This is one of my favorite topics. I kind of wish this was in psychedelic drugs where more people are likely to comment.
Anyway, in my experience the 'best' widely available neurotransmitter precursors are DL-Phenylalanine, tyrosine, tryptophan and 5-HTP.
5-HTP and tyrosine are similar in that they are further down the chain but only useful for some neurotransmitters, whereas phenylalanine and tryptophan require 'more work' but can be used as the building blocks for a wider variety of compounds.
I think tryptophan is probably the most interesting/useful (and the safest), but also the most expensive and hardest to find. I have yet to use it, but plan on ordering some in the not-to-distant future.
SAMe and TMG seem to very promising in my experience and play a crucial role as methyl donors which are needed in the creation of many neurotransmitters. I am particularly hopeful about combining tryptophan with TMG or methionine.
TIHKAL said:
Tryptophan, a natural and nutritionally essential amino-acid, is a centrally active intoxicant and sleep-provider in man. It is converted metabolically to tryptamine which is a little bit psychedelic. When administered with methionine (another amino-acid known to methylate things) it produces methylated tryptamines, the two best studied being N-methyltryptamine (NMT) and N,N-dimethyltryptamine (DMT). The effects that result are hard to categorize, reflecting the diagnostic status of the patient. But something happens. In short, tryptophan, alone or in combination with MAO inhibitors or methyl donors, is a fabulous tool for exploring brain function.
Eros and the Pineal said:
A combination of l-tryptophan and a short-term MAO inhibitor creates a favorable condition for the formation of psychoactive tryptamines within the human pineal gland. Tryptophan loading produces a significant increase in brain tryptophan levels and a subsequent increase in serotonin levels. When its major inactivation pathway is blocked by MAO inhibition, serotonin becomes a substrate for other pineal enzymes. Two methyltransferase enzymes, HIOMT and INMT, are capable of converting excess serotonin into a number of psychoactive derivatives.
HIOMT, localized exclusively within the pineal gland, specifically catalyses the transfer of a methyl group to the oxygen located at the five position an the indole ring. In other words, HIOMT converts a 5-hydroxy-indole into a 5-methoxy-indole. This enzyme converts serotonin, 5-hydroxytryptamine, into a psychoactive compound called 5-methoxytryptamine. In turn, this compound becomes a substrate for INMT, another pineal methyltransferase enzyme.
INMT specifically catalyses the transfer of methyl groups (one at a time) to the amine nitrogen on an indole side chain. The resulting monomethyl intermediate, 5-methoxy-N-methyltryptamine, is also psychoactive, but it is quickly converted to the dimethyl derivative by INMT. The final molecule — endogenously produced in the human pineal gland — is 5-methoxy-N,N-dimethyltryptamine, a relatively unknown but extremely potent hallucinogen.
I really think Cannabis can play a crucial catalyzing role due to its effect on the pineal and melatonin. I would find it hard to believe that Cannabis can have such a dramatic effect on melatonin production but have no effect on levels of other endogenous tryptamines. Given that melatonin is believed by many to be a precursor for the endogenous hallucinogens involved in dreaming (Callaway etc), combining cannabis, methyl donors and/or MAOI's could be quite interesting.
I remember seeing some statistics that a VERY large percentage of the Yogis and ascetics in India use cannabis quite regularly and many seem to have 'self-generated mystical experiences' down to a fine art form. I would assume a mainly rice diet providing high levels of tryptophan could be a factor.
Your Body's Natural Wonder Drug: Melatonin said:
Of all the known ways to stimulate melatonin production, none is more dramatic than smoking marijuana. Marijuana stimulates production of a prostaglandin called PGE2, which may relate to its ability to stimulate melatonin production. Italian researchers discovered that when eight men smoked a cigarette containing the active ingredient in marijuana, THC (tetrahydrocannabinol), they had dramatically higher melatonin levels twenty minutes later. After two hours, their melatonin levels were 4,000 percent higher than at baseline.
*Does anyone know what effect PGE2 could have on other neurotransmitter precursors?*
Another connection to melatonin comes from studying the phenomenon of Kundalini. I experienced this myself 3 years ago and was in a state for many months that was extremely intense mentally and physically. It was similar to, but quite distinct from the psychedelic state and other mental states such as mania and schizophrenia. One of the theories put forward to explain the neurochemistry of Kundalini Awakening (in the book "Kundalini: Evolution and Enlightenment) is that melatonin is converted into 10-Methoxyharmalan which is described as a "potent hallucinogen". Melatonin conversion seems to fit my experience as the intensity seemed to increase when melatonin levels are normally highest. Many nights I had to sleep with the lights on (to inhibit melatonin production) because in total darkness it was extremely bright and visual behind the eyelids, so much so that I couldn't sleep. Definitely something going on in the pineal gland. The beta-carboline hypothesis seems quite possible from my experience. 'Psi' effects seem to be reported more with beta-carbolines like harmaline and harmala than with the more standard psychedelics, and there was plenty of that going on as well. Here is another interesting tidbit of information I came across during my research which may relate to the topic:
Healing Sounds by Jonathan Goldman said:
The pineal is rich in neuromelanin, which, according to scientist Frank Barr, is a phase-timing, information processing interface molecule which is a phototransducer. This is a substance which has the ability, among other traits, of absorbing and converting light energy into sound. It also has the ability to turn sound energy into light. Barr believes that melanin and its brain counterpart, neuromelanin, may be the key link between the mind and the brain.
Through stimulating of the pineal gland, neuromelanin is produced. Neuromelanin, a light-sensitive compound triggers the release of a substance which contains phosphorus, a light-producing chemical.
A connection could also be made between the sexual hormones such as testosterone, estrogen and progesterone and the effects on the biosynthesis of melatonin (and likely other neurotransmitters as well) and how those hormones could be 'modulated' by the application of human pheromones. In the years prior to my kundalini experience I had experimented quite liberally with different pheromones and I don't rule this out as being a factor...
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I apologize for this post being a bit all over the place and my understanding of the topics involved is certainly not "Advanced Drug Discussion" caliber, but if anyone is able to let me know if any of this makes any sense or has any comments, I would appreciate it. After my experiences with Kundalini, psychedelics are a pale substitute and when/if I experience this phenomenon again, I would like to have a greater understanding of the possible mechanisms involved.
A fascinating topic for sure.
