Friday Weird Science: Clomipramine, yawning, and...orgasm!?

Nov 25 2011 Published by under Friday Weird Science, Uncategorized

I was going to start with a brief Storify on this, but Storify is not being kind today. :( Instead we start with one prophetic tweet:

So a) is this true? Can people on clomipramine REALLY experience orgasms while yawning? And b) how the HECK does that work?

I did a little digging, and I've got your answers. Well some of them anyway.

Unusual side effects of clomipramine associated with yawning.
McLean, J. D.; Forsythe, R. G.; Kapkin, I. A.
The Canadian Journal of Psychiatry / La Revue canadienne de psychiatrie, Vol 28(7), Nov 1983, 569-570.

And who knows, if you get bored reading this and you're on Clomipramine, fun times could be headed your way!

(Yawn with your dirty self! Source)

So first up, here's clomipramine:


Clomipramine is an antidepressant known as a tricyclic. The purpose of these drugs is to inhibit the reuptake of neurotransmitters in your brain, specifically norepinephrine and serotonin. The higher levels of these chemicals in your brain are thought, over time, to modify your brain (possibly by the formation of new brain cells, and possibly through modification of cellular connections, and heck, possibly both) and relieve some of the symptoms of depression. While this drug is not the most popular anymore for depression (the side effects are rough, and people find SSRI drugs easier to take), it is still prescribed for some cases of depression, and for other disorders like obsessive-compulsive disorder.

Part of the reason the side effects for this drug (including central nervous system effects like headaches and dizziness, heart effects like arrythmias, hypotension, other effects like dry mouth, constipation, allergic reactions, I could go on...) are so extensive is because clomipramine, one of an older class of antidepressant drugs, is kind of dirty. It's got the effects on serotonin and norepinephrine transport, of course, but it ALSO hits other receptors, including piles of serotonin receptors, dopamine receptors, and adrenergic receptors. And it looks like the adrenergic receptors may be to blame her for this unusual side effect.

But first, CAN you have an orgasm while yawning when you're on clomipramine? YES. In fact, though several patients found it disconcerting, one enjoyed it so much she wanted to continue the medication for as long as allowed. I guess it's a good way to pass time during boring meetings! It is estimated right now that about 5% of patients will have an effect like this (note that not ALL of them are orgasms, some of them are feelings of fatigue and weakness following yawning, or just intense sexual stimulation not resulting in orgasm).

But the question is, how does this work? After all, most drugs, INCLUDING CLOMIPRAMINE, are known to have a side effect of DECREASED libido and ability to orgasm in many patients. The serotonin side effects are responsible for this effect of clomipramine, as well as most other antidepressants that rely on serotonin.

But we've got to remember that clomipramine is dirty (and if it causes orgasms, I guess that makes it ESPECIALLY dirty). It's got affinity for lots of other receptors. And not all of these receptors are only in the brain. In fact, most of them exist throughout the body and contribute to the side effect profile of the drug. For example, the adrenergic receptors in the heart and vasculature contribute the problems with hypotension and other cardiac side effects.

But these specific adrenergic receptors are your genitalia. And this may be where clomipramine is having its unexpected, though pleasureable, side effect. The adrenergic receptor types alpha 1 and alpha 2 are hit by clomipramine, and are heavily expressed in the vasculature, which includes your penis (or vagina). Stimulating receptors in these areas can lead to smooth muscle contraction and vasoconstriction associated with orgasm and ejaculation. Adrenergic receptors are also stimualted by norepinephrine and its metabolites, and so this increase in norepinephrine due to the drug, PLUS the adrenergic stimulation produced by the drug itself, may be enough to create the orgasm effect.

But one question remains: how is this triggered by YAWNING. Well...I don't know. But I have a guess. One of the hypotheses behind WHY we yawn is that, when we are tired, and things slow down, we may not breathe as heavily, and may have higher levels of carbon dioxide build up in the blood. When we need to exhale these and exchange for oxygen, we may yawn (this is just ONE of the hypotheses behind why we yawn, though, and none of them are proven). So my idea is that the intake of oxygen produced by yawning may stimulate neurotransmitters in the brain for increased release, and increase vasodilation in the body. This combination may be potent enough in some clomipramine using individuals to push them over the edge. Keep in mind though, this is JUST my hypothesis and I have no proof one way or another. But I think it's worth studying who has this effect, who doesn't, and why. I think it's time to yawn, and orgasm, for SCIENCE!!!

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