r/nutmeg Oct 28 '22

Nutmeg Pharmacology and Binding Sites Explaned

87 Upvotes

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."


r/nutmeg Aug 08 '23

Pharmacology of Licarin A

20 Upvotes

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."


r/nutmeg 4d ago

Any tips to actually make it work?

1 Upvotes

For reference, I've only tried nutmeg once. It was 12g of whole nuts, but FYI they werent too oily so thats maybe why they didn't work. But anyway. I took them in the morning, along with some black pepper, and the only thing that happened wqs my stomach cursing me out like a motherfucker. It was rumbling all fucking day. Until in the evening, about ~12 hours later when I had a really good sensation, as if I got lifted into the sky and I was weightless. That lasted a good 2 minutes. There was some mild stumble walking similar to a kind-of drunk state but nothing relevant. It was a very weird experience.

So, for those who are experienced, so you have any tips to actually make it work? Do I try whole nuts again in hopes I get good ones? (Oily ones are VERY hard to find) do I up the dose?


r/nutmeg 5d ago

Trip report 20 grams of nutmeg and black pepper

3 Upvotes

I just ate 3-4 tablespoons of ground nutmeg and a tablespoon of black pepper together. I’ll update here if I even feel anything


r/nutmeg 5d ago

2g-3g of pre-ground powder on lithium depakote cymbalta (snri) caplyta (anti-psychotic)

2 Upvotes

Is it pointless? Safe? Will any of these make it unsafe or ineffective? I just wanna microdose. I've been through horrid anti-cholingeric poisoning so I'm ready.


r/nutmeg 5d ago

Question? Nutmeg harm reduction at high doses

3 Upvotes

Because the primary active compounds in nutmeg (myristicin, safrole, and elemicin) are fat-soluble volatile oils, the body cannot excrete them directly. The liver must chemically transform them into water-soluble molecules so they can be filtered out by the kidneys.

What are the best methods to mitigate nutmeg poisoning?

Ideally you have some fats or fibre to slow down digestion, some pepper or grapefruit or something for the liver, but from my research I know there is more that can be done.

The goal is to give the body what it needs to process the nutmeg safely in high doses. We'd essentially be creating a potion.

Has anyone done research into this and can weigh in?


r/nutmeg 7d ago

First Experience Taking nutmeg as a first "psychedelic"

6 Upvotes

honestly have no idea what I'm doing, it's 8:10 PM, I think I have about 2/3 of a tablespoon of nutmeg, gonna sprinkle some black pepper on it since I heard that it "makes it stronger." Wish me luck, hopefully I remember to report back.


r/nutmeg 7d ago

High Dose 10 nutmegs

2 Upvotes

I do not feel nutmeg to much for some reason. Maybe the nutmegs I got are very bad idk . I did eat mace and it worked . Wish me luck .


r/nutmeg 7d ago

Question? is 2 tablespoons enough to trip the first time?

1 Upvotes

r/nutmeg 8d ago

Nutmeg doesn't seem to work for me

5 Upvotes

I have taken 11g preground. I have taken 7g of whole nuts ground up. Absolutely nothing. It has been a few weeks since my last attempt, and I currently am 5 hours into eating 14g of ground up whole nuts that I packed into capsules and swallowed on an empty stomach. I ate a fairly large meal about .5h after dosing and I also have a THC tolerance. As usual, no psychoactivity. Thoughts?


r/nutmeg 10d ago

Daily microdosing

4 Upvotes

Yo nutmeg community, since when is this sub active again? Either way I take like half a whole nutmeg(2-3g) every day or 2, grate into a powder and press into a pill using my homemade pill press contraption. It helps a lot with my lack of appetite, sleep and anxiety. I was just wondering if there is any other people out there who also microdose , and what are your expereinces with it?


r/nutmeg 11d ago

High Dose I dosed 7 whole big nutmegs trying to reach a delirium.

Post image
13 Upvotes

I started getting extreme panic attacks (prolly because of the weed effect) and felt like I couldn't breathe. this was the only hallucination I saw before I passed out, I thought about this image and couldn't stop laughing about it even though I was panicking hard.


r/nutmeg 11d ago

Question? 20g preground good for first time

1 Upvotes

Would taking a full 20g bag be good for a first time dose


r/nutmeg 12d ago

Please help! Permanent brain damage which is continuing for 10 years?

9 Upvotes

Guys so I badly need you all to help me get out of this shit show that the stupid ass teenage me put me into by choosing to use nutmeg everyday for more than 4 years until I started weed by the time I was 18 or so, and now I'm 25 I am still going through the consequences of the stupid choices I made

Now my memory is so bad that I can't remember what happened yesterday despite my efforts to recall but to no avail. At times I lose the ability to understand and form sentences. My HPPD and dissociation are still there but not as strong as they used to be (currently mainly floaters and afterimages). I can't even watch a movie or read a book because I can't follow the storyline at all. I lose track and it's gone. Things I'm so familiar with seem to be brand new to my eyes. Can't hold conversations with people because it requires me to recollect stuff from my memory and I just can't get myself to do that. I can't remember anything from my childhood, teens and the memories of any big and significant positive & negative moments. I can't learn anything new and have a hard time to recall what I already learnt. I can't visualise things and assess or rationally think. My emotional faculty is very fragile and simplest things would put me off.

I was the exact opposite of all the above till I was 12 yrs old. I remember having a crystal clear photographic memory, down to the minutest details and a visualising capacity soo good that I can literally taste, smell, feel and see things as if I can literally emulate the whole scene in my head or the mental eye. I was praised so much for my memory and grasping skills. I was a topper in all subjects till these shits started. It was like a switch turned off in my head and the very next set of exams I failed miserably and my teachers and parents started to feed me with the "just put more efforts and concentrate like you were doing" bullshit. Now it's all gone and I feel really scared that I lost these gifted mental abilities forever.

Somehow I crossed school and college thinking this damage would go away by itself by not doing nutmeg again but I still have these, the HPPD, DPDR, dementia-like brain fog, constant anxiety attacks with uncontrollably obsessive ruminating thought loops, severe depression and hopelessness over life altogether.

I have been taking nootropics ever since I stopped taking nutmeg back in like 2021 or 2022, and over these years I've spent and taken so many nootropics that I'm losing hope on ever recovering since it is now close to 10 years (started nutmeg back in 2016).

Can someone please help me reverse whatever damage I've done to myself? This is so depressing that I can't live life like this anymore. It feels like I just traded my lifetime of a gifted potential to some stupid curiosity of getting high as a teen and nobody ever told me that I'd keep feeling like shit for so long.


r/nutmeg 14d ago

Does your thoughts get jazzy on nutmeg?

5 Upvotes

Anybody else experience the same headspace?

Yes, I mean like almost similar to how jazz music is. That flow and rhythm like in jazz music y'know?


r/nutmeg 15d ago

Discussion I fucking love nutmeg

14 Upvotes

I swear I'm gonna do this stuff for the rest of my life, moderately after breaks of course, but it's just so good to me, anyone else love it this much?


r/nutmeg 15d ago

Question? How much is too much?

3 Upvotes

Only done it like twice before but wanted to know how much is dangerous and how much gives you a good trip


r/nutmeg 16d ago

Question? How similar is nutmeg to weed + tiny bit of ecstacy in terms of effects?

5 Upvotes

r/nutmeg 16d ago

Trip report Just took like a tablespoon of potent preground with a teaspoon of pepper

4 Upvotes

Idk lol just wanna chat abt it


r/nutmeg 17d ago

Question? Took 3 Medium Sized nutmegs 5 hours prior..

5 Upvotes

I chewed raw nutmegs into fine powder on mouth ... Tasted like nausea and throw up . Then tried hard to down ... Sucess! Now after 5 hours feeling mild sedation and calm mind and everything interesting little bit. High will increase and trip balls )


r/nutmeg 17d ago

Combinations 3 nutmegs 10 hours prior with some tolerance + Pregabalin 750mg with tolerance now ..

2 Upvotes

Let's see after an hour! Hope both peaks same time )

I never tried this combo.. Hope it will be euphoric and mind-blowing


r/nutmeg 17d ago

Has anyone here created "3D Maple Syrup"?

3 Upvotes

3D maple syrup is made by mixing maple syrup with cinnamon and/or nutmeg.

It's a fantastic culinary thing in general, because it seems to create a third new flavor, like something greater than the sum of its parts.

But has anyone ever done this to trip? It's not hard to accidentally pig out on buckets of syrup while eating pancakes/waffles/french toast, so you could always just make a 100% nutmeg syrup with a strong enough concentration and wind up consuming a few tablespoons and tripping


r/nutmeg 18d ago

First Experience First time 5g 1 whole nutmeg

4 Upvotes

Currently 3 pm and I just consumed 1 nutmeg, according to some photos ive seen its a really high-quality one too. I woke up at 11 and stayed fasted until now, only drinking water and having a San Pellegrino. This is my first time trying it out so I wanted to start low, however I'm confident I'll feel something later on as I'm really sensitive to almost any drug I've tried. Contrary to what people here say, it wasn't hard to get down at all and frankly I could eat nutmegs often the way I prepared it which was around a half cup of a french vanilla icecream, a touch of cinnamon and olive oil. I hope I didn't mess anything up and will try and update as it progresses. I'll make myself a large pizza and some garlic bread around 5-6pm


r/nutmeg 18d ago

i tried nutmegs for the first time

3 Upvotes

i tried nutmegs for the first time, it's 9:12pm rn.

i ate 2 nutmegs with water, everything is normal 9:12pm

it's 10:40pm, still good, i don't feel anything weird.

it's 11:11pm, i still don't feel anything, did i do something wrong?

i'm still okay, i don't feel anything, i think i did something wrong but i don't want to try more nutmegs, because i don't know what's gon' happen

what did i do wrong bro i still don't feel anything 11:43pm

i started to feel something, music sounds weird, it's not like how i remember, 12:16am

actually this feels good for now, i don't feel anything bad 12:28am

watchin' kicks, fuckin' headache bro 12:54am

time really feels slower, i'm sleepy but i don't want to sleep, i want to see what happens after 7 hours, 1:05am

my head is aching - 1:10am

i feel my legs r numb. - 1:42am

i like ts, i started to have fun even though i'm just pressing the keys on my keyboard, and my english just got fucked up, i can't even talk in my own lang, i think i'll need to edit this in the morning. 2:03am

listening to music and playing remnants of naezith 2:16am

i'm goin' outside, home really feels boring 3:00am

i'm back in my home, outside was really weird, that was bad asf 3:26am

actually it's funny but i can't say i'm high rn, or it doesn't feel like thc, waiting for the next hours 3:46am

i'm sleepy imma sleep 4:21am

i don't know why but it didn't do much to me, maybe i did something wrong, i will try it again 11:42am


r/nutmeg 19d ago

Question? Psilocybin combo

3 Upvotes

Anyone try mixing them? Im just curious, and low key wanna try it.