Let’s talk about sex, baby. Let’s talk about 2-AG.

 

An overview of cannabis and human sexuality

By Deb Karhson, PhD

Sex education will probably never cover the topic of cannabis or the endocannabinoid system. It is as likely as cannabis making an appearance in conversations about long term love. Yet, the cannabinoid system is no stranger to in mechanics of love, sex, and orgasms. I’m your friendly neighborhood neuroscientist, Dr. Deb, and if you are just joining the research #ganggang, you can find the first two science summaries, the latest of which is authored by
Dr. Alan Ceaser, here. Last quarter we were in deep discussion about different facets of pain. This quarter, we are moving from pain to pleasure!

From stress to bliss!

And how cannabis can make all the difference. In much the same way cannabis gives you that tingly feeling in your brain, it also has the ability to leave your loins lubricated. Human sexual response cycle is divided into four phases: desire, arousal, orgasm and resolution. The endocannabinoid system, whom you first met in Dr. Alan’s article, is a regulator of sexual motivation/desire, arousal, orgasm, emotional regulation, and the reproductive cycle. That overlap is wild, no?

Our body, Our Selves

In case a quick refresher is needed, the endocannabinoid system is the entire reason why cannabis has an effect. The “active ingredients” in cannabis are wee molecular keys that activate or unlock the activity of cannabinoid receptors
(the locks).

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And though, researchers only found the endocannabinoid system because they were interested in the mechanisms of the cannabis effect, what was more astonishing is that our body makes a version of these molecular keys. We call those endocannabinoids – of which there are two, the bliss molecule (anandamide) and 2-AG, the “workhorse”. THC biologically imitates the bliss molecule and 2-AG, hence its effects. CBD, the other cannabinoid-cutie, doesn’t really act like the endocannabinoids, instead its actions tend to mimic other helpful molecular keys found in our body, such as serotonin (“happiness” molecule). Both the receptors (“locks”) and the endocannabinoids (“keys”) are located throughout your body in different amounts or expression. The areas with the highest expressions are generally the areas of your body where the endocannabinoid system is really active, such as your brain. Another area with high expression of these locks and wee keys are reproductive organs.

“Star Gentle Uterus”

Within the female reproductive organs, cannabinoid receptors are found in greatest abundance in the uterus and to a lesser extent the in the fallopian tubes, ovaries, vagina and vulva. Knowing that, it should be no surprise to learn that the endocannabinoid system plays a big role in pretty much all reproductive processes. From follicle generation, to ovulation and egg maturation, to egg implantation, pregnancy and childbirth, the endocannabinoid system is very involved in the flow of uterus function1,2. The the rise and fall of hormones like estrogen and progesterone during the menstrual cycle is common knowledge, but what is not so common is awareness that endocannabinoid levels are also rising and falling. On day one of the menstrual cycle, the levels of the bliss molecule, anandamide, start increasing and peak during ovulation, cueing sexy time3,4. But as Cardi B would say: when estrogen dips, bliss dips, we dip. The consequence of the dips in estrogen and the bliss molecule are a very familiar behavioral pattern.

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The classic need for chocolate during the menstrual period, while seeming like a well-worn sitcom trope, may be related to the dip in anandamide, the bliss molecule. During menstruation, levels of anandamide are the lowest, then the uterus starts to a-holler, and your brain responds in kind with a craving to help ease this obvious shortage in bliss. Chocolate is abundant in anandamide, as are truffles, which is information you can use in whatever way you see fit. For example, if you wanted to explain to someone your uterus is in distress due to dangerously low amounts of endocannabinoids and requires truffle butter popcorn and chocolate, science is on your side.

Cannabis can also be used in a pinch since THC mimics the bliss molecule and 2-AG. Beyond providing an excuse to indulge in chocolate, the dip in the levels of the bliss molecule, allows for fertilized eggs to implant themselves to the side of the uterus and 10 months later turn into a tiny human. Throughout pregnancy the levels of the bliss molecule are low and only rise during labor, when the levels quadruple. And during labor, more means less – higher levels of the bliss molecule, anandamide, are related to reduced delivery times5. Basically, the bliss molecule is for baby-making and baby-birthing.

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Obviously, with the high densities of cannabinoid receptors (“locks”) found in lady parts and higher estrogen levels, cannabis should be doing the most in women. However, research is still a bit shy around girls. To date, most research is performed with animal models, so the translation to humans is tricky. Within animal studies, there is increased sensitivity (by 30%) to the pain-relieving qualities of THC in females compared to males, as well as a faster rate of tolerance6,7. This could also be why smaller amounts of cannabis are better at enabling sexual motivation and receptivity in women, but we’re waiting on the research data.

“Look at My Tiny Elephant”

Within males the endocannabinoid system has a far less involved role. In truth, it handles just one job. The small, but important job of producing man-milk! That’s right SPERM! Without the endocannabinoid system in males, there would be no control over the birth of sperm, sperm viability, motility, or even sperm’s ability to wiggle inside an egg8,9. And before February 2019, most evidence suggested cannabis had very NEGATIVE effects on sperm counts and overall sperm health. The urban legend that “smoking makes you sterile” was vigorously repeated and respected. However, earlier this month the latest human research study8 by the Harvard T.H. Chan School of Public Health cast much doubt on the long-held belief that cannabis is bad for sperm counts. By analyzing the ejaculate of 662 males, researchers found that those who reported using cannabis had higher sperm counts than men who reported never having used cannabis. On average, men who cannabis users had "significantly higher" sperm concentrations than those who refrained, by about 20 million sperm per milliliter (cannabis users: 62.7 mil sperm per milliliter vs 45.4 in non-users). Even after factors that affect sperm count, like age, tobacco and alcohol use, cannabis users had on average higher sperm counts by 15%. Moreover, the men who had used cannabis more often had higher testosterone levels than those who used it less.

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But remember, this is one study, so it is hard to say if cannabis makes a person more virile.

“When Our Powers Combine…”

The evidence supporting the combinatorial effects of cannabis and copulation (sex) is, shall we say, rock hard. From the oldest Chinese and Indian pharmacopeias to tantric religious texts, the properties of cannabis have been recommended for a variety of sexual assists, such as stimulating arousal and sexual thoughts, increasing sexual desire, motivation, and receptivity, as well as extending sexual performance10. More recent studies support historical findings as well as giving us a more detailed understanding of the behind-the-scene action. In the largest study to date, Stanford researchers performed a nationwide survey to investigate the cannabis and sex connection. They found that among the 28,176 women and 22,943 men surveyed cannabis use was independently associated with increased weekly sexual frequency, by 22% in men and 34% in women11. In a different study by researchers at St. Louis University in Missouri, of 133 women surveyed, 29% reported using cannabis prior to sex12. The reasons provided were: increased erotic pleasure (72%), belief that cannabis enhanced libido and pleasure of orgasms (62%), as well as pain relief (16%). And I know since we’ve been putting respect on the bliss molecule name, it seems like the responsible party, but when it comes to generating the O-face, anandamide is giving researchers a NO-face. With a nickname like “the workhorse”, you better believe 2-AG is the Rihanna of endocannabinoids when it comes to sex.

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German researchers published a study in 2017 that we are still discussing due to its unexpected findings. They measured blood levels of both endocannabinoids (the bliss molecule and 2-AG) as well as cortisol (a molecular stress indicator) before and after masturbation. Researchers expected the levels of the bliss molecule to be quite high, instead they were surprised to find that during orgasms only levels of 2-AG increased13. Both the bliss and stress molecule levels were unchanged by orgasm. BUT, if cannabis doesn’t contain 2-AG, what effect can it possibly have on your O-face? Good Question! It’s like a 7-layer bean dip of effects. THC, the well-known good-time goto handles the first half of the sexual response cycle: obliterating anxiety while stimulating desire, motivation, and receptivity.

Once the ocean is fully in motion, CBD may take the main stage for orgasm production. While not often discussed, CBD boost the body’s levels of 2-AG, which can improve sexual responses (e.g., better orgasms and repeat performances).

“Hit Me Baby, One More Time + What’s Love Got to Do with It? = Thank U, Next”

Sexual activity is more than just a physical endeavor though; when it comes to coitus, your brain is very much in the mix. Not only is 2-AG released when you, ahem, release, so is the bonding hormone, oxytocin14,15. BONDING as in: the touchyfeelies, closeness, affection, or mushy gushy feelings. While normally oxytocin can put a spell on you (to make you mine), the real reinforcing culprits are the endocannabinoids. As oxytocin and 2-AG go a-walking, love comes a-knocking. You become thirsty for that sweet, sweet dual molecule rush as you are literally unable to forget the feeling thanks to the memory-making action of 2-AG16. In the post-orgasm haze, oxytocin leaves a snail trail of the bliss molecule in your brain to enhance the memory of pleasure17. This “primes the pump” for your next sweet hit of sexual contact, making the act even more enjoyable and memorable the next time. Before you know which way is up, there’s discussion of pair-bonding and weekends lost on the Ikea showroom floor. I’m not saying, all sexual contact will send you head over heels, just that endocannabinoids and oxytocin are a helluva drug.

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And staring into the eyes of your sexual partner(s) post-orgasm will only help your brain to make the connection between that awesome molecule party and those faces. Although, there may be advantages to suffering through a stage-five clinger. In 2017, researchers at McGill University published a study where the results suggest frequent penile-vaginal intercourse (PVI) has a positive effect on memory in women18. Most researchers suggest this effect is related to the same mechanisms that used by exercise to boost memory, others think the effect is related to the involvement of the “reward” molecules that are strongly tied to memory19,20. Both are correct, but only because each of those pathways work through the endocannabinoid system. To me, the data suggests “frog-kissing to find the one” is an evidence-based wellness practice for brain health. Which is to say, brain positivity is also sex positivity in 2019.

The information in the article is for educational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.

Sources

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  3. Klinger, F. G., Battista, N., De Felici, M. & Maccarrone, M. Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle. J. Exp. Clin. Assist. Reprod. 3, 3 (2006).

  4. Lazzarin, N. et al. Fluctuations of fatty acid amide hydrolase and anandamide levels during the human ovulatory cycle. Gynecol. Endocrinol. 18, 212–218 (2004).

  5. Habayeb, O. M. H. et al. Plasma Levels of the Endocannabinoid Anandamide in Women—A Potential Role in Pregnancy Maintenance and Labor? The Journal of Clinical Endocrinology & Metabolism 89, 5482–5487 (2004).

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  9. Cacciola, G., Chioccarelli, T., Fasano, S., Pierantoni, R. & Cobellis, G. Estrogens and spermiogenesis: new insights from type 1 cannabinoid receptor knockout mice. Int J Endocrinol 2013, 501350 (2013).

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  11. Sun, A. J. & Eisenberg, M. L. Association Between Marijuana Use and Sexual Frequency in the United States: A Population-Based Study. The Journal of Sexual Medicine 14, 1342–1347 (2017).

  12. Lynn, B., Miller, C., Thompson, J. & Campian, E. C. 355 The Relationship Between Marijuana Use Prior to Sex and Sexual Function in Women. The Journal of Sexual Medicine 14, S105 (2017).

  13. Fuss, J. et al. Masturbation to Orgasm Stimulates the Release of the Endocannabinoid 2-Arachidonoylglycerol in Humans. J Sex Med 14, 1372–1379 (2017).

  14. Behnia, B. et al. Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples. Hormones and Behavior 65, 308–318 (2014).

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  16. Luchicchi, A. & Pistis, M. Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids. Mol. Neurobiol. 46, 374–392 (2012).

  17. Wei, D. et al. Endocannabinoid signaling mediates oxytocin-driven social reward. PNAS 201509795 (2015). doi:10.1073/pnas.1509795112

  18. Maunder, L., Schoemaker, D. & Pruessner, J. C. Frequency of Penile-Vaginal Intercourse is Associated with Verbal Recognition Performance in Adult Women. Arch Sex Behav 46, 441–453 (2017).

  19. Meccariello, R., Battista, N., Bradshaw, H. B. & Wang, H. Updates in reproduction coming from the endocannabinoid system. Int J Endocrinol 2014, 412354 (2014).

  20. Rapino, C., Battista, N., Bari, M. & Maccarrone, M. Endocannabinoids as biomarkers of human reproduction. Hum. Reprod. Update 20, 501–516 (2014).


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