Author Topic: Can anyone help me understand this??  (Read 102 times)

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Offline kikyo

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Can anyone help me understand this??
« on: December 05, 2018, 10:23:52 AM »

Hello everyone!.  I am here to ask for help and advice.  In the past..like 15 years ago, I was able to enjoy psychedelics.  In the last few years...after a long hiatus I tried them again.  To my shock, nothing happened.  I have tried several times to use acid and mushrooms with  no effect.  I know what I am getting is good, so I am at a loss.
Here is what I know.  I am on medications.  I also get migraines.  I FEEL like it is the Beta Blocker that might be the issue. 
I would like to list my meds and hope someone can help me figure it out. 
1.    CYMBALTA[/size][size=0px]®[/size][/color] (duloxetine delayed-release capsules) is a selective [/font][/color][/size]serotonin[/color][/size] and [/color][/size]norepinephrine[/color][/size] [/color][/size]reuptake[/color][/size] inhibitor (SSNRI) for oral administration. Its chemical designation is (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. The empirical formula is C[/color][/size][size=0px]18[/size][/color]H[/font][/color][/size][size=0px]19[/size][/color]NOS•HCl, which corresponds to a molecular weight of 333.88[/font][/color]
[/size]
https://www.rxlist.com/cymbalta-drug.htm#description[/size]



2,  Metroproplol or Lopressor..It is a Beta Blocker,,.I take for a preventative for my migraines.  I do not have high blood pressure. 
[/size]metoprolol[/color][/b][/color][/size] succinate, is a beta1-selective (cardioselective) adrenoceptor blocking agent, for oral administration, available as extended-release tablets.[/color][/size] TOPROL-XL has been formulated to provide a controlled and predictable release of [/color][/size]metoprolol[/color][/b][/color][/size] for once-daily ..[/color]
 
https://medlineplus.gov/druginfo/meds/a682864.html



3.  RELPAX..to abort a migraine. 




Relpax[/b] (eletriptan hydrobromide) is a selective serotonin receptor agonist used to treat migraine headaches. ... Tell your doctor if you have serious side effects of [/color]Relpax including: ... Our [/color]Relpax Side Effects Drug Center provides a comprehensive view of available drug information on the ...I do not think this is the problem as I have always tried not to take it when I try Psychedelics. 
[/color]https://medlineplus.gov/druginfo/meds/a682864.html[/font]



4. CELEBREX  This medication is a nonsteroidal anti-inflammatory drug (NSAID), specifically a COX-2 inhibitor, which relieves pain and swelling (inflammation). It is used to treat arthritis, acute pain, and menstrual pain and discomfort. ... If you are treating a chronic condition such as arthritis ..
Again..I do not think this is the problem either. 


5,  Xanax...After reading a bit...it seems that this WILL kill a trip...is this my problem??  On the days I tried to trip I am SURE I took a few mg of Xanax...is that it??


would any of these also kill mushrooms?  I am kind of upset about it all...
Any help would be so appreciated...
Grateful for you all..
m

Re: Can anyone help me understand this??
« Reply #1 on: December 06, 2018, 09:43:15 AM »
Honestly, I'm exhausted, and I really get no pleasure out of explaining complicated pharmacology to strangers.

...but I figured it would be polite to at least try.

To be honest, I was incredibly distracted while creating this post, and I left out a TON of information. If I were to have put full effort into this you would end up with the equivalent of 10 pages thoroughly explaining every aspect of the chemistry and pharmacology of these compounds... ...but, at this point in time I really don't care anymore, I'm not interested in teaching others any of this stuff. ...you should have talked to me 4 or 5 years a go.

Any way:


3. SSRIs (like Prozac, Paxil, Zoloft, Celexa, Desyrel) or MAOIs (like Nardil, Parnate, Marplan, Eldepryl, Aurorix, Manerix) are fairly consistently reported to noticeably reduce the effects of LSD. MAOIs seem to cause a greater reduction in the effects of LSD than SSRIs. https://erowid.org/chemicals/lsd/lsd_health3.shtml

Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor) and LSD affects 5-HT1A, 5-HT2A, 5-HT2C, dopamine, D2, and α2 adrenergic receptors and less potently to α1 adrenergic, D1, and D3 receptors.

So, if LSD affects dopamine receptors, adrenergic receptors, and serotonin receptors 1A, 2A, 2C, 5C, and 6 as well as inducing Some glutamate receptor activity, and Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor) then there is going to be some effect.

LSD potently binds to human serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A, 5-HT2A, 5-HT2C, dopamine D2, and α2 adrenergic receptors and less potently to α1 adrenergic, D1, and D3 receptors (Rickli et al, 2015, 2016) (Table 1). LSD also activates rat and mouse trace amine-associated receptor 1 (TAAR1) but not human TAAR1 (Simmler et al, 2016). LSD is a partial agonist at 5-HT2A receptors (Rickli et al, 2016)

As far as psilocybe fungi, the mushrooms are primarily 5HT 2a/c receptor agonists, and while LSD is far more complex pharmacological, affecting dopamine and adrenergic receptor sites, all of the classical psychedelics function through agonising of the serotonin 2a and 2c receptors.

(Serotonin is 5-hydroxy-tryptamine, hence "5-HT" represents 5-hydroxy-tryptamine)b

Quote
LSD potently binds to human serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A, 5-HT2A, 5-HT2C, dopamine D2, and α2 adrenergic receptors and less potently to α1 adrenergic, D1, and D3 receptors (Rickli et al, 2015, 2016) (Table 1). LSD also activates rat and mouse trace amine-associated receptor 1 (TAAR1) but not human TAAR1 (Simmler et al, 2016). LSD is a partial agonist at 5-HT2A receptors (Rickli et al, 2016)

(Table 1). 5-HT2A receptors primarily mediate the hallucinogenic effects of LSD (Nichols, 2016; Preller et al, 2017; Vollenweider et al, 1998; Kraehenmann et al, 2017). The affinity of hallucinogens for 5-HT2A receptors but not 5-HT1A receptors is correlated with psychoactive potency in humans. Although the subjective effects of LSD in humans can be blocked by pretreatment with a 5-HT2A receptor antagonist (Preller et al, 2017; Kraehenmann et al, 2017) and are therefore clearly mediated by 5-HT2A receptor activation, the signaling pathways and downstream effects that mediate the effects of LSD have not been conclusively identified (Nichols, 2016). A key mechanism of action of LSD and other serotonergic hallucinogens is the activation of frontal cortex glutamate transmission secondary to 5-HT2A receptor stimulation. However, interactions between the 5-HT and glutamate systems are unclear (Nichols, 2016). Increases in glutamatergic activity in the prefrontal cortex may result in downstream modulatory effects in subcortical areas and alterations in the gating functions of sensory and cognitive processing. Some notable differences can be seen between the pharmacological profiles of LSD and other serotonergic hallucinogens. First, LSD more potently binds 5-HT2A receptors than psilocybin, mescaline, and DMT (Rickli et al, 2016) (Table 1). Second, LSD is more potent at 5-HT1 receptors (Rickli et al, 2016), which may contribute to the effects of hallucinogens. However, there are no studies on the role of the 5-HT1 receptor in the effects of LSD in humans. Third, LSD binds adrenergic and dopaminergic receptors at submicromolar concentrations, which is not the case for other classic serotonergic hallucinogens (Rickli et al, 2016) (Table 1). In animals, dopamine D2 receptors were shown to contribute to the discriminative stimulus effects of LSD in the late phase of the acute response (Marona-Lewicka and Nichols, 2007). In humans, LSD may indirectly enhance dopamine neurotransmission (Nichols, 2016), with no role of direct D2 receptor stimulation (Preller et al, 2017; Kraehenmann et al, 2017). Serotonergic hallucinogens presumably produce overall similar acute subjective (Hollister and Hartman, 1962; Wolbach et al, 1962) and potential therapeutic effects in humans. The early clinical trials used mostly LSD while most of the recent hallucinogen studies used psilocybin because of its ease of use due to the shorter action and less controversial history (Nichols et al, 2017; Nutt, 2016). However, modern studies need to directly investigate whether the effects of LSD in humans differ qualitatively from those of psilocybin and DMT, notwithstanding LSD’s longer duration of action.

https://www.nature.com/articles/npp201786#t1

Also, you have to understand neurotransmitter release, reuptake inhibition, and receptor site agonism to fully understand this stuff, and in all honesty if I were explaining this in person with chalk board to help me I would be better off than trying to type it out.

When LSD was scheduled it wasn't just taken out of the hands of "the common people" but researchers, therapists and scientists were also banned from using the drug so researchers are unable to tell you as much as they should, but based off of the pharmacological profiles of those substances coupled with anecdotal reports, it seems the conclusions above are probably the best you are going to find.

As for the benzodiazepine drug, these compounds don't so much "end a trip" as they do in aiding one to fall asleep on the tail end of an acid trip. They can surly mess with a trip.

If you want to "end a trip" I have read some really interesting things regarding nicotinic acid (niacin) being able to terminate an LSD experience.

Quote
Niacin (NADH-dependent enzyme) "One of the metabolites of LSD in the human body is 2-oxy-lsd. It is formed by liver microsomes by an NADH-dependent enzyme," Nicholas J. Giarman (1967). ref. (Axelrod 1957; Hoffer 1955) Use of nicotinic acid (niacin, B3) to abort psychosis - "We have given the subject 100 ug. of LSD; at the height of the experience we injected intravenously 200 mg. of nicotinic acid. Our experience has been that, within a matter of two to five minutes, almost all of the LSD phenomena disappeared, and the subject claimed that he was entirely normal," Abraham Hoffer (1956)
-Otto snow ; LSD

Quote:
Niacin is an antidote against d-lysergic acid diethylamide20 (LSD) and against adrenochrome. It reverses the effect of adrenochrome on the electroencephalogram in human subjects,21 and reverses the psychotomimetic effects of adrenochrome when injected intravenously into human subjects.6 It is also a safe and effective therapeutic agent in the treatment of the schizophrenias and several other psychiatric diseases. It is one of the main elements of Orthomolecular psychiatric treatment. Every physician who has duplicated the niacin schizophrenic studies has corroborated our earlier findings. However the treatment is not accepted because it was introduced during the wrong paradigm, the paradigm of vitamins as prevention only. For a full discussion see the reports.22

- "Schizophrenia: An Evolutionary Defence Against Severe Stress" ; A. Hoffer, M.D., Ph.D.
http://orthomolecular.or.../1994-v09n04-p205.shtml

Quote:
MILLER A I,WILLIAMS H L, MURPHREE H B
Niacin, niacinamide, or atropine versus LSD-25 model psychoses in human volunteers.
J.Pharmacol.& Exper.Therap., 119:169 (1957)
Studies in 16 volunteers using the double blind method showed that atropine (1 mg orally), niacin (up to 600 mg orally), and niacinamide (up to 600 mg orally) did not alter the pattern of response to LSD when they were given in combination with LSD (75 mcg orally). Niacin seemed to produce a release from the anxiety associated with the LSD-induced illusions without lessening or eliminating the illusions.
http://www.lycaeum.org/mv/mu/LSD_niacin.html

Quote:
Contrary to what one report on here read (a female who took 200 mg), Niacin does work effectively IN THE CORRECT AMOUNT.

The flushing effect is not a side-effect, that's exactly how it does what it needs to do.. which is to move the toxins out of the cells and excrete them through the sweat function.. the redness of the skin and burning feeling is the success of the Niacin moving the acid out of your system.. The problem experienced by the female was that she did FAR too much Niacin for her body weight and amount of LSD.. Logic here.

(Don't ask a doctor to describe the function of an OTC drug as to relating to a prohibited substance... they just aren't gonna know.)

Let's compare my experience to hers..

Me:
7 hits acid in 170 lb body = 40ng / pound.
60 mg Niacin effectively treated .40ng / lb.

Her:
1 hit acid in 120 lb body = 8ng/lb.
200 mG Niacin was total overkill for 8ng/lb...

Being that I had 5x the amount of acid taken, and she took 333% more Niacin than I did, that means she actually took 16x the appropriate level of Niacin to have an experience more closely matching mine (the redness was there, and itching, but it wasn't swelling, or doctor visits, and it subsided within 1 hours time..)
https://www.erowid.org/e...iences/exp.php?ID=22682

Quote:

HOFFER A
Studies with niacin and LSD.
Lysergic Acid Diethylamide and Mescaline in Experimental Psychiatry, Grune & Stratton Inc. 1956, p 44
200 mg nicotinic acid given i.v. at the height of the effects of LSD (100 mcg) caused almost all the LSD phenomena to disappear with 2-5 minutes. 3 Gm. nicotinic acid given daily for 3 days prior to 100 mcg LSD caused the LSD phenomena to appear after about 1 hour instead of after 15-30 minutes and seemed to prevent most of the perceptual phenomena, the main changes noted being feelings of unreality and depersonalization
http://www.lycaeum.org/mv/mu/LSD_niacin.html

As far as the nicotinic acid terminating an LSD experience, the claims are varied and the evidence murky, but if you are the type of person that enjoys this type of literary psychedelic archaeology, where metaphorically with pick and brush you dig through mountains of detritus searching for valuable lost artifacts of psychedelia, then you should gets kick out of the research.

My best advice to you would be to fully understand the pharmacology of psychedelics as well as the pharmacology of your medication.

https://www.nature.com/articles/npp201786/tables/1
The link above gives you a table elucidating Receptor Interaction Profiles for LSD and Other Classic Serotonergic Hallucinogens at Human Receptors. This should be a good place to start as far as psychedelics go.


https://www.google.com/url?sa=t&source=web&rct=j&url=https://maps.org/research-archive/w3pb/2008/2008_Passie_23067_1.pdf&ved=2ahUKEwiZm87Os4vfAhXuFzQIHV7QCWkQFjACegQIARAB&usg=AOvVaw3l5HqYGJxDpFld940NHRth

Offline kikyo

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Re: Can anyone help me understand this??
« Reply #2 on: December 09, 2018, 10:20:45 PM »
Wow..I can not thank you enough for all that information.  I truly appreciate your time. I am sure it has been asked many times.  Soooooo...I guess I am kind of screwed if I take acid.  I can TRY again...I will not use the Xanax.  I fear it will not be enough to get my trip back.  You are insanely educated in this area.....I am not so great at chemistry.  It is so sad for me though.  There is nothing else I can really do to change it.  dammit!..THANK YOU...any more suggestions are gladly accepted....I knw your time is precious...I thank you for it.
m