• 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5


A day and more on 4F-EPH (insufflated, unexpected effects)
#1
Substance: 4F-EPH
Dose: 90mg cumulative

Set: Not optimal. Mood is benign, but up all the preceding night and tired.
Setting: At home, alone, comfortable, no pressure

0828 15mg 4F-EPH insufflated. Mild burn, nothing eye-watering.

0833 Not much effect has been noted within the first five minutes of insufflation.

0835 First alerts of something. As with 10mg, I'm not really sure quite what.

0840 Hmm. Not really getting what I hoped. Admittedly my starting point is a tough one, sampling at 8.30am and having been up all night, but phenidates normally assert themselves when an effective dose is found. Possible slight increase in focus/alertness/wakefulness.

0843 Slight feeling of tension in chest and upper back, not severe. 

0847 Tea is made. Very minimal increase in alertness, barely perceptible. Hands feel colder. 

0852 Side effects are mild in nature, but any beneficial impact seems negligible. There is perhaps a minimal increase in alertness, but not any obvious reduction in tiredness. Perhaps my starting point is wrong or my expectations too high, but that was basically a waste of time, save for purposes of safe escalation.

0901 Screw it. Redosed with 20mg intranasal, slightly more finely crushed than last time. Burn remains mild but seems to persist for longer with the redose.

0904 Some signs of onset this time. Increase in wakefulness, focus and alertness, still subtle. Couldn't describe it as resembling any sort of a rush.

0909 Further evidence of a (so far) mild stimulant effect. 

0912 Minor fit of sneezing. I do have a cold, so it could be unconnected to the insufflation, but wouldn't be the first time such a thing has happened. This is quickly over but it becomes necessary to blow my nose.

0915 It is observed that mild nasal discomfort persists in the nostril in which I insufflated. The pain is not severe by any means, but the fact that it persists after some 15 minutes suggests the potential for damage, as with ethylphenidate (though less painful, so far at least). On the upside, there is now a definite increase in wakefulness, focus and alertness, and perhaps a subtle boost in mood. Pleasant rather than not, but so far, the perceived benefit for my purposes seems subjectively inferior to (the Chinese batch of) 4F-MPH.  Your mileage may vary.

0920 A saline nasal spray is used, but it doesn't seem to make very much difference. As with ethylphenidate, repeated insufflation feels likely to be damaging to the nasal mucosa and, whilst it could be nice once in a blue moon, it doesn't seem optimal for insufflation. Nor did ethylphenidate, of course, so this might be anticipated. I might try it once or twice more, but probably won't be making a habit of it.

0940 Starts to feel possibly post peak. Maybe some more tea is in order. There is still some very slight improvement in alertness over my starting point, but nothing to write home about.

1000 I have clearly less inclination to redose at T+1h than from lower doses; the perceived benefit is still pretty subtle, but not diminishing quite as rapidly. Some irritation to my nose persists an hour after dosing; it's not greatly painful or distracting but it suggests a risk of damage with this RoA. I may try one or two more experiments intranasally and leave it at that. 

1030 Beneficial effects remain subtle but present, though the wakefulness/alertness is starting to crumble. There is perhaps a mild mood lift, but I would stop some way short of euphoria. Redosing is faintly being considered. 

1050 Redosing is more actively being considered, it seems to be coming down. Slight feeling of dehydration; a further pint of (this time decaffeinated) tea is made. 

...

1215 Between communications and a variety of other distractions, I didn't get actually get around to the intended redose at 11ish. I didn't consciously miss it, and was easily distracted between one task and another, being less than efficient or productive on balance. There is a slight feeling of dehydration; not fancying water or booze, some further decaffeinated tea is made. Distracted again.

1305 Without my paying very much attention, we've gone from T+2h and pondering a redose, to T+4h and not got around to it yet. That's from a total ingestion (by insufflation) of 35mg in two doses by 9am.

1315 Redosed with 25mg intranasally. This might prove underwhelming, having taken a total of 35mg earlier, but it seems imprudent to jump into that as a single dose just yet.

1330 Sneezing, once or twice this time. Onset of some sort of effect is felt; it does feel somewhat underwhelming in the stim/focus department and I can't say I'm getting any great recreational or mood boosting effect from it. Some awareness of (mild) phenidate side effects, somewhat jittery. 

1345 The effect isn't unilaterally negative, but I perceive a slightly greater awareness of the (admittedly mild) side effects than I do of any great benefit. This is reminiscent of how I felt about the fourth bump the other night; it's seemingly reached the point of diminishing returns. This doesn't feel like the result of underdosing; onset was felt and the side effects increased (still mild and short lived, in relative terms). Lesser signs of stimulation, more signs of side effects, mood is benign but no sign of the euphoria reported by other researchers. 

1615 Tiredness is beginning to set in, followed by hunger. One more redose is contemplated, more in hope than in expectation, but it is decided that it might be wise to eat first.

1645 Happily eating a couple of ham and cheese panini, along with a glass of ale. No apparent impact on appetite that I can discern; food is consumed eagerly and enjoyed.

1710 Feeling of ambivalence towards further redosing. On the one hand it didn't obviously achieve much for me earlier, on the other hand I'm still awake, and perhaps one more go would let me stay up a few hours.

1718 Redosed with 30mg intranasal.  

1723 Sneezing, again. This is becoming rather predictable a few minutes after dosing. Happily it's once or twice and not lengthy fits of sneezing, but my nose is making forceful and reproducible efforts to expel the stuff. Not had this happen with any other phenidate, that I can recall.

1728 Light signs of onset, less in the way of perceived unpleasantness than from the earlier 25mg dose (but bear in mind, this time I'd just eaten and consumed a beer). Less everything, really, though. Not too conscious of any stimulation; it is perhaps there, but at sub-threshold levels.  

1745 Further signs of increased activity, a slight mental stimulation is present. Not as perceptible, subjectively, as at the initial dose, but definitely present. I am still noticing an increasing onset at ~30m after dosing, but it's never going to reach the heights of the initial dose. 

1758 Feels like maybe we've reached the plateau; the ascent, inasmuch as there is one, is slower than anticipated. Some stimulation and increased focus are observed. 

1807 Finally I feel clearly somewhat above base line again, there is a pleasant, mild stimulation ad focus, although it does not make me impervious to natural tiredness. Some mood lift is noted, although it doesn't compare, for me, with the euphoria of SRAs I've tried.

1820 A feeling of dehydration is observed, and a pint of water is taken. I begin to feel much more tired than stimulated, but there is still a degree of added alertness. Indeed, it is unusual for me to pull an all-nighter and to remain awake throughout the day, so there has undeniably been at least some stimulant effect, but it is by no means pronounced or lasting. 

1830 Tiredness wins, phenidate or not, I am falling asleep. Decided to go to bed, out like a light.

...

0340 (Boxing Day) I awoke after around 9h of sleep; above average for me even following an all-nighter. Sleep quality was somewhat poor, with some tossing and turning, but I believe that had more to do with a common cold than with any impact from the 4F-EPH. I didn't feel too bad on waking; food and plenty of fluids had been consumed prior to sleep, which may well have helped. However, neither did I feel as refreshed or as energised as might be hoped.

Interpreting this set of experiences is difficult; my testing was not "clean" and my starting point was one of mild sleep deprivation, so it is not proven conclusively that the 4F-EPH is directly responsible for all of the experiences noted. 

It does appear, as noted by other researchers, that the received effects change with redosing, and although I did not experience this as 'euphoric' or as an unusually pronounced boost in mood, the reduced stimulation, increased sedation, appetite for food, apparently soporific effect and apparently increased sleep duration are potentially commensurate with increasing levels of serotonin. I have not felt unduly low, depressed or depleted in serotonin before, during or after the sampling and I consider that there may have been some anti-depressant or mood-boosting activity, to which my response seems somewhat muted as compared with niflheim's. I suspect that there might be some degree of SSRI activity, perhaps of longer duration than first thought. Five hours after waking, some 15h after last dosing, there is still a slightly dreamy, sedated feeling, perhaps with some anti-depressant effect. On eating, this is rapidly replaced by tiredness, and a desire to go back to bed - strong enough that at 0845, I did.  

...                                                                                                                                               
1515 Woke up again, to a phone call. Again, I don't feel particularly bad, but this is almost unprecedented; I have slept for more than 16 of the last 24 hours. Sleep deprivation prior to this experiment was present, but limited, and I do not think that that is the sole explanation.   

1545 There is still a slight feeling of tiredness, of hunger, of a mild anti-depressant effect. It could be placebo or unrelated, but I'm not writing it off as such. 

This is very tentative, but, on two occasions during the latter part of the experience, I have had the suspicion that the after-effects of 4F-EPH may have had a strongly potentiating or synergistic effect on very small amounts of cannabis (relative to tolerance and familiarity), the apparent results of which were a disproportionate stimulation of appetite (unusual for this researcher) followed by a disproportionately sedative and soporific impact. This effect no longer seems to be present at T+24h after last dosing, but it could have been a factor both last night and this morning. 

No definitive conclusions can or should be drawn from this experience alone, and there has been nothing distressing or unpleasant about it, but, whilst it might have its uses, I do not see 4F-EPH as being either a replacement for ethylphenidate, or as subjectively preferable to 4F-MPH. I am in agreement with other researchers that the stimulant effects seem to be limited to an initial effective dose and are not reproducible with redosing. I would add that, at higher or repeated doses, there appears to be some sort of SSRI-like effect, with a duration considerably exceeding 4h.

...

Subsequent to the above, friends visited, food was consumed along with two or three beers and by 11pm (not even awake 8 hours) I was fit to go back to bed. I slept through until 11am Sunday, another ~12h of sleep, despite having already slept ~16h of the preceding 24.

This is now literally unprecedented. I'm not sure it's all down to the 4F-EPH, but, no benzos or other tranquillisers have been used and whilst I have an unpleasant cold, it hardly feels like the 'flu and isn't a causal factor here.

Objectively, the amount of rest could be no bad thing for me, but it's not what I expected from a stim. The only other times I have slept even close to this much (or felt like eating on such a regular basis) have been when taking Seroquel (quetiapine) for a manic episode (a year or two ago). 

One might say that's no bad thing; I have been disinclined towards further stimulants, towards benzodiazepenes, towards less-than-modest consumption of alcohol or cannabis or towards staying up all night, and my mood has remained benign throughout. I am inclined to think that there may be lasting anti-depressant and possibly anti-psychotic effects from sustained re-dosing of 4F-EPH.

Which is interesting, and slightly bizarre. This could be an idiopathic or irreproducible result, I am a little confused by it myself. I shall allow a fairly protracted period before any further sampling, but will be very interested to know what others make of this...
Reply
#2
I don't think phenidates are a very euphoric type of drug. That is why I guess that Ritalin is prescribed more than dex amp. I am ADHD so phenidates effect me differently than other but eph was always mild as hell. I wouldn't stick it up my nose so I can't tell if insulation roa would have been any different. Phenidates just seem to be functional stimulant that are good for what they are designed to do help focus. Not having you withering in pleasure like what you want out if a stim. You can't get cocaine effects from something that is nothing like coke or base speed for that matter. That's my 2 pence.
love the world and it will love you back. chin
Reply
#3
(28-12-2015, 12:06 PM)bigazznugz Wrote: I don't think phenidates are a very euphoric type of drug. That is why I guess that Ritalin is prescribed more than dex amp. I am ADHD so phenidates effect me differently than other but eph was always mild as hell. I wouldn't stick it up my nose so I can't tell if insulation roa would have been any different. Phenidates just seem to be functional stimulant that are good for what they are designed to do help focus. Not having you withering in pleasure like what you want out if a stim. You can't get cocaine effects from something that is nothing like coke or base speed for that matter. That's my 2 pence.

Yes, that's exactly what I'd expect of a typical phenidate, too. 

I wouldn't describe the effects as cocaine-like, but, the 4F analogues don't behave entirely like the rest of the class. As with 4F-MPH, effects seem to change on re-dosing, not to the same extent as reported here, but I would not assume that the normal phenidate SAR applies to anything with a 4F on the front. It doesn't seem to.
Reply
#4
Soon as I get the chance, maybe in the week I'll try to repeat your test with the sleep deprivation added in and see how we go.
Could be interesting to have a look at the TR's side by side :D
Regards
GN
They say pain is relative, it certainly feels like a relative of mine... One that I can't get rid of.
Reply
#5
(27-12-2015, 11:54 AM)magick Wrote: Which is interesting, and slightly bizarre. This could be an idiopathic or irreproducible result, I am a little confused by it myself. I shall allow a fairly protracted period before any further sampling, but will be very interested to know what others make of this...

Methylphenidate activates muscarinic receptors and modulates VMAT2 such that increased dopamine release takes place in the striatum. The increased dopamine from reuptake inhibition is likely behind the D2 activation and the combination of D2 activation and muscarinic activation triggers results in the somewhat complex effect on VMAT2.


Quote:Because MPD has no significant binding affinity for DA receptors (Markowitz et al., 2006), these effects are probably due to MPD-induced increases in extracellular DA concentrations caused by DAT blockade rather than to a direct interaction between MPD and D2 receptors.
...
In summary, the present results elucidate a heretofore-unreported mechanism whereby MPD alters striatal DA transmission. D2 receptors mediate the ability of MPD to: 1) traffic vesicles away from synaptosomal membranes and into the cytoplasm which increases DA transport into cytoplasmic vesicles; and 2) kinetically upregulate VMAT-2 in vesicles that remain associated with synaptosomal membranes such that DA transport into the membrane-associated vesicles is increased as well. This results in a redistribution of DA within the striatum from the cytoplasm and into vesicles and a consequent increase in DA release. The present studies also demonstrate that muscarinic receptor, but not NMDA receptor, activation is required for MPD to affect the actual DA release process. T
Methylphenidate-induced increases in vesicular dopamine sequestration and dopamine release in the striatum: the role of muscarinic and dopamine D2 receptors. Volz TJ, Farnsworth SJ, Rowley SD, Hanson GR, Fleckenstein AE. J Pharmacol Exp Ther. 2008 Oct;327(1):161-7.

In addition to activity at the muscarinic receptors, MPH also has activity at 5-HT1a

Quote:There was measurable, albeit relatively weak, binding affinity of both MPH isomers and the racemate to a number of muscarinic receptors including M1, M2, M3, MM4 and MM5. Generally, binding affinity was similar between the two isomers and racemate, although binding of d-MPH appeared to be significantly weaker than that of l-MPH for the M2p/sub] muscarinic receptor.The potential clinical consequences of this modest binding, if any, are unknown and would require further exploration.

An unexpected finding was the measurable stereoselective binding observed for the 5-HT[sub]1A[sub] and 5-HT[sub]2B
receptor sites. For each of these sites, the binding was largely attributable to d-MPH rather than l-MPH. Although almost all previous investigations, including the present study, have found little interaction of MPH with the 5-HT transporter (SERT), The possibility of direct serotonergic agonist or antagonist activity at these specific 5-HT receptors was of particular interest."
A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R. J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98.


What does all this have to do with anything? Well, it turns out that this is an activity profile associated with the newest antipsychotic drug candidates:

Quote:Brexpiprazole is a serotonin-dopamine activity modulator in clinical development for schizophrenia, adjunctive treatment of major depressive disorder, agitation in Alzheimer's disease and post-traumatic stress disorder. It is a partial agonist at 5-HT1A and D2 receptors with similar potency, and an antagonist at 5-HT2A and adrenergic α1B/2C receptors. Compared with aripiprazole, brexpiprazole is more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors. This unique serotonin and dopamine modulatory activity has shown robust antipsychotic, antidepressant-like and anxiolytic activities, and limited extrapyramidal symptom liability with pro-cognitive efficacy in animal models. Phase III clinical trials have been successfully completed in schizophrenia and adjunctive use in major depressive disorder, with the US FDA approval obtained for these uses; Phase III studies in Alzheimer's disease and post-traumatic stress disorder are ongoing.
The preclinical profile of brexpiprazole: what is its clinical relevance for the treatment of psychiatric disorders? Citrome L, Stensbøl TB, Maeda K.Expert Rev Neurother. 2015 Oct;15(10):1219-29.

Which is to say, your experience appears to be consistent with a plausible pharmacological mechanism for antipsychotic activity in phenidate drugs, where 4F-EPH may have affinities/activity that optimises this activity over other known phenidates.
Reply

Reddit   Facebook   Twitter  




Users browsing this thread:
1 Guest(s)

   
DISCLAIMER
Any views or opinions posted by members are solely those of the author and do not necessarily represent those of the UKCR staff team.