Pharmaceutical Phenotype Enhancement - Part IV by Chris Clancey

Assuming you respond to Pergolide in a manner similar to how I do (and, luckily, the majority of users have been, to the point where I don’t feel like I’m the outlier giving all the advice…), your cycle will probably progress something like this:

Week 1 – You get pill-poppin’ as per my instructions and start easing into your initial, starting dosage. Lethargy, lightheadedness and somnolence will likely strike you throughout the morning and into the early afternoon. In addition, you will also probably notice a decrease in appetite until about 2-3 p.m., which is about the point where you’ll once again have to start exercising some dietary willpower to keep your appetite on the straight and narrow. You may also feel just a little spacey, for whatever that vague characterization might be worth. Two important things to keep in mind are:

1) Make sure you eat a breakfast with at least 10 grams of carbohydrates (CHO) within 60-75 minutes of taking Pergolide. Otherwise, with the insulin-sensitizing actions of the drug, you will likely experience mild hypoglycemia within an hour or two of taking your dose (and remember, the higher your dosage, the more critical it is to keep blood-glucose levels elevated at least slightly while the drug peaks in your system). I don’t recommend trying to use Pergolide in periods where you’re shooting to enter ketosis or there’s a risk you might become hypoglycemic.Pergolide is significantly more potent than Bromocriptine; I consider having teeth pulled to be a more enjoyable experience than any of my repeated efforts to low or no-carb it on Pergolide. Less than 60 g of CHO in a day proved to be essentially intolerable, as did my two attempts to complete high-volume depletion-workouts in the gym. I found I could suffer through a CHO intake in the range of 60 to about 85 g/day, but it was not fun. It’s clear to me that a minimalist dietary glucose intake on Pergolide will aggravate just about every single one of its side-effects while leaving you generally feeling shitty all the live-long day. See what you can get away with if you dare—as there likely is some individual variance—but the drug’s effects are strong enough that I don’t consider this strategy to be prudent or necessary.2) You should avoid any and all other dopaminergics (at least initially). Don’t smoke and don’t chew nicotine gum (I had a very bad bathroom vomiting episode at work that was prompted by Pergolide and a poorly-chosen 4 mg piece of Nicorette that I tried to chew at the same time). It’s also probably best if you avoid taking anything like Deprenyl or Wellbutrin (Buproprion) until—AT THE VERY LEAST—you have spent a full week on Pergolide and can at least begin to get a sense of your tolerance.

Author’s note: those using Avant’s H.E.A.T. Stack along with Pergolide might also want to be wary. While I have not myself had any problems combining H.E.A.T. Stack with Bromocriptine, there is the possibility of a dopamine related over-stimulatory contraindication in individuals who are new to or just overly sensitive to dopaminergics, since two of its ingredients, the amines tyramine and hordenine, both act as MAO-inhibitors [inhibiting A and B, respectively], which reduces DA catabolism, while the former can also convert directly to DA in the brain via the cytochrome isoform CYP2D6 (1,2).

With this in mind, it’s wise to give yourself at least a week of just coping with the sides from Pergolide alone, without having to worry about other drugs and supplements that might be further modifying the ‘DA-picture’ in your brain. Then, as with any act(s) of crazy poly-pharmacological dabbling, wane yourself back onto your laundry list of ill-gotten help-me-diet, numb the pain, and/or ‘ahhhh-that’s-the-shizzy’ drugs, and proceed as [ab] normal.

Week 2 – Most of the initial side effects will begin to diminish; however, all of the original guidelines/advice still apply. Really, Pergolide is a drug that you’re just going to have to feel out in a lot of ways. Now, if you truly feel like the side effects have dissipated significantly, you can attempt to bump up your dose by 125-250 mcg. Obviously, once you do so, everything you experienced initially will of course return.

Raising your dosage any quicker is—of course—risky, but also doable if you find yourself to be one of the rare few who can ramp up Pergolide and still feel like a million bucks (there actually is at least one individual out there for who this is true, although I shudder to think of what the actual physiological implications for this phenomena might be…). Just don’t be stupid. Patience and prudence Daniel-san—you can always just tell your peeps you were waiting until you were sure the beach would be jumpin’ it off or for the stars to align themselves properly to coincide with the Tao of your summer groove-chi.

Week 3 and Onward – By this point, you should have a pretty good sense of whether or not Pergolide is right for you (in other words, whether or not you can stand to be on it). From this point, continue to slowly titrate the drug up at your own pace. Once you start getting above 1.5-2 mg/day, you should begin to start to see a noticeable improvement in nutrient partitioning & insulin sensitivity, as well as some small aesthetic improvements in vascularity as a result of the hemodialation prompted by the drug.

Still, you’re basically going to be running with the side effects from now on. The side effects never really go away once you get over 1 mg– you more just sort of adjust (or perhaps just become so used to them you find them to be less and less of a hassle to put up with) to the point where the somnolence and lethargy become less pronounced and/or noticeable. Also, once you hit this dosage level, you will start to find eating feels like a chore, and a mere bowl of Frosted Flakes will start to leave even the most ravenous endomorphs feeling pretty damn sated, given their NPY levels have been completely normalized concomitant with such a high degree of D1 stimulation.

Just to illustrate: I found a ~ 300 calorie breakfast of sugar cereal, skim milk, and two fish oil caps would leave me feeling full and satisfied for a good four to five hours once I got above 3 mg/day. This general aversion to eating tended to last—at least for me—until about 8 or 9 p.m., after which, finally, my hunger would begin to manifest itself again. At/After this point, there is really little more to do than go with it. Get in that 3-4 mg/day range for a dosage and stay there for as long as you can tolerate/afford it (both are easier said than done).

Once you wish to cycle off of Pergolide, titrate back down by 500-250 mcg/week until you’ve reached a maintenance dose of 500 mcg-1 mg, at which point you can a.) Switch to Bromo, b.) Stay on Pergolide and run this low dose continuously, or c.) Make an effort to keep tapering down until you are off it completely.

“Champagne Supernovas” — A Cautionary Tale

I remember the first swell being subtle but little more than a slight, outward ripple of light across a building I had been approaching from across the quad on campus. Dehydration, I’d thought; I did a few too many sprints and hadn’t been paying attention to my fluid intake. I’d get some water in the dining hall, rest for a few minutes, and I’d be fine, I thought– maybe even fine enough to go back to the gym later that evening for more sprints. But I also knew that I had made the jump from 3.5 mg of Pergolide all the way up to four full milligrams that morning. As always, I’d kept desiring results that were better and better, and had found myself simply too impatient to give my titration scheme another week before taking the “max-out” jump-up in dosage I’d already waited months to reach.

And, as I’d continued my walk towards the student union, I felt, distinctly, that things were different– a very wrong different. Nothing, I remember thinking, felt right to me at that moment. I would take a step, and the sky would seem to pulse at me. Another, and I’d begin to feel the pavement below my feet throbbing upwards, outwards; soon things were so bad I had no choice but to backtrack a few steps so that I could grip a bench I’d just passed a few moments earlier in order to balance myself and stay on my feet. I’d tried to shake the sensations from my head, only to find that the movement itself had seemed to cause my vision to twist in terrifying swirls of color, light and motion.

In those few, final moments I was never even able to fully register or feel any true sense of panic– it was all just too fast, and too overwhelming. Before long, it felt like the entire world was churning over and around me. I want to say I’d yelled something at that point– a call for aid perhaps? But, to be honest, I’m not quite certain I ever actually emitted any sort of audible sound there next to that bench, before I simply lost consciousness, as the colors closed in around me and blocked out the buildings, the grass, the trees, and my afternoon…

Plain and simple, I present the above episode to all of you as my own little reminder that Pergolide is a serious drug that should be used by serious individuals. Pergolide, when misused, can produce some seriously trippy stuff. Between 4 and 4.5 mgs (I think I did the latter for only a day or two), I remember experiencing several other, smaller and less pronounced “Pergolide trips,” but none as bad as the one above, when I’d foolishly decided to jump up 500 mcg in a single day from a 3.5 mg baseline dose.

Generally, if you’ve tried Pergolide at any dosage (even miniscule, low ones), you’ve pretty much experienced Pergolide; there’s not really that much new to undergo as you increase intake in terms of side effects—they basically just a.) Keep coming back and b.) Have a tendency to become slightly harsher if you get too hasty with your dosages. The one exception is the Pergolide trip, a side-effect that I can’t really liken to anything else I’ve experienced but can best describe as a brief period of genuine sensory distortion—especially in regards to how your mind seems to process sights and sounds.

That one trip was far and away the most severe, and this only happened once to me in my entire time on the drug. Nonetheless, I do remember three other instances (which usually occurred in mid-to-later afternoon, well after/apart from the typical morning lethargy phase) where I had similar—albeit generally milder—hallucinatory episodes. None were serious; I was never hospitalized or had to get any form of treatment, but they were quite unsettling, and went a long way towards opening my eyes to the extensive activity Pergolide can have on perception and cognitive function when misused.

Pergolide Post Cycle Therapy (PCT) Perhaps?

This is a subject that has been getting kicked around the forums recently, so I figured I might as well reiterate and summarize my position regarding where you’re going to stand when it’s all said and done. One way I like to conceptualize Pergolide’s (or Bromocriptine’s) role in dieting is the classic, Loki-conceived “Spotter-in-the-Gym/Waffle House” metaphor™, which goes a lil’ (or actually, a lotta) sumthin’ like this: you’re in the gym, kicking out reps, you’re nearing the end of your workout—you’re reaching the point where you body just can’t sustain the effort and expenditure required of it to keep putting the weights up. So you call over to Bo, who does Tri-extensions with small children, and have him come over to help you keep knocking out sets past your sticking point.

Here, we’re talking about physically going to failure. With a DA agonist, you’re basically allowing your body to exceed dieting ‘failure’ by allow you to continue to ‘pile on the plates’ beyond what you’d normally be physiologically capable of without immediately incurring the stress-response that would normally coincide with such activity. So, to quickly wrap up the first layer of this seemingly-aberrant little analogy, Pergolide is not acting internally to enhance how your body operates relative to its set-point in any way, just like how having a spotter on hand doesn’t actually augment your own strength and muscular endurance in the gym. Instead, both are acting like crutches that are propping up your system to maintain homeostatic signaling levels and energy expenditure, respectively.

Take Pergolide, and it will keep telling your body that basal dopamine is in the normal, non-starvation range (and, when you take it at higher doses, that you are even OVER-feeding) rather than the truth: basal DA levels are in fact abnormally low, because you ARE in fact starving, or at least, you’ve reached a point where your body finds the present state of the energy deficit you’ve initiated a tad unsettling for its tastes, and it wants to kick in the survival response and conserve those last few ‘situation-critical’ fuel-stores (re: your stubborn adipose tissue).

Of course you’re not actually starving—there’s probably like a Waffle House or something right at the end of the block where you could get enough Belgian flapjacks to meet your body’s glucose requirements for the next calendar year. But you can’t just tell your body it’s there, your body has to sense the fed-state catecholamine response. This is why, once you hop on enough Pergolide, you could be sprinting all the live-long day back and forth in the damn parking lot while eating basically nothing; your body will think the Waffle House just gave you a platter and a free pass into the kitchen….

The issue though remains, that the longer you trick the system and the farther you exceed your physiological set-point, the more F.U.B.A.R. things are going to be when the amount of drug induced DA-signaling starts to decrease again. A DA-signaling decrease happens when a) Your receptors become desensitized to the drug, which isn’t that much of an issue (please refer back to Part II for further elaboration on this point) and/or b.) When you start to withdraw the drug by titrating your dosage back down. Remember, you only need about 500 mcg-1mg of Pergolide to elicit enough DA-stimulation to serve as a maintenance dose and signal energy homeostasis. This is not a lipolytic dose, but it will keep your body’s sex hormone (especially the critical anabolic/anti-catabolic hormone testosterone, and, consequently, your libido) and thyroid hormone levels in the mid-normal range, while suppressing the cortisol overproduction and extreme hunger cravings normally associated with long term dieting.

Now say you cut out that maintenance signaling, forcing your body to rely only on the receptor relaying coming from the natural leptin/DA relationship discussed in Segment I, and do so after you’ve gotten yourself 3 percentage points of bodyfat leaner than your body feels comfortable with. What will likely follow is an immediate spike or shift in levels of NPY, Corticotropin-releasing factor, and various other stress response hormones whose release is mediated by the hypothalamus. Thyroid and sex hormone levels will also dip simultaneously, producing a markedly more anti-anabolic & lipogenesis-promoting metabolic and hormonal milieu.

It stands then that a sensible course of action for cycling off of a DA-agonist like Pergolide is to gradually taper the dosage all the way down to the low hundred-microgram levels and plateau there for a short period of time before going off completely. Also, non-DA mediated or only DA-potentiating supplements like Ephedrine & Caffeine, 7-OXO-Dehydroepiandrosterone, and/or LeptiGen would also be good adjuncts to curb appetite and promote effective nutrient utilization during the initial adjustment phase.

Nonetheless, the simple fact of the matter is that you’ll likely have to closely monitor your energy intake relative to your level(s) of activity/expenditure for as long as you wish to retain the leanness you worked so hard to achieve. If you wanna’ stay cut, calories are most likely going to have to stay cut, and you might be doing yourself a favor if you were to relocate a few blocks farther away from that delectable, ever-tempting Waffle House and maybe choose to settle in the midst of an organic Spinach co-op instead.

Still, Pergolide usage will not damage or retard your body’s capacity to recognize basal dopamine or relay its effects. Remain calm; Pergolide is not going to leave you synaptically scarred for life. This is because (for the last time) Pergolide’s pharmacokinetics do NOT produce an increase in post-synaptic levels of DA, do NOT exert an effect on neurotransmitter flow, will NOT cause mutations in the D1 or D2 receptor genes, and will NOT cause functional upregulation of nAChr’s in the same manner as a chemical like nicotine will (3,4,5).

Meanwhile, evidence that DA-agonists like Pergolide actually promote receptor down-regulation or desensitization (by eliciting a quantitative deproliferation of DA-responsive receptor cells) remains sparse, often contradictory, and generally inconclusive. I personally do not view it as likely/significant enough a phenomenon to really consider it a troubling consequence to Pergolide usage that makes it an unsuitable drug for body (re)composition purposes (6,7,8).

Cogito (Thy) Ergot, Son (Take Two)

And with that, it’s time to close the curtains on my treatment of Pergolide use in practice; the rest I leave to you, the ever resourceful reader. In the months that follow, I expect we’ll be seeing a lot more feedback on Pergolide as more and more individuals begin to experiment with it to further their body composition goals. Until this new data and information emerges, may your conscience (and this article series) be your guide with Pergolide. Still, I’ll be rather displeased if any of you out there still manage to go and fuck up with this one, so save me some sleep and try to exercise at least a minute degree of common sense.

Lastly, if you are taking any neuroleptics (not to mention any DA-antagonist drug—although this basically goes without saying), especially drugs like Haloperidol, Thiothixene, Phenothiazine, or Metoclopramide, just pass on the Pergolide, because any/all of these drugs will seriously antagonize/inhibit the positive effects of Pergolide and could also worsen its sides (3). So with that final, titillating contraindicative tidbit, it’s time for me to bid both Pergolide and my readers adieu, ‘cause I’m out like the beta run for PhenoGen… Cheers all.


1. B A Faraj, J T Fulenwider, E B Rypins, B Nordlinger, G L Ivey, R D Jansen, F M Ali, V M Camp, M Kutner, F Schmidt, and D Rudman. Tyramine kinetics and metabolism in cirrhosis. J Clin Invest. 1979 August; 64 (2): 413–420

2. Hiroi T, Imaoka S, Funae Y. Dopamine formation from tyramine by CYP2D6. Biochem Biophys Res Commun. 1998 Aug 28;249(3):838-43.

3. PermaxB Pergolide Mesylate. Eli Lilly & Co. 5.0 PV 2271 UCP_v2

4. Clarke C E, Speller J M. Pergolide for levodopa-induced complications in Parkinson’s disease (Cochrane Review). The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.

5. Friedman E, Adams EF, Hoog A, Gejman PV, Carson E, Larsson C, et al. Normal structural dopamine type 2 receptor gene in prolactin-secreting and other pituitary tumors. J Clin Endocrinol Metab. 1994;78:568-74

6. Soares BGO, Lima MS, Reisser AAP, Farrell M. Dopamine agonists for cocaine dependence (Cochrane Review) The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.

7. Wilson JM. et al. Dopamine D2 and D4 receptor ligands: relation to antipsychotic action. Eur J Pharmacol (1998) 351:273-86.

8. McDonald, L. Bromocriptine. Lyle McDonald Publishing; (2002); 104-121.


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