Tryptamines, Beta-carbolines, and You

Summer 1993 Vol. 04, No. 2 So Close Yet So Far

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J.C. Callaway
Dept. of Pharmaceutical Chemistry
University of Kuopio
POB 1627
Kuopio, Finland

Tryptamines and beta-carbolines are two classes of psychoactive indoles found in plants and animals (1). They have been implicated in a host of neurological functions and display a wide range of neurological activity, which is dependent on their molecular configurations (2). A subgroup of (beta)-carbolines found in some plants are known as the harmala alkaloids; e.g. harmaline in Peganum harmala or Banisteriopsis caapi. Some beta-carbolines have been detected in the tissues and fluids of mammals, including humans, where they are thought to be produced from endogenous tryptamines such as serotonin, 5-methoxy-tryptamine and tryptamine itself. Psychoactive methylated tryptamines such as dimethyltryptamine (DMT), 5-methoxy-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-dimethyltryptamine (bufotenine) and have been detected in normal human beings as well (3,4,5), though their biological purpose remains a mystery.

The psychoactive indoles are interesting not only for their exogenously induced effects on the human mind, but also for their natural occurrence in humans. In the early 1950’s, Osmond and Smythies, in their transmethylation hypothesis, proposed endogenous ‘schizotoxins’ to be responsible for the symptoms characteristic of hallucinatory psychoses, and initiated an era of search for the chemical basis of undesirable states of mind (6). This search was later confounded by the fact that these substances were also found in otherwise normal humans, in addition to many of the other animals in the scientific barnyard. At that time, the psychedelics were commonly referred to as ‘psychotomimetics’ and ‘models for psychosis’, and it was difficult to rationalize a normal function for an endogenous psychedelic. Unfortunately, the idea of normal dreaming did not occur to the early pioneers as a possible function for the natural occurrence of endogenous psychedelic substances (7,8).

The Tryptamines Serotonin, melatonin, bufotenine, DMT, 5-MeO-DMT, and tryptamine are well known examples of this group. They primarily originate from tryptophan, an essential amino acid obtained through the diet. All of these tryptamines interact within the central nervous system. DMT is a very potent psychedelic chemical when smoked or injected, but is orally inactive. The onset of its effects are known to be extremely fast, brief and intense. One could say that DMT evokes a transient psychedelic test pattern, exploding with color imagery. 5-MeO-DMT shares similar properties, but is often devoid of visual imagery at effective doses. Its effects have been described as primarily emotive. Bufotenine shares similar properties with these two, especially in terms of a fast onset and short duration of intense action. However, at effective doses, any psychoactivity of interest is essentially lost in the physiological noise it elicits through the serotonergic system. Early reports on the effects of bufotenine in humans clearly indicate its psychoactivity (9), though its polar quality apparently hinders significant passage into the brain. Perhaps the psychoactivity of bufotenine is actually due to its enzymatic conversion to 5-MeO-DMT.

Their Activity The concurrent use of methylated tryptamines with beta-carbolines has been employed by indigenous peoples of the Amazon since prehistoric times. The psychoactivity of these indole alkaloids can be attributed to their similarity to biogenic amines produced in the brain on a regular basis.

Monoamine oxidase type A (MAO-A) is an enzyme which normally inactivates tryptamines, though it can be chemically blocked to prevent their destruction and thus facilitate their activity. Some of the older antidepressant drugs work this way. In general, though with some reservations, beta-carbolines will inhibit this enzyme. Another mechanism of tryptamine inactivation, particularly for serotonin, is by reuptake into pre-synaptic vesicles. Newer classes of antidepressants act by blocking this uptake, and neuronal activity is facilitated by preventing the retreat of excess serotonin, and probably other tryptamines, into the pre-synaptic neuron for storage and recycling. Certain endogenous beta-carbolines can also inhibit this (re)uptake of the serotonin (10). These two routes, MAO metabolism or (re)uptake into pre-synaptic vesicles, account for most of the inactivation of endogenous tryptamines, and some endogenous beta-carbolines can inhibit both pathways. Pinoline (6-methoxytetrahydro-beta-carboline) and tetrahydro-beta-carboline are good examples of this, and both have been shown to possess specific binding sites in the pineal, adrenals and specific areas of the brain (11).


The beta-carbolines can also facilitate the neuronal transmission of exogenous tryptamines. In Ayahuasca, for example, harmaline and other beta-carbolines are extracted from species of Banisteriopsis to promote the activity of DMT (obtained from other plant sources). Harmaline chemically blocks MAO for several hours and thereby allows DMT to become orally active.

Harmaline, like other harmala alkaloids, does not seem to possess classical psychedelic activity (that activity similar to LSD, psilocybin/psilocin or mescaline). Even at high doses (5 mg/kg), the best one can expect from harmaline would be intense nausea, diarrhea, nystagmus and perhaps the sound of rushing water. A 0.5-1.0 mg/kg dose of harmaline (orally) is sufficient to block MAO for 4-6 hours without much of the physiological noise encountered at the higher doses. During this time, one can take DMT (0.5 mg/kg) or 5-MeO-DMT (0.1 mg/kg) orally to induce an interesting psychedelic state which is similar, but qualitatively different, from smoking either of the two tryptamines alone. Smoking DMT or 5-MeO-DMT after ingesting only harmaline yields a similar, yet distinctly different, state which lasts a little longer and provides more volitional control within the smoking experience.


Since these same Psychoactive tryptamines occur in humans, it is possible that their activity may be promoted by the actions of endogenous beta-carbolines for normal psychological processes; e.g. the production of visual / emotive imagery in sleep. The periodic altering of consciousness in sleep may even be necessary for the maintenance of normal mental health, since only a few days of sleep deprivation will result in a seepage of hallucinatory phenomena into the waking state. On a similar line of reasoning, an offset dreaming mechanism may explain some aspects of hallucinatory psychoses. The willful induction of a psychedelic state presents us with another option which is probably an extension of an intrinsic desire, at least in some, to know. Such an experience offers a unique glimpse of the soul as a temporary dream-like state. Thus it seems quite normal that some choose to induce such a state for the purpose of examining the psyche within the frame work of a waking state of mind.

A Note of Caution

It is not the intent of this author to encourage others to ingest psychoactive substances, but to provide accurate information for those who may. The combination of MAO inhibitors with psychoactive substances other than tryptamines should be avoided. Tryptamines have other routes of metabolism, though many phenethylamines (e.g. MDMA) are highly dependant on MAO for their metabolism, and its inhibition may result in life threatening situations. Foods containing tyramine should also be avoided in conjunction with MAO inhibitors. Be aware! Acknowledgements The experimental data and subjective information reported in this article was obtained through informal interviews. Thanks to these individuals who provided this information of their private experiences. No funding was requested or required for this type of study.


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