Dopamine Spikes When On-Cycle and Desensitization

Conclusion: PEDs enhance feeling of well-being through the testosterone-dopamine relationship. Over time, dopamine receptors can become de-sensitized. No special recommendation from this, just an FYI.

Last week I wrote up a quick article on the side effects of PEDs. My intention was to immediately follow this up with an article on the benefits of PEDs, and started by looking at the feeling of well-being and higher motivation PEDs users often report. I expected to be writing about a fairly simple testosterone to dopamine relationship. But it's a big subject, far larger than I had thought, and I feel a little like Alice falling down the rabbit hole. I have also become increasingly frustrated by even the scholarly articles pushing an agenda. Just give me the facts, Jack. Anyway.

Testosterone increases dopamine and serotonin. Testosterone also seems to be rewarding to the organism its applied to, with

rats display(ing) a preference for an environment previously paired with TST (testosterone) administration as opposed to an environment paired with saline administration.

Huh – even rats want to get swole.

I don’t know about you, but when taking a supraphysiological dose of testosterone, any dose of SARMs, or other AAS, I am pretty motivated. I am distracted by little, and will work from wake up to sleep being driven by the thought of just getting shit done. So the test to dopamine relationship makes sense based on my personal experience and aside from growing my pecs is the favorite thing to me about being on cycle. But how about dopamine desensitization? The longer I am on PEDs, the higher the risk for this to occur, or is it a myth?

I guess it has some anecdotal evidence, if the #nofap crowd are to be believed. An incredibly subjective article was written about this here and they might be on to something. In rats at least, downregulation of dopamine receptors has been shown in studies of psychostimulants and opioids, suggesting a stimulation of the reward circuit through an increase in accumbal dopamine levels. This sustained stimulation produces desensitization through receptor internalization that ultimately produces a decrease in protein expression.

If this is true of other drugs that increase dopamine which in turn over time desensitized receptors, it’s probably true with PEDs. You feel great on cycle, at least at the start, and then when you go off-cycle you just can’t wait to get back on. It’s not just for the gains but because your dopamine receptors have become desensitized. Fortunately, receptors recover their sensitivity over time. Just like how when you travel with family for a week and can’t watch porn, and when you get home, load up your favorite Thai ladyboy video, and it feels like the best thing ever. Don't pretend you don't know what I am talking about.

Footnote: In a post by The Finnish Antidoping Agency, an article that was clearly anti-PEDs, they reference a study where nandrolone has long-last effects on dopamine and serotonin production.

It took five times the administration period for the dopamine levels to return to baseline, and six times for serotonin. They even conclude with a very relevant note: Our study results suggest that the breaks generally observed by users in between the administration periods are not long enough to recover the studied neurotransmitter pathways activity to their basic level. When a new administration period begins before the neurotransmitter pathways activity has been recovered, the new changes can be greater and the effects can last even longer than before.

In Are You Ready For Your Next Cycle, I make the argument that blood work is the method for how to determine if you are ready or not (among other things). I have since edited the article to add a reference to the Finnish site. Similarly, in Side Effects General. The Fins are not going to change my practice in any way, but I’ll throw that out there for each user to make their own decision on what is best for their health.