Corticosteroid euphoria

[mad_scientist]

Some corticosteroids such as prednisone and dexamethasone cause euphoria as a side effect especially at the start of treatment, although it diminishes after a few days once your body becomes tolerant to the steroid, and indeed with prolonged treatment at high dose the opposite effect develops and you get depressed and irritable.

Is anyone aware of research into the mechanism for this? It seems to be directly mediated through the steroid receptors according to this paper;

http://www.ncbi.nlm.nih.gov/pubmed/8983088

but I can't find much more information out about it. Seems like another potential target for euphoria-inducing drugs, I wonder if it would be possible to make a drug which acted via this target but lacked the various side effects of corticosteroid drugs, and didn't produce tolerance to the euphoria so quickly. Certainly seems to be quite seperate from the mechanisms of any conventional drugs of abuse, although I bet secondary dopamine release is involved to some extent.

 

[MeDieViL]

Corticosteroids have been reported to work for social anxiety too, hmm reducing anxiety and causing euphoria not bad.. but they are LESS healthy then most recreational drugs but i gues if because of these drugs they find differend routs to cause euphoria that would be interesting

 

[Ham-milton]

I know they tend to stimulate mania in bipolar patients. Perhaps a serotonergic mechanism, then.

 

[Recept]

Excessive amounts of serotonin is only one likely cause for mania. Other neurotransmitters, such as dopamine, NE, GABA, and glutamate are also proably involved in the process.

 

[negrogesic]

Did you see the following article?

The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor agonists was investigated in vitro. After a 4-min in vitro exposure to morphine (less selective mu agonist), D-Ala2-N-methyl-Phe4-Gly5-ol)-enkephalin (DAGO; highly selective mu agonist) and trans(+/-)-3,4-dichloro-N-methyl-N-[2(1-pyrrolidynyl)cyclohexyl]- benzeneacetamide (U50-488H; highly selective kappa agonist) a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (highly selective delta agonist). Dexamethasone treatment before or after the opioid agonists tested was capable of both preventing and reverting the naloxone-induced contracture after exposure to mu opiate agonists morphine and DAGO in a concentration- and time-dependent fashion. Also, the steroid reduced naloxone-induced contracture after the exposure to U50-488H only when injected before the kappa opiate agonist. Finally, it did not affect the naloxone contracture after exposure to deltorphin. Pretreatment with RU-38486, a glucocorticoid receptor antagonist, inhibited dexamethasone antagonism on responses to both mu and kappa agonists, whereas pretreatment with cycloheximide, a protein synthesis inhibitor, blocked only the antagonistic effects of dexamethasone on responses to the mu opioid agonists. Overall, these data indicate that dexamethasone induces significant effects on mu-mediated opiate with-drawal in vitro, which suggest an important functional interaction between corticosteroids and the opioid system primarily at the mu receptor level. The ability of RU-38486 and cycloheximide to block dexamethasone effects indicates that the steroid interference on mu-mediated withdrawal involves a protein synthesis-dependent mechanism via glucocorticoid receptor.

PMID: 8632345
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Im not sure if this explain mood changes though. This may sound stupid, but would corticosteroids increase the synthesis of opioid peptides? Would this only explain an interaction?

It does appear as though there is some sort of a synergistic effect when tramadol and prednisone are combined, i've heard this a few times (on this board, fairnymph had mentioned having experienced a strong interaction, maybe she was exaggerating).

 

[cyanide_sunshine]

Phenanthrene nuclei are well known for their ability to improve mood in the beginning, but the 3? keto group in pred prevents it from binding from androgen ligands and then you just get shitty immunosuppressive effects from then on. Testosterone and estrogen are known for mood swings... thusly. Improvement may indicate an underlying inflammatory process.

 

[nuke]

I've seen them (especially dexamethasone) induce bizarre psychiatric effects ranging from euphoric psychosis to suicidal depression. Dexamethasone is also a trytophan-hydroxylase inhibitor (type II CNS) and likely decreases central serotonin, if anything.

 

[KompelZ]

From my own personal experience this is true. I've been taking prednisone for my asthma since I was a little kid (usually only once or twice a year when it gets really bad and I need to be hospitalized).

It isn't exactly an enjoyable 'euphoria' though (not one you would want to repeat, in other words) it is definitely a more manic-hyperactive feeling. And I have no history of bipolar disorder in case you're wondering.

 

[Ham-milton]

Did I read that right? Dexamethasone induces withdrawal? That doesn't sound like a plausible mechanism for inducing euphoria/mania, does it.

That's interesting that it should decrease SE. It it possible that SE-related mania induction isn't due to higher levels in the synapse but rather the decreased reuptake. Besides decreased reuptake, what would the two states (normal SE levels with blocked reuptake, and lower SE leves so then lower reuptake) have in common?

 

[negrogesic]

Yea, that article is a bit confusing...

Here is another, which is more clear:

Dexamethasone has been shown to inhibit opiate withdrawal, in an in vitro model. In this respect, we suggested that dexamethasone could reduce opiate withdrawal by blocking the release of prostaglandins' precursor, arachidonic acid through protein synthesis dependent-mechanisms (1). Since arachidonic acid is released by the enzyme phospholipase A2 (PLA2) in the present paper we evaluate whether dexamethasone effect may by related to inhibition of PLA2 activity. Therefore, the effect of a neutralizing anti-lipocortin-1 antibody and a polyclonal anti-type II extracellular phospholipase A2 antibody on the opiate withdrawal in vitro was considered. Following a 4 min in vitro exposure to morphine a strong contracture of guinea-pig isolated ileum was observed after the addition of naloxone. Dexamethasone at concentration of 5x10(-5) M reduces of 50% morphine withdrawal and the polyclonal anti-type II extracellular PLA2 antibody (in a dilution 1:1000) mimicked dexamethasone inhibitory effect. Incubation of the ileum preparation with a neutralizing anti-lipocortin-1 antibody (at a dilution of 1:10.000) 30 min before dexamethasone reverted the steroid effects. These results suggest that dexamethasone inhibition of opiate withdrawal is due to extracellular type II PLA2 inhibition through lipocortin-1.
http://www.ncbi.nlm.nih.gov/pubmed/9296341

This is a stretch, but the end of another article

These results suggest that the EOS is not directly involved in the negative feedback triggered by low doses of Dex of the HPA-a, and that there might be a possible glucocorticoid-opioid interaction for the modulation of some aspects of mood.PMID: 9695140
http://www.ncbi.nlm.nih.gov/pubmed/..._DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2

I had looked this stuff a while ago, when trying to figure if dexamethasone had any value in treating opioid withdrawal. Needless to say, i was somewhat unsure.

All this said, i dont think endogenous opioids have much to do with what is causing the mood changes in regard to corticosteroids...

 

[Riemann Zeta]

I've certainly seen a case of corticosteroid-induced mania ("roid rage?"). After a high-dose prednisone injection, I witnessed an 80 year old woman with some severe cardiac problems (as in, she had just gotten back from open-heart surgery) claim that she was perfectly fine and didn't need to be in a hospital any more. She ripped out her IVs and said she was going downstairs to catch a cab...until the psychiatric nurse showed up with some olanzapine and some ativan.

 

[KompelZ]

Dexamethasone has also been known to induce CYP2D6, the enzyme that converts codeine into morphine...I might try to score some one day and perform a little self-experiment.

 

[Jamshyd]

This is very interesting, since the narco-phobic middle eastern doctors only prescribe corticosteroids for pain, and people there are not what I'd describe as "healthy".

 

[polymath]

I decided to resurrect this old thread, because I found it interesting. I have actually tried to get high on corticosteroids once myself... Years ago my father was sick and was on high-dose prednisone for over 6 months. After that there were lots of leftover pills in his medicine cabinet and I decided to take a large dose myself, as I knew they cause euphoria in some people and have little acute toxicity even in huge doses. The dose left me feeling a bit irritable for a few days, but caused no euphoria.

Is there any new knowledge about the central effects of corticosteroids, maybe a dopaminergic connection or something? Why are the effects so different in different people? Drugs like amphetamines certainly cause hypomanic symptoms consistently in everyone.

 

[sekio]

Some steroids like DHEA bind to the sigma receptor. I'm sure there are a large variety of receptors and ion channels that steroidal compounds actually target in addition to the gluco/mineralocorticoid receptors.

 

[StaySedated]

i've had to take prednisone a few times to bring down inflammation and never felt anything remotely similar to euphoria.

it actually made me feel kinda shitty.

 

[polymath]

People are different... I saw an article that described the case of a woman that was given a single shot of corticosteroids and that was enough to get her manic and she had to be given high-dose antipsychotics to control it... I know that mania is not alwaýs pleasurable, but anyways...

 

[ebola?]

I get irritability and insomnia, followed by hypersomnia and depression (I might also soon be out of luck, as my auto-immune reaction is continuing, and given the rebound adrenal suppression from corticosteroids, and my prior two treatment cycles, I might lack an option. :/).

ebola

 

[negrogesic]

I've was taking some of the very potent c-steroid triamcinolone acetonide (inhaled) , and I noticed some rather pronounced and unpleasant dizziness, dysphoria, weakness etc. This was at higher doses (400 mcg), and while short lived, it was no fun. There was a clear anxiogenic effect, accompanied by a fine tremor. Perhaps GABA mediated, but rather opposite to the anesthetic neurosteroid alphaxalone........

Supposedly the anabolic-androgenic steroid methandrostenolone has some unique mood alterating properties (positive), but I have never taken the compound........

AAS's like oxymeth and tren are known to have some unpleasant mood altering properties.

Pinpointing the precise mechanism behind such phenomena is would require intensive study.....even then.......

 

[polymath]

It's unfortunate that the corticosteroid receptor doesn't have many subtypes, so one cannot make a steroid with only central euphoric effects without the Cushing-syndrome like peripheral side-effects...

I've never tried anabolic steroids myself. I suppose they all have a psychostimulant-like effect in addition to building mucle.