Why Do Magic Mushrooms Cause “The Yawns”?

The serotonin 5-HT2C receptor may play a key role.

August 16, 2019 -

Excessive yawning is a side effect many people experience when they ingest psilocybin mushrooms (aka magic mushrooms). For some, it’s just annoying. For others, it’s a real distraction from their experience. In contrast, some people anticipate yawning and look forward to it because it lets them know the compounds in the mushrooms are coursing through their veins. But, what is it about magic mushrooms that cause yawning in some people?

What is a Yawn and Why Do People Do It?

Before delving into yawning and magic mushrooms, it’s best to understand what yawning is and why people yawn at all. Various research papers define yawning something like this; a long inspiration and rapid expiration that is accompanied by a “coordinated motor pattern” of opening of the jaw, closing the eyes and contracting the muscles in the face. Yawns sometimes include stretching of the neck arms and trunk.

The exact location of a yawning center (also called the yawing network or yawning zone) in the human brain has not been experimentally proven. Current theories suggest that the areas involved include parts of the cortex, limbic system, hypothalamus, and brain stem.1 Scientists have learned from malformations and lesion studies that the core of the yawning center is located in the brain stem. Contagious yawning may arise from external pattern recognition in the neocortex, limbic system, and thalamus. Interestingly, several neurotransmitters and peptides have control over yawning. They include acetylcholine, dopamine, oxytocin, nitric oxide, excitatory amino acids, opioid peptides, and serotonin.1,2

Over the years, scientists have developed four main hypotheses (in addition to contagious yawning, see below) to explain why people yawn.1 They are the respiratory hypothesis, communication hypothesis, arousal hypothesis, and the brain-cooling hypothesis. More than one of these reasons may be at work in a given situation, and there are likely more yet undiscovered.

The respiratory hypothesis was first posed by the Dutch author Johannes de Gorter in 1725.3 He attributed the need for yawning “to a need for faster blood circulation and to cerebral anemia.” Other writers and scientists from that time until today have speculated that yawning was due at least in part to anemia and poor circulation in the brain, or as one early writing put it, “bad air in the lungs.” 1 Several modern-day studies support the idea that yawning is caused by a low oxygen level in the brain (cerebral hypoxemia) or excessive carbon dioxide in the blood (hypercapnia). Krestel et al. reviews and discusses these studies in a 2018 paper in Progress in Neurobiology.

The communication hypothesis is basically what it says. Yawning is a means of communicating tiredness and boredom between humans which synchronizes group behavior.4 It is interesting to note that people who view uninteresting and repetitive stimuli have been shown to yawn more frequently.5

According to experts, the arousal hypothesis and the brain-cooling hypothesis need more research to determine their validity.1 The arousal hypothesis contends that yawning is a biological response that helps regulate the waking state and activity level. Currently, the brain-cooling hypothesis of yawning is thought to be more valid in cats and dogs who do not exchange heat as effectively as humans via their body surface.

And, yes, scientific studies have shown that not only is yawning is contagious, but some people are more susceptible than others to contagious yawning. How it works in the brain is not completely understood, though. One study using transcranial magnetic stimulation (TMS) found that trying to resist yawning increases the urge to yawn. However, it doesn’t change a person’s propensity for contagious yawning.6 From these behaviors and the TMS data, the authors hypothesized that cortical excitability and physiological inhibition in the primary motor cortex may be the areas of the brain that control a person’s propensity for contagious yawning.

Is Yawning a Good or Bad Side Effect?

The term “side effect” carries with it connotations of unpleasantness and potential negative consequences. Although some magic mushroom users find yawning annoying or distracting or both, others anticipate and welcome it as part of the whole psychedelic experience. Here are some examples of comments from sites like Bluelight, Erowid, Shroomery, and Reddit.

“I find it’s really therapeutic. The yawning, crying, sweating etc… on shrooms. Its feels like all the pressure and energy is being released.”

“Some trips you get normal yawns, some you get the crazy long psychedelic yawns, I personally love that feeling intense yawns are the best.”

“Yeah I have yawns that like stretch my jaw when I’m tripping balls, weird feeling, doesn’t feel like a normal yawn. One time I thought I got possessed by mushrooms because of this.”

Interestingly, information from experience reports and online discussion boards indicates that yawning often occurs on the “come up.” This observation could be important for understanding the pharmacology of magic mushroom components. Here are some examples:

“That’s [yawning is] always the sign for me that things are setting into waking dreamworld.”

“I have noticed a pattern that [yawning] happens more often than not when I ingest shrooms, where an exponential increase in the amount of yawns I experience occurs as I approach the peak of the trip. The closer I get to the peak, the more im yawning, and the less I am able to control it.”

“I’m kinda used to it, but I know when the come-up is about to start because I get the yawns.”

“Yeah, on the come-up and the first hour or so it’s yawn city.”

“I yawn a lot during the come up of tryptamines (especially psilocybin and 4-aco-mipt), but once through the come up, the yawns stop.”

Magic Mushrooms and Excessive Yawning

There are no scientific studies directly examining why magic mushrooms or the compounds in them cause some people to yawn excessively. However, revealing some hints may be possible by extrapolating what is known about the physiology of yawing to the compounds found in magic mushrooms, particularly psilocybin analogs like serotonin and other derivatives, and how well they bind to serotonin receptors.

The involvement of serotonin in causing yawning was first proposed in 1979 in studies using rats.7 Since that time, additional research has found that serotonin binding to 5-HT2C receptors is likely the conduit that results in yawing in humans.8 The binding of agonist compounds to 5-HT2C has been found to increase yawning in a dose-dependent manner, and the binding of antagonists to the receptor reduces yawning.

The next piece of information needed for this analysis is data indicating if and how well compounds in magic mushrooms bind to the 5-HT2C receptor. The PDSP Ki database maintained by the US National Institute of Mental Health contains binding affinity data for hundreds of compounds and molecular targets. In particular, the binding inhibition constant, Ki indicates how strongly a compound binds to a receptor. Lower Ki values indicate less binding inhibition and higher binding affinity for a receptor.

For example, the Ki for serotonin on the human 5-HT2C receptor is anywhere from 2.0 – 56.0 nM depending on the test conditions. Psilocybin’s Ki value at 5-HT2C is >10,000 nM. This makes sense based on what is known about psilocybin being a prodrug of psilocin, meaning psilocybin should have a higher Ki and hence a less affinity for the receptor. And then there’s psilocin. It’s Ki at 5-HT2C is around 97.0 nM, meaning it has a greater affinity for the receptor than psilocybin, which also makes sense. But back to the point of yawning, these data indicate that psilocin could cause yawning even though its affinity for the 5-HT2C receptor is less than that of serotonin.

Scientists know that different compounds can have different effects when binding to the same receptors. For example, the neurotransmitter serotonin elicits feelings of well-being and happiness when it binds to the 5-HT2A receptor. Serotonin also modulates learning, memory, and a myriad of physiological processes.9 In contrast, the magic mushroom agonist compound psilocin (the active dephosphorylated version of psilocybin) causes the psychedelic effect when it binds to 5-HT2A.10 However, it is conceivable that the binding of magic mushroom agonist compounds to serotonin receptors could elicit a response similar to serotonin, e.g., causing yawning by binding to 5-HT2C. Another intriguing fact to ponder in this context is that all known psychedelic compounds are agonists at both the 5-HT2A and 5-HT2C receptors.11 Searching through discussion boards and experience reports reveals that yawning is also a side effect reported by people using LSD and 4-AcO-DMT.

It’s important to note that there are scattered reports on discussion boards of people yawning after ingesting a species of magic mushrooms but not the next time. This could be due to the chemical variability between batches of mushrooms that is brought on by soil conditions, climate, and other variables. It could also be related to the physical health and metabolism of the user.

The Bigger Picture – What Does This Mean?

The side effects of magic mushrooms such as yawning pose issues when using whole extracts from the plant flesh or the mushrooms themselves for therapeutic use. Granted, yawning is not a serious side effect and may be more of an annoyance for most people. However, any side effect could be better understood and possibly controlled by studying the individual compounds in magic mushrooms along with the entourage effect between the components.  It’s also important to know from a physiological standpoint why magic mushrooms cause yawning and some people. What it comes down to is formulations containing precise amounts of certain compounds may prevent many side effects and may also result in more effective therapies and user experiences.

    References
  1. Krestel H, Bassetti CL, Walusinski O. Yawning—Its anatomy, chemistry, role, and pathological considerations. Progress in Neurobiology. 2018;161:61-78. doi:10.1016/j.pneurobio.2017.11.003
  2. Argiolas A, Melis MR. The neuropharmacology of yawning. European Journal of Pharmacology. 1998;343(1):1-16. doi:10.1016/S0014-2999(97)01538-0
  3. de Gorter J. De Perspiratione Insensibili Sanctoriana-Batava: Tractatus, Experimentis Propriis in Hollandia. Sumptibus Auctoris & Prostant apud Janssonios Vander, Lugduni Batavorum; 1725.
  4. Daquin G, Micallef J, Blin O. Yawning. Sleep Medicine Reviews. 2001;5(4):299-312. doi:10.1053/smrv.2001.0175
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  7. Urba-Holmgren R, Holmgren B, Rodriguez R, Gonzalez RM. Serotonergic modulation of Yawning. Pharmacology Biochemistry and Behavior. 1979;11(3):371-372. doi:10.1016/0091-3057(79)90153-9
  8. Collins GT, Eguibar JR. Neurophamacology of Yawning. In: Walusinski O, ed. Frontiers of Neurology and Neuroscience. Vol 28. Basel: KARGER; 2010:90-106. doi:10.1159/000307085
  9. Nichols DE. Structure–activity relationships of serotonin 5-HT2A agonists. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 2012;1(5):559-579. doi:10.1002/wmts.42
  10. Madsen MK, Fisher PM, Burmester D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. January 2019:1. doi:10.1038/s41386-019-0324-9
  11. Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. doi:10.1124/pr.115.011478