Strassman - Spirit Molecule - "Anti-DMT"

[OrionFyre]

Another factor normally protecting the body from pineal production of psychedelic amounts of DMT resides within the pineal gland itself. A particular kind of small protein, first discovered in blood, has been shown to interfere with the activity of the DMT-forming enzymes. The pineal has quite high levels of this protein, a sort of "anti-DMT." If this inhibitor itself were blocked, DMT formation is more likely. Where better to provide an anti-DMT for preventing potentially dangerous excessive DMT formation than where it is made—in the pineal gland?

I've been unable to locate reference to this 'anti-dmt' in other literature. I'm usually quite adept at locating information such as this through google, but it escapes me still. Any ideas? Many thanks.

 

[Nathanial.Dread]

Do we even know what enzymes in the brain form (or would form) DMT? I thought the jury was still out about endogenous DMT in the pineal gland.

Strassman's original work was ground-breaking, but I have been feeling more and more like he might be a bit of a loon. You may not be able to find a citation because one doesn't exist.

There are synthetic compounds that do what you described (inhibitors of indoleamine-N-methyltransferases), but nothing suggests they appear in the body.

Inhibition of Dimethyltryptamine Biosynthesis by N,N'-Bis-(3-methyl-2-thiazolidinylidene)Succinamide (I) and 2-Imino-3-Methylthiazolidine (II)

N,N'-bis-(3-methyl-2-thiazolidinylidene)succinamide ( I ) and 2-imino-3-methylthiazolidine ( II ) are inhibitors of indoleamine-N-methyltransferase, the enzyme which biosynthesizes N,N-dimethyltryptamine. I was designed as a neutral compound which will form the active basic metabolite II in...

molpharm.aspetjournals.org

Anyway, anti-DMT wouldn't be the enzyme inhibitor, anti-DMT would be something like quetiapine or risperidone (two very, very scary molecules, IMHO).

Blessings
~ND

 

[RAM]

Dr. Strassman is a very nice guy; you could try asking him directly through his website.

And I'm no scientist, but doesn't MAO (monoamine oxidase) break down DMT, which is why when consumed orally we need to also ingest a MAOI (monoamine oxidase inhibitor)? So MAO could be the anti-DMT of which you speak.

 

[Nathanial.Dread]

Dr. Strassman is a very nice guy; you could try asking him directly through his website.

And I'm no scientist, but doesn't MAO (monoamine oxidase) break down DMT, which is why when consumed orally we need to also ingest a MAOI (monoamine oxidase inhibitor)? So MAO could be the anti-DMT of which you speak.

We're looking at an enzyme that creates DMT by combining or modifying some precursor drug, sort of the opposite of what MAO does.

The theory presented here is that there is some compound in this body, that acts as an inhibitor of the enzyme that makes DMT. I imagine the direction this is going is that, under circumstances, the body stops producing this compound, allowing the brain to suddenly synthesize much more DMT than it normally does (giving the mythic 'endogenous DMT dump,' ).

I have serious doubts about this. Even if such a compound did exist, I'm not sure stopping it's endogenous production would suddenly cause the N-methyltransferases to start pumping out DMT.

Blessings
~ND

 

[OrionFyre]

We're looking at an enzyme that creates DMT by combining or modifying some precursor drug, sort of the opposite of what MAO does.

The theory presented here is that there is some compound in this body, that acts as an inhibitor of the enzyme that makes DMT. I imagine the direction this is going is that, under circumstances, the body stops producing this compound, allowing the brain to suddenly synthesize much more DMT than it normally does (giving the mythic 'endogenous DMT dump,' ).

I have serious doubts about this. Even if such a compound did exist, I'm not sure stopping it's endogenous production would suddenly cause the N-methyltransferases to start pumping out DMT.

Blessings
~ND

Like you I'm beginning to think Strassman is well into the Gavia genus as of late. Honestly I've thought that since my first introduction to his book. He cites supporting evidence for statements of fact or theory in some cases, but in others offers little to no evidence. This "anti-DMT" being just one such instance. Citations are one thing, but he even fails to outright name this particular kind of small protein (his words). Furthermore he goes on to say in the same thought that it's been shown to interfer with this enzyme. Shown by WHOM? This type of statement of fact alone demands citation.

 

[dreamer042]

The next paragraph goes on to say:

Data from psychosis research also support this contention. Individu-
als with schizophrenia received pineal gland extracts as an experimental
treatment in the 1960s. Their symptoms improved markedly. The expla-
nation for this finding was that the pineal extracts provided patients with
an additional dose of the anti-DMT that their own pineal glands lacked.
Thus, they were better able to combat pathologically high levels of DMT,
and their psychotic symptoms improved. 4

Pg. 87

The citation given is:
L. Bigelow, "Effects of Aqueous Pineal Extract on Chronic Schizophrenia," Biological
Psychiatry 8 (1974): 5-15

Apologies, I am unable to find an electronic version of the full text. I'll look into obtaining and scanning a hard copy when I get the chance.

 

[DreaMTripper]

That would be great dreamer042 I would be very interested to read it. The only endogenous neurotransmitter I can think of that might nullify the effects of DMT are glutamate and or glutamine and anandamide in large ammounts.
I would expect there to be more data on the composition of this extract somewhere on the web if it was effective.

 

[Nathanial.Dread]

The next paragraph goes on to say:

Data from psychosis research also support this contention. Individu-
als with schizophrenia received pineal gland extracts as an experimental
treatment in the 1960s. Their symptoms improved markedly. The expla-
nation for this finding was that the pineal extracts provided patients with
an additional dose of the anti-DMT that their own pineal glands lacked.
Thus, they were better able to combat pathologically high levels of DMT,
and their psychotic symptoms improved. 4

Pg. 87

The citation given is:
L. Bigelow, "Effects of Aqueous Pineal Extract on Chronic Schizophrenia," Biological
Psychiatry 8 (1974): 5-15

Apologies, I am unable to find an electronic version of the full text. I'll look into obtaining and scanning a hard copy when I get the chance.

Wow, that's certainly a surprising finding.

Here's the abstract:

Investigated the finding that extracts of beef pineal glands have therapeutic value in schizophrenia. 10 19-31 yr old chronic schizophrenic patients were given daily intramuscular injections of either aqueous pineal extract or of placebo in a double-blind clinical study. The degree of psychosis as measured by a 28-item nurses' rating scale was reduced significantly in 5 patients. When all 10 patients were considered as a group, extract treatment was superior to placebo (p < .005). The degree of improvement in most cases was modest or consisted of accelerating an apparent trend to improvement. Since the material given is derived from a biological source, results may offer a clue to the etiology of some forms of schizophrenia. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Not going to lie - I'm very, VERY skeptical, but I'd love to read the paper.
I have to say, if the findings were robust, I'm surprised no one has spent more time looking into this, since all the antipsychotics are so unpleasant and have such a low compliance.

Blessings
~ND

 

[Infectedstyle]

It would be really really helpful if to know which protein that Strassman is talking about.. Someone give him a call please

 

[pitubo]

Related, but earlier research:

Some Effects of Aqueous Extracts of Acetone-Dried Beef-Pineal Substance in Chronic Schizophrenia

Mark D. Altschule, M.D.
N Engl J Med 1957; 257:919-922November 7, 1957 DOI: 10.1056/NEJM195711072571904

EARLIER work from this laboratory showed that certain beef-pineal extracts reversed some of the biochemical abnormalities encountered in schizophrenic patients.1 Clinical improvement also was noted in those earlier studies; this finding accorded with that previously reported by other authors who had used pineal extracts in schizophrenia.2 This report describes some effects of several different aqueous extracts made from acetone-dried beef pineal glands.

 

[jamie]

does DMT actually make anyone feel psychotic? I thought it was believed to be an anxiolytic?

 

[Infectedstyle]

It does not necessarily make me psychotic. It warps thoughts just like any other psychedelic. It's just hard to even notice that it's there.

 

[DreaMTripper]

The term psychosis is very broad if you were to judge an intense pyschedelic experience using that definition you could say it does cause psychotic symptoms however when you compare and contrast the finer details the differences become apparent. Ive seen someone during a prolonged acute pyschosis and they did not look or sound like they were on a endogenous psychedelic trip and her accounts of it afterwards also support this.
The two spheres of experience do seem to inhabit some common ground but this use of a psychedelic model for studying psychotic illness is very limited in my opinion.
Besides, there were some studied carried out in the 60s on psychotic children using LSD that improved their condition dramatically, some were actually brought out of a psychotic episode.

 

[pitubo]

Besides, there were some studied carried out in the 60s on psychotic children using LSD that improved their condition dramatically, some were actually brought out of a psychotic episode.

MAPS - Volume 7 Number 3 Summer 1997 - Treatment of Childhood Schizophrenia Utilizing LSD and Psilocybin

 

[Endurance]

The citation given is:
L. Bigelow, "Effects of Aqueous Pineal Extract on Chronic Schizophrenia," Biological
Psychiatry 8 (1974): 5-15

Apologies, I am unable to find an electronic version of the full text. I'll look into obtaining and scanning a hard copy when I get the chance.

The above paper is now available for download in the Access to full text or reprints thread.

 

[digitalvygr]

Anyone ever figure out the protein he was talking about? I read the paper cited and it does not say what the protein was...

 

[dreamer042]

Here is the full text from sections referenced 2-4 in Chapter 4 of TSM.

2
Neuroscientists believe this barrier to pineal activation exists because it would be problematic for an animal to experience its environment as "dark" during daylight hours. Since the pineal normally releases melatonin only at night, daytime melatonin release would "feel" as if it were dark at the "wrong" time, and the animal would be disoriented. However, this explanation is weak. Daytime melatonin secretion is hardly "dangerous" enough to merit such a complex and efficient secu rity system. Melatonin effects are not immediate, but rather take hours to days to materialize. In addition, daylight almost instantly suppresses melatonin production to near zero, returning the system to baseline before any internal disruptions occur.

However, consider what might happen if stress easily triggered the pineal to produce DMT, rather than melatonin. DMT is physically immobilizing and produces a flood of unexpected and overwhelming visual and emotional imagery. Certainly, frequent bursts of DMT release would be much more dangerous for an animal than would be those of melatonin. It may be that melatonin is so hard to make during the day because any breach in the pineal security system is intolerable. The pineal erects a barrier to inordinate stress that protects equally everything behind it. So, one set of circumstances in which pineal DMT may form is when stress-induced catecholamine output is just too great for the pineal shield to withstand.

It also is possible that the pineal security system does not function normally in psychotic individuals. There are strong indirect data supporting this idea. Stress worsens hallucinations and delusions in psychotic patients. DMT levels in those patients are related to the degree of psychosis—the more intense the symptoms, the higher the levels of DMT. We know that DMT also rises in animals exposed to stress. More common levels of stress induced catecholamines may overwhelm inadequate pineal defenses in psychosis, thus producing too much DMT. This DMT then brings on or worsens symptoms in psychotic patients. 3

Another factor normally protecting the body from pineal production of psychedelic amounts of DMT resides within the pineal gland itself. A particular kind of small protein, first discovered in blood, has been shown to interfere with the activity of the DMT-forming enzymes. The pineal has quite high levels of this protein, a sort of "anti-DMT." If this inhibitor itself were blocked, DMT formation is more likely. Where better to provide an anti-DMT for preventing potentially dangerous excessive DMT formation than where it is made—in the pineal gland?

Data from psychosis research also support this contention. Individuals with schizophrenia received pineal gland extracts as an experimental treatment in the 1960s. Their symptoms improved markedly. The explanation for this finding was that the pineal extracts provided patients with an additional dose of the anti-DMT that their own pineal glands lacked.
Thus, they were better able to combat pathologically high levels of DMT, and their psychotic symptoms improved. 4

Reference Number 3 is listed as:
Robin M. Murray, Michael C. H. Oon, Richard Rodnight, James L. T. Birley, and Alan
Smith, "Increased Excretion of Dimethyltryptamine and Certain Features of Psychosis. A
Possible Association," Archives of General Psychiatry 36 (1979): 644-49.

and 4 is the one previously listed:
L. Bigelow, "Effects of Aqueous Pineal Extract on Chronic Schizophrenia," Biological Psychiatry 8 (1974): 5-15.

The only reference to a protein present in these papers is in the references section of #3, which mentions the following paper:
Boarder MR, Oon MCH, Rodnight R: Mass spectrometric identification of N-monomethyltryptamine following incubation of tryptamine with brain protein and S-adenosylmethionine or 5-methyltetrahydrofolic acid. Biochem Pharmacol 25:2109-2112, 1976.

That paper is kind of a dead end as far as the "anti-DMT" protein search goes. It does mention a "dialysed supernatant protein" obtained from rat brain and gives the following reference for it:
Boarder, M.R. and Rodnight, R. Submitted to Brain Research.

A quick google scholar search turns up a paper that appears to be the one referenced:

Boarder, Michael R., and Richard Rodnight. "Tryptamine-N-methyltransferase activity in brain tissue: a re-examination." Brain research 114.2 (1976): 359-364.

This one only states that they used a "dialysed supernatant protein" from rat brain, human brain, and rabbit lung respectively. However it makes no mention of the makeup of those proteins and their use of these proteins is actually in demonstrating the ability of the brain to biosynthesize methylated tryptamines rather than inhibit them.

I also did some independent searching around scholar to see if I could identify this protein found in blood and present in the pineal that "has been shown to interfere with DMT forming enzymes." There is extensive research on using bovine and buffalo pineal extracts with schizophrenics and on rats, but I was unable to find any relevant citations to back up Dr. Strassman's claim.

It is rather curious the previous and following paragraphs are cited, but the "anti-DMT" one mysteriously isn't, particularly with the "has been shown" line included in there. :?

I'm beginning to think ND may be correct, we can't very well track down a reference that does not in fact exist. Maybe someone should shoot Rick an email and ask him wutsup withat?

 

[digitalvygr]

Here is the full text from sections referenced 2-4 in Chapter 4 of TSM.

2
Neuroscientists believe this barrier to pineal activation exists because it would be problematic for an animal to experience its environment as "dark" during daylight hours. Since the pineal normally releases melatonin only at night, daytime melatonin release would "feel" as if it were dark at the "wrong" time, and the animal would be disoriented. However, this explanation is weak. Daytime melatonin secretion is hardly "dangerous" enough to merit such a complex and efficient secu rity system. Melatonin effects are not immediate, but rather take hours to days to materialize. In addition, daylight almost instantly suppresses melatonin production to near zero, returning the system to baseline before any internal disruptions occur.

However, consider what might happen if stress easily triggered the pineal to produce DMT, rather than melatonin. DMT is physically immobilizing and produces a flood of unexpected and overwhelming visual and emotional imagery. Certainly, frequent bursts of DMT release would be much more dangerous for an animal than would be those of melatonin. It may be that melatonin is so hard to make during the day because any breach in the pineal security system is intolerable. The pineal erects a barrier to inordinate stress that protects equally everything behind it. So, one set of circumstances in which pineal DMT may form is when stress-induced catecholamine output is just too great for the pineal shield to withstand.

It also is possible that the pineal security system does not function normally in psychotic individuals. There are strong indirect data supporting this idea. Stress worsens hallucinations and delusions in psychotic patients. DMT levels in those patients are related to the degree of psychosis—the more intense the symptoms, the higher the levels of DMT. We know that DMT also rises in animals exposed to stress. More common levels of stress induced catecholamines may overwhelm inadequate pineal defenses in psychosis, thus producing too much DMT. This DMT then brings on or worsens symptoms in psychotic patients. 3

Another factor normally protecting the body from pineal production of psychedelic amounts of DMT resides within the pineal gland itself. A particular kind of small protein, first discovered in blood, has been shown to interfere with the activity of the DMT-forming enzymes. The pineal has quite high levels of this protein, a sort of "anti-DMT." If this inhibitor itself were blocked, DMT formation is more likely. Where better to provide an anti-DMT for preventing potentially dangerous excessive DMT formation than where it is made—in the pineal gland?

Data from psychosis research also support this contention. Individuals with schizophrenia received pineal gland extracts as an experimental treatment in the 1960s. Their symptoms improved markedly. The explanation for this finding was that the pineal extracts provided patients with an additional dose of the anti-DMT that their own pineal glands lacked.
Thus, they were better able to combat pathologically high levels of DMT, and their psychotic symptoms improved. 4

Reference Number 3 is listed as:
Robin M. Murray, Michael C. H. Oon, Richard Rodnight, James L. T. Birley, and Alan
Smith, "Increased Excretion of Dimethyltryptamine and Certain Features of Psychosis. A
Possible Association," Archives of General Psychiatry 36 (1979): 644-49.

and 4 is the one previously listed:
L. Bigelow, "Effects of Aqueous Pineal Extract on Chronic Schizophrenia," Biological Psychiatry 8 (1974): 5-15.

The only reference to a protein present in these papers is in the references section of #3, which mentions the following paper:
Boarder MR, Oon MCH, Rodnight R: Mass spectrometric identification of N-monomethyltryptamine following incubation of tryptamine with brain protein and S-adenosylmethionine or 5-methyltetrahydrofolic acid. Biochem Pharmacol 25:2109-2112, 1976.

That paper is kind of a dead end as far as the "anti-DMT" protein search goes. It does mention a "dialysed supernatant protein" obtained from rat brain and gives the following reference for it:
Boarder, M.R. and Rodnight, R. Submitted to Brain Research.

A quick google scholar search turns up a paper that appears to be the one referenced:

Boarder, Michael R., and Richard Rodnight. "Tryptamine-N-methyltransferase activity in brain tissue: a re-examination." Brain research 114.2 (1976): 359-364.

This one only states that they used a "dialysed supernatant protein" from rat brain, human brain, and rabbit lung respectively. However it makes no mention of the makeup of those proteins and their use of these proteins is actually in demonstrating the ability of the brain to biosynthesize methylated tryptamines rather than inhibit them.

I also did some independent searching around scholar to see if I could identify this protein found in blood and present in the pineal that "has been shown to interfere with DMT forming enzymes." There is extensive research on using bovine and buffalo pineal extracts with schizophrenics and on rats, but I was unable to find any relevant citations to back up Dr. Strassman's claim.

It is rather curious the previous and following paragraphs are cited, but the "anti-DMT" one mysteriously isn't, particularly with the "has been shown" line included in there. :?

I'm beginning to think ND may be correct, we can't very well track down a reference that does not in fact exist. Maybe someone should shoot Rick an email and ask him wutsup withat?

Way to track down the references, I only got as far as one paper among those.

I will write him and see if he remembers, will report back in a few days if I get an answer.

 

[digitalvygr]

Strassman kindly got back to me and let me know that the small protein was never identified, but that perhaps the following paper would have more information on that:

Chu, U. B., et al. (2014). "Noncompetitive inhibition of indolethylamine N-methyltransferase by N,N-dimethyltryptamine (DMT) and N,N-dimethylaminopropyltryptamine."

and that in general Nick Cozzi might have more info on this line of inquiry. Will read that and see if anything comes up...

 

[dreamer042]

Thanks for inquiring about that! :thumb_up:

Attached the article for easy reference.

Chu, Uyen B., et al. "Noncompetitive inhibition of indolethylamine-N-methyltransferase by N, N-dimethyltryptamine and N, N-dimethylaminopropyltryptamine." Biochemistry 53.18 (2014): 2956-2965.