cannabidiol (CBD).
Traditionally, marijuana has been used to treat a variety of inflammatory and gastrointestinal ailments. It has also been used to reduce anxiety and help alleviate cognitive decline.
Today, marijuana is used an adjuvant treatment for cancer, meaning it is taken alongside other drugs. Although Marijuana is not a potent anti-cancer agent by itself; it is used alongside chemotherapy because it increases appetite which helps to prevent weight loss associated with chemotherapy, greatly improving patient survival rates during cancer treatment.
Marijuana acts on two receptors, located on cell walls. These cannabinoid receptors are named after the plant and are known as the first cannabinoid receptor (CB1) and the second cannabinoid receptor (CB2).
CB1 is responsible for the immediate and psychoactive effects of marijuana, while CB2 determines the long-term and anti-inflammatory effects.
Using marijuana can lead to tolerance, which means more marijuana will be needed to achieve the same effect. Tolerance is caused by a process called internalization where the CB1 receptor is internalized, withdraws into the cell and can no longer come into contact with THC.
Internalization doesn’t just lead to marijuana tolerance. Other receptors associated with the CB1 receptor will follow CB1 into the cell.
For example, the N-methyl-D-aspartate (NMDA) receptor is internalized along with CB1. This leads to protective effects against anxiety and epilepsy, but it also causes the temporarily impaired memory retention associated with marijuana.
The establishment of the World Anti-Doping Agency (WADA) and subsequent penalization of athletes for cannabis use has prompted greater scrutiny of the effects of cannabis on athletic performance(1).
Cannabis use has increased, in large part due to decriminalization.
Despite this enhanced usage; it remains unclear what proportion of athletes use cannabis and to what extent it influences athletic performance and recovery.
A recent systematic review was conducted which included cannabis usage among athletes, including epidemiology, effect on performance, and recovery. There was a total of 37 studies that met the inclusion criteria, many of which were cross-sectional studies on elite and university athletes.
The results from this review suggest that approximately 25% of athletes report using cannabis within the past year. Based on the available evidence, cannabis does not appear to positively affect performance(2).
Another recent and extremely in-depth systematic review was recently completed on the chronic effects of cannabis consumption on physiological parameters of athletic performance, in order to determine whether chronic cannabis consumption negatively affects athletic performance; improves performance potentially through enhanced recovery; or has no effect at all.
This review included cross-sectional, longitudinal, and intervention studies up to January 2020 and measured the effects of cannabis consumption on sports performance outcomes such as VO2Max (maximal oxygen uptake) and PWC (physical work capacity)(3).
Across the studies that met the inclusion criteria; no significant difference between cannabis users and non-users was observed for peak work capacity, cardiorespiratory fitness (VO2Max), other pulmonary measures (such as FEV1), strength and endurance measures (such as hand-grip strength), perceived exertion, or blood pressure.
Another very recent systematic review examined the acute effects of cannabis and showed that consumption prior to exercise causes decrements in performance (reduced ability to maintain effort, physical/maximal work capacity), undesired physiological responses (increased heart and breathing rate as well as oxygen demand on the heart muscle) and neurological effects on balance (i.e. increased sway)(4).
Based on data of the acute effects of cannabis, cannabis consumption has an ergolytic (i.e. impair performance) effect on exercise performance and therefore does not act as a sport performance enhancing agent as raised by popular beliefs.
Therefore, cannabis consumption prior to exercise should be avoided in order to maximize performance in sports(4).
Men and women of reproductive age are the most prevalent users of cannabis; therefore the impact on fertility and the reproductive system is of special importance. Cannabinoids, including THC, were found to exert anti-androgenic effects by binding to androgen receptors and acting on the hypothalamus-pituitary-adrenal (HPA) axis(5).
Animal research has demonstrated that cannabis influences several endocrine processes affecting sexual hormones as well as other hormones like melatonin and growth hormone(5,6). In addition, animal models show that cannabis is related to testicular atrophy, reduced libido, and sexual function(7). However, until now, such effects have not been observed in human studies(7).
Luteinizing hormone (LH) levels appear to be lowered and levels of the follicle-stimulating hormone (FSH) are unchanged, except in heavy chronic use cases(7). The role of FSH is known in supporting developing spermatozoa by stimulating Sertoli cells, while LH stimulates testosterone production from Leydig cells in the testis(8). Lower levels of FSH and LH by THC can cause reduced testosterone production by the Leydig cells(9).
Moreover, chronic cannabis use may increase prolactin concentrations in men, which may lead to gynecomastia via secondary hypogonadism(10).
The influence of cannabis on female reproduction has not been fully studied. In order to investigate the effect of cannabis on female reproductive system; female mice were given different concentrations of cannabis extract orally by micro-pipette. Results demonstrated that chronic cannabis exposure induced oxidative stress and impairment in the female mouse reproductive system characterized by a significant decrease in ovarian and uterine weight(11).
Another study on healthy adult females demonstrated that cannabis smoking causes an acute decrease in prolactin concentrations, but prolonged use may increase these concentrations, leading to galactorrhea(10). Cannabis can reduce estrogen and progesterone production by disrupting the hypothalamic release of gonadotropin-releasing hormone (GnRH), which may lead to an ovulatory menstrual cycle and reduced female fertility(11).
Cannabis inhalation during the luteal phase of the menstrual cycle may result in transient suppression of levels of prolactin and LH(12). Nevertheless, there is no conclusive evidence of cannabis’ effect on menstruation or on levels of estrogens, progesterone, testosterone, prolactin, LH, or FSH in women (13).
In general, cannabis-related endocrine changes may not be significant in adults, but they may be of high importance in prepubescent males and females, in whom cannabis may suppress sexual maturation(10). Multiple animal studies showed that cannabis (specifically exposure to THC) can lead to pubertal delay and affect pubertal maturation(14). However, evidence in humans is limited except for a case of a 16-year-old youth who showed delayed puberty and low testosterone levels with heavy cannabis smoking.
Upon discontinuing cannabis smoking, his testosterone levels increased and pubertal development advanced(12). Therefore, an urgent understanding of the effect of cannabis on pubertal timing and tempo in children is drastically needed.
Since the 1970s, a dose-related decrease in testosterone levels has been shown in chronic marijuana smokers(15). Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana, indicating that cannabis acts via a central mechanism to decrease testosterone levels(16).
Other research failed to demonstrate statistically significant differences in plasma testosterone levels between occasional and chronic marijuana smokers(17), between occasional smokers and controls(18), or between daily marijuana users and controls(19).
A recent population study on over 1,500 U.S. men found no differences in serum testosterone levels among ever users of marijuana compared to never users. However, testosterone concentrations were higher in men with more recent marijuana use, especially in men aged 18–29(20). A study on over 1,200 young healthy men reported, similarly to tobacco smokers, an increase in testosterone levels in marijuana smokers(21).
A recent systematic review on 15 clinical studies and 21 animal/in vitro (outside the body) studies concluded that there wasn’t a significant relationship between long-term cannabis consumption and alteration of the hypothalamic–pituitary–testicular axis hormones(22).
Despite these conflicting data, an inhibitory central mechanism of THC is plausible since it has been demonstrated that CB1 receptors are present both at the pituitary (especially in lactotrophs and gonadotrophs) and hypothalamic (in GnRH neurons) level.
Endocannabinoids depress the pituitary secretion of thyroid-stimulating hormone (TSH), LH, growth hormone (GH), and prolactin, and the hypothalamic GnRH release in rats(23) . Specifically, the CB1 receptor agonist anandamide suppresses LH and testosterone secretion(24). In vitro (outside the body); it has been demonstrated that endocannabinoids inhibit gamma-aminobutyric acid (GABA) A receptors drive in GnRH neurons, causing a decrease in GnRH neuron firing rate(25).
However, a direct effect of THC in testis has also been demonstrated in animal models. Acute and chronic administration of THC significantly depressed testosterone formation in testis microsomes(26). In in vitro studies, murine Leydig cells incubated with THC produced less testosterone in response to Human Chorionic Gonadotropin (HCG) and dibutyryl-cAMP(27). Furthermore, a reduced expression of LH receptor on testis and a reduced activity of testicular 3β-hydroxysteroid dehydrogenase has been demonstrated in mice fed with a preparation containing cannabis(28).
In summary, the data from both animal models and cell studies show there is an inhibitory effect of THC on testosterone.
Some research suggests that marijuana use facilitates an anti-inflammatory response, yet the relationship between marijuana use and inflammation, as measured by C-reactive protein (CRP), remains poorly understood. CRP is a substance produced by the liver in response to inflammation. This means an increase in CRP is correlated to an increase in inflammation. A recent study examined the association between recency of marijuana use and serum CRP levels in a nationally representative sample of adults(29).
It was demonstrated that marijuana use does not confer an anti-inflammatory effect and recency of use is not relevant. Given expanding marijuana use legislation and discourse surrounding the consequences of marijuana for health, continued research is needed to elucidate the effect of marijuana on inflammation and subsequent risk of chronic disease(29).
Previous research has associated cannabis use with altered circulating neurotrophins (regulate many aspects of neuronal function) and biomarkers of immune health, but these relationships have yet to be fully explored in physically active individuals.
A recent study explored the relationships between biomarkers of neural health: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), immune health: interleukin 6 (IL-6), CRP, and cortisol, as well as the presence of depression, in physically active cannabis users and nonusers(30).
Plasma BDNF was significantly lower in physically active cannabis users compared with nonusers. Low BDNF levels are associated with chronic stress and depressive-like symptoms. In addition, cannabis users were classified at moderate risk for cardiovascular disease based on average circulating CRP compared with low risk for nonusers(30).
The true impact of marijuana on the cardiovascular system remains unclear. Cannabis mainly exerts its effects via the sympathetic and parasympathetic nervous systems, with different doses affecting different cannabinoids receptors.
Research has shown that marijuana plays a role in thrombosis, inflammation, and atherosclerosis. In recent review was conducted in order to provide a basic understanding of the physiological effects of marijuana on the cardiovascular system and cardiovascular diseases linked to marijuana use in adults(31).
It was found that many cases have linked marijuana to myocardial infarction, especially in young healthy men with no other risk factors. Marijuana has also been associated with a worse mortality rate post myocardial infarction. Cases of marijuana precipitating arrythmias, stress cardiomyopathy, and arteritis have all been described(31).
With the rise in cannabis use among older patients, who are the most vulnerable to cardiovascular events, it is expected that these reports will increase in the next few years. The pathophysiology of these events is still debated, with contradictory studies available in the literature. The expansive presence of the endocannabinoid receptors in the human body makes drawing conclusions extremely challenging. The interactions of the endocannabinoid system with the autonomic nervous system seem to be the driving force behind the reported cardiovascular adverse events(31).
Another very recent systematic review of the literature analyzed published papers for cannabis-induced myocardial infarction in order to derive a strong relation between cannabis use and myocardial infarction and understand the pathophysiology(32).
They found a strong relationship between marijuana use and the incidence of myocardial infarction and mortality of patients after cannabis-induced myocardial infarction. Many cases in their research show that after marijuana use, even for the first time, there can be an event of myocardial infarction, indicating that marijuana use should be considered a significant risk for myocardial infarction(32).
Various studies have proposed the pathophysiology of how these events occur. It’s safe to say that cannabinoids act on the cannabinoid receptors to affect the cardiovascular system.
They cause a mismatch in oxygen supply and demand in the myocardium, which can lead to ischemia. In addition, it can also increase platelet aggregation, which can lead to atherosclerosis, ultimately myocardial infarction(32).
The lack of laboratory studies regarding the impact of marijuana on human cardiac physiology makes interpreting case reports very difficult. However, the alarming rate of adverse cardiovascular events reported over the past decade necessitates that physicians remain vigilant in everyday practice to recognize these effects and counsel their patients accordingly.
People use marijuana for a variety of reasons including sleep, pain management, and more, and just like anything else, it's important to know the risks and benefits so you can make informed decisions about your choices.
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