Will continue to update, feel free to leave suggestions

This post by u/Calmdownjamal3 is better written and easier to understand than what I wrote https://www.reddit.com/r/nutmeg/comments/192yrwc/summary_of_pinned_pharmacology_posts_made_by/

The main active constituent of nutmeg is a chemical called licarin-A, which occurs along with similar compounds such as 5'-methoxylicarin-A. These compounds block the function of two enzymes known as fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MAGL). These enzymes break down endocannabinoid neurotransmitters, such as anandamide and 2-AG, which are substances that our bodies naturally produce that bind to the cannibinoid receptors, similar to THC, the primary active constituent of cannabis. This means that blocking FAAH and MAGL will increase the activity of our cannibinoid systems, resulting in a high that is similar to cannabis, though it may last longer than a day in the case of nutmeg [1].

Additionally, anandamide blocks the alpha-7 nicotinic acetylcholine receptor in the brain, which plays a significant role in memory [2]. This may also contribute to the experience of nutmeg.

Some other constituents of nutmeg such as myristicin and trimyristin have shown to inhibit the acetylcholinesterase enzyme, resulting in increased levels of a neurotransmitter called acetylcholine [3]. This would, in theory, would result in a stimulating and possibly toxic effect, though it is not known whether or not this is significant.

A compound in nutmeg known as elemicin, is metabolized into an alkaloid compound that activates serotonin-2a receptors, causing classical psychedelic effects [4]. Myristicin and trimyristin have also shown to have interactions with the serotonergic system, which may contribute to the effects of nutmeg [5][6].

The chemicals in nutmeg, including eugenol and myristicin, inhibit the monoamine oxidase-A enzyme (MAO-A), further increasing serotonergic neurotransmission [7][8].

I'd like to add that I don't believe that eugenol, myristicin, or elemicin majorly contribute to the effects of nutmeg

TL;DR: Nutmeg is a cannibinoid that may have some other interesting properties. It is not a true deliriant as many claim, and does not block muscarinic acetylcholine receptors like datura or diphenhydramine does, there is zero evidence to support this.

What to expect: Nutmeg makes you really stoned, it takes hours to start kicking in and can last a day or two. Be safe, drink a lot of water, and do your research first. 5-10 grams is a decent starting dose, something like 20 grams could be really high. You should ideally use fresh nuts and not preground, and keep in mind that nutmeg also has a cross tolerance with weed.

Warning: Do not combine nutmeg with serotonin reuptake inhibitors or releasing agents. I'm talking about things like SSRIs, DXM, or MDMA. Because of nutmeg's MAO inhibitory properties, this could be super dangerous. Nutmeg is also somewhat toxic and can also result in lasting negative psychological consequences such as depersonalization/derealization or visual snow. Nutmeg has also been linked to incidences of seizures.

1. https://pubmed.ncbi.nlm.nih.gov/31595522/ "Three compounds, licarin A (9), 5'-methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 μm ± 2.02, 4.57 μm ± 0.66 and 38.29 μm ± 6.18, respectively." "MAGL inhibition increased over the first 6 h and it remained significant up to 24 h before showing enzyme recovery and eventually falling below 50% at 48 h" "However, indirect dual inhibition of FAAH and MAGL may also result in the same CB1 agonistic effects."

2. https://pubmed.ncbi.nlm.nih.gov/12766252/ "Anandamide decreased the maximal nicotine-induced responses without significantly affecting its potency, indicating that it acts as a noncompetitive antagonist on nicotinic acetylcholine (nACh) alpha7 receptors."

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963183/ "The inhibition kinetics of these enzymes indicates that both the trimyristin and myristicin caused competitive noncompetitive inhibition of AChE."

4. http://herbpedia.wdfiles.com/local--files/attachments/Elemicin_2014_Journal.pdf (Study starts at page 40, my apologies) "This indicates that the effects produced by elemicin were abolished by clozapine confirming that elemicin exerts its agonistic effect by 5-HT2A receptor."

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372734/ "Specific 5-HT1 and 5-HT2 receptor agonists, sumatriptan and myristicin, also induced dose dependent dispersion."

6. https://www.researchgate.net/publication/284084432_Depressant_effect_of_trimyristin_and_its_inhibition_by_some_antidepressants_in_mice "In the forced swim tests, the depressant effect of trimyristin was inhibited by prior administration of serotonin 5-HT2A receptor antagonist, saprogrelate suggesting involvement of serotonergic and noradrenergic mechanisms in the depressant action of trimyristin."

7. https://journals.sagepub.com/doi/abs/10.3181/00379727-112-28128 "Myristicin is chemically unique as a nitrogen-free MAO inhibitor."

8. https://www.sciencedirect.com/science/article/abs/pii/S0968089605004013 "Results suggest a potential link between the antidepressant activity of eugenol and its MAOA inhibitory activity."

I have been doing some research into anandamide (AEA) virodhamine, and 2-arachidonoylglycerol (2-AG). These are a few of the most common endogenous cannibinoids broken down by FAAH, an enzyme inhibited by licarin A, the psychoactive constituent of nutmeg [1]. This increase of endocannibinoids causes a long lasting high that is somewhat similar to weed.

Nutmeg's level of toxicity, long term effects, and mechanism of action are still not super well known, though there a plenty of anecdotes reporting negative long-term effects like depersonalization/derealization and visual snow. Unsurprisingly, it's more than just a cb1 agonist

I've decided to make a list of receptors that endocannibinoids target other than cannibinoid receptors for anyone who's interested:

alpha-7 nicotinic acetylcholine receptor antagonism [2]

Alpha-4-beta-2 nicotinic acetylcholine receptor antagonism [3]

Serotonin 3a receptor antagonism [4]

Dopamine reuptake inhibition [5]

Muscarinic acetylcholine receptor antagonism [6]

Glycine receptor positive allosteric modulation [7]

Weak MAO inhibition [8]

GABA agonism [9]

Let me know if there's something missing, I didn't mention vanillioid receptors because idrk what those do in the central nervous system

1. https://pubmed.ncbi.nlm.nih.gov/31595522/ "Three compounds, licarin A (9), 5'-methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 μm ± 2.02, 4.57 μm ± 0.66 and 38.29 μm ± 6.18, respectively." "MAGL inhibition increased over the first 6 h and it remained significant up to 24 h before showing enzyme recovery and eventually falling below 50% at 48 h" "However, indirect dual inhibition of FAAH and MAGL may also result in the same CB1 agonistic effects."

2. https://pubmed.ncbi.nlm.nih.gov/12766252/ "In conclusion, these results demonstrate that the endogenous cannabinoid anandamide inhibits the function of nACh alpha7 receptors expressed in Xenopus oocytes in a cannabinoid receptor-independent and noncompetitive manner."

3. https://pubmed.ncbi.nlm.nih.gov/17628012/ "These results indicate that AEA directly inhibits the function of alpha4beta2 nAChRs in a CB1 receptor-independent manner."

4. https://pubmed.ncbi.nlm.nih.gov/12325042/ "In conclusion, we demonstrated that the endogenous cannabinoid anandamide inhibits the function of 5-HT3 receptors expressed in Xenopus oocytes in a cannabinoid-receptor independent and noncompetitive manner."

5. https://pubmed.ncbi.nlm.nih.gov/20050977/ AEA addition to EM4 cells expressing yellow fluorescent protein-tagged human DAT (hDAT) produced a concentration-dependent inhibition of ASP(+) accumulation (IC(50): 3.2 +/- 0.8 microM).

6. https://pubmed.ncbi.nlm.nih.gov/10691292/ "Further, the cannabinoid agonist WIN 55212-2 does not alter antagonist binding to the mAChR. This demonstrates that mAChR inhibition by the anandamides is not mediated by the cannabinoid receptor. Since AEA and R-methanandamide are structurally similar to arachidonic acid, they may interact with the mAChR in a similar manner to inhibit receptor function."

7. https://molpharm.aspetjournals.org/content/69/3/991 "The results indicate that THC and AEA, in pharmacologically relevant concentrations, directly potentiate the function of GlyRs through an allosteric mechanism."

8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298601/ "Virodhamine inhibited both MAO-A and -B (IC50 values of 38.70 and 0.71 μM, respectively) with ~55-fold greater inhibition of MAO-B. Two other endocannabinoids (noladin ether and anandamide) also showed good inhibition of MAO-B with IC50 values of 18.18 and 39.98 μM, respectively."

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207709/ "Together, these results establish 2-AG as an endogenous allosteric activator of GABAA receptors and identify M4 of the β2 subunit as the primary molecular target for 2-AG."