Extreme stim tolerantie

djeemen schreef:Dit zal denk ik verschillen per persoon (fysiologisch/neurologisch) en ook per levensstijl. Als je gezonder leeft herstel je sneller. Tolerantie is imo ook een vorm van herstellen na gebruik. Ik denk dat je met 2 maanden wel een eind zal komen maar you don't know until you try.

Druks schreef:Ik denk dat je vooral te maken hebt met down regulation van de receptoren, niet zozeer van te weinig dopamine. Tyrosine B6 verhoogt je dopamine maar doet niet perse iets tegen de down regulation. 2 Maanden pauze nemen zou afdoende moeten zijn om je tolerantie flink te verlagen.

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2C-B_receptor_profile.png (9.7 KiB) 1381 keer bekeken

Receptor affinity profiles of psychedelic drugs, ordered by decreasing affinity. The vertical axis is normalized pKi (npKi). Horizontal axis is a list of forty-two receptors, arranged in order of decreasing affinity for each individual drug.

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Normalization

The raw Ki values are distributed over several orders of magnitude, thus a log transformation is a good first step in the analysis. In addition, higher affinities produce lower Ki values, thus it is valuable to calculate: pKi = −log10(Ki). Higher affinities have higher pKi values, and each unit of pKi value corresponds to one order of magnitude of Ki value. Table S4 presents the raw data transformed into pKi values. Generally, the highest Ki value generated by NIMH-PDSP is 10,000, which produces a pKi value of −4 (although a value of 10,450 was reported for 5-MeO-TMT). For non-PDSP data gathered from the literature, some Ki values greater than 10,000 are reported (i.e. 12,500, 14,142, 22,486, 39,409 and 70,000 for ibogaine).

When the primary assay did not produce >50% inhibition, the Ki value is treated as >10,000. When the primary assay hit, but the secondary assay was not performed, the Ki value is also treated as >10,000. If a secondary assay produced a Ki value significantly greater than 10,000, it is usually also reported as >10,000. The lowest Ki value in the data set of this study is 0.3 (lisuride at 5-HT1A) and the highest value is 70,000 (ibogaine at D3), thus collectively, the data in this study cover nearly six orders of magnitude of Ki values. However, ignoring values reported as >10,000, the Ki values for a single drug in this study never exceed four orders of magnitude in range.

The goal of the normalization used in this study is to factor out potency, in order to allow easy comparison of the multi-receptor affinity profiles of different drugs. The normalization will adjust the highest pKi value for each drug to a value of 4, and set all Ki values reported as >10,000 to a value of zero. Ki values actually measured as greater than 10,000 are not set to zero (i.e. 5-MeO-TMT and ibogaine). We will call this normalized value npKi. Let the maximum pKi value for each drug be called pKiMax. For each individual drug:

If Ki treated as >10,000, then npKi = 0
npKi = 4+pKi−pKiMax
With this normalization:

higher affinities have higher values
affinities too low to be measured will be reported as zero
for each drug, the highest affinity will be set to a value of 4
each unit of npKi value represents one order of magnitude of Ki value
potency is factored out so that drugs of different potencies can be directly compared
This normalization effectively factors out the absolute potency of each drug, and allows us to focus on the relative affinities of each drug at each receptor.

Each compound is initially assayed at 10 µM against each receptor, transporter or ion channel (primary assay). Those that induce >50% inhibition (“hit”) are then assayed at 1, 10, 100, 1,000, and 10,000 nM to determine Ki values (secondary assay). Each Ki value (equilibrium dissociation constant, concentration at which 50% of the hot ligand is displaced by the test ligand) is calculated from at least three replicated assays. Details of how individual assays were conducted can be found at the NIMH-PDSP web site: http://pdsp.med.unc.edu/pdspw/binding.php.

Paradise schreef:Bij mij ging dit snel als ik ging redosen en nachten overslaan.
En 2FMA door de lange werking de downregulatie ook wel in de hand werkt, meer dan kortwerkende 2FA.

spikeycloud schreef:

Paradise schreef:Merk jij ook dat de kater veel groter en langer is als je redosed en een nachtje overslaat?