- Jul 2024
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twin.sci-hub.st twin.sci-hub.st
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Periodic Limb Movements of Sleep measurementsconfirmedthat ULDNallowed equivalent control of limb movements at half the prior dose of D2/3 agonists. Although the naltrexone dosewas 0.15 ug, the effect was retained at 100 ug and 1 mg(Bear and Kessler, 2014a,2014b).Thus, naltrexone proved effective forRLS, putativelyby facilitating sensitization of D2/3 agonists.
The sources are patents. 2014a and 2014b.
It is interesting that the benefits were retained over a large dose range. Oddly, full doses (when combined with benzos) can help treat tardive dyskinesia. Thus, it seems plausible that the benefits for RLS are retained at even higher doses. I've not yet checked the sources to see if higher doses were tested. That is, doses over 1 mg. I doubt they were, because it would probably have been mentioned here.
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- Aug 2022
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Dosage and administration: The recommended starting dosage of mirtazapine is 15 mg/day for 4 days, then 30 mg/day for 10 days.
4 days is enough time to develop tolerance to the antihistamine sedation, but not to the adrenergic effects. Tolerance to yohimbine takes two weeks.
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- Apr 2022
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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3. Favourable results were obtained mainly from patients affected by negative symptom schizophrenia.
It's not often you find effective treatments for negative symptoms. As a schizoid myself, this looks like a valuable tool. I'd be fascinated to see how LDN and ULDN perform.
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- Jan 2022
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Both the 2 and the 4 mg oral dosages showed an absolute bioavailability of approximately 15%.
Combined with the fact that smoked nicotine is about 50% bioavailable, melatonin in an electronic cigarette should be roughly three times more bioavailable compared to oral.
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- Nov 2021
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively)
Given how cheap and easy this intervention is, I'd say this is adequate evidence that all ME/CFS patients should be taking these supplements. Moreover. given that the p-value is so low, it is almost certain to be replicated.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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In the group with daily supplementation of 400 mg of magnesium, HRV parameters clearly increased
This is as I'd expect. I'd like to know if there's a dose relationship. I'll also need to see if this translates to clinical significant improvements in things like schizophrenia and CFS.
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sci.bban.top sci.bban.top
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The average circulating blood volume in schizo-phrenia is 3917 cc. as compared with 4573 cc. in manic-depressivepsychosi
That's nearly a 15% reduction! It's also comparable to reductions seen in CFS (though CFS was per weight rather than per surface area, they should be comparable metrics). However, this is in comparison to bipolar, who themselves probably lack normal blood volume, so it's possible schizophrenia is a more extreme version of CFS where the blood volume is radically reduced. Will need more studies.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Although these findings may cause speculation that the observed vagal tone disruption merely results from anxiety produced by the presence of positive symptomology, additional studies have identified similar parasympathetic dysfunction among nonpsychotic relatives of individuals with schizophrenia.
This implies a causal role. The low parasympathetic tone precedes psychosis.
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Predictions.
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www.thermofisher.com www.thermofisher.com
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Polypropylene containers are autoclavable. The recommended autoclave cycle for empty containers is 121°C at 15 psi for 20 minutes. Care must be taken to allow free air circulation into and out of vessels during the autoclave cycle, especially during the venting and cooling stages. If the container is not properly vented, collapse or implosion (sometimes confused with melting) can occur. When autoclaving bottles and carboys, the cap threads must be completely disengaged from the container; the cap can be set loosely over the mouth opening at a rogue angle to ensure the threads don’t inadvertently engage. Once the container is completely cooled, the cap can be aseptically tipped into place and tightened down.
This is virtually identical to pressure cooker conditions. Thus these tips likely apply equally to cooking. Moreover, I take this as evidence that is appropriate for cooking food in the pressure cooker, though it may warp under stresses (so stacking containers may cause warping).
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin.
Could administering melatonin earlier in the day counter this effect? Presumably 6 hours before bedtime would maximize phase advance.
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- Oct 2021
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ift.onlinelibrary.wiley.com ift.onlinelibrary.wiley.com
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A simplified freezing point depression (FPD) equation was derived for calculating water activity (aw) of food systems. The aw values as calculated by FPD data agreed with literature data for a variety of foods to within ± 0.01 aw units. The FPD equation was found particularly useful for calculating aw values of frozen foods at temperatures between 273.1.5–233.15 °K (0 to −40°C).
± 0.01 aw? That's crazy accurate. Temperature is extremely easy to measure at home, which makes this a perfect technique for home food preservation. In particular, it can be used with sugar-free, salt-free, and other obscure recipes for which water activity is hard to estimate.
Additionally, this accuracy could be run in reverse. Knowing the water activity of ice-cream can tell you the freezing point. Moreover, a mini fridge could keep select food items chilled below 0°C for better preservation. In particular, I plan to dissolve erythritol into unsweetened plant milks and lower my fridge temp accordingly.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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However, the decrease in BV was greater in men (8.0 +/- 0.8 mL/kg versus 5.8 +/- 0.8 mL/kg)
That's a substantial fraction of the 11 point lower blood volume in ME/CFS found in one study. Moreover, this was achieved with only 13 days bed rest. I can only imagine the long-term effects of a sedentary lifestyle. It's likely that this is the primary cause of most ME/CFS. Nonetheless, exercise is unlikely to be the optimal treatment.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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59 (8)
I notice the standard deviation is low for their sample size. Normally smaller sample sizes increase SD. However, comparing to a study with 30 subject per group, we can see the expected SD for blood volume (ml/kg) in this sample size of 20 should be greater than ±22.
The reason for this small SD is probably that subjects with ME/CFS are scrunched up against the lower end of the curve. The body simply will not allow blood volumes below a certain level. Judging by this study, I'd say around 50 ml/kg is the lowest possible number.
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journals.lww.com journals.lww.com
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mirtazapine is used to treat akathisia probably because of its antagonistic property at H1 postsynaptic receptors and dopaminergic action in the frontal cortex.
That's an interesting hypothesis. I wouldn't have thought histamine was involved. Though, histamine being a stimulant, it also makes some sense. I'd have thought the primary mechanism is serotonin blockade, which would work in part by dopamine dis-inhibition as mentioned here.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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The kappa agonist spiradoline failed to produce cross-sensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the kappa antagonist nor-binaltorphimine.
This suggests to me that it is the opioid tolerance itself that determines cocaine sensitivity. To test this, I'd like to see a study that administers a KOR agonist after tolerance to opioids has been established, and see if this reverses cocaine sensitivity.
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puppylinux.com puppylinux.com
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Tahrpup64 6.0.5
224 MB
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Tahrpup 6.0.5
205 MB
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Slacko64 Puppy 6.3.2
238 MB
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Slacko Puppy 6.3.2
210 MB
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Slacko64 Puppy 7.0
343 MB
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Slacko Puppy 7.0
323 MB
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XenialPup64 7.5
330 MB
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XenialPup 7.5
325 MB
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BionicPup64 8.0
354 MB
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BionicPup32 8.0
274 MB
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Raspup 8.2.1
372 MB
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FossaPup64 9.5
409 MB
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www.youtube.com www.youtube.com
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4:42 "as monks and mediators, we only eat once in the morning." This seems quite plausibly an acquired wisdom, as opposed to a quirk of the practice. While I've not yet read much of the science myself, I've heard a great deal about the benefits of intermittent fasting. Moreover, there's interesting research suggesting that making breakfast your biggest meal provides benefits. I would not be at all surprised if eating only once in the morning is the optimal approach.
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www.reddit.com www.reddit.com
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I've been rotating kratom and phenibut for about 6 mos. I never take more than 4g of kratom/day or 2g of phenibut/day. I've opted to alternate 2 days of kratom, 1 day of phenibut. Doing so seems to have prevented tolerance and dependence on both ends.
Sounds promising, but it's partly because they have kepped dosage to a minimum. They have "miss" is their name, so it appears to be a woman. Men may be able to take a bit more.
It's a dangerous protocol. I couldn't recommend it to anyone who's risk averse. Ideally, one would have a third compound to cycle.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Sleep was then impaired during withdrawal, as indicated by decreased duration and poorer subjective quality, being worst on the 3rd withdrawal night.
My guess is that this is caused by a sleep surplus. I'd analogize it to the CBT-i recommendation to avoid napping because it will impair sleep drive that night.
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DIRECTORY (in progress): This post is my directory. This post will be tagged with all tags I ever use (in chronological order). It allows people to see all my tags, not just the top 50. Additionally, this allows me to keep track. I plan on sorting tags in categories in reply to this comment.
External links:
Tags categories will be posted in comments of this post.
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- Sep 2021
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PSA: everyone with insomnia should know that there are two recent double-blind, placebo-controlled trials on antioxidant blends for sleep, (1, 2). Given that the blends in each study are completely different, probably any antioxidants will do. I suggest amla powder as a cheap and available antioxidant source. Though, you may want to hedge your bets by adding other antioxidants. Antioxidants synergise, so the fact that they were blends may be important. Note: the benefits appear to take weeks to accumulate.
(1) A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning
(2) Sleep Promoting Effects of IQP-AO-101: A Double-Blind, Randomized, Placebo-Controlled Exploratory Trial
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www.hindawi.com www.hindawi.com
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All individual parameters (Items 1 to 8) were also significantly improved from baseline after 6 weeks of IQP-AO-101 intake. Analysis of variance with baseline values as covariates showed statistically significant improvements across all individual parameters for IQP-AO-101 when compared to placebo.
That's quite impressive. It's worth noting that benefits accrued throughout the entire study duration. There's likely further benefits over longer durations. I take the benefit to be from antioxidants.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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After 30 days, PBB improved diary sleep quality (p = 0.008) and reduced insomnia severity (p = 0.044) when compared to placebo.
This was achieved by a single size 0 capsule. The benefits would likely be proportionally greater with higher doses. Though, there is probably a cap depending on one's starting antioxidant status. I take it to be antioxidants that are providing the benefit.
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www.youtube.com www.youtube.com
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I did go to a therapist though, and she explained CBT to me, but only with hypotheticals relating to situations I had told her. How she described it, it would not help me because I have rational and realistic thought.
That's what I'd expect, and it's one of the main reasons I don't think CBT will help me. That said, I intent to try CBT. I'm also interested to know if this is the consensus or if it is the opinion of this particular doctor. It seems plausible that some CBT practices have subconscious effects.
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restlesslegssyndrome.sleep-disorders.net restlesslegssyndrome.sleep-disorders.net
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while the severity of RLS did not significantly change after CBT-i treatment, both sleep quality and anxiety symptoms were improved.
This is exactly what one would expect. Though, I'd not be surprised if there were small reductions in RLS severity over time.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Neither fentanyl (0.0003–0.02 mg/kg) nor SNC80 (0.03–0.3 mg/kg) changed either ACTH or cortisol basal levels. In contrast, U-50488H (0.01–1 mg/kg) dose-dependently stimulated ACTH and cortisol release in both male and female monkeys. Importantly, the stimulatory effects of U-50488H on the secretion of ACTH were blocked by a selective kappa opioid receptor antagonist, nor-Binaltorphimine.
Fascinating. I'd expect mu and delta opioids to reduce cortisol, if only indirectly via relaxation.
Likewise, it is important to understand the mechanism by which kappa agonism increases cortisol. Kappa is known for its dysphoric effects, which would naturally increase cortisol. However, kappa agonism is also consistent with extreme euphoria. This is known from reports with Salvia divinorum and Tabernanthe iboga. Whether this euphoria decreases cortisol or if it is, rather, a form of eustress is a very interesting question.
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pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.govLimonene1
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Miscible with alcohol
This conflict with this CaymanChem PDF. The PDF states that limonene has a solubility of 20 mg/ml.
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www.caymanchem.com www.caymanchem.com
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(+)-Limonene is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide. The solubility of (+)-Limonene in these solvents is approximately 20 mg/ml.
This conflicts with the PubChem page, which says limonene is miscible in alcohol. The PubChem page doesn't mention the other solvents.
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sagewisdom.org sagewisdom.org
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Salvinorin A was notsoluble in 100% propylene glycol to our surprise. However,solubility increased in propylene glycol by adding increasingconcentrations of DMSO. A 9:1 mixture ended up beingsuitable for our studies
I'm quite a novice in chemistry. I assume a 9:1 ratio would work with other solvents replacing the 9 parts propylene glycol. That is to say, given that salvinorin A was not soluble in propylene glycol, I'm assuming the propylene glycol plays little to no role.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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4,000 μg/mL
This is not concentrated enough for ejuice. I imagine the maximum capacity is much higher. DMSO is extremely powerful. Additionally, given that I don't like throat hit, I'd probably swap the PEG for VG. Once I can get pure salvinorin A, I can test if VG hinders solubility somehow.
Edit: Glycerol and DMSO are probably not miscible. This is based on the fact that glycerin and acetone aren't. I may try to see if terpenes and DMSO are miscible.
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SA was soluble in 25% dimethyl sulfoxide (DMSO)/75% polyethylene glycol 400 (PEG-400) at 4,000 μg/mL and was stable for 6 days, as determined by LC-MS/MS, with only trace amounts of the hydrolysis product salvinorin B (SB) forming.
As with DMSO and propylene glycol, I suspect that the DMSO is doing the dissolving. Given that it appears to only take 10% DMSO to dissolve salvinorin, naturally the 25% works. Unfortunately, I see no mention of whether salvinorin A is soluble in pure PEG-400. I suspect it is not.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Exceptionally, chlorophyll b was not found in any of the top phases. The lack of chlorophyll a and chlorophyll b in some ATPSs could be due to low extraction efficiencies or a change in the molecule structure by oxidation. Chlorophyll stability is affected by temperature, light irradiance, acids, bases and oxygen, causing the loss of its magnesium ion and/or phytol group40 and a change in colour to olive‐brown.41
Which one it is should be possible to determine by running multiple washes and visually assess how much pigmentation is removed. The idea is to dissolve acetone plant extract, add PEG-400, let the acetone evaporate, pour PEG-400 leaving sediment and/or crystals, then repeat. While I'd probably be doing this with salvia divinorum, any leaf should work for testing chlorophyll washing.
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Chlorophyll a was recovered by PEG400‐Ch DHp (50.6 ± 2.3%), but it was not detected in the other two systems at 660 nm [Fig. 2(b)].
They seem to be saying that PEG dissolved 50% of the chlorophyll? I also don't know what what Ch or DHp means. I'm somewhat outside my wheelhouse.
Assuming PEG-400 does not dissolve salvinorin A, then it may be an excellent option for purification of salvinorin A.
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www.dmt-nexus.me www.dmt-nexus.me
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4. Allow acetone to evaporate in a dark, well-ventilated area. You will be left with a bright green powder – about 1g per 100g of leaf. This powder is about 2 parts chlorophyll to 1 part salvinorin A.
This is incredibly useful information.
I noticed my extract had some bitter taste and some earthy notes. I don't know what salvinorin and chlorophyll taste like, but I assume the taste comes from other impurities. However, I extracted for many minutes (10 or so); next time, I should do only the 3 minutes suggested here (3 times 1 minute).
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www.researchgate.net www.researchgate.net
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When salvinorin A isolated from leaves of Salvia divinorum was irradiated with 300 nm UV light in ethyl acetate, it degraded from 100 μg/mL to 2.84 ± 0.05 μg/mL in 30 min. The calculated average rate constant k of this degradation was 0.12/min and the half-life was 5.7 min. When authentic salvinorin A was irradiated by UV light in an organic solution or an aqueous solution, it degraded over 90% within 40 min, whereas when it was irradiated by natural sunlight, it took 8 h to degrade 50% both in an organic and an aqueous solution.
Incredible. I may have destroyed my current batch. I'll have to start over. Good thing I only made a moderate amount.
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www.researchgate.net www.researchgate.net
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our Lab. for extracting terpenes and sterols from plant materials, we used petroleum ether (40-60), followed by acetone and finally methanol. Terpenes were found in petroleum ether- and acetone-extract.
This is the first confirmation I've seen of using acetone as a solvent for terpenes. I'd be surprised had acetone not dissolved them.
I'm using a method of adding terpenes to my salvia divinorum extract, then evaporating the acetone. This creates an instant e-juice. It's a relatively crude method, containing large amounts chlorophyll. Nonetheless, the contents should be safe for inhalation.
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www.nature.com www.nature.com
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sildenafil and vardenafil, caused a significant improvement in sleep quality and depression in this cohort of HD patients with ED.
These are the effects I was expecting to find. cGMP plays a role in SCN nighttime signalling, though I expect it has other mechanisms as well.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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In severe OSA, the use of sildenafil 50mg at bedtime plays a detrimental role on respiratory parameters
This is probably due to nasal congestion.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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We found an association between short-term secondhand exposures to EC emissions, measured by nicotine concentrations, and decreased HRV as well as shortening of the QTc
It's hard to say what this tells me about my hypothesis that the 7 mg patch increases HRV. It really depends on their blood levels. The second-hand smoke machine is extremely unrealistic. They were exposed to 30 puffs of 1.8% nicotine e-juice in the first measurement interval. Assuming 150 puffs per ml, that's 3.6 mg smoked in a single 15 minute interval! I've not read the full study to confirm this calculation. Nonetheless, it's clear that these insane conditions require scrutiny. That's not even counting the fact that there's no placebo (Or even control). How am I supposed to know if this is not just an effect of being concern about inhaling e-smoke? I'm still searching for studies on low concentration of nicotine and HRV.
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- Aug 2021
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.
This confirms that thyroid function probably lacks any (direct) effect sleep. Of course, not this evidence alone, but rather this combined with "Effects of Supraphysiological Doses of Levothyroxine on Sleep in Healthy Subjects: A Prospective Polysomnography Study"
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www.sciencedirect.com www.sciencedirect.com
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Due to the paucity of research and significant heterogeneity in studies, definitive conclusions about the effects of these micronutrients on HRV cannot be made at this time. However, there is accumulating evidence suggesting deficiencies in vitamins D and B-12 are associated with reduced HRV, and zinc supplementation during pregnancy can have positive effects on HRV in offspring up until the age of 5 y.
Odd they don't mention vitamin E or other antioxidants. They do cite that placebo-controlled vitamin E study in diabetics. I ought to see what other important information they've left out of the abstract.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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nicotine supplementation significantly decreased HRV
This disproves my suggestion that 2 mg might increase HRV, but I was looking for 1 mg rather than 2. The 2 mg gum is still plausibly a higher dose than a 7 mg patch. I'm struggling to find studies in the lower doses. This may be because everyone wants to prove the harm of nicotine. There may even be publication bias (especially if there's no effect).
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Heart rate variability showed no differences between the 2 nights, but the low to high ratio (a parameter indicative of sympathetic nervous system activity) positively correlated with wake after sleep onset in night with nicotine patch.
This was with a 14 mg patch. A 21 mg patch would probably reduce HRV given that a 4 mg lozenge does so.
I still expect to find enhance HRV with 7 mg. This study supports that hypothesis to an extent. That it, it shows that 14 mg may be the tipping point between increased or decreased HRV from nicotine.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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4 mg oral nicotine lozenge or placebo.
Assuming a half life of two hours, I calculated a 7 mg per day patch delivers a peak dosage of around 0.8 mg. Given that a 4mg lozenge has a bioavailability of 79%, this is equivalent to a 21 mg patch.
Given that we know anything above a 7 mg patch disrupts sleep (while 7 mg enhances sleep), it's unsurprising that HRV was reduced. I expect that a 1 mg lozenge or gum would increase HRV. Given that the above citation lists the bioavailability of a 2 mg lozenge at 50%, 2 mg may also increase HRV.
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ajp.psychiatryonline.org ajp.psychiatryonline.org
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it undergoes first-pass hepatic metabolism, resulting in low (30%–40%) bioavailability.
I'll need to review this later. This is a more precise figure than I was familiar with. I think I read somewhere between 20% and 50%; I believe I cited that figure in one of my college papers.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40–49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.
This may partly represent the salvia "afterglow". It also demonstrates how rapidly tolerance-like mechanism can occur.
I find it odd that 0.32 mg/kg had little prolonged effect when twice that dose had a very large effect. I'd expect more of a gradient. The graph (figure 4) shows a nonsignificant drop in KOR binding of ~13% at 1 hour at 0.32 mg/kg, which I'm certain would become statistically significant in a larger sample. Still, that's nowhere near the 45% seen at 0.6 mg/kg. At 0.18 mg/kg, we see ~9%.
I calculated the human equivalent dose to be 6.8mg (0.6mg0.16270). This is an very high dose, so likely does not represent an accurate dose conversion.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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On the contrary, either repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that repeated stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas repeated stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
That's quite interesting. I have a vague memory of reading that morphine tolerance upregulates KOR, but that memory may be mistaken. Alternatively, it could be that KOR was upregulated in this study, but it took greater KOR agonism due to mu/delta not providing baseline analgesia due to downregulation. Lastly, there is also the possibility that it takes simultaneous mu and delta agonism to upregulate KOR; this possibility seems likely.
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Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists
Just confirming what I believed to be the case. I couldn't remember whether I'd read results of this specific sort, so I figured I should look it up. Chronic KOR agonism appears to be an ideal opioid hack.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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This study confirmed the variability of baobab with different origins
I'm considering switching back to amla for this reason. Amla is cheaper due to its potency. While I don't like the taste of amla, it's easily tolerable provided I know why I'm taking it.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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TST
This effect was quite substantial. It was over 100 minutes greater increase than in the placebo, for both healthy subjects and insomniacs. Total Sleep Time (TST) increased in the placebo group by 1 hour in healthy subjects and 2 hours in insomniacs. Of course, most of that was probably not placebo, but rather getting used to the sleeping conditions. As I said, ashwagandha increased sleep time 100 minutes more than that. In real world conditions, I think it's reasonable to expect an hour increase after 8 weeks of ashwagandha. Indeed, this effect implies it's not just an antioxidant, as antioxidants didn't have an effect that significant on TST.
Edit: actually, the increase in TST appears not to be that great, assuming the graph is to be trusted. Given that TST was reported as such low numbers, I had assumed it must be change in TST from baseline. However, the graphs show a 20 or so minute increase. The reported numbers in the table are all messed up. Sleep onset latency is reported as 85 in the healthy group taking ashwagandha. Time in bed is reported as 20 minutes. None of it makes sense, and none of it matches up with the graphs. That table isn't trustworthy. Best to go by the graphs, which show decent but more realistic benefit.
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In both healthy and insomnia subjects, there was a significant improvement in the sleep parameters in the Ashwagandha root extract supplemented group. The improvement was found more significant in insomnia subjects than healthy subjects.
Benefits accrued throughout the 8 weeks. I recall reading on Longecity forum that ashwagandha takes a month for benefits to kick in. This study demonstrates that benefits continue to increase over two months. I suspect they continue even further than that.
Interestingly, this is pretty similar to the two placebo controlled studies on antioxidants for sleep. Thus, I wonder of the benefits of ashwaganha extract are largely antioxidant capacity. This would be a bit surprising because the ORAC of dried ashwaganda is just slightly above raw pinto beans. Based on the recommended doses, the extract isn't vastly more potent than the whole root. Though, this comment saying that the Withanolide/Withaferin A (edit: withaferin A is purportedly cytotoxic) reside mostly in the leaves has greatly confused me. Either the extract has more antioxidant activity than I realize (directly or indirectly), or the benefits come primarily from the purported mechanisms of ashwagandha (which include cortisol reduction and GABAergic activity). Edit: the full text mentions a 15 to 1 extract ratio, which is enough to put the antioxidant mechanism back on the table. It's probably a partial explanation, but after seeing the full text I think the benefits are too great to be simply from antioxidants.
I see no mention of the time of day of administration. I'm assuming it was in the morning, which contrasts with the near bedtime dosing in the antioxidant studies. If I later find out that antioxidants in the morning don't help with sleep, then that will suggest ashwagandha works by other mechanisms. However, I expect antioxidants at any time of day help with sleep. Nonetheless, I'm not discounting that ashwagandha may work by other mechanisms.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Conclusions: While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension.
This supports that study on vitamin E in diabetics.
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sci-hub.se sci-hub.se
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Participants were instructed to have one capsule twice daily with either milk or water for 8 weeks. Each capsule was of 300 mg dosage.
This was most likely morning and bedtime. 300 mg times 15 equals 4.5 grams. In other words, they administered the equivalent of 9 grams ashwagandha root per day.
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The herb to extract ratio is 15:1.
This is likely the standard. It is a sufficient ratio to give it a high ORAC, meaning the antioxidant mechanism is back on the table. Nonetheless, the benefits appear greater than that of mere antioxidants.
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www.cambridge.org www.cambridge.org
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Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep
I believe this roughly equates to the benefits from an increase in SWS.
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slow-wave sleep
There was a trend towards increased SWS. I suspect this will bear out in larger or otherwise better studies.
There seems to be an error in reporting of SWS. The reported increase was actually fairly substantial. It was reported as 19.2 in the CGA compared to 15.7 in the placebo, but I'm sure that must be missing a digit or something. In any case, assuming it is otherwise accurate, that would be a 22% increase.
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academic.oup.com academic.oup.com
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Conclusions: Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes. Such an effect might be mediated by a decline in oxidative stress.
This is plausibly the reason why antioxidants enhance sleep. Though it is likely that there are other mechanisms as well, such as reduced neuroinflammation. Come to think of it, given that ME/CFS appears to be caused by high sympathetic tone during sleep, antioxidants are the perfect treatment. Antioxidants are proven in placebo-controlled trials to help with sleep in healthy subjects and insomniacs alike. I doubt that antioxidants can cure ME/CFS, but I'm confident they will help.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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PBB did not impair neurocognitive functioning, and some improvement was noted in vigilant attention, working memory, and risk assessment.
This suggests measurable enhancements in sleep architecture.
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Participants were instructed to take the supplement 30 min before bedtime
I suspect near bedtime is optimal, but I'd be interested to see effects of daytime administration.
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www.nature.com www.nature.com
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Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions.
That is indeed unexpected. However, this may be explained by a nap, mentioned in an article which appears to be based on the same data.
Edit: they measured on day 9, whereas the first placebo was administered on day 8, so the may have accumulated SWS surplus on night 8.
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journals.sagepub.com journals.sagepub.com
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withdrawal conditions
Oddly, the strong adenosinergic pressure from ~20 hours wake combined from caffeine withdrawal didn't lead to increased SWS. Indeed, there was a nonsignificant trend towards a decrease in SWS. One possibility is that caffeine induced SWS surplus accumulation over the previous week, reducing SWS drive. However, this could alternatively be explained by the 60 minute nap.
Withdrawal restored REM sleep under these conditions. The withdrawal condition looks quite similar to placebo (both REM and SWS), which is rather surprising.
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A 60-min evening nap preceded each sleep episode and reduced high sleep pressure levels.
I see. I believe this could possibly explain the lack of increase in SWS. They don't mention taking any measurements during this nap.
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www.webmd.com www.webmd.com
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Big dinners make you temporarily drowsy but prolong digestion, which interferes with a good night's sleep.
Appears to be proven incorrect.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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ConclusionContrary to the existing literature, shifting dinner timing from 5 hours before sleep to 1 hour before sleep in healthy volunteers did not result in significant adverse changes in overnight sleep architecture. In fact, LD was associated with deeper sleep in the beginning of the night and lighter sleep in the latter part of the night in healthy volunteers. This novel manifestation of postprandial hypersomnia may have therapeutic potential in patients with sleep disorders.
This aligns with intuition. However, they only tested a single night in each condition. The harm of eating at night may be a zeitgeber effect, taking multiple days to accumulate.
These results bring into question advice about avoiding food at night. Food quality likely plays a critical role. It remains unclear whether eating before bed is advisable, but this data gives reason to at least avoid making recommendations against it.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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The lower the level of selenium in the diet the more reports of anxiety, depression, and tiredness, decreased following 5 weeks of selenium therapy.
Though the effect was stronger in those with lower intake, the effects on mood in those with higher intake were still quite substantial, (full text). That is to say, both groups benefited. Selenium improved anxiety only in the low intake group, (full text).
Interestingly, the high and low intake groups had the same baseline scores. That is to say, it's not that selenium brought the low intake group up to normal, but rather that they were lifted above the high intake group. It's possible that they had adapted to their low intake, be it psychological or physiological adaptation. I recall a similar effect with creatine and cognitive performance in vegetarians.
This raises the question: does the benefit disappear over time as one adapts to their new selenium levels? Perhaps, but I find it more likely that the benefit drops only slightly. That is, I think what may be occurring is a a positive feedback loop where better mood makes you more optimistic, thus improving your mood; I expect this psychological mechanism to fade, leaving the biological component intact.
Of course, there is the possibility that this is a statistical fluke. Nonetheless, I'd expect the above mechanism to occur in general. If I learn more about statistics I could probably run a p-value test.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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However, addition of naltrexone significantly improved TD
Interesting. They were using full naltrexone doses, not LDN. I'd expected full doses would make movement disorders worse.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer.
Thus, your typical selenium supplement will not provide this benefit. I wonder, however, if higher doses might. Indeed, it is often closer to toxic doses that are effective against cancer (for various compounds).
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www.lifeextension.com www.lifeextension.com
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A 1989 study in China estimated 800 mcg per day to be the safe upper limit and reduced that amount to 400 mcg per day to ensure a large margin of safety.48
Good. I thought 400 was likely safe. Though I'm considering taking 400 mcg daily, 200 mcg is probably more than adequate.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively.
That is a moderate but worthwhile benefit over placebo.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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ResultsImprovement (decline IRLS score >10) was significantly higher in selenium (50 and 200 μg) than placebo group.
Not only was is significant, but it was impressive! The 200 μg dose cut the score over 50%, compared to 20-22% reductions in the placebo. Everyone with RLS should be given selenium.
However, I disagree with the authors that this should be a replacement. Multiple treatments are likely necessary to achieve adequate relief.
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Selenium prescription in daily recommended dose of 50 μg
Not sure why 50 instead of 200. Though the superiority of 200 μg was not statistically significant, I doubt there is any risk to such a dose.
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link.springer.com link.springer.com
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Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms.
As expected. This study was placebo controlled, too.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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A total of 10 smokers
This study doesn't say much given that they only included smokers.
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www.cambridge.org www.cambridge.org
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acetylcholine
This is supported by a single-blind study on nicotine for akathisia.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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14 mg nicotine
I'd be interested to see the effect of a 7 mg patch. 14 mg is too high for sleep, so I wonder if it is also too high for akathisia.
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- Jul 2021
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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ConclusionThere is autonomic dysfunction in children with ADHD - reduction in overall HRV with sympathovagal imbalance with sympathetic dominance.
Unsurprising. This supports my hypothesis that ADHD is a sleep disorder. This hypothesis should hold sound regardless of EEG. That said, I also expect to find EEG disturbance during sleep in ADHD.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Collectively, these results indicate that mirtazapine may help to maintain abstinence in opioid dependent patients.
I concur. This merits human analysis. I'd be curious to know the subjective effects of combining the two. In particular, I'm wondering if mirtazapine reduces "wanting" while enhancing "liking".
The main reason I'd been thinking this is due to comparison to similar drug combos in humans. I'd heard that combining hydroxyzine and opioids was sometimes prescribed to enhance the effectiveness of opioids and/or use lower opioid doses; I'd also read on some harm reduction forum that some people enjoy combining opioids with antihistamines. Given that mirtazapine is to a large extent just hydroxyzine but with added adrenergic effects, it seems likely that much of these data can be cross-applied (between mirtazapine and hydroxyzine in particular).
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www.reddit.com www.reddit.com
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Yes. I took ten grams at once. It wasn't bad; an hour later I felt incredibly relaxed, like I was just the teeniest bit high, but not much other than that. Not the cheapest habit to maintain, but it was a good one-time experiment.
This is the highest dose of L-theanine I've seen taken. At one dolar per 10 grams, It's actually reasonably affordable to take daily for medical purposes. I may try it, but I'm unlikely to implement it long term. If it's a significant effect, it would be a useful tool. However, I'd be concerned about tolerance.
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link.springer.com link.springer.com
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The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia.
In contrast, sildenafil appears not to provide any acute benefit, (study). I'd only expected benefit due to sleep enhancement, so lack of acute benefit was unsurprising to me.
Given that risperidone was likely taken at night, and sildenafil was likely taken at the same time, it's my opinion that the benefits in this study were due to sleep improvement. This may be via the circadian clock, or a more direct effect on sleep, or both.
My remaining question is whether sildenafil improves sleep in healthy subjects. I'm especially interested in combining sildenafil with 100 to 300 mcg melatonin. Will they have synergistic effect? I expect so.
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journals.lww.com journals.lww.com
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Sildenafil did not alter heart rate nor heart rate variability to a significant extent
I'm somewhat surprised. I was under the impression that cAMP signalled the wake phase, and cGMP signalled the sleep phase. I thus expected cGMP to increase parasympathetic tone (and therefore increase HRV)
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- Jun 2021
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jamanetwork.com jamanetwork.com
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mild
That's important. It seems what we should care about is the effect in severe cases.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Individual elimination half-life values ranged from 0.6 to 3.3 hours and were independent of dose.
This could potentially be explained due to variation in Tmax. That is to say, it may not be that half life varies dramatically. Rather, absorption into the bloodstream after intramuscular injection may be the cause. I'm no expert on IM injections.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients.
This is not surprising. It seems that L-theanine is clinically useful in the exact ways one would expect.
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- May 2021
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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but there was no difference in levels of withdrawal between those on NRT patches and those on placebo.
Data like this seems to be definitive proof that nicotine is nothing like tobacco. I'm not aware of any evidence that nicotine itself is addictive, save for a few anecdotes. I don't put much stock in these anecdotes because people also report habit-withdrawal symptoms when they quit zero nicotine e-juice. That is to say, without placebo controls we cannot conclude drug withdrawal is the cause because it can also be explained by psychology.
That said, I'm reasonably certain that nicotine contributes to tobacco addiction. While I think nicotine is fairly non-addictive, I believe it enhances the addictiveness of other drugs. I think this is partly due to an entourage effect that alters the high, and also a memory-enhancing effect so one remembers the high more vividly.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Conclusion: The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea.
From the full text, they used 5 micrograms of naltrexone. Naltrexone dose is very finicky. There's low dose (LDN), very low dose (VLDN), and ultra-low dose (ULDN). This is a ULDN. I believe the type of effects I'm looking for occur at VLDN and LDN doses. If I recall correctly, I think 2 mg is optimal for analgesia, but I don't remember whether this was with or without morphine. 0.125 mg and 0.25 mg are effective in opioid withdrawal when combined with methadone. Thus, it's not too surprising that 5 mcg had little effect. At those doses, the effects it does have are like mediated by different mechanisms.
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www.frontiersin.org www.frontiersin.org
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Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders
I think this may be the best review of salvinorin A that I have ever looked at. I definitely need to sit down and read the full article at some point.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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In contrast to its acute administration, repeated salvinorin A administration did not modify dialysate DA levels. Similarly, neither basal extracellular DA levels nor DA uptake was altered. Unlike synthetic KOPr agonists, prior repeated administration of salvinorin A did not attenuate the locomotor activating effects of an acute cocaine (20 mg/kg, i.p.) challenge. However, cocaine-evoked DA overflow was enhanced.
Fascinating and useful stuff. This is close to what I was expecting. Though, I was expecting chronic exposure to upregulate dopamine beyond baseline. If I'm understanding this correctly, it was upregulated in the sense that it enhanced the dopaminergic effects of cocaine. I've not yet read the full study.
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jpet.aspetjournals.org jpet.aspetjournals.org
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Systemic administration of ultra-low doses of naltrexone (16.7, 20.0, and 25.0 ng/kg) with morphine (1.0 mg/kg) extended the duration of the morphine-induced conditioned place preference.
This is important because it suggests mood-brightening. Contrast this with combining L-type calcium channel blockers with opioids, which appears to limit tolerance to opioid analgesia that does not correspond to mood brightening.
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jamanetwork.com jamanetwork.com
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with 4 catatonic, 2 hebephrenic and 2 paranoid subjects having a systolic tension less than 100.
That's not a large enough sample to draw conclusions out subtypes. Interesting nonetheless.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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On the basis of our open study findings ritanserin could be classified as a substance with antidepressive effects, with a low incidence of side-effects and a rapid onset of action.
Low incidence of side effects certainly sounds superior to atypical antipsychotics and tricyclic/tetracyclic antidepressants.
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headachejournal.onlinelibrary.wiley.com headachejournal.onlinelibrary.wiley.com
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Ritanserin was highly effective in reducing Pain Total Index and analgesic consumption in chronic headache, and its activity was similar to that observed during amitriptyline treatment. A significant improvement of HRSD and HRSA(Hamilton Rating Scale for Anxiety) scores was observed during both treatments.
This may mean ritanserin is superior. Amitriptyline is a dirtier drug affecting more than just serotonin receptors. Therefore, ritanserin likely has fewer side effects. However, I'm not currently aware of any studies demonstrating this.
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- Apr 2021
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www.youtube.com www.youtube.com
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Stolen Childhood (2019)
30:55 Ibuprofen rescue. Interesting concept, though I am somewhat skeptical.
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www.youtube.com www.youtube.com
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What you Need to Know about Loneliness
18:03 Loneliness leads to microarousals. Could this be a potential root cause of ME/CFS.
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www.quora.com www.quora.com
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Day 2: extremely difficult. My brain was convincing me time and again to light one . It was trying to convince me that i Needed one. Almost lit one but put it down. It felt like i had gulped down a pre workout or a protein shake and had not worked out. Felt frisky and restless. Dependent on a vape - 9/10
Sounds like withdrawal. Why is information like this so hard to find?
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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In seven out of the eleven subjects in whom core body temperature could be sampled, the nadir of body temperature was advanced during L-T4 intake by 15 minutes to 270 minutes.
This supports my speculation from another study, found here.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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However, coadministration of nefiracetam (5 or 10 mg/kg, p.o.), enprofylline (30 mg/kg, p.o.) and rolipram (0.3 or 1 mg/kg, i.p.) with morphine during the pretreatment period, significantly reduced the withdrawal signs, moreover, the tolerance was significantly attenuated.
Looks promising. It's odd that theophylline had a lesser effect.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Conclusion: Our data suggest that the combination of VLF with morphine may be a relevant therapeutic implication to manage pain even when tolerance to morphine exists. Moreover, our data demonstrates the involvement of L-Arg/NO/cGMP pathway in the prevention of morphine tolerance and dependence by venlafaxine.
It's not clear if this has relevance to the subjective effects. I'm starting to think that I won't get an answer anytime soon.
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link.springer.com link.springer.com
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Sildenafil treatment enhanced the development of tolerance to the motor impairing effects, but not to the sedative effects, of DZ.
I'm not sure what conclusions I should draw from this.
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www.psicothema.es www.psicothema.es
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Results: The administration of sildenafi l reduced all of the morphine withdrawal symptoms.
An acute effect. Interesting but not particularly consequential. It does mean, however, that I need to be wary of studies using withdrawal as a netric when combining PDE5 inhibitors with opioids.
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www.researchgate.net www.researchgate.net
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Results: Tadalafil showed anti-nociceptive effect when given alone at different doses (p<0.05). However, tadalafil significantly decreased the analgesic effect of morphine (p<0.05). In addition, tadalafil significantly increased the tolerance to morphine (p<0.05). Conclusions: The phosphodiesterase type 5 inhibitor tadalafil have anti-nociceptive properties and it decreases analgesic effect of morphine, in addition improves tolerance development. These effects probably may occur via NO/cGMP pathway.
This is analgesia, so is not necessarily relevant for my purposes. Nonetheless, there implies some relevance of cGMP, but the direction isn't yet clear.
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www.nature.com www.nature.com
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Repeated KOR agonist exposure, on the other hand, can result in opposing effects on the dopamine system [27], and desensitization of the KOR [28]
If they mean what I think they mean, then this implies that chronic KOR is useful. I'll need to check citation 27.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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These data suggested that PAT, an indirect-acting KOR agonist, share the common pharmacological property of KOR agonists on morphine tolerance
PAT is apparently an herbal medicine I should look into. They also imply that KOR agonists act as I expect they do, but I'll need to read the full study to be sure.
Edit: yup, it appears that chronic KOR agonism is probably a good idea.
from full text "Utility of KOR agonists is a promising pharmacological tool for attenuating morphine tolerance (Pan, 1998), however, it is difficult to find effective KOR agonists that are devoid of dysphoric and psychotomimetic adverse effects in humans"
This is the cited study.
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www.ijaweb.org www.ijaweb.org
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Oral nimodipine (120 mg.day -1 ) was noted to significantly reduce the daily requirement of morphine, provided the patients have been already on morphine therapy for some period of time.
Interesting. It is not clear the ideal time/order of administration.
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The results also showed that diltiazem was able to selectively potentiate the analgesic effect of morphine but not of fentanyl (the reason was not known).
Fascinating. However, this provides no insight into the subjective effects. However, it does reduce my certainty that any given combination of drugs (sharing these mechanism) will work. There doesn't seem to be consistent results with these L-CCBs plus opioid studies.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers.
Yes. That also means that most of the rat studies I've been reading are useless for my purposes.
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however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period.
That's a shame. I still need to find out the long term effects on mood. There seem to be only three human studies on calcium channel blockers combined with opioids. I infer that from google search results plus the review that lead me here.
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MBG scores
Morphine Benzedrine Group (ARCI-MBG) scale was designed to measure benzodiazepine-induced mood elevation.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Administration of L-CCBs alone, particularly diltiazem, increased pain in the formalin test. In contrast, co-administration of these L-CCBs with morphine led to decreased pain response
There is still the question of subjective effects. Given that I'm primarily interested in this combination as a psychological treatment and as a transhuman upgrade, increased pain is not a deal-breaker. It's also not quite clear how this holds up in the long term. That is, do the effects of L-CCBs on pain change after supersensitization to opioids?
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Treatment with both morphine and forskolin appeared to cause an additive effect in desensitizing mu-opioid receptor.
This is getting very odd. It is hard to draw useful conclusions. This is partly because I'm out of my depth.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Theophylline (2.5-100 mg/kg) in combination with morphine (5 mg/kg), during conditioning sessions, decreased the acquisition of morphine conditioned place preference dose independently. Administration of theophylline (2.5-100 mg/kg) before testing also caused a significant reduction of the expression of morphine-induced conditioned place preference in a dose-independent manner.
Shame. It may prevent tolerance partly by reducing the subjective effects. Though, there are other possible explanations.
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www.nature.com www.nature.com
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Future studies should be conducted to test if the decreased cortical brain activity after nimodipine is associated with improved working memory performance in patients with schizophrenia, particularly those who carry the risk-associated genotype.
Interesting hypothesis.
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www.ijaweb.org www.ijaweb.org
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However, long-term treatment may not be useful.
I wish they would expand on that. I may have to read the full text later to see what they mean.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Results:Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period.
Weird and surprising.This plausibly implies that L-type calcium channel blockers may not be as effective as it first appears.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference being statistically significant (P=0.03).
Consistent with rat data. This is from 1998. I'm sure there's more evidence by now. It's been a while since i researched this, but I think I've previously seen at least one other study.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.
Excellent. This implies that theobromine may help prevent opioid tolerance.
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However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome.
Worth noting.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Humans can easily digest and excrete methylxanthines, the half life of theobromine being 2-3 hours.
That is absurdly shorter than other citations. It is almost certainly wrong.
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link.springer.com link.springer.com
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Bleuler defined schizophrenia with his four ‘A’s’, referring to the blunted Affect (diminished emotional response to stimuli); loosening of Associations (by which he meant a disordered pattern of thought, inferring a cognitive deficit), Ambivalence (an apparent inability to make decisions, again suggesting a deficit of the integration and processing of incident and retrieved information) and Autism (a loss of awareness of external events, and a preoccupation with the self and one’s own thoughts)
I stumbled upon this accidentally. I was going to add to my prediction that schizophrenia might be related to autism, but now that I've found this I need to publish my draft.
Edit: Here was the prediction I wrote. Copied unmodified, ensuring transparency.
March 28, 6:15pm Prediction: Some cases of schizophrenia are being misdiagnosed as autism. I recently took a Coursera.org course on schizophrenia. The negative symptoms look similar to some autism symptoms.
Before I look it up, there are a few other predictions I should make. Do I think schizophrenia and autism will be linked? If there’s cross-diagnosis, will this link be artificial or real? Last time I looked, people with aspergers had (more or less) normal sleep EEGs. In contrast, schizophrenia is associated with disrupted sleep spindles. I already know that schizophrenia and bipolar are genetically linked, but I don’t know what the bipolar sleep EEG looks like. That is to say, I don’t know if the lack of sleep abnormality in autism is evidence against a link to schizophrenia. All in all, I predict that there will be a real link (for example, genetic), but I have a low confidence in this prediction. The reason is that I expect there is little EEG sleep changes in bipolar, implying that there is a supra-mechanism causing all these effects; somewhat like metabolic syndrome, the same cause may manifest in different ways.
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pubs.rsna.org pubs.rsna.org
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After World War II, many antioxidants were found to protect against the harmful effects of ionizing radiation when administered prior to exposure.
Both interesting and completely unsurprising. However, I'm curious about protection against fission specifically. That is to say, can we protect against existential risk by nuclear weapons by stocking nuclear bunkers with antioxidants.
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