God Molecule or Barnacle Repellent?
Mar 26 2013
Illustration by Santtu Mustonen. Background photo courtesy of the NOAA.
Writing almost exclusively about psychoactives, it is not unusual for me to be contacted by strangers who wish to report on the effects of various drugs. Most of these reports are uninteresting, but occasionally I receive something unusual. The following letter from a pseudonymous tryptamine chemist serves as a prime example:
CLOCKWISE FROM TOP LEFT: DMT is present in the leaves of Psychotria viridis; bufotenine is present in the seeds of Anadenanthera colubrina; 5-Br-DMT and 5,6-DiBr-DMT are present in the body of Smenospongia aurea.
Modest though it may be, what we have contained in this letter is possible evidence of the first psychedelic drug of marine origin.1 In 1997 Alexander Shulgin wrote of marine tryptamines, “5-Bromo-DMT and 5,6-dibromo-DMT are found in the sponges Smenospongia aurea and S. echina resp. I have no idea if they are active by smoking (the 5-Br-DMT just might be)... I had the fantasy of trying to scotch the rumor I’m about to start, that all the hippies of the San Francisco Bay Area were heading to the Caribbean with packets of Zig-Zag papers, to hit the sponge trade with a psychedelic fervor. This is not true. I refuse to take credit for this myth.” And so in his semifacetious remark Shulgin sparked what has now been well over a decade of speculation on the possibility of poriferan psychedelics. A priori, there is no reason why 5-Br-DMT should not possess psychedelic activity. The substitution of a hydrogen for a bromine atom actually increases the lipophilicity, giving 5-Br-DMT a pharmacokinetic edge over its close relatives DMT and bufotenine when partitioning into the brain. And it is a well-known fact that the 5-position of the tryptamine molecule accepts a wide variety of substituents while retaining activity.
This mysterious letter describes the first tests of 5-Br-DMT on humans, but the chemical had already been the subject of rodent studies by a group of researchers at the University of Mississippi. The alkaloid 5,6-DiBr-DMT exhibited anxiolytic and, somewhat ambiguously, “antidepressant-like” activity in the rodent forced-swim test, yet 5-Br-DMT did not. Instead 5-Br-DMT reduced locomotor activity in mice, leading the authors to suggest a sedative action. However, the extraordinarily potent hallucinogen 5-MeO-DMT has also been shown to lead to reductions in locomotor activity in numerous rodent models; the same is true for DMT at high doses. Generally the effect of psychedelics on locomotion is dose dependent, with stimulation at low doses but locomotor inhibition at high ones. Anyway, let’s get back to sponges, which are what make 5-Br-DMT so interesting.
The sponges began in warm Precambrian waters that were near twice the salinity of today’s ocean, rife with submarine volcanoes belching halogens onto the sea floor—ancient chimneys of glass and mucus inhaling the superocean Panthalassa with microscopic flagella. Sponges are situated at the very base of the phylogenetic tree of life, somewhat controversially beneath or directly beside the taxonomic branch that gave rise to neurologically endowed humans. In examining natural products extracted from marine organisms it is important to recognize that they live in an environment possessing a very different chemistry from that of the land. Concentrations of the four stable halogens iodine, bromine, chlorine, and fluorine are far greater than can be found terrestrially. Of particular interest here is bromine, situated below chlorine but above iodine on the periodic table, first discovered in the burned ashes of seaweed and still industrially extracted from the ocean and certain lakes. Concentrations of bromine are so high that one cubic mile of seawater holds over 279 kilotons, more than enough to satisfy the total annual consumption of the bromine in the US.
Now let us examine the honeycombed curiosity that is Smenospongia aurea, the species primarily associated with the presence of 5-Br-DMT and other related tryptamines. S. aurea is a small reef-dwelling sponge that rarely grows beyond the size of a human hand. It is widely distributed in both shallow coastal waters and deep-reef twilight zones, from the Gulf of Mexico through the Florida Keys and into the western Bahamas and Caribbean. In life, S. aurea exhibits color morphs ranging from cinnamon tan to creamy yellow with occasional purple and green accents. Of particular interest to spongologists is the fact that Smenospongia species exhibit a curious aerophobic color-change reaction; when removed from the water the sponge becomes rubbery, exuding copious quantities of mucus and spontaneously transforming from brown to violet black, a color that is preserved after drying. The prominent spongologist Felix Wiedenmayer was the first to note the species’s unusual necrotic behavior: “The flesh becomes slimy soon after death, flowing out of the specimens, so that in most dry ones the black remainders of flesh merely coat the fibers and tympanize some of the meshes.” Multiple Aplysina species produce the tryptamine 5,6-dibromo-hypaphorine and also display aerophobic color-changing reactions, evolving from yellow in life though darkening shades of blue when removed from the water and proceeding to blackness in death. Similarly, Verongula species, which contain both 5-Br-DMT and 5,6-DiBr-DMT, display a dramatic aerophobic empurplement, accompanied by necrotic slime exudation. The response is analogous to the discoloration reaction observed in tryptamine-containing fungi, which form indigo-colored bruises when plucked from their substrate or are otherwise roughly handled.2
With few exceptions, man’s relationship with the sponge has been an exploitative one. In ancient Rome they were used as toilet paper; in the Florida Keys many species were fished to near extinction by commercial spongers whose avarice and lust for their absorbent, fibrous bodies knew no bounds. Sponges (possibly) gave us life, gave us the antiviral herpes medication vidarabine, gave us the first marine psychedelic, and we repay them by desiccating their flesh and exfoliating our skin with their skeletons. Even a rare disorder called sponge fisherman’s disease, afflicting the eponymous population and producing both searing pain and dermal lesions, is not the result of a sponge-derived toxin, but rather the sponge’s tendency to agglomerate nematocysts from various species of sea anemone. This brings me to my next point, the sponge—ever known for its ability to absorb and retain foreign materials—may not truly be responsible for the biosynthesis of 5-Br-DMT. There is some suggestion that the presence of 5-Br-DMT in sponges stems from a relationship with an elusive symbiont, perhaps of bacterial origin. Supporting this claim is intraspecific variability in alkaloid presence, similar tryptamines have been found in taxonomically distant sponge species and both 5-Br-DMT and 5,6-DiBr-DMT are present in Bryopsis algae. Should such a symbiont be cultivable, it might allow the facile production of 5-Br-DMT in large quantities, the possible utility of which I will discuss shortly.
From the very beginning, serotonin has been associated with marine life. The first large-scale isolation of pure serotonin was conducted by Vittorio Erspamer, who employed acetone to extract 30 kilos of salivary glands excised from the mouths of 30,000 fresh octopuses. Erspamer’s research was followed by Betty Twarog, who soaked common mussels in a specially designed chamber to demonstrate serotonin’s ability to inhibit smooth muscle contraction, opening shells. Serotonin mediates regenerative processes in immortal Planaria, while both protists and bacteria, organisms without nervous systems, have been observed using serotonin for chemical signaling. It has even been proposed that serotoneric ciliary bands in bivalves served as the evolutionary basis for the neural tube in vertebrates, giving serotonin a central role in the genesis of the nervous system.
It would be a tragically anthropocentric mistake to assume that Smenospongia aurea produces 5-Br-DMT and related tryptamines to provide terrestrial vertebrates such as you and me with a transient psychedelic high. Serotonin is present in nearly every living organism, yet appears to be conspicuously absent from the Porifera, having only been detected on a handful of occasions in the history of sponge analysis. Let me propose a simple explanation: Serotonin is an extraordinarily potent barnacle attractant. So potent a barnacle attractant is serotonin that it’s used as the gold standard in the Kawahara barnacle-settlement assay. Low micromolar concentrations are sufficient to induce frenzied cyprid metamorphosis and attachment, which catalyzes a chain reaction in which settled barnacles release pheromone-type signaling molecules to encourage new barnacles to attach. In tidal zones so crowded that living organisms grow on top of one another and build massive towers upon bodies of the dead, feeding sponges must be able to circulate water through the labyrinth of interlacing canals, chambers, and pores that constitute their bodies. Serotonin may be vital for sophisticated neurotransmission, but what good is a nervous system when you are suffocated by barnacles?
But what’s more important than the lack of serotonin in sponges is the abundance of close serotonin derivatives. In the same manner that serotonin induces barnacle settlement, drugs that modify serotonin neurotransmission, specifically SSRIs like the pharmaceutical antidepressant imipramine, act as potent biocides repelling barnacles and other would-be colonizers. Given the almost certain serotonergic activity of bromo-DMT compounds, it is possible they might play a key role in keeping the species free of burdensome epibionts. Further supporting this theory are the numerous bromo-indoles known to act as essential biocides found in a variety of sedentary marine species. In an ocean dangerously polluted with antifouling biocides like tributyltin, a future in which boats are painted with the psychedelic essence of Smenospongia aurea is an uplifting prospect.
As promised in the letter, a small folded weighing paper containing approximately 10 mg of pale yellow crystals was provided. The material was analyzed via melting point, GC-MS, 1H, and 13C NMR, and was consistent with 5-Br-DMT. It is my opinion that the report is real.3
1 Yes, I am aware of the infamous “dream fish” said to be Sarpa salpa as well as various Kyphosus and Siganus species. Little chemical analysis of these fish has been published and their precise activity is uncertain, but what has been documented suggests a long-lasting delirium not typical of serotonergic psychedelics. Only one report compared the observed symptomatology to that of LSD and was published in the ichthyological rumor mill that is Practical Fishkeeping magazine; apparently gossip pieces about which giant isopods have eating disorders weren’t selling the ads.
2 I am very much interested in the possibility that these dark pigments result from the dimerization of bromoindoles into tyrian-purple type pigments. I have personally seen a dram vile containing a small quantity of methanolic Smenospongia extract, and true to the reports, the color was a deep violet tending toward black. Additionally, any experienced tryptamine chemist will testify that synthetic intermediates (particularly crude acid chlorides) quite literally come in all the colors of the rainbow.
3 FB (from hexanes) MP: 99-102.3°C. Consistent with reference material (99.6- 102.0°C) and 98-99°C reported by Djura et al. 1979.
GC-MS: Under the conditions utilized, two GC peaks were observed with the freebase. The smaller GC peak gave the MS ion spectra consistent with the par- ent compound. MS (EI) (m/z, %): 268 (100), 267 (50), 254 (90), 239 (20) 154 (10), 127 (10). The second and larger GC peak suggested a degradation artifact. MS (EI) (m/z, %): 129 (10), 102 (10), 58 (100) 42 (10). While the analysis was not optimized, altering the GC parameters did alter the peak ratios. Likewise the HCl salt, more susceptible to degradation, gave only the single artifact peak. Finally, the results were consistent with the behavior of reference material. These factors suggest artifact formation occurred.
1H NMR (400 MHz, CDCl3): δ 8.3 s(1 NH), 7.74 d(J = 1.85 Hz, 1H), 7.27 dd(J = 8.61, 1.85 Hz, 1H), 7.19 dd(J = 8.65, 0.46 Hz, 1H), 7.02 d(J = 2.25 Hz, 1H), 2.91 t(J = 7.95 Hz, 2H), 2.64 t(J = 7.95, 2H), 2.36 s(2 CH3)
13C NMR (100 MHz, CDCl13): δ 134.01 (1 Ar-H), 129.31 (1 Ar-H), 124.71 (1 Ar-H), 122.78 (1 Ar-H), 121.42 (1 Ar-H), 114.22 (1 Ar-H), 112.52 (1 Ar-H), 112.47 (1 Ar-H), 60.13 (1 CH2), 45.47 (2 CH3), 23.56 (1 CH2)
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