If you’re wondering how pre workout stimulants increase energy and focus, you want to read this article.

I love pre workout.

There’s something irresistible about the increased energy, tunnel vision focus, and heightened mood that pre workout supplements provide. It’s borderline addictive, I swear.

Pre workout supplements exert their glorious effects through a combustible cocktail of stimulants, nootropics, and ergogenics, that culminate in an experience rivaled by few things and, on top of that, they can actually help you to perform better in your workouts too.

In other words, pre workouts are awesome.

And if that’s not enough to entice you, pre workouts also taste pretty damn good, too, or they should in this day and age.

Yet, as commonplace as pre workouts are, few consumers really understand how they increase energy, focus, and performance.

That’s why we’re here.

In today’s article, we’re going to give a “primer” of sorts into the many stimulants you’re likely to encounter the next time you purchase your tub of pre workout.

And with that, let’s begin our dive into the best pre workout stimulants!

Pre Workout Stimulants

Caffeine

Let’s get something clear right off the bat, the reason so many people love pre workout supplements is because of caffeine. It’s the rock-solid foundation upon which 99.9% of all great pre workouts are built (the other 0.1% is for those rare exceptional stimulant free pre workouts).

Caffeine can be found far and wide these days. It’s not only found in coffee, tea, and chocolate, but supplement companies and food manufacturers have now put it in candy bars, peanut butter, and whey protein shakes too!

Most of you know that caffeine is a godsend when you’re struggling to shake off the cobwebs and keep your eyes open. But, how does it give that unmistakable boost in energy and focus

First and foremost, caffeine acts as an adenosine receptor antagonist, meaning that caffeine more or less “blocks” the slot on receptors where adenosine could dock.

Why is this important?

Adenosine is purine nucleoside that binds or “docks” to adenosine receptors in the brain. In doing so, adenosine causes a reduction in nerve cell activity, resulting in feelings of fatigue and tiredness.

Since caffeine has the extremely rare ability to easily cross the blood-brain barrier (BBB), it can “elbow out” adenosine, leading to greater energy and alertness.

Now, the second reason caffeine is awesome has to do with its effects on dopamine levels. You see, a nice “side effect” of adenosine receptor antagonism is that your dopamine system works more efficiently.

In case you weren’t aware, dopamine is the neurotransmitters that has a massive impact on motivation, decision-making, and mood. It also affects movement and memory too!

Research notes that caffeine causes a significant increase in dopamine production, and with greater dopamine levels, you get the enhanced motivation, determination and focus to crush your workout.[1]

In addition to increased energy and motivation, caffeine also exerts some unique effects on exercise performance too. Research has shown it up-regulates fatty acid oxidation (a.k.a. “fat burning”), which may spare glycogen stores for the more intense work in your training. It also helps reduces neuromuscular fatigue, improves stamina, and at certain doses (400-600mg) boosts strength.[2,3]

When you take all of those benefits into account, it’s no wonder why caffeine is the pre workout stimulant.

Effective dose: 3-6mg/kg of bodyweight

Synephrine

When running through the list of the best pre workout stimulants available, you won’t get very far without running into our next stimulant in synephrine.  

Naturally occurring in Citrus Aurantium (bitter orange), synephrine (or p-synephrine) is structurally similar to another well-known stimulant in ephedrine. However, ephedrine is a derivative of phenylpropanolamine and does NOT contain a para-substituted hydroxy group, like synephrine does.

Why is this important?

The addition of the parahydroxygroup on the p-synephrine molecule, as well as the lack of the methyl group on the side chain affect the stereochemistry and, as a result, the receptor binding characteristics and the pharmacokinetic actions, including the ability of p-synephrine to cross the blood-brain barrier.

This is all in addition to the fact that synephrine is considerably safer for human consumption, and actually legal to use in pre workout supplements, too! (More on that in a moment)

The differences between synephrine and ephedrine don’t end there either. They also differ in regards to which receptors they bind to in the body.

Ephedrine and m-synephrine (a relative of the p-synephrine) have a greater affinity for alpha, beta-1, and beta-2 receptors, which can lead to increased heart rate and/or blood pressure.

Synephrine (or p-synephrine) exhibits little or no binding to α‐1, α‐2, β‐1, and β‐2 adrenergic receptors, meaning that it does not come with the adverse cardiovascular effects (increase in heart rate and blood pressure) that other phenylethylamine and phenylpropylamine derivatives (i.e. ephedrine) do.[4,7]

Benefits of Synephrine

As a beta receptor agonist, synephrine triggers lipolysis, which liberates stored fatty acids from adipose tissue, freeing them up to be oxidized (“burned”) for energy. Greater availability of free acids in the bloodstream during training may help preserve glycogen reserves, saving them for the really intense work at the end of your training session when you’re trying to do those hardcore “finishers”.

This may also be the reason that when synephrine is taken prior to exercise it has been shown to enhance performance and reduce the onset of fatigue.[6]

Several other studies have also noted that synephrine leads to greater thermogenesis, glucose and cholesterol metabolism. It may also reduce food intake. Due to these effects, synephrine is quite frequently found in thermogenic supplements and fat burners to help individuals lose weight rapidly.

One final reason to embrace synephrine, is that among the stimulants commonly found in pre workout supplements, synephrine is one of the few that actually had a fair amount of research conducted in humans demonstrating its effectiveness on performance and fat loss.

Effective Dose: 26-100mg

Hordenine

Another popular stimulant found increasingly in pre workout supplements these days is Hordenine. It’s naturally occurring in a variety of plants, namely bitter orange and barely.

Similar to synephrine, hordenine functions as a central nervous system stimulant and beta adrenergic receptor agonist, meaning it leads to an increase in adrenaline and noradrenaline. This has the added effects of triggering lipolysis, which enhances fatty acid availability.

In addition to its pro-fat burning benefits, where hordenine really appeals to supplement manufacturers is actions as an MAO inhibitor.[7]

MAO (Monoamine oxidase) is an enzyme that degrades monoamines, such as dopamine, adrenaline (epinephrine), and noradrenaline (norepinephrine).

By inhibiting MAO, hordenine “protects” these powerful brain chemicals from breakdown, which helps their energy and focus boosting effects to last longer during training.

Hordenine also functions as a noradrenaline reuptake inhibitor which prevents noradrenaline (norepinephrine) from being reabsorbed.[8,9] This again increases the amount of time you feel amped up and ready to unleash seven kinds of hell on the iron.

To date, no studies have been performed assessing exercise performance using hordenine in isolation. There have been a handful of studies involving products which include hordenine showing benefit, but whether those benefits are solely attributable to hordenine isn’t certain.[10]

Dosage: There is a distinct lack of human research with hordenine, as such, there is no effective or “ideal” dose noted in the literature. However, based upon anecdotal feedback the target dose to use as well as the dose most commonly found in pre workouts is 50mg.

References

1. https://www.drugbank.ca/drugs/DB00201#pharmacology
2. Goods PSR, Landers G, Fulton S. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers. Journal of Sports Science & Medicine. 2017;16(1):93-98.
3. Hodgson AB, Randell RK, Jeukendrup AE. The Metabolic and Performance Effects of Caffeine Compared to Coffee during Endurance Exercise. Earnest CP, ed. PLoS ONE. 2013;8(4):e59561. doi:10.1371/journal.pone.0059561.
4. Sidney J. Stohs, Harry G. Preuss, and Mohd Shara, “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects,” Oxidative Medicine and Cellular Longevity, vol. 2011, Article ID 482973, 9 pages, 2011. doi:10.1155/2011/482973
5. Stohs SJ, Preuss HG, Shara M. A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine. Int J Med Sci 2012; 9(7):527-538. doi:10.7150/ijms.4446.
6. Ratamess NA, Bush JA, Kang J, et al. The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance. Journal of the International Society of Sports Nutrition. 2015;12:35. doi:10.1186/s12970-015-0096-5.
7. Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine. Phytotherapy Research. 2017;31(10):1463-1474. doi:10.1002/ptr.5879.
8. Frank M, et al; Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse; Equine Vet J. (1990)
9. Barwell C.; School of Pharmacy; “Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat;” 1989
10. Hoffman JR, Kang J, Ratamess NA, Hoffman MW, Tranchina CP, Faigenbaum AD. Examination of a pre-exercise, high energy supplement on exercise performance. Journal of the International Society of Sports Nutrition. 2009;6:2. doi:10.1186/1550-2783-6-2.