2011 Thomas S. Ray study: Breadth of Receptor Binding, 4.00=max, 0.00=min
Dr. Nichols (Heffter.org LSD paper):
5-ht1a inhibition by entheogens (in green above) theoretically cause this filter system to be lifted, and the infinite mind to manifest in combination with oral dmt from traditional psychotria for example with the caapi and/or harmalas providing the 5-ht1a inhibition, just as bufotenine in snuff's provide the 5-ht1a inhibition combined with the dmt in the snuff's, resulting in a 3 hour experience ie both examples of Teamwork on how these entheogens are used traditionally in the Amazon.
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. Ibogaine inhibits both serotonin and dopamine reuptake transporters, it is an SDRI or serotonin & dopamine reuptake inhibitor. Tetrahydroharmine is a serotonin reuptake inhibitor, it is an SRI found in caapi. In other words, both are strong serotonin reuptake inhibitors which inhibit over 80% of brain 5-ht at 5-ht1a.
In contrast, as an example, Cocaethylene (coca leaf tea bags soaked in wine, the orally active & potent ingredient formed in the liver from cocaine + ethanol in the 1860's "Vin Mariani" wine popular with both Popes, Thomas Edison and scores of other famous people) increases the levels of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain by inhibiting the action of the serotonin transporter, norepinephrine transporter, and dopamine transporter. These pharmacological properties make cocaethylene a serotonin-norepinephrine-dopamine reuptake inhibitor [SNDRI; also known as a "triple reuptake inhibitor"].
Cocaethylene has a higher affinity for the dopamine transporter than does cocaine, but has a lower affinity for the serotonin and norepinephrine transporters. In McCance-Katz et alia's 1993 study cocaethylene "produced greater subjective ratings of 'High' in comparison with administration of cocaine or alcohol alone."
------------------------------------------------
See this confusion quite a bit on the forums, and will address why Ayahuasca is completely different from smoked or injected dmt. It all started when Western Explorers in the Amazon equated Ayahuasca completely to "orally activate dmt" and ignored the Elephant in the room, which is Caapi.
One difference is that dmt by itself has been found in the Receptorome study to not block serotonin...while the following traditional team players have been found to strongly block serotonin: 5-ho-dmt in Amazonian snuffs, 5-meo-dmt in Amazonian snuffs and the 2nd largest alkaloid in caapi (thh or tetrahydroharmine). All 3 are thus anti-serotonin.
Serotonin blocking is a main effect of all the natural oral entheogens like the semi-synthetic LSD, mescaline, Ayahuasca, mushrooms, 5-meo-dmt & bufotenine (found in snuffs). See 2011 receptorome chart below.
Ibogaine inhibits both serotonin and dopamine reuptake transporters (it is an SDRI or serotonin & dopamine reuptake inhibitor).
Another difference is that these team player master plants in addition to blocking serotonin also provide awake dream effects, completely un-related to night time dreams (Shannon, Antipodes of the Mind) complete with story lines, static, animated & interactive scenery, etc. see "Core corpus of visions" from Benny Shanonon compiled from interviews with hundreds of Ayahuasca session participants several posts below.
DMT is super potent at all the other 5-ht receptor sites, way exceeding even psilocin (see chart below), but in doing so, it must give up 5-ht1a binding, (serotonin blocking) which makes up over 80% of brain 5-ht, so when you combine admixture with components of caapi or rue, you get a "team action".
Question asked:
5-HT1A receptor agonists have traditionally been used in the treatment of mood and anxiety woes.
Great question: LSD, mescaline, Ayahuasca, mushrooms, Amazonian snuffs and 5-meo-dmt not only activate 5-ht1a (80% of brain 5-ht) which in turns breaks down the barriers/gates/doors/filters in the brain which allow us to survive and help to form the ego...but they also act in the place of serotonin (at the other 20% of brain 5-ht receptors). This is what makes the psychedelic molecules different from just the "man-made" 5-ht1a agonist only.
Ayahuasca is named after Caapi, and doesn't even need dmt to call itself Ayahuasca, Plant admixture psychotria DMT mainly acts to light up and color the visions from the Caapi vine according to Ayahuasca Shamans. Experienced Ayahuasqueros can see the visions even in low light or with very little if any admixture plant. DMT can also be made complete with tiny amounts of 5-meo-dmt as it fills in for the missing 5-ht1a serotonin blocking action that is missing with DMT.
New discovery: the recently discovered adrenoglomerulotropine (a hormone of the pineal gland, otherwise known as 6-Methoxytetrahydroharman) is an isomer of tetrahydroharmine, found in caapi. Caapi was said by the Indians to have Telepathine qualities as Ayahuasca was said to facilitate telepathic communication among tribal members.
Also contrary to what Wikipedia states, mescaline does not work thru the 5-ht2a receptor, but mainly thru the adrenal sites and it's strong serotonin blocking action.
Dr. Nichols:
journals.plos.org
hxxp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009019
Breadth of Receptor Binding, 4.00=max, 0.00=min
An example of the importance of adding the serotonin reuptake inhibition properties of 5-meo-dmt for example to dmt (which totally lacks 5-ht1 reuptake properites on it's own) is shown below. This is the same way the snuff's are used in the amazon, as they naturally combine dmt with additives which cause the reuptake of 5-ht like bufotenin for example.
Oroc's experiment of combining 5-meo-dmt with DMT sounds imho very much like a short beautiful transcendental Ayahuasca experience, from his book "Tryptamine Palace":
DMT + tiny amounts of 5-meo-dmt [perhaps similar theoretically to Amazonian snuffs which have a makeup of 7.4% bufotenin (potent 5-ht1a agonist), 0.04% 5-MeO-DMT (potent 5-ht1a agaonist) & 0.16% DMT (zero potency as 5-ht1a agonist)]:
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.
bottom = tetrahydroharmine (serotonin reuptake inhibitor)
------------------------------------------------LSD: 5ht1a = 3.73, DMT: = 0.00, psilocin = 2.88, mescaline = 3.61, 5-meo-DMT: = 4.00 (these serotonin filters/gates/barriers/doors make up >80% of brain 5-ht & are broken down when 5-ht1a is agonized)
Dr. Nichols (Heffter.org LSD paper):
As we go thru day to day life, the 5-ht1a brain serotonin filters (gates, or day to day survival filters as I like to call them) which make up over 80% of brain 5-ht 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". 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".LSD has very strong potency in blocking the action of serotonin. LSD is strongly "anti-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. 5-ht1a makes up >80% of brain 5-ht receptors.
5-ht1a inhibition by entheogens (in green above) theoretically cause this filter system to be lifted, and the infinite mind to manifest in combination with oral dmt from traditional psychotria for example with the caapi and/or harmalas providing the 5-ht1a inhibition, just as bufotenine in snuff's provide the 5-ht1a inhibition combined with the dmt in the snuff's, resulting in a 3 hour experience ie both examples of Teamwork on how these entheogens are used traditionally in the Amazon.
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. Ibogaine inhibits both serotonin and dopamine reuptake transporters, it is an SDRI or serotonin & dopamine reuptake inhibitor. Tetrahydroharmine is a serotonin reuptake inhibitor, it is an SRI found in caapi. In other words, both are strong serotonin reuptake inhibitors which inhibit over 80% of brain 5-ht at 5-ht1a.
In contrast, as an example, Cocaethylene (coca leaf tea bags soaked in wine, the orally active & potent ingredient formed in the liver from cocaine + ethanol in the 1860's "Vin Mariani" wine popular with both Popes, Thomas Edison and scores of other famous people) increases the levels of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain by inhibiting the action of the serotonin transporter, norepinephrine transporter, and dopamine transporter. These pharmacological properties make cocaethylene a serotonin-norepinephrine-dopamine reuptake inhibitor [SNDRI; also known as a "triple reuptake inhibitor"].
Cocaethylene has a higher affinity for the dopamine transporter than does cocaine, but has a lower affinity for the serotonin and norepinephrine transporters. In McCance-Katz et alia's 1993 study cocaethylene "produced greater subjective ratings of 'High' in comparison with administration of cocaine or alcohol alone."
------------------------------------------------
See this confusion quite a bit on the forums, and will address why Ayahuasca is completely different from smoked or injected dmt. It all started when Western Explorers in the Amazon equated Ayahuasca completely to "orally activate dmt" and ignored the Elephant in the room, which is Caapi.
One difference is that dmt by itself has been found in the Receptorome study to not block serotonin...while the following traditional team players have been found to strongly block serotonin: 5-ho-dmt in Amazonian snuffs, 5-meo-dmt in Amazonian snuffs and the 2nd largest alkaloid in caapi (thh or tetrahydroharmine). All 3 are thus anti-serotonin.
Serotonin blocking is a main effect of all the natural oral entheogens like the semi-synthetic LSD, mescaline, Ayahuasca, mushrooms, 5-meo-dmt & bufotenine (found in snuffs). See 2011 receptorome chart below.
Ibogaine inhibits both serotonin and dopamine reuptake transporters (it is an SDRI or serotonin & dopamine reuptake inhibitor).
Another difference is that these team player master plants in addition to blocking serotonin also provide awake dream effects, completely un-related to night time dreams (Shannon, Antipodes of the Mind) complete with story lines, static, animated & interactive scenery, etc. see "Core corpus of visions" from Benny Shanonon compiled from interviews with hundreds of Ayahuasca session participants several posts below.
DMT is super potent at all the other 5-ht receptor sites, way exceeding even psilocin (see chart below), but in doing so, it must give up 5-ht1a binding, (serotonin blocking) which makes up over 80% of brain 5-ht, so when you combine admixture with components of caapi or rue, you get a "team action".
Question asked:
5-HT1A Receptor Agonists (from chipur document): aripiprazole (Abilify), buspirone (BuSpar), clozapine (Clozaril), LSD, nefazodone (Serzone), psilocybin, trazodone (Desyrel), vilazodone (Viibryd), yohimbine, ziprasidone (Geodon).So what does this mean for those who take something that's not Psychedelic but activates the 1A receptor?
5-HT1A receptor agonists have traditionally been used in the treatment of mood and anxiety woes.
Great question: LSD, mescaline, Ayahuasca, mushrooms, Amazonian snuffs and 5-meo-dmt not only activate 5-ht1a (80% of brain 5-ht) which in turns breaks down the barriers/gates/doors/filters in the brain which allow us to survive and help to form the ego...but they also act in the place of serotonin (at the other 20% of brain 5-ht receptors). This is what makes the psychedelic molecules different from just the "man-made" 5-ht1a agonist only.
Ayahuasca is named after Caapi, and doesn't even need dmt to call itself Ayahuasca, Plant admixture psychotria DMT mainly acts to light up and color the visions from the Caapi vine according to Ayahuasca Shamans. Experienced Ayahuasqueros can see the visions even in low light or with very little if any admixture plant. DMT can also be made complete with tiny amounts of 5-meo-dmt as it fills in for the missing 5-ht1a serotonin blocking action that is missing with DMT.
New discovery: the recently discovered adrenoglomerulotropine (a hormone of the pineal gland, otherwise known as 6-Methoxytetrahydroharman) is an isomer of tetrahydroharmine, found in caapi. Caapi was said by the Indians to have Telepathine qualities as Ayahuasca was said to facilitate telepathic communication among tribal members.
Also contrary to what Wikipedia states, mescaline does not work thru the 5-ht2a receptor, but mainly thru the adrenal sites and it's strong serotonin blocking action.
Dr. Nichols:
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.
Thomas S. Ray, Psychedelics and the Human Receptorome (2010):5-ht1a makes up >80% of brain 5-ht...5-ht1a agonism blocks serotonin
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...
Breadth of Receptor Binding, 4.00=max, 0.00=min
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". 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 theoretically causes this filter system to be lifted, and the infinite mind to manifest in combination with dmt for example.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 (sensual & entactogenic)
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)
An example of the importance of adding the serotonin reuptake inhibition properties of 5-meo-dmt for example to dmt (which totally lacks 5-ht1 reuptake properites on it's own) is shown below. This is the same way the snuff's are used in the amazon, as they naturally combine dmt with additives which cause the reuptake of 5-ht like bufotenin for example.
Oroc's experiment of combining 5-meo-dmt with DMT sounds imho very much like a short beautiful transcendental Ayahuasca experience, from his book "Tryptamine Palace":
DMT + tiny amounts of 5-meo-dmt [perhaps similar theoretically to Amazonian snuffs which have a makeup of 7.4% bufotenin (potent 5-ht1a agonist), 0.04% 5-MeO-DMT (potent 5-ht1a agaonist) & 0.16% DMT (zero potency as 5-ht1a agonist)]:
professor8 (11/1/2010, he writes like a poet with special powers of imagination & expression):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.
69ron on harmalas:Tetrahydroharmine (THH) 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.
Question asked:Ayahuasca is Banisteriopsis caapi. It contains mostly harmine, thh & harmaline. B. caapi itself contains no DMT and can be used as is to produce visionary states that are like mental day dreams which lack true visual content. Often admixtures are used to increase the visual content of the ayahuasca dreams. Most admixture plants contain DMT.
Harmine & harmaline & thh used alone, can produce a mild dreamy psychedelic experience in which daydreams or lucid dreams can be experienced if the user chooses to do so. These dreams from the harmalas alone are vague and lack visual content, but usually have story lines and can be quite complex just like a real dream. The harmalas allow one to go in and out of dream consciousness at will. It takes some practice to learn how to enter a lucid dream with the harmalas alone. The harmalas won’t make you enter a lucid dream. You have to do it yourself by allowing your mind to drift off into a lucid dream.
DMT used alone, produces an intense visual experience, often very chaotic and fast moving, and quite amazing to watch. The visions of DMT alone usually lack meaningful content. The DMT visions are often just constantly morphine colors and shapes. Most of it makes absolutely no sense. Rarely will the visuals present to you a full blown dream with people, places, a story line, etc. But this does sometimes happen. But usually you just get a bunch of bazaar visions that are difficult to understand.
When combined, as in ayahuasca, the harmalas brings a dreamy quality to the DMT experience that makes it more like one is experiencing an actual dream, not just a bunch of fancy colors. With the two together, you have the visuals of DMT, plus the dream content of the harmalas. The harmalas are the boss here in this combination if used in ayahuasca proportions where the harmalas are not just used as an MAOI but is used specifically to allow dream consciousness to be entered by the user. DMT is just an additive used to increase the visual portion of the harmala induced dreams.
Using harmalas in very low doses, just as an MAOI, is not the same as using properly made ayahuasca. If the harmalas are used in low doses just for it’s MAOI effects, the trip lacks dream content and is just a bunch of bazaar DMT visual effects. This is not ayahuasca-like, it’s just orally activated DMT. That’s not the same. Its true that some ayahuasca is prepared this way, but such Ayahuasca is considered inferior by most natives. With Ayahuasca, the DMT is just an additive, not the main course. This is why Ayahausca made with only caapi is still called ayahuasca and considered nearly as powerful as Ayahuasca made with additive plants containing DMT.
This is something a lot of people don’t get. Ayahuasca is not simple orally activated DMT. It is the dream consciousness effects of the harmalas that are at play in ayahuasca. In order to experience lucid dreams from harmine without DMT, you need to practice a lot. But once you know how to do it, you don’t need DMT added to it anymore, unless you want the extra visual depth that DMT adds to the dreams.
So, “Dmt Or Ayahuasca?”, well that question is a personal question. Some people prefer DMT-less ayahuasca. Some people prefer just orally activated DMT. Some people prefer ayahuasca with a side order of DMT. Some people prefer the truly bazaar effects of smoked DMT alone.
My personal opinion is that DMT alone is FUN and can be quite frightening. It’s like a roller coaster ride and I like roller coasters. But don’t expect a deep meaningful life changing experience from it. Its pure visual FUN and nothing more. If I want a more meaningful experience I’d use an oral ayahuasca extract, or a smoked Yopo extract (not as effective as ayahuasca because Yopo is low on harmala-like alkaloids)
Authentic ayahuasca, high in harmine, thh & harmaline, and low on DMT, is like entering a full blown 3D dream with dream characters, storylines, etc. This can be a life changing experience. It’s more like sitting in a theater for several hours absorbing a story that’s meaningful because its about you. You leave with memories of places, things, people, etc., and possibly a new view on life.
Ibogaine binds directly to the serotonin transporter (SERT), so it does have to go thru the 5-ht1a substrate pathway. This could be likely what happens with tetrahydroharmine, as THH and ibogaine have similar basic beta-carboline structures.As for THH binding to and activating the 5-ht1a receptor, do we have any sources that state this?
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.
top = 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
bottom = tetrahydroharmine (serotonin reuptake inhibitor)