Psychostimulant information that will cause you sadness :(

[Seppi]

Sadness:
ADHD psychostimulants + orgasms = increased risk for (joint psychostimulant-/sex-) addiction due to an interaction through ΔFosB.
I guess that's why some methamphetamine abusers end up fucking for over 24 hours straight during some of their binges...

Silver lining:
The good news from the review (1st ref) is that some natural rewards seem to be a better avenue for addiction recovery than pharmacological intervention. I.e., while "sexual reward" and amphetamine don't get along, "(aerobic) exercise reward" and "Novelty/Sensory Stimulation/Environmental Enrichment" (which I suppose means things like pleasant music and visually appealing surroundings) seem to fare better than drugs, especially when multiple natural rewards are involved.

Refs
* Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions".Neuropharmacology PMC 3139704.PMID 21459101.
* Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". J. Neurosci. PMC 3865508.PMID 23426671.

Other reviews covering stimulants and sex addictions independently with ΔFosB are contained in https://en.wikipedia.org/wiki/ΔFosB

 

[MeDieViL]

Sensitization is the main mechanism on how drugs program themself in the brain, memantine would prevent that from occurring:

Pharmacol Biochem Behav. 2000 Oct;67(2):241-6.

NMDA antagonists block expression of sensitization of amphetamine- and apomorphine-induced stereotypy.

Battisti JJ1, Shreffler CB, Uretsky NJ, Wallace LJ.


Author information




Abstract


We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both single and multiple pretreatment paradigms. In the present study, we tested whether NMDA receptor antagonists and an inhibitor of nitric oxide synthesis inhibit expression of sensitization in either of these models. Male CF-1 mice were pretreated with a single dose or with three daily doses of amphetamine (14 mg/kg) or apomorphine (40 mg/kg). Two days following these pretreatments, mice were injected with ((+/-)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP, 20 mg/kg), dizocilpine maleate (MK-801, 0.1 mg/kg), 7-nitroindazole (25 mg/kg), or vehicle 30 min before receiving amphetamine (7 mg/kg) or apomorphine (3 mg/kg). The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine, indicating that sensitization had developed. CPP, MK-801, and 7-nitroindazole prevented the expression of the sensitized stereotyped response induced by either amphetamine or apomorphine in both paradigms. These drugs did not attenuate the stereotypy elicited by amphetamine and apomorphine in drug-naïve mice. The effect of 7-nitroindazole was reversed by pretreatment with 500 mg/kg of L-arginine but not by D-arginine. These results suggest that glutamatergic transmission and subsequent NMDA receptor activation and the production of nitric oxide play a critical role in the expression of the sensitized stereotyped behavioral response elicited by amphetamine or apomorphine.

 

[sekio]

So what are you saying? Stimulant abusers are also prone to being hypersexual?

What a great discovery! I'm sure nobody's ever thought of this before.

 

[MeDieViL]

So what are you saying? Stimulant abusers are also prone to being hypersexual?

What a great discovery! I'm sure nobody's ever thought of this before.

Hahahahaha made me lol this one.

 

[ebola?]

I'm having trouble making out the miniscule font you chose. Could you please resize your text to allow for reading viewed from multiple rooms away?

ebola

 

[NeighborhoodThreat]

I was under the impression that this was pretty common knowledge. I mean look at the threads in OD and EADD about jerking off all night after smoking meth or vaping MDPV.

References from 2011 aren't exactly groundbreaking imo.

 

[Seppi]

So what are you saying? Stimulant abusers are also prone to being hypersexual?

What a great discovery! I'm sure nobody's ever thought of this before.

lol, no I guess I did a pretty shitty job at being witty here.
The gist of it is, you can run an ultramarathon all day and seemingly cure a drug addiction (well, maybe not in 1 day...) but you can't jerk off all day to cure it if you're addicted to a psychostimulant (this hasn't been established with other drug-sexual reward pairs and probably isn't the case either).

Life's unfair.

 

[Seppi]

I was under the impression that this was pretty common knowledge. I mean look at the threads in OD and EADD about jerking off all night after smoking meth or vaping MDPV.

References from 2011 aren't exactly groundbreaking imo.

I was really just looking for interactions between delta fosb and sex addictions to find these papers. The interaction between psychostimulant induced ΔFosB and "sexual reward" induced ΔFosB was just something that I came across. I actually think it's quite interesting because I haven't seen a neuroscientific explanation for an interaction between a behavioral addiction and a drug addiction until now. Dopaminergics and orgasms aren't an explanation for addiction. ΔFosB induced neuroplasticity is the actual pathophysiology behind both forms of addiction. It's been known for quite a while that dopaminergics enhance sexual behaviors - the short term effects are also mediated in the nucleus accumbens, but not by ΔFosB.

Accumulation of ΔFosB in the nucleus accumbens is very bad not just because of addiction, but because it induces neuroplastic changes that fuck up the other parts of the mesocorticolimbic projection, most notably, your prefrontal cortex.

In any event, besides my failed attempt at humor, the other reason I pointed this link out was that chronic acquisition of all natural rewards increase ΔFosB in the nucleus accumbens; I'm not entirely sure why ΔFosB induction by one form of reward does or doesn't interact with another reward.

 

[ebola?]

Life's unfair.

Heh...I don't in general expect extremely enjoyable activities to also promote mental health, let alone to the point of curing mental disorders.
So life's not unfair in this respect; rather, it's just not startlingly awesome in this instance.

ebola

 

[Seppi]

Sensitization is the main mechanism on how drugs program themself in the brain, memantine would prevent that from occurring:

I know that NMDAR activation in the nucleus accumbens is a major part of amphetamine's signaling cascade that induces ΔFosB, but I'm not sure about sex addictions; I'm not familiar with the neuroscience of orgasms.
In any event, long-term ΔFosB (phosphorylated ΔFosB) accumulation is slow, which is the neuroscientific explanation as to why it's not possible to get addicted to any substance after just a couple uses. This diagram illustrates how ΔFosB builds over time with frequent administration. Repeated exposure to a sufficiently large "dose" of natural reward or a drug is required before ΔFosB starts to phosphorylate (in a nutshell, phosphorylated ΔFosB is extremely stable and has a half life of about one to two MONTHS).

Also, I'm more or less finished with my ΔFosB diagram for psychostimulant addictions on wikipedia - https://en.wikipedia.org/wiki/ΔFosB#Delta_FosB (this version of the diagram is complete/annotated).

 

[rakketakke]

I think it's a prominent fact that is overlooked in most addiction centers.

Along with the hefty DA release and it's effects on the mesolimbic system I don't understand they look past it. Speaking from personal experience, orgasm is abnormally longer in duration, one can feel an orgasm before the actual ejaculation (thus multiple) and is much heftier, at times it will be delayed before ejaculation but the feeling of orgasm is present before that happens. No wonder when signalling in the mesolimbic system is more adequate but it does boggle my mind that the feeling gets there before the actual physical response.

http://books.google.be/books?id=2As...Q6AEwAA#v=onepage&q=science of orgasm&f=false
^is a great read as a whole

Sadly there isn't much specific information to be found so if anyone can chime in, any knowledge is much appreciated.

edit.

 

[InterestingFACT]

This stuff about delta fosb is new to me, and very interesting. I'm surprised there hasn't been more research done on the matter. However, I think the interesting implication here (unless I'm misunderstanding) is that intermittent use of multiple drugs should be similarly reinforcing as the more frequent usage of a single drug. ie. Even with occasional use (without developing a dependency) of some combination of methamphetamine, PCP, alcohol, masturbation, or nicotine (wikipedia seems to implicate delta fosb in all of these), one might develop a similarly powerful dependency on vice itself, without regard for the vice used?

That... seems to ring true from what I've seen of the world. Though it would be interesting to see a study on the topic. Any thoughts here?

EDIT: I also wonder whether delta fosb is implicated in the subjective high as well as the longer-term addiction? It would be interesting if, through concurrent administration of a delta-fosB antagonist or a delta-junD agonist, it would be possible to create a truly non-reinforcing high.

 

[Seppi]

I mentioned somewhere earlier in my rant that "I'm not entirely sure why ΔFosB induction by one form of reward does or doesn't interact with another reward." I've only seen those 2 papers that go into the topic of an interaction between drugs, but it seems like an active area of research.

Unrelated, but I changed the link in my post above to where the complete diagram is located. Haven't captioned it yet though.

 

[Black]

This stuff about delta fosb is new to me, and very interesting. I'm surprised there hasn't been more research done on the matter. However, I think the interesting implication here (unless I'm misunderstanding) is that intermittent use of multiple drugs should be similarly reinforcing as the more frequent usage of a single drug. ie. Even with occasional use (without developing a dependency) of some combination of methamphetamine, PCP, alcohol, masturbation, or nicotine (wikipedia seems to implicate delta fosb in all of these), one might develop a similarly powerful dependency on vice itself, without regard for the vice used?

That... seems to ring true from what I've seen of the world. Though it would be interesting to see a study on the topic. Any thoughts here?

EDIT: I also wonder whether delta fosb is implicated in the subjective high as well as the longer-term addiction? It would be interesting if, through concurrent administration of a delta-fosB antagonist or a delta-junD agonist, it would be possible to create a truly non-reinforcing high.

that article has been brought up before in npd. i'd rather suspect that they're involved more in the habit forming than the pleasure.
also i think that as the different variants of fos and jun are involved in lots of different processes (including regulating cell growth/death), you'd probably run intro problems with getting a compound that's specific enough to the subtype you want as well as problems cytotoxicity or cancer. it's probably only worth it for cytostatic drugs.

 

[Zilpe]

Do we really need such a complicated explanation? Sex triggers a large reward and stimulants tend to ramp up your sex drive as well as making things normally rewarding even more rewarding (assuming said activity doesn't interfere with mechanism responsible for making stimulants rewarding). Considering the fact that people coming off of stimulants usually have a decreased libido it seems like the desire to get high and engage in sexual activities doesn't need to be explained by some intricite neuropharmacological interaction. If there was a higher than average incidence of ex-stimulant users with a seuxal addiction then we might want to start looking for possible mechanisms.