Cardio = Move, Cannabinoids = Stop and eat
A hypothesis about the rhythms of foraging
This post was written in a single day as part of the Inkhaven residency. Epistemic status: uncertain about mechanisms; uncertain about the quality of cited RCTs; confident about the sensory clarity effect being real; mostly confident about relationship between sensory clarity and foraging rhythms.
I’ve been lifting regularly since last November, but slacking off with my cardio practice – until this past Saturday, when Sean Herrington taught me to use the rowing machine here at Lighthaven. After our workout I was shocked by the intense taste of the same old flavour of carbonated water I’d been drinking for weeks. I was overwhelmed by the cheesiness of a slice of cheese pizza. I was captivated by sights and smells and music, as though they were new again.
Why did the intensity of my senses increase so much?
What are the subjective effects of cardio?
The acute mental effects of cardio, i.e. a “runner’s high”, classically include:
an increase in baseline hedonic tone (d=0.47, moderate effect; dose-dependent on duration and intensity)
a decrease in the perception of pain (d=0.41-0.59, moderate effect)
a slight decrease in anxiety (Hedge’s g=0.16)
“Sedation” is sometimes also included in this cluster. I put it in quotes because it refers to studies where rodents run on treadmills for a while, then lose interest in continuing to run on treadmills. This does not imply sleepiness, and it would be more accurate to call it “movement satiation”. There’s no study that provides evidence that this occurs in humans. Though (n=1) I become relaxed and unmotivated (but not sleepy) after cardio, but not after strength training.
There is also evidence that the sense of taste is altered during and immediately after cardio. The reported intensity of sweet and umami flavours increases; the preference goes up for sweetness, and down for umami. Cardio burns calories; if certain tastes become more intense or appealing, does that mean we’re more likely to eat food and replenish those calories? Not necessarily: appetite is suppressed for 30-60 minutes after the end of a cardio session. What’s up with that?
Endorphins vs. endocannabinoids
A popular folk theory says that the effects of cardio are caused by the release of endorphins. However, people still get high if you give them naltrexone, a drug that blocks the effects of endorphins – so, they aren’t necessary to cause the high.
A recent meta-analysis asks whether the cause of the high is the release of endocannabinoids (eCBs). In 14 out of 17 human studies that were included in the analysis, blood levels of anandamide (a major eCB) increased after cardio. They mostly failed to correlate this with any of the classical effects except for elevated hedonic tone, but at first glance the eCB hypothesis fits with my n=1 observation that cardio makes food more interesting: THC is well-known to have this effect, and it works by the same mechanism as eCBs.1
The other classical effects of cardio also overlap with the effects of cannabis: euphoria (i.e. an increase in hedonic tone) and a decrease perception of pain. The slight decrease in anxiety seen with cardio is harder to explain, given that THC also causes anxiety. However, this may not be surprising given the outsized effect of recreational THC compared to normal levels of eCBs.
It’s already been shown in mice that the cannabinoid receptor CB1 – the site where THC and eCBs produce their effect – is necessary for the analgesia and anxiolysis of cardio. This is encouraging, though there is no such evidence yet in humans because the current consensus is that it’s unethical to administer CB1 antagonists; they cause crippling depression.
An answer to the puzzle
Back to my original question:
Why did the intensity of my senses increase so much?
Suppose eCBs are a proximal cause of the runner’s high: we know that eCBs are similar to THC, and that THC is mildly psychedelic and increases sensory intensity, among other effects associated with a runner’s high.
But why do eCB levels increase after exercise, leading to these effects? What’s the advantage, the bigger picture? Why would evolution recruit this mechanism?
Consider:
An animal is a bounded agent, and must decide how to spend its attention: exploit familiar environments, or explore unfamiliar ones?
Our ancestors were all foragers of some kind. There’s a natural rhythm to foraging: a bout of energetic movement, followed by a bout of gathering/hunting/feeding/rest, followed by another bout of movement, and so on. Oscillating between explore and exploit.
To our ancestors, cardio generally meant moving through the environment to a different place than they started from. Hamsters run on stationary hamster wheels, but this is not an ancestral setup, any more than a rowing machine. There are some limited examples that might count as stationary cardio, such as hovering (e.g. hummingbirds) or lekking, but they are in addition to foraging, and don’t interfere with our logic.
Cardio changes the internal state of the body, e.g. due to prolonged energy expenditure in the muscles, or motor rhythms in the brain. The body may produce (and observe) signals of these changes, in addition to signals direct from the external environment.
Evolution takes advantage of reliable statistics. If a certain internal state of my body is strongly correlated to a certain external state of the world, even if it is not caused by it, then my body may rely on the internal state as a proxy for the external state.
Here’s a sketch: an animal decides to move to a new location to search for food. It moves for some time, which shifts its metabolism to a “cardio state”. Some internal signal of this state is produced. Its nervous system receives the signal, and it gets ready to switch to a bout of hunting/gathering/feeding. In particular, it becomes more sensitive to stimuli, perhaps in a biased way (e.g. the difference we saw in sweetness vs. umami) so that it’s well-prepared to sample the environment, and to decide when to slow down and start sampling in a smaller area.
Point 5 is necessary to explain my experience after the gym. A rowing machine is stationary. I’m not actually moving through my environment when I use it; I’m not seeing the world move past my eyes. Yet my brain still reacts as though I am exploring, and getting ready to gather and feed and rest. That suggests it’s relying on some internal signal as a proxy.
As for the eCBs, they are the proposed internal proxy signal. They’re synthesized peripherally, increasing their blood levels, from where they cross into the brain and stimulate CB1 receptors to cause behavioural changes. It’s unknown where the synthesis happens, but we at least know that the machinery for eCBs is expressed in muscle and fat. So, blood eCBs might be a low-level signal sent from muscle or fat cells, to the brain. This is a clean fit with our hypothesis since these cell types play a direct role in the physiology of cardio.
Complete hypothesis, and final thoughts
To restate the hypothesis altogether: prolonged muscle activation (i.e. during cardio) induces the release of endocannabinoids from muscle or fat cells into the blood, which enter the brain and drive it towards a high-salience (i.e. “high sensory intensity”) state suitable for gathering/hunting and ultimately resting. This happens even when the cardio is stationary, because ancestrally, cardio was so strongly correlated with not being stationary that our bodies evolved eCBs as an internal signal of when we’re performing bouts of movement through the world, and thus when we should be exploring versus exploiting. Now, the signal has become decoupled, and the eCBs are only a proxy.
Raichlen & Alexander 2017 proposed a similar hypothesis linking cardio and cognition in the context of foraging rhythms, but they did not frame it in terms of reinforcement learning (explore-exploit) or internal signals/proxies.
If true, this hypothesis provides insight into the phenomenology of cannabis. If we treat THC as a larger-than-life version of the signal that prepares our bodies to enter the gathering/feeding/resting stage of foraging, this explains its stereotypical effects: it makes you lazy, shortens your planning horizon, and it makes it easier to enjoy everything.
Appendix I: Some gripes
What if you’re moving through the environment not because you’re intentionally foraging, but because a predator is chasing you? Well, if you escape the predator, you might as well gather/feed/rest when you get the chance to stop. The statistics and the incentives are similar, assuming you have to deal with sneaky predators regardless.
A preliminary RCT suggests that the cardio → eCB connection might only be relevant for species that are adapted for running. This is fine; we’re focusing on humans, and humans are adapted for running.
CB1 receptors are located throughout the brain, and I’m not sure it makes sense to isolate one or more circuits and say they are “responsible” for the downstream effects of eCBs released during cardio.
A lot of the evidence depends on the cardio being of a certain duration and intensity. I have mostly avoided dealing with this in this post. I assume there will be individual differences, and methodological weirdness, but that there is a general foraging-based mechanism that
I’ve not addressed strength training in this post.
It’s more in-place, and not as clearly related to foraging dynamics as cardio is.
There are many more studies of cardio, than there are of strength training.
It has an even stronger painkilling effect than cardio. However, it doesn’t increase plasma eCBs nearly as much as cardio does, which suggests the hypoalgesia might have multiple causes.
I find its mental effects quite different from those of cardio. This aligns with eCBs not being synthesized nearly as much.
Appendix II: Central mechanisms of eCBs, once they are released
Evidence here is limited and I’ve had little time to review it, so this is just a sketch.
CB1 receptors are located throughout the brain, and I’m not sure it makes sense to isolate one or more circuits and say they are “responsible” for the downstream effects of eCBs released during cardio. But there are a couple of circuits worth mentioning:
The dopamine neurons that project from the VTA to NAc synthesize their own eCBs which diffuse backward across the synapse and bind to CB1 receptors on GABA terminals, decreasing the inhibition of the respective dopamine neuron. That is, the neurons are “self-unblocking”. In the literature, this is associated with a positive feedback process of “wanting” things, i.e. motivation to pursue reward.
NAc expresses its own eCBs and CB1 receptors independently of the VTA→NAc pathway. In the literature, this is associated with an unconditional reward state.
The locus coeruleus (LC) is implicated in global control of the explore-exploit tradeoff across the brain. It expresses CB1 receptors, which are generally inhibitory on firing of LC norepinephrine neurons. It’s unclear how this affects high-salience exploratory behaviours, and during exercise there are other signals that drive up LC activity. I suppose there’s some dynamical balancing act here, related to the 30-60 minute post-exercise appetite suppression.
eCBs also modulate the LC input to prefrontal cortex, and this might be part of the cause of the “loose attentional filter” seen in cannabis phenomenology.
n=1, but THC also has a transient hunger-suppressing effect that is similar in duration to the 30-60 minute effect seen after cardio, before the hunger kicks in. Coincidence?