THH

[Virgin]

This paper basically says that it is not an MAOI.

https://wiki.dmt-nexus.me/w/images/2/26/Pharmacokinetics_of_hoasca_in_healthy_humans.pdf

 

[Ginkgo]

Thanks, this is a very interesting subject. A quote from the paper you linked to:

In the present study, plasma concentrations of harmine alone were several orders of magnitude greater than its reported EC50. By considering the high concentrations of harmala alkaloids in hoasca that are typically ingested, it could be argued that this amount is aufficient to inhibit both isozymes of MAO. Due to its weak affinity, and in the presence of high harmine concentrations, THH may not play a significant role in the inhibition of MAO. Instead, THH may contribute psychoactivity indirectly by inhibiting the uptake of 5-HT in platelets and presynaptic neurons (Airaksinen et al., 1980), further increasing extracellular 5-HT levels over those seen from MAO inhibition alone, as significant amounts of this alkaloid are known to occur in B. caapi (Rivier and Lindgren 1972; Callaway et al., 1996). The pharmacokinetic profile of THH (Fig. 2) and related parameters (Table 2) also suggests some independence from interactions between harmine and MAO. It is possible that the activity of THH may even be potentiated by MAO inhibition.

It must be noted that the consensus is that higher dosages is needed for THH to enable oral DMT than other harmala alkaloids. I don't know what to really make of this, as most of the samples of "THH" likely isn't THH at all, as they are from Flowing Visions. I look forward to see what other people have to say about this subject!

 

[SnozzleBerry]

This paper basically says that it is not an MAOI.

https://wiki.dmt-nexus.me/w/images/2/26/Pharmacokinetics_of_hoasca_in_healthy_humans.pdf

Imo, that's a very misleading way of putting it...

Due to its weak affinity, and in the presence of
high harmine concentrations, THH may not play
a significant role in the inhibition of MAO. Instead,
THH may contribute psychoactivity indirectly
by inhibiting the uptake of 5-HT in platelets
and presynaptic neurons (Airaksinen et al., 1980),
further increasing extracellular 5-HT levels over
those seen from MAO inhibition alone, as significant
amounts of this alkaloid are known to occur
in B. caapi (Rivier and Lindgren 1972; Callaway
et al., 1996). The pharmacokinetic profile of THH
(Fig. 2) and related parameters (Table 2) also
suggests some independence from interactions between
harmine and MAO. It is possible that the
activity of THH may even be potentiated by
MAO inhibition.

 

[Virgin]

This paper confirms that THH is only a very weak MAOI.

Recombinant human monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) were obtained from BD Biosciences (Bedford, MA). To investigate the effect of extracts on MAO-A and MAO-B, the kynuramine deamination assay was adapted for 96-well plates. The inhibition kinetics of MAO-A and MAO-B by inhibitors/extracts was determined in a range expected to produce 30–90% inhibition. The IC50 values for extracts, pure compounds and reference standards were determined at five concentrations of 1, 0.1, 0.01, 0.001 and 0.0001 μg/mL for MAO-A, where as for MAO-B, percent inhibitions of all crude extracts were evaluated at three concentrations, 100, 10 and 1 μg/mL. All experiments were carried out in duplicate. A fixed substrate concentration and varying inhibitor concentrations were used to determine the IC50 value at the point where 50% inhibition of the catalytic activity of the enzyme occurred. For MAO-A, the substrate concentration of 80 μM kynuramine was chosen because the apparent Km value for substrate binding has been reported previously was approximately 40 μM (Parikh et al., 2002). Since Km is the substrate concentration at half Vmax, therefore, 2 × Km (2 × 40 = 80 μM), was selected for determining IC50 values. Similarly, for MAO-B, substrate concentration of 50 μM kynuramine was chosen. The assay was performed with the addition of inhibitor. Inhibition was calculated as percent of product formation compared to the corresponding control (enzyme–substrate reaction) without the inhibitors. The reactions were carried out in 0.1 M potassium phosphate buffer at pH 7.4. Incubations mixtures contained 5 μg/mL of MAO-A (50 μL in buffer) and 10 μg/mL of MAO-B (50 μL in buffer). The inhibitor was dissolved in DMSO or in buffer (if not dissolved in DMSO). The total reaction volume was 200 μL yielding a final DMSO concentration of 1.0% in the reaction mixture. The reaction mixtures were pre-incubated for 10 min at 37 °C followed by the addition of MAO-A/MAO-B to initiate the reactions. Reactions were incubated for 20 min at 37 °C and were stopped immediately by the addition of 75 μL of 2N NaOH. The formation of 4-hydroxyquinoline was determined fluorometrically by SpectraMax M5 fluorescence plate reader (Molecular Devices, Sunnyvale, CA) with an excitation and emission wavelength of 320 and 380 nm, respectively, using the SoftMax Pro program.

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease - PubMed

Collectively, these results give additional basis to the existing claim of Banisteriopsis caapi stem extract for the treatment of Parkinsonism, including other neurodegenerative disorders.

www.ncbi.nlm.nih.gov

 

[SnozzleBerry]

But you would agree, would you not, that there is a big difference between being a weak RIMA and not an RIMA?