Still see a lot of confusion on this topic to this present day, will present an overview of the major difference:
Metta_morpheus said (concerning a rue seed based journey):
Differences between caapi and rue: What are Ayahuasca analogues?
hxxp://www.ayahuasca.com/amazon/botany-ecology/what-are-ayahuasca-analogues/
Thh or tetrahydroharmine causes serotonin reuptake inhibition. Serotonin reuptake inhbition is also caused by traditional cactus, shrooms, ibogaine, Amazonian snuff's (which work for 3 hours) and the semi-synthetic discovered acid or Hofmann's potion.
"Serotonin reuptake inhibition is stimulating" (Ref 5), and also allows the day to day survival filters in the brain (the 5-ht1a receptors which make up more than 80% of brain 5-ht) to be shut down so that the mind can really expand beyond the filtered boundaries and doors which allow us to survive in everyday life...to achieve a new level of higher consiousness.
Have dreamed of caapi + hawaiian psychotria over 60 times over the years, it is phenomenal divine "mysterious tea" as the UDV calls it.
Further below in the chart from the PLO study, we see that 5-meo-dmt is the world's strongest 5-ht1a receptor agonist, or SRI with a reading of 4.00max, which means it is off the charts strong when it comes to serotonin reuptake blockage.
It is often found in combination with dmt in Amazonian snuff's as dmt on it's own lacks this SRI (serotnin reuptake inhibiton) quality. But when combined with either 5-meo-dmt or bufotenin (another strong SRI) you get the full monty or combination of DMT's extremely strong agonism at the rest of the brain's other 20% of 5-ht receptors, with 5-meo-dmt or bufotenin from the snuff's blocking the rest of the brain's 80% of brain 5-ht at 5-ht1a.
"DMT" cannot do it all...in order to be as potent as it is at 20% of brain 5-ht, it must give up the agonism of 5-ht1a which requires another molecule such as 5-meo-dmt, bufotenin, thh, or other SRI acting molecules in combination with it, ie "teamwork".
James Oroc, "The New Psychedelic Revolution", 2018 said
hxxp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009019
Breadth of Receptor Binding, 4.00=max, 0.00=min
Thomas S. Ray's study shows a value of 3.57 at SERT for Ibogaine (4.00 is max). Ibogaine has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate.
Thomas S. Ray Receptorome study, 4.00=max, 0.00=min.
Tetrahydroharmine (serotonin reuptake inhibitor, it is an SRI)
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Additional 1988 study which backs up the 2011 Thomas S. Ray receptorome study:
Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture - PubMed
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As we go thru day to day life, the brain serotonin filters (or gates) are in place so that we will not be overwhelmed by the perception of the way things would appear to an un-filtered mind, or "Mind at Large" as Aldous Huxley describes it in "Doors of Perception" as "infinite or eternal". (Ref 5) He also referred to the visions as coming from "the other world" in his book "Moksha". I prefer to think of it in similar terms as well "the spirit world" or "the other world". 5-ht1a inhibition while the psychedelic molecule works in the place of serotonin at the other 20% of brain 5-ht theoretically causes this filter system to be lifted, and the infinite mind to manifest in combination with psychotria for example.
References:
(1) Ray, Thomas S. "Psychedelics and the Human Receptorome", Feb 2 2010, PLOS one research article.
(2) Naranjo, Claudio. "Psychotropic Properties of the Harmala Alkaloids", Ethnopharmacologic search for psychoactive drugs, Jan 28-30, 1967.
(3) Nichols, Charles D. "Serotonin Receptor Signaling and Hallucinogenic Drug Action", The Heffter Review of Psychedelic Research, Volume 2, 2001.
(4) Dumuis, Sebben, Bocaert. "Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture", Molecular Pharmacology, Feb 1988; 33(2):178-86.
(5) Goodman Ph.D, Neil. "The Serotonergic System and Mysticism", 2002.
(6) Bulling, Schicker, Zhang, Steinkellner, Stockner, Gruber, Boehm, Freissmuth, Rudnick, Sitte, Sandtner, "The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters", J Biol Chem. 2012 May 25; 287(22): 18524-18534.
(7) Nichols Ph.D, David. "LSD and it's Lysergamide Cousins", The Heffter Review of Psychedelic Research. 2001;2:80-87.
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This quote from Trips might help provide some clarity:
Quote from TIHKAL by Dr. Shulgin "More studies on tetrahydroharmine are absolutely imperative."
Trips (from this forum here on 12/2/2011):
Metta_morpheus said (concerning a rue seed based journey):
The nodding off like sedation is from the rue seeds, give caapi a dream, real traditional Ayahuasca consist of Caapi + psychotria or chaliponga. The high levels of thh in caapi are stimulating like coffee. Rue contains less than 1% thh. However, thh is the 2nd highest alkaloid in caapi. This stimulated entheogenic state interacts with the minor sedating harmaline in the caapi, resulting in an otherworldy wide awake trance or dream-like state (stimulation + the sedation). This yin and yang is often found in the plant world.But to me it looked like they were napping for an hour and a half basically. Is it usually that sedative, or maybe to much rue tea?
Differences between caapi and rue: What are Ayahuasca analogues?
hxxp://www.ayahuasca.com/amazon/botany-ecology/what-are-ayahuasca-analogues/
Thh or tetrahydroharmine causes serotonin reuptake inhibition. Serotonin reuptake inhbition is also caused by traditional cactus, shrooms, ibogaine, Amazonian snuff's (which work for 3 hours) and the semi-synthetic discovered acid or Hofmann's potion.
"Serotonin reuptake inhibition is stimulating" (Ref 5), and also allows the day to day survival filters in the brain (the 5-ht1a receptors which make up more than 80% of brain 5-ht) to be shut down so that the mind can really expand beyond the filtered boundaries and doors which allow us to survive in everyday life...to achieve a new level of higher consiousness.
Have dreamed of caapi + hawaiian psychotria over 60 times over the years, it is phenomenal divine "mysterious tea" as the UDV calls it.
Further below in the chart from the PLO study, we see that 5-meo-dmt is the world's strongest 5-ht1a receptor agonist, or SRI with a reading of 4.00max, which means it is off the charts strong when it comes to serotonin reuptake blockage.
It is often found in combination with dmt in Amazonian snuff's as dmt on it's own lacks this SRI (serotnin reuptake inhibiton) quality. But when combined with either 5-meo-dmt or bufotenin (another strong SRI) you get the full monty or combination of DMT's extremely strong agonism at the rest of the brain's other 20% of 5-ht receptors, with 5-meo-dmt or bufotenin from the snuff's blocking the rest of the brain's 80% of brain 5-ht at 5-ht1a.
"DMT" cannot do it all...in order to be as potent as it is at 20% of brain 5-ht, it must give up the agonism of 5-ht1a which requires another molecule such as 5-meo-dmt, bufotenin, thh, or other SRI acting molecules in combination with it, ie "teamwork".
James Oroc, "The New Psychedelic Revolution", 2018 said
LSD scientist & founder of Heffter Institute Dr. Nichols:One of my favorite metaphors of the 5-meo experience is that you are a drop, and then you return to the ocean. Just as a drop of water can no longer distinguish itself from the rest of the sea, so too my consciousness can no longer distinguish itself from the whole of the cosmic ocean.
Dr. NicholsLSD has very strong potency in blocking the action of serotonin. The morpholide lysergamide cousin had only about 1/10th the potency in blocking serotonin. Of the 5 diferent dialkylamides we studied LSD was the most potent and specific serotonin antagonist. (Ref 7)
Thomas S. Ray, Psychedelics and the Human Receptorome (2010):5-ht1a makes up >80% of brain 5-ht...5-ht1a agonism blocks serotonin. (Ref 3)
Psychedelics and the Human Receptorome
We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference...
journals.plos.org
Breadth of Receptor Binding, 4.00=max, 0.00=min
Ibogaine binds directly to the serotonin transporter (SERT), so it does not have to target the 5-ht1a substrate pathway. This could be likely what happens with tetrahydroharmine, as THH and ibogaine have similar basic beta-carboline structures.LSD: 5ht1a = 3.73, DMT: = 0.00, psilocin = 2.88, mescaline = 3.61, 5-meo-DMT: = 4.00 (make up >80% of brain 5-ht)
LSD: 5ht1b = 4.00, DMT: = 0.00, psilocin = 2.19, mescaline = 0.00, 5-meo-DMT: = 2.41
LSD: 5ht1d = 3.70, DMT: = 3.91, psilocin = 3.40, mescaline = 0.00, 5-meo-DMT: = 3.48
LSD: 5ht1e = 2.62, DMT: = 3.28, psilocin = 3.03, mescaline = 3.16, 5-meo-DMT: = 1.72
LSD: 5ht2a = 3.54, DMT: = 2.58, psilocin = 2.14, mescaline = 0.00, 5-meo-DMT: = 0.98
LSD: 5ht2b = 3.11, DMT: = 3.91, psilocin = 4.00, mescaline = 3.97, 5-meo-DMT: = 0.69
LSD: 5ht2c = 3.11, DMT: = 3.42, psilocin = 2.52, mescaline = 0.00, 5-meo-DMT: = 1.55
LSD: 5ht5a = 3.64, DMT: = 3.16, psilocin = 2.83, mescaline = 0.00, 5-meo-DMT: = 1.84
LSD: -5ht6 = 3.75, DMT: = 3.35, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 2.73
LSD: -5ht7 = 3.77, DMT: = 4.00, psilocin = 2.82, mescaline = 0.00, 5-meo-DMT: = 3.69
LSD: ---D1 = 2.34, DMT: = 3.51, psilocin = 3.37, mescaline = 0.00, 5-meo-DMT: = 2.38
LSD: -A-2A = 2.93, DMT: = 2.75, psilocin = 1.36, mescaline = 2.92, 5-meo-DMT: = 0.00 (aesthetic/beauty adrenal a2a)
LSD: -A-2B = 0.00, DMT: = 3.53, psilocin = 1.57, mescaline = 0.00, 5-meo-DMT: = 0.86 (aesthetic/beauty adrenal a2b)
LSD: -A-2C = 0.00, DMT: = 3.53, psilocin = 1.03, mescaline = 4.00, 5-meo-DMT: = 1.57 (aesthetic/beauty adrenal a2c)
Thomas S. Ray's study shows a value of 3.57 at SERT for Ibogaine (4.00 is max). Ibogaine has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate.
Thomas S. Ray Receptorome study, 4.00=max, 0.00=min.
Ibogaine (inhibits both serotonin and dopamine reuptake transporters, it is an SDRI or serotonin & dopamine reuptake inhibitor)Ibogaine: 4.00 Sigma2, 3.57 SERT, 3.02 DAT, 3.01 NMDA, 2.88 KOR, 2.67 MOR, 2.55 Sigma1, 2.22 M3, 2.16 5ht2a, 1.96 M1, 1.72 M2, 1.47 D3;
0.00: DOR, 5ht1b, 5ht1d, 5ht1a, H1, 5ht2c, D2, D1, Beta1; ND: Alpha2C, D5, D4, Alpha2B, Imidazoline1, NET, Alpha2A, 5ht5a, 5ht6, 5ht7, Alpha1B, 5ht1e, 5ht2b, M4, M5, Alpha1A, H2, CB2, CB1, Ca+Channel, Beta2
Tetrahydroharmine (serotonin reuptake inhibitor, it is an SRI)
----------------------------------------------------------------------------
Additional 1988 study which backs up the 2011 Thomas S. Ray receptorome study:
Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture - PubMed
N-Methyltryptamine (NMT) found in barks: N-Methyltryptamine - Wikipedia5-HT1A agonist: All the tryptamine derivatives substituted in position 5 of the indol were potent agonists [5-HT, 5-CT, 5-MeO-N,N-DMT, 5-methoxytryptamine, and bufotenine (5-ho-DMT)],
whereas tryptamine, N-methyltryptamine (NMT), and N,N-dimethyltryptamine (DMT) were very poor agonists.
------------------------------------------------------------------
As we go thru day to day life, the brain serotonin filters (or gates) are in place so that we will not be overwhelmed by the perception of the way things would appear to an un-filtered mind, or "Mind at Large" as Aldous Huxley describes it in "Doors of Perception" as "infinite or eternal". (Ref 5) He also referred to the visions as coming from "the other world" in his book "Moksha". I prefer to think of it in similar terms as well "the spirit world" or "the other world". 5-ht1a inhibition while the psychedelic molecule works in the place of serotonin at the other 20% of brain 5-ht theoretically causes this filter system to be lifted, and the infinite mind to manifest in combination with psychotria for example.
References:
(1) Ray, Thomas S. "Psychedelics and the Human Receptorome", Feb 2 2010, PLOS one research article.
(2) Naranjo, Claudio. "Psychotropic Properties of the Harmala Alkaloids", Ethnopharmacologic search for psychoactive drugs, Jan 28-30, 1967.
(3) Nichols, Charles D. "Serotonin Receptor Signaling and Hallucinogenic Drug Action", The Heffter Review of Psychedelic Research, Volume 2, 2001.
(4) Dumuis, Sebben, Bocaert. "Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture", Molecular Pharmacology, Feb 1988; 33(2):178-86.
(5) Goodman Ph.D, Neil. "The Serotonergic System and Mysticism", 2002.
(6) Bulling, Schicker, Zhang, Steinkellner, Stockner, Gruber, Boehm, Freissmuth, Rudnick, Sitte, Sandtner, "The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters", J Biol Chem. 2012 May 25; 287(22): 18524-18534.
(7) Nichols Ph.D, David. "LSD and it's Lysergamide Cousins", The Heffter Review of Psychedelic Research. 2001;2:80-87.
----------------------------------------------------------------------------
This quote from Trips might help provide some clarity:
Quote from TIHKAL by Dr. Shulgin "More studies on tetrahydroharmine are absolutely imperative."
Trips (from this forum here on 12/2/2011):
professor8 (here at this forum, see his vitamin c experiments: 11/1/2010):As to how the THH altered the experience -> I find rue extract+DMT to be very similar to mushrooms. I found the THH added to the rue+DMT to shift the experience to a state much closer to that provided by LSD. It was more clear, more energetic, more focused, and when confusion struck it was definitely more "acid-like".
DMT + tiny amounts of 5-meo-dmt (from Oroc's book):Tetrahydroharmine has the ability to raise your vibration in a most powerful, yet subtle way. It brings a crystalline prismy texture to spice and adds a super clear watery dimension to Aya, like looking down through 10meters of shimmering Caribbean Sea on clear blue day.
It brings a dimension of pure light to the entheogenic experience and encourages entities & intelligences of only the Highest Order. If one is not accustomed to perceiving these experiences with a spiritual perspective most of the nuances & subtleties THH brings on are overlooked and remain unseen and one would better enjoy Harmaline as a house painter chooses a roller over a brush, its about preference & choice.
-----------------------------------------------------------------------------As an experiment (and in a foreign land) I smoked the last of the Bufo alvarius venom (the story of whose collection is described within the pages of Tryptamine Palace) with some ‘regular’ DMT (extracted from Jurema Preta.). In the vast majority of my early nigerine (DMT) experiences, I encountered visual fields of ‘dots’ that would come together to form images, much like the pointillism style of painting developed by Georges Seurat or the Australian Aboriginal song-line paintings.
With the addition of the 5-MeO-DMT containing toad-venom to the DMT however, the visual characteristic was completely different and totally unique to my experiences so far. On this occasion there was a complete lack of ‘dots’ or ‘points’ of any kind, the fine lines of the constantly changing imagery were like those painted with a single-hair brush on Tibetan thangkas and due to the overwhelming artistry of what I was seeing, I could only think of the vaulted ceiling of the Sistine Chapel in comparison.
Sistene Chapel: This was without a doubt the most ‘visionary’ experience I have ever been fortunate enough to encounter and I lay there with my eyes shut watching the most fantastic parade of the Collective Unconsciousness imaginable, wishing that it would never end, and as I sit here now I can not even describe one tiny corner of it, since every image in the multitude of imagery was in such constant motion that they defied all but a glimpse. And then moments later, like a tent collapsing when its ropes are cut, the vision is gone. Leaving only a struggle of words to explain it, since nothing before or after has come close to this experiences visual majesty.
This experience leads to the interesting question of selectively combining DMT and 5-MeO-DMT for a more visionary and somewhat less overwhelmingly transcendental experience. (Or for the other way around). This combining of the two endogenous entheogens is being tested in changa blends (reportedly at a 90% DMT to 10% 5-MeO-DMT ratio), while many Pharmahuasca urban-shamans are also adding 5-MeO-DMT to their ayahuasca-analogues to transform and deepen that experience. It seems likely to me that the combining of DMT and 5-MeO-DMT in various ratios and manners will only become more popular as the exponentially increasing number of psychonauts search for new psychological terrain to explore.