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17/F    The one big quest of her heart is knowing what keeps the world from falling apart ~ Zarish~
29/M/Selangor    Still searching the best of me.

Poems

I thought it right to assess some antidepressants, which philosophers are more inclined to call mood enhancers.
This was during my foray into human enhancement, substances intended to enhance physicality, cognition or mood. Nootropic compounds concern the latter two categories.

The most commonly prescribed mood enhancers are serotonin reuptake inhibitors (SRIs), but it takes over a week for these compounds reach their peak effect.
Thus I approached them with the notion that a limited dosage might point to their character, though  not reveal. These considerations in mind, I set about acquiring a few miscellaneous anti-D's.

Fluoxetine was the first successful selective serotonin re-uptake inhibitor (SSRI), better known by its original brand-name Prozac. Fluoxetine has an acute biological half-life of between 1-3 days. Presence of a trifluoromethyl group on the compound deserves note, I wonder what the presence of electronegative fluorine atoms add to the psychoactive flavor of a compound (subjective effects).
I administered a single dose by mouth, there was some indication of subjective character. Light serotonergic sensations and seemingly benign mood-dampening, there is a ****** towards the positive. Waking headspace relatively uninteresting. Observed hints of oneirogenesis, did not manifest in enough character to be detailed - a sort of vivid, 'pulsive wandering, more pronounced in contrast to its waking character.
Good experiment, interesting results.
Ligand     Ki (nM)   Ki (nM)
Target      Flx            Nflx
SERT        1               19
NET         660           2700
DAT         4180         420
5-HT2A   200           300
5-HT2B    5000         5100
5-HT2C    72.6          91.2
α1             3000         3900
M1            870           1200
M2            2700         4600
M3            1000         760
M4            2900         2600
M5            2700         2200
H1            3250         10000

Sertraline is another popular SSRI, also known by it's original brand-name Zoloft. Sertraline has a variable half-life, on average 26 hours.
It's metabolite, desmethylsertraline, has a half life between 62-104 hours but is a far less potent Serotonin Releasing Agent (SRA).
The presence of two chlorine atoms is interesting. The usual, phenomenal serotonergicity is present and pushing towards the positive.
Some nausea, particularly when hungry (this disappeared after some minestrone soup). Some faintness after physical exertion. This dose did not promote onirogenesis. There was a moment of cognitive distortion when the proportions of a focal object seemed to be growing in-and-out, shifting in size.
Site                 Ki (nM)
SERT              0.15–3.3
NET               420–925
DAT               22–315
5-HT1A       >35,000
5-HT2A          2,207
5-HT2C          2,298
α1A        ­        1900
α1B                 3,500
α1D                 2,500
α2                  477–4,100
D2                  10,700
H1                  24,000
mACh           427–2,100
σ1                   32–57
σ2                   5,297

Escitalopram is an SSRI commonly prescribed for major depression and generalised anxiety. It is the (S)-stereoisomer of citalopram. The biological half-life is of escitalopram is between 27-32 hours.
I administered a dose and thought the phenomenal serotonergicity less apparent than fluoxetine but then gastro-intestinal disturbance was noted, I surmised it has a high affinity for 5-HT2C.
Any oneiric qualities were not readily apparent after a single dose, relatively little visual imagery which is understandable given its lack of affinity for 5-HT2A. I found this to be philosophically interesting. Mood elevation observed in bursts of conversation and as odd sensations, possible mental discomfort.
Ligand,
Recptr     Ki (nM)
SERT       2.5
NET        6,514
5-HT2C   2,531
α1            3,870
M1           1,242
H1           1,973

Venlafaxine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI). Venlafaxine and its metabolites are active for about 11 hours.
Initial subjective effects similar to a very light empathogenic stimulant. Perception of altered attention-span/increased reflexive response; energizing yet paradoxically much yawning.
Ligand,  Vnfx      Dvnfx
Recptr    Ki(nM)  Ki(nM)
SERT  ­    82           40.2
NET       2480        558.4

Tianeptine is a tricyclic antidepressant (TCA) with an unusual mechanism of action. It is an atypical agonist of the μ-opioid receptor and has been described as a (selective) serotonin reuptake enhancer (SRE). It has a short duration as sodium salts [prescribed form] of between 2-4 hours but as sulfate this can be notably extended, some of its metabolites are active for longer than tianeptine itself.
Definitely anxiolytic, quite artificial; possible aphrodisiac. I find its opioid activity dissuading, requires caution.
Site          Ki (nM)
MOR       383–768 (Ki)
                 194 (EC50)
DOR      >10,000 (Ki)
                 37,400 (EC50)
KOR      >10,000 (Ki)
                 100,000 (EC50)
All other transporter/receptor/sub-receptor values are >10,000 (Ki).

Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) with affinity for some nicotinic receptors. Bupropion and its metabolites are active for between 12-36 hours. Interestingly it is a substituted cathinone.
Initial subjective effects similar to a fairly light stimulant. Perception of increased attention-span and improved cognition. It is an onirogen that is neutral in quality, enhancing vivid dreaming (a boon of its nicotinic affinity which is counteracted if the stimulant component impinges on sleep). Completely absent of serotonergicity, curious.
The N-tert-butyl group's effect is most interesting, how it affects metabolism and to what extent ROAs alter pharmacokinetics.
I took 150mg ******, as extended and as instant release (the latter was more pronounced). I thought an altered pharmakinetic profile might result from bypass of hepatic metabolism, so I tried 25mg insufflated and felt as if there was effect that it differed slightly from oral ROAs, but also worried that its metabolic fate is thence unknown (compare to the neurotoxic 3-CMC). What of other bupropiologues,
for example, 3-Methyl-N-tert-butyl-methcathinone? Indeed.
                        Bupropion    R,R-Hydroxybuprpn   Threo-hydrobuprpn
AUC               1                     23.8                                  11.2
Half-life         11 h                 19 h                                 31 h
IC50 (μM)
DAT               0.66                  inactive                          47 (rat)
NET               1.85                   9.9                                  16 (rat)
SERT              inactive          inactive               ­            67 (rat)
α3β4 nic         1.8                   6.5                                   14 (rat)
α4β2 nic         12                     31                                   no data
α1β1γδ nic     7.9                    7.6                                  no data

Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA), its monoamine oxidase inhibition lasts about 8–10 hours and wears off completely by 24 hours. Inhibiting the decomposition of monoamines (e.g. serotonin, norepinephrine and dopamine) increases their accumulation at an extracellular level. It tends to suppress REM sleep and so it lacks oneirogenic properties.
Feeling of well-being, less constrained by the usual anxieties; openness. Relatively unnoticeable side-effects when diet is carefully managed. Made the mistake of eating a cheese and turkey sandwich (i.e. foodstuff rich in tryptophan/tyramine), indications of serotonergicity later became apparent: feelings of overheating and flushing, slight sweating, racing thoughts and anxious discomfort. A stark reminder of Shulgin's old adage: "there is no casual experiment".
Combination with a select few tryptamines (not 5-MeO-xxT) should be safe, and synergistic (perfect for pharmahuasca); reputed to potentiate GHB. However, generally it is extremely dangerous to combine with serotonergic drugs.
Anais Vionet  Aug 2022
junkavore
Anais Vionet Aug 2022
Sophy’s mom sent her a giant case of “Fun dip” - a thousand packets of sour, fruit-flavored sugar. Is there anything more junkavore a parent can buy a child - well, ok, an 18 year old?

She LOVES them and so does Leong who’s from China where, apparently, you can’t get useless, non-nutritional snacks. The two of them are running around, all sugar hyped with their emo-grape-chemical-lips, sticking out phosphorescent-green-tongues and threatening to tickle everyone with cherry-red-fingers. It has me wondering, should I switch to dentistry?

Our college prep has moved to a new phase - with just 16 days until we move back into our residential college. We’re suddenly sleeping-in. It’s nothing we planned or even discussed, it just started happening. We go to sleep around 10pm and sleep until 10am - or later. I think we all subconsciously realized that soon we’ll be back to sleeplessness.

I’m peachy - in a great mindspace - these days. I’m well rested (see above), we’re killing our sophomore prep - even the physics, my period was a nothing, we spent over two hours in Ulta sampling perfumes, I have a new Macbook M2 (see below) and I painted my nails in tropical colors.

The FedEx man rolled up yesterday. “Anyone expecting something?” Anna asked the crowd of roommates attracted by the driver bringing packages to the door, two at a time. No one was expecting anything. Eventually he’d delivered 8, back to school, M2-Macbooks (2 in each color) - one for everyone - from my Grandmère.

If that sounds needlessly ostentatious, then you’re thinking she went to the mall and paid full price, but she probably just traded Tim Cook a half ton of lithium or something - one of her companies mines it - in Chili - I think. But still, my roommates were blagabloo.

I picked a starlight one. An odd thing about the new, flat Macbook Air design is that you can’t pick it up with one hand - unless you hook it underneath with a long fingernail - what are guys going to do?
BLT Marriam Webster word of the day challenge: Ostentatious: something overly elaborate that attracts envy.

Slang:
junkavore = someone who eats completely unhealthily
peachy = happy and healthy
blagabloo = ecstatic