Myristicin - A Psychedelic MAOI with Therapeutic Application

Myristicin is a phenylpropene, a natural organic compound that is found naturally in plants such as nutmeg, parsley, dill anise, star anise, black pepper, carrot, common fennel and sweet fennel. Examples of other phenylpropenes include eugenol, chavicol, safrole and estragole- which all can be found in essential oils of plants.

Chemical Structure diagram of myristicin — Chemical structure of myristicin

Myristicin is naturally used by plants as a insecticide and acaricide (a poisonous substance that kills mites &/or ticks).

Myristicin is insoluble in water, but is soluble in ethanol and acetone. Myristicin has a molecular formula of C₁₁H₁₂O₃, a molecular weight of 192.214 g/mol, a density of 1.1437 g/cm³ at 20 °C, a melting point of 25 °C, and a boiling point of 173 °C at 40 mmHg. The molecular formula of myristicin can be translated to 5-allyl-1-methoxy-2,3-(methylenedioxy)benzene.

Table of Contents

1 Myristicin as a MAOI
2 Myristicin as an Anticholinergic
3 Myristicin & MMDA
4 Myristicin Pharmacology
5 Related Links

Myristicin as a MAOI

Myristicin is also a mild MAO inhibitor, meaning that it stops the enzymes in the body that break down monoamine neurotransmitters– such as dopamine, serotonin, and norepinephrine. This results in an increase in the level of monoamine neurotransmitters in the body and in the brain.

Nutmeg red aril brown nuts brown powdered nutmeg — Nutmeg is a very rich source of psychoactive compounds like Myristicin, along with elemicin and safrole.

In general, MAO inhibitors have an antidepressant & motivational effect. Generally speaking, increasing serotonin levels in the brain causes a lift in mood- SSRIs does exactly that to lift depression. And generally speaking, increasing the level of dopamine in the brain increases a person’s motivation. Although honestly, substances that raise the level of dopamine in the brain can be addictive for this reason. Like coffee, Ritalin, exercise, sex, and cocaine. Whereas ADHD is associated with low dopamine levels in the brain. So dopamine does influence how much drive, focus, and attention that we have in a task.

Note that a MAOI shouldn’t be combined with another MAOI, as too much MAO inhibition can be dangerous.

Myristicin as an Anticholinergic

Myristicin is a chemical with psychoactive drug with anticholinergic properties, meaning that myristicin works somewhat similar to DXM, which also is an anticholinergic. Due to the anticholinergic effect, myristicin may have a dreamy dissociative effect that may impair one’s memory in the process. That’s because proper acetylcholine levels is important for memory. In fact, some people use substances like “Huperzine-A” to increase the level of acetylcholine in the brain for memory improvement.

Myristicin & MMDA

Myristicin is traditionally used as a precursor ingredient for the production of MMDA, which is a psychedelic and empathogen. Psychedelics are hallucinogens that alters cognition and perception such that thoughts, visual, & auditory senses are changed. Whereas empathogens are a type of psychoactive substances that produce experiences of emotional communion, oneness, relatedness, emotional openness- in other words, empathy or sympathy.

Because myristicin is a traditional precursor to MMDA, a researcher by the name of Alexander Shulgin believed that myristicin may be metabolized by the liver into MMDA through transamination.

User reports indicate that MMDA mixes MDMA’s feelings of love and MDA’s psychedelic cinematic trip. Except MMDA gives a more clearer, more vivid lucid movie-like imagination.

I personally have found that consuming nutmeg tea, which has some myristicin in it, improves my imagination with significant lucidity. It’s a lot easier to see what you imagine, whether in a dream or while daydreaming.

Myristicin Pharmacology

In this section, I will simply list away the various different findings that scientists have made on the pharmacological properties of myristicin.

I already mentioned above that myristicin is a mild MAOI. That means myristicin can enhance motivation and mood by increasing monoamine neurotransmitter levels.

On the other hand, myristicin is shown to promote anxiety^[1]. So that means one should avoid consuming too much myristicin. I suppose this explains why people who abuse nutmeg by consuming it in excessive amounts may experience paranoia and feelings of impending doom.

Metabolism of Myristicin & Enzyme Interactions

The human liver uses the cytochrome P450 3A4 and 1A2 enzymes to oxidize & thereby metabolize myristicin^[2].

In a rat study, it was shown that myristicin (i.p., 500 mumol/kg) caused 2-20 fold increases in liver cytochrome P450 1A1/2, 2B1/2, and 2E1 enzyme activities by increasing the level of mRNA related to the production of those enzymes^[3].

Note that the metabolism of myristicin in the body resembles that of safrole.

And you might be wondering, what does myristicin metabolize into? Both in vitro & in vivo, myristicin transforms into two metabolites: 5-allyl-1-methoxy-2,3-dihydroxybenzene and 1′-hydroxymyristicin^[4].

As an Anticancer & Chemopreventive Agent

Myristicin has also shown to have anti-cancer properties^[5], specifically causing the apoptosis of cultivated human neuroblastoma in vitro. A neuroblastoma is a type of malignant tumor that comes from neuroblasts, and neuroblasts are are dividing cells that develop into a neuron after migrating to the required location in the body. In simpler words, a neuroblastoma is a cancer of nerve tissue.

Another study^[6] shows that Myristicin is a highly active inducer of the detoxifying enzyme Glutathione S-Transferase (GST) in the liver and the mucous membrane lining the inside of the small intestines. Researchers performed testing with myristicin, and dihydromyristicin- which is produced through the reduction of myristicin. Researchers noted that dihydromyristicin still retained the GST-inducing action of myristicin. However, myristicin was able to inhibit the multiplication of lung tumors by 65%, whereas dihydromyristicin was mostly ineffective at reducing lung tumor formation. In the forestomach, myristicin again inhibited tumor formation by 31%, whereas dihydromyristicin inhibited forestomach tumor multiplication by 27%.

To summarize, myristicin shows usefulness for increasing GST liver enzyme levels and preventing the spread of tumors in the body. Also do note that this study^[6] was done on A/J mice, an inbred breed that is highly susceptible to carcinogens- such that they acquire tumors very easily.

Hepatoprotective Effect

In one study, researchers damaged the liver of laboratory rats by giving them lipopolysaccharide (LPS) plus d-galactosamine (D-GaIN). LPS is a endotoxin produced by bacteria. And D-GaIN is an amino sugar that is toxic to the liver. The researchers then orally administered nutmeg to these rats, and found that the myristicin from the nutmeg showed potent hepatoprotective activity. Specifically, myristicin inhibited the increase of TNF-alpha concentrations and liver DNA fragmentation caused by the liver toxins LPS & D-GaIN. So this inhibition indicates that myristicin may protect the liver by stopping white blood cell macrophages from (over-)releasing TNF-alpha^[7].

Note that TNF stands for Tumor Necrosis Factor. TNF-alpha is a cell signaling protein (cytokine) that controls immune system cells, being able to cause fever, cell apoptosis, cachexia, and inflammation. TNF-alpha may also stop tumor growth and the spread of viruses. In layman’s terms, TNF-alpha is the immune system’s firebombs that causes collateral damage while killing enemies.

Although nutmeg consumed in excess is shown to cause fatty-liver, like with drinking alcohol, the myristicin may help blunt the negative effect nutmeg has on the liver. Of course, acquiring myristicin from a different route (parsley, for example) is another option that circumvents nutmeg’s negative effect on the liver.

Contraindication – High Doses of Myristicin May Be Harmful

But take this information with a grain of salt. One thing that I noticed is that the beneficial effects of nutmeg, as an anti-cancer and hepatoprotective, are shown in studies where the nutmeg/myristicin dosage are small and reasonable. My conjecture is that a small amount of nutmeg/myristicin induces an adaptive response where the benefits outweighs the cons.

But in studies that use a ridiculously high dose of myristicin or nutmeg, negative effects start manifesting. Fatty liver develops^[8], cancerous effects are observed^[8], and parts of the brain are harmed^[9] in rodents.

On the other hand, the metabolism of animals are different than those of humans. What may act as a carcinogen in a rodent, may actually be an anti-carcinogen in humans (safrole is a good example).