What is Marijuana and How Does it Work?
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).
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.
How Does Marijuana Impact Athletic Performance?
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 the increase in usage, it remains unclear what proportion of athletes use cannabis and to what extent it influences athletic performance and recovery. Recent evidence of cannabis usage among athletes demonstrated that approximately 25% of athletes report using it within the past year. Based on the evidence to date; cannabis doesn’t appear to positively affect performance [2].
Recent evidence investigated the chronic effects of cannabis use 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 systematic review included cross-sectional, longitudinal, and intervention studies up to January 2020 and measured the effects of cannabis consumption on sports performance outcomes [e.g. VO2Max (maximal oxygen uptake), PWC (physical work capacity)] [3].
There was no significant difference between cannabis users and non-users for peak work capacity, cardiorespiratory fitness, other pulmonary measures (e.g., FEV1), strength and endurance measures, perceived exertion, or blood pressure across all studies.
Another very recent systematic review examined the acute effects of cannabis and showed that consumption prior to exercise causes decrements in performance (i.e., reduced ability to maintain effort, physical/maximal work capacity), undesired physiological responses (i.e., increased heart and breathing rate as well as myocardial oxygen demand) and neurological effects on balance (i.e., increased sway) [4].
Based on data of the acute effects, cannabis consumption may impair 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].
How THC Affects Testosterone/Hormone Levels
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 decrease and levels of the follicle-stimulating hormone (FSH) are unchanged (except in heavy chronic use cases) [7]. FSH supports developing spermatozoa by stimulating Sertoli cells, while LH stimulates testosterone production from Leydig cells in the testes [8].
Therefore, lower levels of LH can reduce 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]. There is also a high potential for aromatization to occur from chronic cannabis usage.
The influence of cannabis on female reproduction is not fully understood.
A recent study investigated this by giving female mice different concentrations of cannabis extract orally by a 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 [211].
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 demonstrated 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 1500 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 1200 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 (i.e., 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 conceivable 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]. 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 testes has also been demonstrated in animal models. Acute and chronic administration of THC significantly depressed testosterone formation in testes 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 testes 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 indicate that there is an inhibitory effect of THC on testosterone.
How Does Marijuana Impact the Muscles?
To be quite honest, the number of human studies investigating the effects of marijuana on muscle growth is sparse, but there is some insight to be gleaned from the available body of literature.
Muscle Growth
Over the last few years, there’s been a lot of buzz around marijuana and bodybuilding. The talk is whether nor not marijuana could help a lifter achieve their bodybuilding goals and most of the debate focuses on testosterone levels, appetite, muscle recovery ad performance.
A recent study investigated the effect of acute administration of CBD on molecular signaling in skeletal muscle after eccentric exercise. Results showed the overall effect on protein levels in skeletal muscle after exercise was modest [29].
There was a tendency for increased anabolic signaling and a simultaneous decrease in inflammatory signaling with administration of CBD. This research wasn’t able to determine whether the decrease in inflammatory markers was the result of a direct effect of CBD on muscle or an indirect effect on inflammatory cells.
A follow up study determined whether the decreased inflammation and tendency to increase anabolism in vivo were the cause of a direct action on muscle cells. Results demonstrated that CBD had no effect on anabolic signaling through the mTORC1-axis [29]. It appears unlikely that there is a direct physiological role for CBD in anabolic and inflammatory signaling within skeletal muscle tissue.
It is still possible that CBD could exert indirect effects in vivo through modulation of immune cells that interact with skeletal muscle or by causing systemic changes to circulating cytokines and hormones that affect the central nervous system, immune system, and other endocrinologically active tissues. Future research needs to further elucidate whether such indirect effects could be clinically relevant and whether they can be elicited without requiring toxic dosages of CBD.
Muscle spasms
There’s a solid amount of research on the use of cannabis for muscle spasms stemming from scientists researching treatments for multiple sclerosis, an autoimmune disease that affects the nervous system. Cannabinoids extracted from marijuana (Cannabis sativa), as well as synthetic forms have been well-characterized for their anti-inflammatory properties [30].
Cannabinoids have also been shown to ameliorate spasticity and neuropathic pain in multiple sclerosis patients.
Essentially, the cannabinoids in marijuana bind to cannabinoid receptors in the body and reduce the number of inflammatory proteins, causing a decrease in muscle spasms.
A 2019 study used the combination of cannabinoids, THC and CBD, to address the potential ability of these components in ameliorating the symptoms multiple sclerosis (i.e, spasms). Collectively, this study indicates that the combination of THC+CBD suppresses neuroinflammation and attenuates experimental autoimmune encephalomyelitis [30].
More recent research investigated how CBD limits excessive neuroinflammation in experimental autoimmune encephalomyelitis.
Findings demonstrated the beneficial effect of CBD treatment on autoimmune neuroinflammation, regulating inflammatory macrophage activity, and limiting low-grade inflammation in the GI tract, culminating in the reduction of experimental autoimmune encephalomyelitis [31].
Muscle recovery
There are quite a few professional athletes who have stated that they use either marijuana or hemp CBD to enhance recovery time.
In addition, many non-professional athletes and fitness lovers have stated they use cannabis to aid recovery. They claim it reduces muscle pain, decreases delated onset muscle soreness, and shortens the inter-session workout recovery time.
There is very little research to help us understand why cannabis may help with muscle recovery.
The only research I found was a recent observational study that aimed to establish the prevalence of CBD use in a large sample (>500) of professional rugby league players. Results showed that >25% of all athletes surveyed have either used or continue to use CBD. The major reasons cited for using CBD were to enhance pain relief/recovery and to improve sleep quality [32].
As this was only an observational study, future research should assess the efficacy of CBD supplementation on factors influencing recovery (e.g., pain, soreness, inflammation, sleep).
Anecdotally, we can infer that cannabis may help muscle recovery due to its anti-inflammatory effects. We know that NSAIDs help speed muscle recovery by providing anti-inflammatory effects. The theory that cannabis seems to have anti-inflammatory properties is fairly widely accepted in the scientific community. This anti-inflammatory role of cannabis could be the mechanism behind why so many people say it helps with muscle recovery.
Muscle pain
Cannabis has been traditionally used as a holistic treatment for pain and is still one of the most popular alternative treatments for pain. People use cannabis to address numerous types of pain, including nerve pain, arthritic pain, pain caused by injuries, joint pain, and muscle pain.
Laboratory studies and clinical trials suggest that cannabinoids are weak analgesics, and it is unclear whether perceived reductions in pain from before to after cannabis use relate to factors such as dose, method of administration, phytocannabinoid content, or the age or gender of the user.
A recent investigation determined whether inhalation of cannabis decreased self-reported pain ratings as well as whether user gender, age, time, method of administration, THC/CBD content, or dose of cannabis contribute to changes in these ratings. The research also examined whether tolerance may develop to the analgesic effects of cannabis over time. Results demonstrated that inhaled cannabis reduces self-reported pain severity by ∼42-49%.
However, these reductions appear to diminish across time, causing patients to use larger doses, suggesting that analgesic tolerance develops with continued use [33].
Although the exact mechanisms haven’t been elucidated, the idea is that cannabis acts to relieve muscle pain through its anti-inflammatory properties.
Some studies show that cannabis and CBD may have a general balancing effect on the endocannabinoid system.
The endocannabinoid system helps regulate pain sensation in the body.
Potentially, cannabinoids like CBD may help balance out feelings of pain by interacting with the endocannabinoid system.
References:
1. Hilderbrand, R.L., High-performance sport, marijuana, and cannabimimetics. J Anal Toxicol, 2011. 35(9): p. 624-37.
2. Docter, S., et al., Cannabis Use and Sport: A Systematic Review. Sports Health, 2020. 12(2): p. 189-199.
3. Kramer, A., et al., Chronic cannabis consumption and physical exercise performance in healthy adults: a systematic review. J Cannabis Res, 2020. 2(1): p. 34.
4. Charron, J., et al., Acute effects of cannabis consumption on exercise performance: a systematic and umbrella review. J Sports Med Phys Fitness, 2021. 61(4): p. 551-561.
5. E.B., R., Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. 2013, Abingdon, UK: Routledge.
6. Rettori, V., et al., Hypothalamic action of delta-9-tetrahydrocannabinol to inhibit the release of prolactin and growth hormone in the rat. Neuroendocrinology, 1988. 47(6): p. 498-503.
7. Payne, K.S., et al., Cannabis and Male Fertility: A Systematic Review. J Urol, 2019. 202(4): p. 674-681.
8. du Plessis, S.S., A. Agarwal, and A. Syriac, Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility. J Assist Reprod Genet, 2015. 32(11): p. 1575-88.
9. Harclerode, J., Endocrine effects of marijuana in the male: preclinical studies. NIDA Res Monogr, 1984. 44: p. 46-64.
10. Hollister, L.E., Health aspects of cannabis. Pharmacol Rev, 1986. 38(1): p. 1-20.
11. S., G., Natural Products-From Bioactive Molecules to Human Health., in Cannabis Effect on Female Reproductive Health. 2020, IntechOpen Limited: London, UK: Rijeka, Croatia: .
12. Mendelson, J.H., N.K. Mello, and J. Ellingboe, Acute effects of marihuana smoking on prolactin levels in human females. J Pharmacol Exp Ther, 1985. 232(1): p. 220-2.
13. Block, R.I., R. Farinpour, and J.A. Schlechte, Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women. Drug Alcohol Depend, 1991. 28(2): p. 121-8.
14. Sims, E.D., et al., The effect of cannabis exposure on pubertal outcomes: a systematic review. Adolesc Health Med Ther, 2018. 9: p. 137-147.
15. Kolodny, R.C., et al., Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med, 1974. 290(16): p. 872-4.
16. Cone, E.J., et al., Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects. Pharmacol Biochem Behav, 1986. 24(6): p. 1749-54.
17. Mendelson, J.H., et al., Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med, 1974. 291(20): p. 1051-5.
18. Cushman, P., Jr., Plasma testosterone levels in healthy male marijuana smokers. Am J Drug Alcohol Abuse, 1975. 2(2): p. 269-75.
19. Friedrich, G., W. Nepita, and T. Andre, [Serum testosterone concentrations in cannabis and opiate users]. Beitr Gerichtl Med, 1990. 48: p. 57-66.
20. Thistle, J.E., et al., Marijuana use and serum testosterone concentrations among U.S. males. Andrology, 2017. 5(4): p. 732-738.
21. Gundersen, T.D., et al., Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men. Am J Epidemiol, 2015. 182(6): p. 473-81.
22. Rajanahally, S., et al., The relationship between cannabis and male infertility, sexual health, and neoplasm: a systematic review. Andrology, 2019. 7(2): p. 139-147.
23. Fasano, S., et al., The endocannabinoid system: an ancient signaling involved in the control of male fertility. Ann N Y Acad Sci, 2009. 1163: p. 112-24.
24. Wenger, T., et al., The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun, 2001. 284(2): p. 363-8.
25. Farkas, I., et al., Retrograde endocannabinoid signaling reduces GABAergic synaptic transmission to gonadotropin-releasing hormone neurons. Endocrinology, 2010. 151(12): p. 5818-29.
26. List, A., et al., The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat. Drug Metab Dispos, 1977. 5(3): p. 268-72.
27. Jakubovic, A., E.G. McGeer, and P.L. McGeer, Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro. Mol Cell Endocrinol, 1979. 15(1): p. 41-50.
28. Banerjee, A., et al., Effects of chronic bhang (cannabis) administration on the reproductive system of male mice. Birth Defects Res B Dev Reprod Toxicol, 2011. 92(3): p. 195-205.
29. Langer, H.T., et al., Cannabidiol Does Not Impair Anabolic Signaling Following Eccentric Contractions in Rats. Int J Sport Nutr Exerc Metab, 2021. 31(2): p. 93-100.
30. Nagarkatti, P., et al., Cannabinoids as novel anti-inflammatory drugs. Future Med Chem, 2009. 1(7): p. 1333-49.
31. Dopkins, N., et al., Effects of Orally Administered Cannabidiol on Neuroinflammation and Intestinal Inflammation in the Attenuation of Experimental Autoimmune Encephalomyelitis. J Neuroimmune Pharmacol, 2021.
32. Kasper, A.M., et al., High Prevalence of Cannabidiol Use Within Male Professional Rugby Union and League Players: A Quest for Pain Relief and Enhanced Recovery. Int J Sport Nutr Exerc Metab, 2020. 30(5): p. 315-322.
33. Cuttler, C., E.M. LaFrance, and R.M. Craft, A Large-Scale Naturalistic Examination of the Acute Effects of Cannabis on Pain. Cannabis Cannabinoid Res, 2020.
