Ecstasy and oxytocin

Ecstasy pills

Although the drug methylenedioxymethamphetamine, better known as MDMA or ecstasy, is often lumped into the category of hallucinogens, it has a unique set of effects that make it very distinct from other drugs in this class. Specifically, along with creating a positive mood state and reducing anxiety, MDMA is known for fostering strong feelings of empathy and compassion.

In some ways, MDMA appears to act on the brain in a manner similar to other amphetamines. Specifically, it is taken up into neurons and promotes the release of neurotransmitters like serotonin, norepinephrine, and dopamine. This excess neurotransmitter release is associated with alertness and a positive mood, along with the desire to continue using the drug. But the mechanism underlying MDMA's ability to create feelings of empathy is still somewhat unclear.

Some have suggested that enhanced compassion during MDMA use is due to increased release of oxytocin, a hormone synthesized by the hypothalamus. In addition to its roles in childbirth and breastfeeding, oxytocin has been dubbed "the love hormone" because it seems to increase trust, promote social bonding, and foster compassion.

In a study published this month in Nature Neuropsychopharmacology, researchers compared the effects of MDMA and oxytocin (in the form of a nasal spray) to see how similar they really are. Over a series of 4 sessions they gave MDMA, oxytocin, or placebo to a group of 65 MDMA users and then administered a series of tests to determine the overlap between the effects of MDMA and oxytocin.

They found that MDMA caused users to report feeling friendlier, more insightful, and more likely to enjoy social interaction. Interestingly, it also increased feelings of anxiety (perhaps because the participants were forced to experience the drug alone and it is a drug that increases the desire for social affiliation). On a task where participants were asked to identify angry, fearful, happy, or sad emotions in computer-generated faces, MDMA decreased the ability to recognize anger or fear. Thus, the effects of MDMA corresponded to what has been seen before in that it generally promoted positive feelings, sociability, and a decreased awareness of negative emotions in others.

The effects of intranasal oxytocin, however, were more ambiguous. It mildly increased reports of positive feelings, only impaired the identification of emotion in faces when it came to recognizing sadness (and this effect was only seen in female participants), and didn't influence the desire to socialize. Also, while the effects of MDMA increased with dose, the effects of oxytocin were inconsistent, with some effects being increased at the lower dose and reduced at the higher dose.

Overall, MDMA and oxytocin administration didn't result in similar effects in this study. One major shortcoming of the study was that the experiments were conducted with previous users of MDMA; a previous history of MDMA use certainly could have influenced the experience participants had with MDMA administration (and with oxytocin administration if there really are similarities between the two). However, there is also a lot we do not know about oxytocin and its effects on empathy and sociability. Whenever we give a moniker like "the love hormone" to something like a hormone or neurotransmitter we are chagrined to realize some years later that the actions of that substance are far too complex to preferentially attribute one function to it. The same may be true for oxytocin.

Kirkpatrick, M., Lee, R., Wardle, M., Jacob, S., & de Wit, H. (2014). Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing Neuropsychopharmacology, 39 (7), 1654-1663 DOI: 10.1038/npp.2014.12

Sex smells: pheromones in humans

Communicating with pheromones.

By the middle of the 20th century, biologists had become aware of a unique type of communication occurring among insects. The communication involved the secretion of substances that were similar to hormones in some ways, but also very different. While hormones are secreted into the bloodstream to elicit some reaction in the body, these newly identified substances exited the body and were used to elicit a reaction in a conspecific (another organism of the same species). They were given the name pheromones, from the Greek pherin (to transfer) and hormon (to excite).

Since that time, a number of pheromones have been identified in invertebrates and vertebrates alike. For example, when a honeybee hive is disturbed, guard bees produce a pheromone that alerts other bees in the hive; it encourages them to exit the hive and promotes aggressiveness. Beekeepers know all about this signal; they use smoke to calm an angry hive of bees because smoke inhibits receptors in bee antennae that detect the pheromone.

Pheromones that elicit a variety of behaviors have been identified in a number of species. Some pheromones, like those seen in bees, are used to call conspecifics together to attack or defend something, some aid in marking territory, and others leave trails that conspecifics can follow (to a stash of food, for example). Many pheromones also are associated with sex.

A large number of species, from microorganisms on up, release pheromones that play some role in mating. Some species of bacteria use pheromones to tell other bacteria to prepare to receive a transfer of genetic material in a very unromantic form of bacterial "sex" called conjugation. Even mammals, however, communicate with sex pheromones. Males of a number of species investigate the anogenital region of females with their nose, which contains a special pheromone-detector called the vomeronasal organ. Through exposure to pheromones, the male may be able to tell if the female is ovulating and will be receptive to his advances.

Although pheromones have been detected in many species, it has long been debated if they play any role in human communication. One reason that some have argued against an important role for pheromones in humans is that evidence suggests we don't have a functional vomeronasal organ. However, there do seem to be some examples of hidden chemical signaling between people.

Perhaps the best known putative pheromone mechanism in humans is the McClintock effect. The McClintock effect describes menstrual synchrony, which is when the menstrual cycles of women living in proximity to one another begin to synchronize, or start at around the same time. The effect was named after psychologist Martha McClintock, who hypothesized that pheromones were responsible for the synchronization.

The McClintock effect is controversial, and some argue that it isn't a real biological effect much less something caused by pheromones. But a number of other studies have also found indications of possible human pheromonal communication. From these studies, two steroids in particular have emerged as potential pheromones: androstadienone and estratetraenol.

Androstadienone, a metabolite of testosterone, is found in male semen and in secretions from the armpit area. Research has suggested it may promote physiological arousal in women, but not in heterosexual men. Estratetraenol, on the other hand, is an estrogen found in female urine. Estratetraenol has been found to affect autonomic arousal in men. Thus, some studies suggest (though this is still a controversial area) that androstadienone and estratetraenol are pheromones that contain some information detectable by the opposite sex.

A point-light walker used to demonstrate human gait.

A point-light walker used to demonstrate human gait.

A study to be published this month in Current Biology investigated information about gender that might be conveyed by these two putative pheromones. The investigators, Zhou et al., explored the effects of androstadienone and estratetraenol on the attribution of gender to point-light walkers (PLWs) displayed on a screen. PLWs are a collection of dots that represent human movement (see gif to the right). By changing settings, PLWs can adopt a more masculine or more feminine gait.

Zhou et al. exposed heterosexual and homosexual or bisexual men and women to either androstadienone, estratetraenol, or a control solution while viewing PLWs that displayed a spectrum of walking styles that ranged from a feminine gait to a masculine gait, with gender-neutral gaits falling in between the two. The participants, after watching the PLW walk very briefly, had to make a judgment as to whether the figure was masculine or feminine.

The researchers found that exposing heterosexual males to estratetraenol decreased the frequency of "male" responses, but it didn't affect ratings from heterosexual females. Exposing heterosexual females to androstadienone increased the frequency of "male" responses, but this didn't occur in heterosexual males. The results from the homosexual and bisexual groups were a little more ambiguous; estratetraenol didn't have an effect and androstadienone increased "male" responses in homosexual men but only to a gender-neutral PLW (and even then it was barely statistically significant).

Zhou et al. hypothesize that estratetraenol and androstadienone were biasing men and women, respectively, to discern the opposite sex in the movement of the PLWs. Thus, the authors argue that these substances convey information about masculinity and femininity. If true, what this means for everyday male-female interactions is unclear. The concentrations of the steroids that Zhou et al. used were much higher than you'd be exposed to just by standing next to someone on the subway.

So, there is much still to be learned about human pheromones. Even if androstadienone and estratetraenol are capable of communicating gender-specific information, their actual effect on human behavior today may be negligible. Thus, human pheromones may just be vestigial artifacts from our evolutionary history that we don't really have a use for anymore. On the other hand, there may be a complex system of communication occurring between people all the time that we are completely unaware of. And this system of communication could be shaping important decisions in your life, such as who you mate with, without your conscious realization.

Zhou, W., Yang, X., Chen, K., Cai, P., He, S., & Jiang, Y. (2014). Chemosensory Communication of Gender through Two Human Steroids in a Sexually Dimorphic Manner Current Biology DOI: 10.1016/j.cub.2014.03.035

Why Pretzels and Gunshot Wounds Make Us Thirsty

I re-watched one of my all-time favorite movies the other night: Unforgiven. After William Munney (Clint Eastwood) shoots his first victim, the camera zooms in on the fallen cowboy as he begins complaining about how thirsty he is, begging his companions for water. In a moment of compassion, Munney agrees to put down his gun to allow the cowboy’s friends to bring him a canteen.

You’ve probably all seen a similar scene before in another movie, if not this one (hopefully you’ve never seen it in person). Victims of gunshot wounds, or other wounds that involve a drastic loss of blood, are often portrayed as being very thirsty. I’m not sure if the reason why this occurs is common knowledge, but in case it’s not, I thought I would write a quick explanation.

First, a little about water in the body. The cells in our body not only contain water, but also are surrounded by what is called interstitial fluid. This fluid bathes the cells in a “seawater” type solution that contains water, sodium (Na), amino acids, sugars, neurotransmitters, hormones, etc. The cell is normally in an isotonic, or balanced, state in relation to its extracellular environment, meaning water doesn’t generally leave or enter the cell at large rates.

Water is also an important constituent of blood. It is essential for keeping blood volume at a level that allows for proper functioning of the heart. If volume gets too low, the atria of the heart don’t fill completely, and the heart cannot pump properly.

The need to keep the fluid balance in the body at a regular level results in the occurrence of two types of thirst that affect us when that equilibrium is disturbed: osmometric thirst and volumetric thirst. Osmometric thirst occurs when the osmotic balance between the amount of water in the cells and the water outside the cells becomes disturbed. This is what happens when we eat salty pretzels. The Na is absorbed into the blood plasma, which disrupts the osmotic balance between the blood plasma and the interstitial fluid. This draws water out of the interstitial fluid and into the plasma, now upsetting the balance between the cells and the interstitial fluid. The result is water leaving the cells to restore the balance.

The disruption in the interstitial solution is recognized by neurons called osmoreceptors, located in the region of the anterior hypothalamus. They send signals that cause us to drink more water, in order to restore the osmotic balance between the cells and the surrounding fluid. In the case of pretzel eating, if we don’t drink more water, eventually the excess Na is simply excreted by the kidneys.

Now, to the graver situation of a gunshot wound, and the other type of thirst: volumetric. Volumetric refers to the volume of the blood plasma, which is highly dependent upon water content of the body. As mentioned above, maintaining an adequate blood plasma volume is essential to proper functioning of the heart. If it gets too low, the heart can’t pump effectively.

When someone is injured and loses a lot of blood volume (known as hypovolaemia), less blood reaches the kidneys. This causes the kidneys to secrete an enzyme called renin, which enters the blood and catalyzes a hormone called angiotensinogen to convert it into a hormone called angiotensin. One form of angiotensin (angiotensin II) causes the pituitary gland and adrenal cortex to secrete hormones that prompt the kidneys to conserve water as a protective measure. Angiotensin II also affects the subfornical organ (SFO), an organ that lies just outside the blood-brain barrier. Through the SFO angiotensin II stimulates thirst.

There are also receptors in the heart that recognize decreases in blood plasma. Known as atrial baroreceptors, they detect reductions in blood plasma volume and subsequently stimulate thirst by signaling neurons in the medulla. So, when someone is shot and losing a lot of blood, it is because of the decrease in blood plasma volume that brain regions are stimulated through both of the above pathways to stimulate thirst.

Processes that stimulate thirst are really much more complicated than this brief explanation. But, I thought this was enough to give a general idea of why salty foods and gunshot wounds have similar effects on our desire to drink water.

Ghrelin and the Omnipresence of Food

It really is difficult to travel a mile in this country without being exposed to something trying to entice you to eat. Billboards, mini-marts, and restaurants have saturated our environment with visual cues that remind us of the importance of feeding. When at home the television, radio, or internet can be helpful if one has a tendency to forget the necessity of food—especially that of the fried, dripping, or cheesy variety. The advertisers behind all of these reminders are hoping that when you encounter them, your stomach will be coincidentally flooding your hypothalamus with ghrelin.

Ghrelin is a hormone produced by the gut. You may have heard of ghrelin’s counterpart: leptin, a hormone that is integral in letting the brain know you have had enough to eat. This is important, as can be seen by looking at mice with a genetic mutation that results in an inability to produce leptin:

Obese mouse

Ghrelin seems to play the role opposite to leptin’s, it lets you know that the stomach is getting empty and it is time to eat. Ghrelin levels are highest before a meal and lowest afterwards. When ghrelin levels are raised experimentally, people are found to eat more than those administered a placebo.

Ghrelin receptors (and leptin receptors) are especially prevalent in the hypothalamus, but a recent neuroimaging experiment shows that ghrelin may have a much more widespread effect on the brain.

A study published this week in Cell Metabolism describes the use of functional magnetic resonance imaging (fMRI) to investigate ghrelin-related brain activation. Participants were scanned while looking at food and nonfood images. Some of the subjects received an infusion of ghrelin before the fMRI.

The ghrelin injection resulted in an increase in brain activation in areas associated with evaluating the hedonic value of a stimulus—the “reward centers” of the brain, along with a large network that includes visual and memory areas. These are some of the same regions thought to be responsible for drug-seeking and other types of addictive behavior.

Thus, high levels of ghrelin may make our advertisement-laden and food-available environment a dangerous one in which to live. But the hormone may also represent a plausible method for treating obesity. Vaccines that raise an immune response against ghrelin have been shown to be effective in reducing weight gain in rats. Their use with humans is currently being investigated.

Until (and if) they are found to be effective it is best just to try to ignore the constant urgings all around us to “eat, eat, eat”.