Tree-Hugging Dirt Worship

February 24, 2013

The Great Nutmeg Question

Nutmeg is the seed or kernel of Myristica fragrans tree fruits, grated down into a musky-smelling spice. Lately, it seems as if few people are cooking with nutmeg except to sprinkle it on Christmas cookies or other holiday dishes. It was once greatly popular and expensive in Europe, as people liked it for medicine and flavor, but they had no idea where it came from. The fact that people had to buy the spice from Sindbad-like Arab traders who would not reveal the spice’s faraway source lent it a certain mystique.

It turns out that nutmeg is more than it seems, a potent mind-bending drug, which can induce long journeys away from the everyday perception of reality. The fact that a totally innocuous kitchen spice can do this raises certain questions about people’s relationships with the plant, and the relationship of the essential oils in spices to psychoactive drugs.

Firstly, the human-plant relations side of it: as nutmeg is a powerful plant drug, I would assume that there are indigenous people somewhere in the world who are familiar with its use in ritual. I would assume wrong. By the time Europeans and history discovered the Banda Islands, the secret source of nutmeg, the natives were already exporting the whole lot to meet world demand for nutmeg as a flavoring and make money. Nutmeg does have traditional uses as a sedative, sleep aid and analgesic. Writers occasionally note it as a mood elevator or health tonic. As the kernels traveled the world, people occasionally used them in smoking mixtures, snuff or chew, to nobody’s concern. And then, around the turn of the twentieth century, things took a strange turn.

A rumor went around the United States that nutmeg was an abortifacient. Perhaps this is true at a dosage that drives one to death’s door… in any case, young women would sometimes take down spoonfuls of nutmeg hoping to cause an abortion, and then, to their surprise, become highly inebriated with untrustworthy senses and delusions about the nature of the world. Nutmeg’s effects can last for over twenty-four hours after taking it. Some women thought that they were going mad or did mad things and ended up in newspaper stories. In 1902, a Dr. E.E. Hinman reported on treating nutmeg poisonings to the Northwestern Lancet: “In all cases of nutmeg poisoning there was prostration with partial or complete coma. Most of them had vertigo, delirium, chiefly hallucinations of sight, rapid, feeble pulse, and free urination. In five instances the nutmegs were taken to produce abortion, and in every case without accomplishing the desired result.”

Hysterical woman falling out of chair.

Prostrated by nutmeg.

Soon, prisoners caught on to the story about nutmeg causing delirium and hallucinations, and they were smuggling it out of the kitchen to experience the terror and insanity for themselves, such is the human drive to experience altered states. Actually, the experience may not run so terribly for everybody (prisoner Malcolm X measured doses out in a matchbox, and described the effects as being like four or five joints). Still, the seed is surprisingly strong stuff. Fortunately, most people don’t like it as a drug — the heavy effects of higher doses come with heavy side effects — so it is little abused, and the US government hasn’t snatched it out of our spice racks yet. Periodically, the news media notices that teenagers or ultra-poor people are getting high on nutmeg, and there is almost a big deal made of it. Occasionally, someone takes enough to do themselves in.

So, that is the anthropology of nutmeg in brief. There is still the question of how nutmeg does its thing. Since we don’t really understand how the human brain correlates with consciousness all that well, we can’t really truly describe the mechanism of action of any psychoactive drug whatsoever. We can, however, take a stab at relating the chemical constituents of the seed to better-understood drugs and their pharmacology.

One of the first strong efforts at dissecting the action of nutmeg took place in the mid-1960’s, to be published in 1967. Alexander “Sasha” Shulgin, a prolific American inventor of synthetic psychedelics, and two Chilean colleagues, Thornton Sargent and Claudia Naranjo, submitted an article to Psychopharmacology Bulletin: “The Chemistry and Psychopharmacology of Nutmeg and Several Related Phenylisopropylamines.” The team assumed that nutmeg’s power lay in the volatile or “essential” oil fraction of the spice, not in its fatty butter or pulpy cellulose structure. So, they pressed the kernels to express the butter, and steam distilled the essential oil from the crushed remainders. They fractionally distilled the oil, meaning that it was distilled and redistilled until each individual compound was almost completely separated from every other compound. By analyzing each fraction, the team could determine exactly which compounds were in nutmeg oil and how much of each.

Many of the chemicals in nutmeg oil are common throughout nature or well-understood, and thus were seen as poor candidates for explaining its psychoactivity (for example, pinene and sabinene are present in high concentrations across many plant species. However, the most interesting thing known about their pharmacology was that they are irritants.) Other chemicals are present in such tiny amounts that they are probably not the main contributors to nutmeg’s action (unless they are extremely potent).

Eventually, the researchers focused their attention on three “phenylisopropylamine” compounds: safrole, myristicin, and elemicin. These components of Oil of Nutmeg bear a striking resemblance to a series of synthetic psychedelics Sasha Shulgin was working on, modifications of the mescaline molecule. — — The researchers hypothesized that the human liver adds nitrogen to the three phenylisopropylamines as they pass through, so converting them into their psychedelic amphetamine counterparts — safrole to MDA, myristicin to MMDA, and elemicin to TMA. The liver is known to “transaminate” many kinds of compounds, lending the hypothesis some plausibility.

Nutmeg oil components and their hypothetical products

Phenylisopropylamine Psychedelic Amphetamine

SAFROLE

SAFROLE

MDA

MDA

ELEMICIN

ELEMICIN

TMA

TMA

MYRISTICIN

MYRISTICIN

MMDA

MMDA

If the researchers’ hypothesis is true, the effects of nutmeg should roughly correspond to the effects of MDA, MMDA, and TMA in the same proportions as nutmeg oil contains safrole, myristicin, and elemicin. All three psychedelic amphetamines have been explored somewhat as single compounds. MDA catalyzes an opening of empathy and creates sparkling visual changes. MMDA is a psychedelic generally reported as being relaxing, while exhibiting the wrinkle that impressive visual effects are only achieved with the eyes closed. TMA is definitely psychedelic and nausea-causing, but I cannot find enough reports on it to comment as to the particular character of its activity. In general, psychedelics activate certain serotonin receptors which cause “sensory gating channels” in the brain and mind to open up, increasing awareness and the sense of novelty, as well as sometimes creating special effects such as synesthesia. Psychedelics do not necessarily act as stimulants, even though many are chemically described as “amphetamines.”

Sasha Shulgin devised a way to challenge the transamination theory. He prepared a cocktail of psychedelic amphetamines to imitate the effects of 5 grams of average nutmeg, assuming that the phenylisopropylamines would be metabolized with 100% efficiency. It consisted of 100 mg of white powder, divided into 1 part (by mass?) MDA, 2 parts TMA, and 5 parts MMDA. He reports that the cocktail “produced quite a sparkle and considerable eye-dilation. But then, I have never taken 5 grams of nutmeg, so I cannot make any comparisons.” Nice experimental design, Dr. Shulgin! Couldn’t you have taken 2 or 3 days out of your busy life to get high on nutmeg (as an experimental control)? Writing in the Entheogen Review, Ibo Nagano describes 5 grams of nutmeg as a threshold dose “marked by euphoria, relaxation, mood elevation, hilarity and enhancement of the senses,” which I suppose could mean the same as “quite a sparkle.” Please note that nutmegs vary considerably in their potency and exact composition, and you cannot presume to get certain effects at certain dosages unless you know already know your source pretty well — and in that case, put down the shaker bottle, you addict!

Shulgin’s imitation nutmeg amphetamine cocktail superficially supported the transamination hypothesis. However, on another occasion, human volunteers consumed myristicin in the amount present in almost 40 g nutmeg — a dosage seen in typical emergency room visits — yet the volunteers experienced only subtle effects. As myristicin is by far the most abundant aromatic in Oil of Nutmeg, and it makes such a lame psychedelic, we can rule out the idea of it being converted efficiently by the liver. If 100% of the material was converted, each volunteer would have synthesized about 400 mg of MMDA in their own body, and likely been knocked on their butt. Additionally, while the transamination reactions were made to work in laboratory liver cultures, several investigators have not been able to demonstrate such a reaction in living animals.

There is still a possibility for partial transamination of the phenylisoproylamines in the human body. Perhaps small amounts of nutmeg oil are transformed into psychedelic amphetamines, which act synergistically to create a stronger effect than any one would produce alone. On the other hand, the phenylisoproylamines might be active at some of the same receptors as psychedelics, but at a weaker level. In the end, the 1967 research suggested a lot of things and proved almost nothing.

No one seemed interested in the problem again until 2000, when Bernard C Sangalli and William Chiang submitted a paper to Clinical Toxicology. A young woman swallowed roughly 20 g of nutmeg on a friend’s advice without really knowing what it was. When she woke up the next morning still feeling drunk and high after dreaming of being covered in centipedes, she asked her mother to take her to the hospital — thus, becoming the case study that spurred Sangalli and Chiang to investigate nutmeg. (She recovered after a few days’ rest.)

The duo list many components of nutmeg oil with notes about any known actions of those compounds. Some are stimulants, others depressants, others anesthetics, and so on. Where information is lacking, the authors suggest a strategy of comparing nutmeg to other plant materials containing some of the same or similar chemicals. For example, methysticin and kavain are two compounds from kava kava, which contain within them structures strongly resembling myristicin. The kava compounds are known local anesthetics, which work by inhibiting voltage-operated sodium channels (making nerves less conductive). Thus, the anesthetic medicinal/side effect of nutmeg may be tentatively pinned on myristicin and its interaction with the voltage-gated sodium channels. To hypothesize about each nutmeg effect and compound in this way, and then to test each hypothesis, sounds like a fun project to amuse a few research teams for the next several decades. Nutmeg is not amenable to a simplistic, reductionist approach — there are clearly multiple compounds working together to create the nutmeg syndrome, and quite possibly none of these compounds will create impressive effects working alone. I must say that this is less satisfying than Shulgin’s transamination hypothesis, but it does seem to be the truth: this is one tough nut to crack. At least it is providing us with good questions to ask.

One final note. Sangalli and Chiang lament that nutmeg’s “use is perpetuated in easy access resources such as the Internet.” Nutmeg use was perpetuated throughout the twentieth century, mostly in the absence of the Internet. I believe that having a lack of information perpetuates nutmeg use. People with adequate information would probably turn nutmeg down, or at least keep the dose limited to levels that others report enjoying. People who end up in the E.R. were usually working from ignorance or faulty information, so the researchers’ attitude of “let’s keep this information locked up in libraries where no one will look at it” is completely counterproductive. I kind of have to celebrate the honest people who share their awkward nutmeg experiences via Youtube and Erowid and the like. This young woman didn’t regret her experience but I hardly think she’s going to inspire a thousand imitators (I believe that she is a smaller person who took about 20 g, based on her previous “Nutmeg High” video):

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