harmalas psychadelic effect due to maoi activity or inherent character

[Jin]

is harmalas psychadelic effect due to maoi activity or due to its inherent character ?

if its because of maoi activity do other prescription maoi's have a similar psychadelic effect ?

 

[embracethevoid]

It's a good question. From my own experience I would say that it is their intrinsic nature. Once monoamine oxidase is maximally inhibited or at least inhibited such that there is enough free harmala in the brain, psychedelic effects begin; this would be at say 4g of syrian rue while 3g would be totally MAO inhibiting without any psychedelia.

Then any additional harmala creates an incredibly steep dose-response curve, with 5g of rue being twice as subjectively intense as 4g and 6g being many more times intense than 5g. This of course supports the above hypothesis.


Here's some digging around I did:

Binding of b-carbolines and related agents at serotonin (5-HT2
and 5-HT1A), dopamine (D2) and benzodiazepine receptors

4.4. Hallucinogenic activity and binding
It has been shown that a relationship exists between the 5-HT2A receptor affinity of the classical hallucinogens and their human hallucinogenic potencies (Glennon, 1996, 1998 ).
Furthermore, examples of the different classes of agents (e.g. DMT, 5-methoxy DMT, DOB, DOPR as well as harmaline) have been demonstrated to produce common stimulus effects in rats trained to discriminate DOM from vehicle (Glennon, 1996 ).

Most of the b-carbolines in Table 1 have not been examined in humans; however, harmine and harharmaline are generally considered hallucinogenic (reviewed: Grella et al., 1998 ). Although their low human potencies are consistent with their modest affinities at 5-HT2A receptors (Table 1; Grella et al., 1998 ), it cannot yet be concluded that their hallucinogenic effects are mediated via a 5-HT2A mechanism. It can be concluded, however, that their hallucinogenic effects, or common stimulus effects in DOM-trained animals, likely do not involve a 5-HT1A, D2 or BZ mechanism.

The b-carbolines examined, except for b-CCM, lack affinity for BZ receptors. Certain indolealkylamine hallucinogens such as DMT and 5-methoxy DMT display high affinity for 5-HT1A receptors (Table 2), but harmine and harmaline lack 5-HT1A receptor affinity. Furthermore, potent classical hallucinogens such as DOB and DOPR (Table 3) display little to no affinity for 5-HT1A receptors. Likewise, the b-carbolines, like the phenylisopropylamine hallucinogens, lack affinity for dopamine D2 receptors.

This paper delivers quite the motherload, a large list of binding affinities for some harmaloids incl. harmaline: Binding of -Carbolines at 5-HT2 Serotonin Receptors


My pharmacology knowledge isn't up to scratch so I can't really comment on how these receptor affinities create the subjective experience. All I know, from bioassay, is that there is a floor effect at which psychedelia starts and additional inhibition stops; such that the dose reaching your mind actually "begins" at say 3g of syrian rue; so that 5g corresponds to 2g hitting the brain while 4g => 1g in the brain.

 

[jamie]

Harmalas are active for me long BEFORE MAO is fully inhibited..not just after.

Harmalas hit many receptors beyond just their MAO activity..they are NMDA antagonists for one...