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    Thread: Menthol as a Dream Enhancer

    1. #576
      BeemanChickenQuailDaddy Xanous's Avatar
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      I know I added mugwort but I still think its worth reporting. Highlander, I am stealing your format.

      Dose: 5 tablespoons Peppermint Leaves + 5 Tablesppons Mugwort + 3 cups water. 20 min simmer.
      Side Effects: Slight insomnia (30 min), sexual images
      Sleep Duration: 5 hrs before/2 hrs after
      WBTB: Yes brief
      Lucid: YES brief
      Vividness: Extremely High
      Stability: Mid ranged
      Dream Comments: Lack of concentration but high recall. Missed a few dream signs but was close. MILD didn't work. Heavy HI prompted me to try WILD. I got a really fun dream with a lot of fast action. The latter dream was very vivid but confusing. Also, This is the first time I got any sexual side effect from menthol. Perhaps my overall dose was higher than usual?

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      @dutchraptor: Can you extract any herb with that? It would be cool if I was able to somehow use it for my mugwort.

    2. #577
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Quote Originally Posted by Xanous View Post
      I know I added mugwort but I still think its worth reporting. Highlander, I am stealing your format.
      Actually, it's the thread's official recommended format.

      And thanks for posting that here!
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    3. #578
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Research Update!

      Alright guys, check this out.... I thought some of you might find this interesting.

      I've been doing more research on the role of endocannabinoids in dreams lately, and different topics of discussion going on around the forum here have been fueling my desire to learn even more lately. First, let me start with this. Anandamide, one of the big endocannabinoids, which exist in the hippocampus, has been shown to induce REM without tolerance or withdrawal through CB1 receptors when administered there. Here's a study on that: link.

      Quote Originally Posted by Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.
      Abstract

      Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation.
      Potent inhibitors of fatty acid amide hydrolase, the enzyme that breaks down anandamide, have also been shown to have a REM-increasing effect. This would normally be cool research for cannabinoids if it weren't for the fact that exogenous cannabinoid administration reduces REM through other mechanisms, meaning that the only way to really work with this would be to enhance the efficiency of endogenous cannabinoids like anandamide.

      Anandamide is synthesized in the body from a chemical called N-arachidonoyl phosphatidylethanolamine, or NAPE. There are a few different metabolic pathways involved in this, most of which aren't easily accessible to us. However, one of the enzymes, known as phospholipase C, is said to be activated by the kappa-opioid receptor. This could mean that by taking menthol we're actually strengthening the process by which our body creates one of the chemicals involved in the generation of REM sleep and likely some of the aspects of the dream world. Isn't that neat!? Furthermore, NAPE is synthesized in the body from arachidonic acid, which is known to be safe for supplementation.... I wonder if it would make a good dream supplement in its own right, and furthermore, if supplementing with both arachidonic acid and menthol would create a synergistic effect? I don't know, but I'm definitely interested now!

    4. #579
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      Quote Originally Posted by Xanous View Post
      @dutchraptor: Can you extract any herb with that? It would be cool if I was able to somehow use it for my mugwort.
      I can extract almost any organic matter to an extent. I guess I could try mugwort, it does grow in some places in Ireland. Although I thought mugworth is said to have quite strong properties, so it's probably not necessary to steam distill it.

      @Aly That is really cool. Would that mean that the half life of menthol in the body doesn't matter that much either and that we could take menthol before sleep?
      Last edited by dutchraptor; 03-10-2013 at 02:43 PM.
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    5. #580
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Quote Originally Posted by dutchraptor View Post
      @Aly That is really cool. Would that mean that the half life of menthol in the body doesn't matter that much either and that we could take menthol before sleep?
      Well, I've always thought that personally lol. I've only ever taken it before sleep. How much this directly applies to it I'm not sure, but I suppose it's possible. Kappa-opioid receptors are known for having long-lasting effects. I've heard anecdotally that the cAMP depletion it causes doesn't re-balance itself as quickly as the drug effects wear off. I also know that kappa agonists are known to have long-lasting anti-addictive effects. (Maybe even caused by that same cAMP depletion?) And though it's not the exact same, but is the same receptor, I think kappa antagonists are the shining star of long-term effects. Selective ones tested in labs have been shown to have antidepressant effects lasting for weeks after a single dose, effects that are not reversible by using kappa agonists. So clearly they have a lingering effect in the body.

      One thing I really wonder about with the anandamide potentiation is the sexual effects.... I didn't include this in the research post because I think it's too theoretical, but I always link the hippocampus to the imagination, and smoking weed makes my imagination become highly sexual. And if dreams, which are also hippocampal in origin, are just the imagination forced to encompass reality, I think it could make sense that increased cannabinoid activity there could account for the same kind of effects in dreams. I also wonder about its implications on the perception of spacetime, but that's a thought for another post....
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    6. #581
      BeemanChickenQuailDaddy Xanous's Avatar
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      Dose: 2mg melatonin prebed. 6 tablespoons peppermint leaves wbtb.
      Side Effects: wakefulness, sexual HI
      Sleep Duration: 4hrs/ 1.5hrs after
      WBTB: Yes 20min
      Lucid: YES
      Vividness: High
      Stability: Average

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    7. #582
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      I'm recovering from an illness, so this led to a really poor night of sleep. My cough was quite annoying, so I decided to take the peppermint tea pre-bed rather than at WBTB. I wound up taking melatonin at about 4 am because I was so desperate to get some sleep today.

      Fortunately, against all odds I did get a lucid dream!

      Dose: Pre-bed: 6 bags peppermint tea. WBTB: 250mg DMAE. Late morning: 1.5 mg melatonin out of desperation to sleep.
      Side Effects: Unknown
      Sleep Duration: 4 hrs total
      WBTB: Yes (30 minutes intentional + 90 minutes unintentional)
      Lucid: Yes!
      Vividness: High
      Stability: Medium
      Dream Comments: Some spicy non-lucids before WBTB, then a very tame lucid dream late in the morning.

      The lucid dream:
      Floodlights - Dream Journals - Lucid Dreaming - Dream Views
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    8. #583
      BeemanChickenQuailDaddy Xanous's Avatar
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      Am I the only one to get action packed dreams from menthol or is this as common as the sexual effects? Or are they somehow linked to the same chemicals/neurons whatever in the brain? Action and sex seem to go hand in hand for most guys I think.
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    9. #584
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Very nice guys, I love the results. I hope you feel better soon, Canis! Sorry I haven't been on really in the last couple of days, but I've been experiencing a prolonged nerdgasm. But before I go back to bulk buying realistic fake Yu-Gi-Oh! cards, I felt I should pop in to respond to this:

      Quote Originally Posted by Xanous View Post
      Am I the only one to get action packed dreams from menthol or is this as common as the sexual effects? Or are they somehow linked to the same chemicals/neurons whatever in the brain? Action and sex seem to go hand in hand for most guys I think.
      There are two amygdalae in the brain, one in the right hemisphere and one in the left. The right one is linked to aggression, and the left one is linked to euphoria, regardless of sexual orientation. But the right one also corresponds with sexual attraction to women, while the left one corresponds with attraction to men. So yes, for you they are linked.
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    10. #585
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      Last night was my weekly galantamine run. My cough has been screwing up my sleep lately, so I thought, "Hey! You know what's great at fixing annoying coughs? Menthol." So here's a little data point on a trial of galantamine + choline + cough drops.

      Dose: Pre-bed: 10.8mg menthol (cough drops), 100mg 5-HTP, 1 cup apple juice WBTB: 10.8 mg menthol (cough drops), 4mg galantamine, 200mg choline citrate, 250mg choline bitartrate, 300mg Alpha-GPC, 400 mg L-theanine. After waking: 1600mg Piracetam.
      Side Effects: Badass night of dreaming in spite of weak sleep
      Sleep Duration: 6 hours
      WBTB: Yes (30 minutes)
      Lucid: Yes! (Twice!)
      Vividness: High
      Stability: Medium
      Dream Comments: Two great lucids, and recall was extremely high. I recalled 7 dreams total if you include the two lucids. That's really high for me. (The highest, in fact, since the previous menthol night. I'll be keeping an eye on that!)

      The lucid dreams:
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      Great night... one of my most successful in quite some time!
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    11. #586
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Congrats, Canis! Sounds like you had an awesome night! It's interesting that you just decided to try that combination, because I was just thinking about it the other day. You know that thing I said up above about how kappa-opioid receptors increase endocannabinoid synthesis by activating phospholipase C? I later read that muscarinic acetylcholine receptors actually work through this exact same process, and these two also increase the release of inositol trisphosphate and calcium to enhance long-term potentiation (involved in learning and memory), so I was thinking that combining choline and menthol could actually be synergistic in this way. So I'm glad to see this, very interesting results!
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    12. #587
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      Quote Originally Posted by Alyzarin View Post
      Congrats, Canis! Sounds like you had an awesome night! It's interesting that you just decided to try that combination, because I was just thinking about it the other day. You know that thing I said up above about how kappa-opioid receptors increase endocannabinoid synthesis by activating phospholipase C? I later read that muscarinic acetylcholine receptors actually work through this exact same process, and these two also increase the release of inositol trisphosphate and calcium to enhance long-term potentiation (involved in learning and memory), so I was thinking that combining choline and menthol could actually be synergistic in this way. So I'm glad to see this, very interesting results!
      Thanks, Aly, I did! To the point where I have to ask myself the question whether I'll make this "a thing" every few weeks...? (As if I wasn't already a big enough menth-head.) So many exciting freakin combinations out there.

      I am really liking your thoughts on the possible synergies between the kappa-opioid receptors and the mAChR's. That makes a whole lot of sense. When I get a little time I will need to catch up on some reading in this area! I may have to try some more modest experiments with a little choline bitartrate, for example. Galantamine is such an ACh power tool that I'd like to see what less aggressive, more subtle approaches do.

      This is fun!
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    13. #588
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      Quote Originally Posted by CanisLucidus View Post
      Thanks, Aly, I did! To the point where I have to ask myself the question whether I'll make this "a thing" every few weeks...? (As if I wasn't already a big enough menth-head.) So many exciting freakin combinations out there.
      Aww, this is making me all warm and fuzzy. "Menth-head", I love it!! I hope you don't take this in a weird way, but I think you would have made a good drug user, because this is like drug use for the cautious and you're super into it. I'm all excited because I love corrupting people introducing people to new tools to explore their mind with, so I'm really happy that you like it so much!

      And I'll definitely eagerly await results if you do make this a regular thing!

      Quote Originally Posted by CanisLucidus View Post
      I am really liking your thoughts on the possible synergies between the kappa-opioid receptors and the mAChR's. That makes a whole lot of sense. When I get a little time I will need to catch up on some reading in this area! I may have to try some more modest experiments with a little choline bitartrate, for example. Galantamine is such an ACh power tool that I'd like to see what less aggressive, more subtle approaches do.
      As always, let me know if you find anything cool in your research! And you could definitely do that to help feel out the effects, since galantamine is more than just direct increases of acetylcholine, too. It would probably help to get a good sense of what choline does on its own if you plan to combine it with other things a lot. It may surprise you what choline alone can do!

      Quote Originally Posted by CanisLucidus View Post
      This is fun!
      I know, isn't it great?
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    14. #589
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      Quote Originally Posted by Alyzarin View Post
      Aww, this is making me all warm and fuzzy. "Menth-head", I love it!! I hope you don't take this in a weird way, but I think you would have made a good drug user, because this is like drug use for the cautious and you're super into it.
      Ha ha, I find that super flattering to hear! I can now go through life believing that in some alternate reality my cautiousness and meticulous, somewhat dorky recordkeeping could have made a major contribution to the scene.

      Quote Originally Posted by Alyzarin View Post
      As always, let me know if you find anything cool in your research! And you could definitely do that to help feel out the effects, since galantamine is more than just direct increases of acetylcholine, too. It would probably help to get a good sense of what choline does on its own if you plan to combine it with other things a lot. It may surprise you what choline alone can do!
      I agree! You got great results just from adding 250 mg choline bitartrate, so there are so many different ways to go. It'd be nice to open these possibilities up for easier, cheaper substances than G. Apart from being gentler on the wallet, choline bitartrate, soy lecithin, etc. aren't to me drugs in the way that galantamine is a straight-up drug.
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    15. #590
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      Quote Originally Posted by CanisLucidus View Post
      Ha ha, I find that super flattering to hear! I can now go through life believing that in some alternate reality my cautiousness and meticulous, somewhat dorky recordkeeping could have made a major contribution to the scene.
      As if it can't already. You're already helping this scene, and it's all really the same thing! Anything we figure out about how the brain works applies equally to drugs and supplements, and some of these things like menthol work directly on the same receptors. In fact, salvia is really the only recreational (and I use that word lightly) drug that acts potently on kappa-opioid receptors, there are a couple synthetic analogues but they're like almost completely unknown, which means that menthol is really the only other one that's being experimented with for mind-expanding purposes. You're part of a group of pioneers!



      Quote Originally Posted by CanisLucidus View Post
      I agree! You got great results just from adding 250 mg choline bitartrate, so there are so many different ways to go. It'd be nice to open these possibilities up for easier, cheaper substances than G. Apart from being gentler on the wallet, choline bitartrate, soy lecithin, etc. aren't to me drugs in the way that galantamine is a straight-up drug.
      You're definitely right about that! It feels a lot easier to take a vitamin or nutrient supplement than something from a plant, because I mean... what's there to worry about?
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    16. #591
      BeemanChickenQuailDaddy Xanous's Avatar
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      First of all. I know we avoid this but I feel its relevant to post this in both Menthol and Caffeine thread. I took a higher dose of caffeine this time because I wanted to WILD on the back side of peek plasma levels. I added melatonin and menthol as an afterthought. So really this was a caffeine experiment but I wanted to mention the menthol effects here as well.

      Dose: Pre-bed: A little Guinness WBTB: 4AM 200MG Caffeine, 5:41AM 1MG Melatonin, 6:05AM 2 tablespoons peppermint leaves in tea.
      Side Effects: mildly upset stomach
      Sleep Duration: 5hrs/1hr
      WBTB: Yes 2(brief then 1 hrs 40min)
      Lucid: Yes (sort of)
      Vividness: Medium to high
      Stability: Low
      Dream Comments: I woke a little after 5am from a non vivid NLD about texting my friend Zack in the cart garage at a Wal-Mart. I lay down and stared at a celling fan when I woke up. I definitely could tell my tolerance to caffeine has been significantly lowered since I reduced my daily intake. I felt very awake and could tell that heart rate went up and started breathing faster.

      Later the menthol gave me very strong sexual HI and made it very difficult to relax for awhile. Finally around 7AM I started going to sleep.

      Ok now the interesting part. I had maybe 6 or 7 DILDs after this. The only problem was that as soon as I realized I was dreaming I would immediately wake up. Each time I would be still not moving and continue to WILD. I tried several tricks. Counting, repetitive "motion", focusing on the body, and SSILD. All were effective but with each DILD I still woke up. I don't remember the dreams because I didn't want to move to record them. I unsuccessfully tried to commit them to memory but they were just random little snippets anyway. Then, the alarm got me at 8am. (I had something I had to do at 9) I snoozed for a while but didn't have time to DILD before the next alarm. I really think that if I had had a few more hours to sleep I would have eventually got it. I may repeat this next Saturday morning only with a slightly smaller caffeine dose. Overall, I really think the menthol added that little extra "boost" and was quite pleased with the result.
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    17. #592
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      6 or 7!! That's crazy! It sounds like if you tweak that to have just a little less restlessness you would be able to get some pretty incredible results. Neat stuff!

    18. #593
      BeemanChickenQuailDaddy Xanous's Avatar
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      Yeah it was interesting. I really lost count there so I am just guessing the total count. I mean, it was literally, watch the dream form. Lucid. Wake. Wash. Rinse. Repeat. And I am 100% positive it wasn't just vivid HI/HH either. Cool stuff.
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    19. #594
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      That does sound really great, I'm jealous.
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    20. #595
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      Another menthol night for me last night. This cough has had em coming more frequently lately. I had high hopes that the addition of choline bitartrate might be enough for an LD, but it didn't happen last night. That won't be the last time that I play with including choline bitartrate, though. I feel like there could be something there.

      Dose: Pre-bed: 16.2mg menthol (cough drops), 3mg melatonin, 1 bag popcorn WBTB: 16.2mg menthol (cough drops), 500mg choline bitartrate
      Side Effects: Unusually long duration of, uh, "morning excitement" after waking
      Sleep Duration: 8 hours
      WBTB: Yes (30 minutes)
      Lucid: No
      Vividness: High
      Stability: N/A
      Dream Comments: Final dream was absurdly sexy. Previous dreams amusing and very tame. Good vividness and recall throughout.

      The last dream before wake-up (a non-lucid) was comically sexy. Literally every DC that I encountered was an attractive female. Even though I didn't wind up actually doing anything with them, I had two points at which I imagined performing a sex act with one of these DCs. On each occasion, I was surprised by how incredibly vivid my imagination was. I'll try to drill into my head that an exceedingly vivid imagination is a dream sign.

      I am not sure whether this extraordinary vividness of imagination is just a general dream thing or more specifically a menthol thing. It's come up for me before in a menthol dream, so it's interesting. I'll keep looking for it.

      Next time, I'd like to try piling all of this menthol into WBTB. Another potential lever to pull: consider having choline bitartrate before bed instead of at WBTB. Choline bitartrate at WBTB seems to make the most logical sense to me, but Alyzarin had great results with a modest dose pre-bed. Definitely worth a try.
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    21. #596
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      Interesting side effect there CL Im starting to wonder if menthol nights should be preceded by prebed whoopie time.
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    22. #597
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      Quote Originally Posted by Xanous View Post
      Interesting side effect there CL Im starting to wonder if menthol nights should be preceded by prebed whoopie time.
      LOL, I know. I'm starting to learn that menthol reports are sometimes a little embarrassing. You get to a certain dosage with this stuff and man. The trip reports from 3 bags of peppermint tea were certainly way less soul-baring to write!

      Your suggested enhancement to the menthol experiment sounds good, just so long as we're not required to include this info in our reports.
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    23. #598
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      Quote Originally Posted by CanisLucidus View Post
      Dream Comments: Final dream was absurdly sexy. Previous dreams amusing and very tame. Good vividness and recall throughout.

      The last dream before wake-up (a non-lucid) was comically sexy. Literally every DC that I encountered was an attractive female. Even though I didn't wind up actually doing anything with them, I had two points at which I imagined performing a sex act with one of these DCs. On each occasion, I was surprised by how incredibly vivid my imagination was. I'll try to drill into my head that an exceedingly vivid imagination is a dream sign.
      Hehehe. I couldn't take all these reports anymore, I finally went out and got some more cough drops. Hopefully I'll see some nice results of my own soon.

      Quote Originally Posted by CanisLucidus View Post
      I am not sure whether this extraordinary vividness of imagination is just a general dream thing or more specifically a menthol thing. It's come up for me before in a menthol dream, so it's interesting. I'll keep looking for it.
      I would guess both. Well, I know the former is true, but I'm guessing the latter contributes as well. I'd say it's likely that menthol's effects on imagination will become increasingly more severe with the dose. After all, kappa-opioid agonists are very powerful hallucinogens in high doses, maybe some of the strongest. Any receptor that can cause such a powerful and dissociative psychedelic delirium must be distorting the mind in some pretty bizarre ways even at low activation.

      Quote Originally Posted by CanisLucidus View Post
      Next time, I'd like to try piling all of this menthol into WBTB. Another potential lever to pull: consider having choline bitartrate before bed instead of at WBTB. Choline bitartrate at WBTB seems to make the most logical sense to me, but Alyzarin had great results with a modest dose pre-bed. Definitely worth a try.
      You should try it and see if it works for you! You never know.

      Oh, and I don't think you're the first person to report that particular side effect. I believe we used that as a good sign for the validity of menthol's sexual effects!
      Xanous and CanisLucidus like this.

    24. #599
      BeemanChickenQuailDaddy Xanous's Avatar
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      Quote Originally Posted by Alyzarin
      Oh, and I don't think you're the first person to report that particular side effect. I believe we used that as a good sign for the validity of menthol's sexual effects!
      I have to agree. It wasn't until I got the sexual side effects that I started getting lucid. But I haven't got both at the same time from it. I'll call that a good thing. I really would do other things in a dream but that's me.

      Quote Originally Posted by CanisLucidus View Post
      LOL, I know. I'm starting to learn that menthol reports are sometimes a little embarrassing. You get to a certain dosage with this stuff and man. The trip reports from 3 bags of peppermint tea were certainly way less soul-baring to write!

      Your suggested enhancement to the menthol experiment sounds good, just so long as we're not required to include this info in our reports.
      I know right? I mean the HI I got was like literally watching porn. Geez I don't know if this batch of bulk peppermint leaves is just extra strong or what but I never had to contend with any of that with cough drops or regular boxed bagged teas. Speaking of which I need to get off the computer. JK. No really. What? nevermind.
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    25. #600
      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Breaking News!! Another Research Update!!

      Alright guys... I think the rules just changed. We're playing ball in a new court now.

      This is going to open a whole new realm of possibilities for things to research.

      A-type GABA receptor as a central targe - PubMed Mobile
      Quote Originally Posted by A-type GABA receptor as a central target of TRPM8 agonist menthol.
      Abstract

      Menthol is a widely-used cooling and flavoring agent derived from mint leaves. In the peripheral nervous system, menthol regulates sensory transduction by activating TRPM8 channels residing specifically in primary sensory neurons. Although behavioral studies have implicated menthol actions in the brain, no direct central target of menthol has been identified. Here we show that menthol reduces the excitation of rat hippocampal neurons in culture and suppresses the epileptic activity induced by pentylenetetrazole injection and electrical kindling in vivo. We found menthol not only enhanced the currents induced by low concentrations of GABA but also directly activated GABA(A) receptor (GABA(A)R) in hippocampal neurons in culture. Furthermore, in the CA1 region of rat hippocampal slices, menthol enhanced tonic GABAergic inhibition although phasic GABAergic inhibition was unaffected. Finally, the structure-effect relationship of menthol indicated that hydroxyl plays a critical role in menthol enhancement of tonic GABA(A)R. Our results thus reveal a novel cellular mechanism that may underlie the ambivalent perception and psychophysical effects of menthol and underscore the importance of tonic inhibition by GABA(A)Rs in regulating neuronal activity.
      So yes, this thing is saying that menthol seems to not only be a positive allosteric modulator of GABA(A) receptors but also a direct agonist, and this was verified specifically for the hippocampus. In case you're wondering what type of PAM it is, it seems to be fairly unique. This next study claims that it's unlike the typicals like benzos and barbiturates and actually shares some properties with the very obscure and particularly euphoric anesthetic propofol, one of the drugs implicated in contributing to Michael Jackson's overdose.

      Menthol shares general anesthetic activ - PubMed Mobile
      Quote Originally Posted by Menthol shares general anesthetic activity and sites of action on the GABA(A) receptor with the intravenous agent, propofol.
      Abstract

      Menthol and related compounds were investigated for modulation of recombinant human gamma-aminobutyric acid type A (GABA(A), alpha(1)beta(2)gamma(2s)) receptor currents expressed in Xenopus oocytes. Sub-maximal (EC(20)) GABA currents were typically enhanced by co-applications of 3-300 microM (+)-menthol (e.g. by approximately 2-fold at 50 microM) > isopulegol > isomenthol> alpha-terpineol >> cyclohexanol. We studied menthol's actions on GABA(A) receptors compared to sedatives (benzodiazepines) and intravenous anesthetics (barbiturates, steroids, etomidate and propofol). Flumazenil (a benzodiazepine antagonist) did not inhibit menthol enhancements while currents directly activated by 50 microM propofol were significantly inhibited (by 26+/-3%) by 50 microM (+)-menthol. GABA(A) receptors containing beta(2) subunits with either a point mutation in a methionine residue to a tryptophan at the 286 position (in transmembrane domain 3, TM-3) or a tyrosine to a tryptophan at the 444 position (TM-4) are insensitive to modulation by propofol. Enhancements of GABA EC(20) currents by menthol were equally abolished in GABA(A) alpha(1)beta(2)(M286W)gamma(2s) and alpha(1)beta(2)(Y444W)gamma(2s) receptors while positive modulations by benzodiazepines, barbiturates and steroids were unaffected. Menthol may therefore exert its actions on GABA(A) receptors via sites distinct from benzodiazepines, steroids and barbiturates, and via sites important for modulation by propofol. Finally, using an in vivo tadpole assay, addition of (+)-menthol resulted in a loss of righting reflex with an EC(50) of 23.5+/-4.7 microM (approximately10-fold less potent anesthesia than propofol). Thus, menthol and analogs share general anesthetic action with propofol, possibly via action at similar sites on the GABA(A) receptor.
      Now where does this leave us? Well damn... there are a lot of things I could say, but I think I'll hold off on too much for now. But some immediate observations....

      First, there's the link with propofol. This makes it pretty unique, and it looks like it's still not exactly the same receptor site. But just as a quick overview, propofol is supposed to be one of the much more euphoric GABAergics and maybe mildly hallucinogenic, and I have actually heard about sexual effects from it before. However, it's also been found to have multiple mechanisms of action, with some belief that the endocannabinoid system may be playing a role, so it's probably best not to speculate there.

      What really interests me is the direct agonist effect.... That alone could make it have hallucinations, though I would expect it to from the kappa-opioid agonism by the time it was a high enough dose for that. Makes me wonder what the effects would be like from a strong trip, though.... But anyway, here's what comes to mind. GABA has been reported by people to induce vivid and lucid dreams, which is interesting considering the effects that drugs like benzos have on dreams, but it could just be that they effect memory and REM-related functions too specifically. It's easy to see with them at lower doses, and drugs like alcohol, that GABA can positively effect dreams, so maybe a direct agonist like GABA itself can more easily get these effects. The other big thing is muscimol, the main desired active chemical in Amanita muscaria and Amanita pantherina mushrooms. Just like how salvia is unique in that it's really the only commonly used hallucinogen that binds to the kappa-opioid receptors for a significant effect, the amanita mushrooms are basically in the same situation but for GABA(A) receptors. Muscimol binds directly to GABA(A) and has powerful hallucinogenic effects at high doses. One thing it's also pretty well-known for is inducing bizarre dreams. There are actually many users of it who claim that it's one of its most desirable effects, saying that the way it works is that first you can take them and then sleep into a deep sleep of powerful or meaningful but very psychedelic dreams that are usually extremely vivid and often lucid, and then if you took enough you'll trip later when you wake up. But the dream effects can be gotten even at a lower dose, and I know people have used teas to that end before. I can't help but wonder if higher doses of menthol may be drawing from these kinds of effects as well....

      There are so many new things to consider now!!

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