Health - Legal highs and depression

[bbdd]

i suffer from depression! are there any legal highs that are suitable for a depressed state of mind or would it make it worse?

[imyourlittlebare]

there are several different things that could help

st. johns wort after 6 weeks of consumption would help. talk to a pharmacist about interactions with this drug however

if you find anxiety to be a culprit to your depression, kava root is very effective. again with all of these consult a pharmacist about interactions. liver problems arising from kava use is .3 per million which is much safer than 2.14 per million for diazapam.

new theories about depression stem from inadequacies in the opiate pathways. swims method of dealing with anxiety and depression involve kratom and kava use and swim finds it very helpful. there are also leaved that you can chew from africa that effect seritonin that effect mood and have an antidepressent effect. i will find out there name.

[bananaweed]

mate is a good antidepressant.

[snapper]

Rhodiola rosea, picamilon and phenibut may also help. The latter two address anxiety.
Kava does not cause liver failure if it is the root only. The current thought is that the whole plant was used to make extracts and that some factor not in the root is responsible, so it is safe if only root is used.
Keep in mind that though some legal highs have antidepressant effects, they can trigger depression when they wear off. A classic example of this for SWIM is kratom. Feel great while on it, but after depression for SWIM feels worse.

[imyourlittlebare]

Originally Posted by snapper

Rhodiola rosea, picamilon and phenibut may also help. The latter two address anxiety.
Kava does not cause liver failure if it is the root only. The current thought is that the whole plant was used to make extracts and that some factor not in the root is responsible, so it is safe if only root is used.
Keep in mind that though some legal highs have antidepressant effects, they can trigger depression when they wear off. A classic example of this for SWIM is kratom. Feel great while on it, but after depression for SWIM feels worse.

That is a possibility. But a theory now is that depression is caused by problems in the opiate pathway. Thats why groups of psychiatrists, and soon to bes like myself are hoping to introduce bunephorine into the ranks as an immediate helping medicine in combo with something longer lasting.

And if your interested in kava im going to post a crap load of articles supporting that it does not cause liver harm. in fact, it may not be the plant itself. It may be if the company produces the extract using ethyl alcohol. I have a ton of research youll be excited to see the advancements of kava in therapy!

[snapper]

Maybe true - buprenorphine certainly has powerful antidepressant effects, though they may not be related to opiate receptors at all. It is however known that if not used consistently, an opiate drug's serum level will wax and wane. If one is depressed due to an opiate deficiency as you postulate, then the troughs in the blood levels would create worse periods of depression after alleviating them during the peaks. The alternative is constant use, which usually implies addiction and a tolerance. It is a very slippery slope.

Reputation Comments on this post:

great observation about pain meds. opened up a great debate

[imyourlittlebare]

Originally Posted by snapper

Maybe true - buprenorphine certainly has powerful antidepressant effects, though they may not be related to opiate receptors at all. It is however known that if not used consistently, an opiate drug's serum level will wax and wane. If one is depressed due to an opiate deficiency as you postulate, then the troughs in the blood levels would create worse periods of depression after alleviating them during the peaks. The alternative is constant use, which usually implies addiction and a tolerance. It is a very slippery slope.

its a compex matter and im glad your inquisitive. if it is a problem with the opiate pathways the drugs of the future would enhance are own endorphin system. however, for now you are right unless the painkiller is administered with a nmda antagonist. this prevents addiction and tolerance. or one or the other i forget but it takes care of one of them. the thing about it is if you talk to depressed people or psychiatrists about ssris, the main thing is they will say if they stop the medicine they will
a. go throw withdrawal
b. become depressed again and even worse due to ssris destroying seritonin receptors by flooding your extracellular fluid with seritonin

sound familiar? so rather than administering a drug for life that only works for some people, have one that works for most all people. understand? or do you want me to elaborate more or post any sources? im glad you asked that question.

[candy_kid]

there are a lot of interactions due to it being a MAOI, however, a single dose of syrian rue has many a time in the past cleared mild depressions for swim (being a MAOI)

[imyourlittlebare]

Originally Posted by candy_kid

there are a lot of interactions due to it being a MAOI, however, a single dose of syrian rue has many a time in the past cleared mild depressions for swim (being a MAOI)

hes right. you have to avoid things like cheese, wine, and everyday things like that. talk to a pharmacist before having it. it does work for depression there are a class of antidepressents called mao inhibitors. they work on the enzyme mao a and b that would otherwise break down norepinepherine, dopamine and seritonin. so it works rather well esp having more dopamine in your system. however, not recommended if anxiety has been a problem.

[snapper]

NMDA antagonists are used as adjunct to pain management not because the control tolerance (this has not been proven though if SWIY has some references, SWIM would love to see them - SWIM would be happy to admit SWIM is wrong) but rather to control pain through a different pathway. It is common to use a low dose ketamine infusion with other constant rate infusions of opiates and the combo is far superior to the opiate alone. However, a tolerance does develop as usual.
SWIM must also consider the consequences of addiction. With most SSRIs, there can be a severe physical withdrawal, as with, for instance, morphine, but many of the other quality of life issues, including apathy, increasing tolerance, risk of overdose, and of course abuse potential for recreational reasons are not present.
That said, GHB also presented a huge capacity for use as an antidepressant, mostly through the induction of high quality sleep and subsequent dopamine rebound in the morning, but it also had abuse potential.
Buprenorphine has shown some promise, but it still forms a tolerance and has abuse potential. SWIM is sure there are newer molecules down the road which may be more appropriate for this use. Kratom is about the closest thing there is right now though, not bup.

[imyourlittlebare]

i disagree. kratom works for about three hours. bup has a half life of 34 hours which is great. and it is a partial agonist/antagonist meaning if you take more than the dosage your supposed to, you lose any painkilling effect at all. I had read articles about ketamine being used for pain management as well. Here are some articles supporting me


Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the un paired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [d-Trp[sup 11] ]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes. [ABSTRACT FROM AUTHOR]as tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the un
one that says another thing modulates the mechanism

Abstract: Adaptations to the chronic administration of opioids reduce the utility of these drugs in treating pain and support addiction. Recent genetics-based approaches have implicated the beta2 adrenergic receptor (beta2-AR) in controlling some of these responses. We do not know, however, whether this receptor can modulate tolerance, dependence or changes in gene expression caused by chronic opioid administration. For our studies we used C57BL/6 mice and beta2-AR knockout mice in the FVB background. Morphine dose-response relationships were established both prior to and after chronic morphine treatment. In some cases, the selective beta2-AR antagonist butoxamine was administered along with or after morphine. Physical dependence was assessed using naloxone-precipitated withdrawal. The expression of calcitonin gene related peptide (CGRP) and substance P (SP) were measured in spinal cord and dorsal root ganglion (DRG) tissues using both real-time PCR and enzyme-linked immunoassay (ELISA). Both the co-administration of butoxamine with morphine and the administration of butoxamine after chronic morphine reversed morphine tolerance. Morphine failed to cause tolerance in beta2-AR knockout mice. Physical dependence was reduced under the same circumstances. The chronic administration of butoxamine with morphine reduced or eliminated the normally observed up-regulation of CGRP and SP in spinal cord and DRG tissues. Our results suggest that the beta2-AR modulates both opioid tolerance and physical dependence. Activation of beta2-ARs appears to be required for some of the key neurochemical changes which characterize chronic opioid administration. Therefore, beta2-AR antagonists show some promise as agents to enhance chronic opioid analgesic therapy.

one for me

Title: Primary afferent NMDA receptors increase dorsal horn excitation and mediate opiate tolerance in neonatal rats.
Author: Zeng, Jinsong; Thomson, Lisa M; Aicher, Sue A; Terman, Gregory W
Institution: Department of Anesthesiology and the Graduate Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Appears In: The Journal of neuroscience : the official journal of the Society for Neuroscience. vol. 26, no. 46 (2006 Nov 15): 12033-42.
Journal Info: Abbreviation: J Neurosci. Journal Subset: IM.. Country of Publication: United States.
Abstract: Repeated exposure to opiates produces analgesic tolerance, which limits their clinical usefulness. Whole-cell voltage-clamped lamina I cells in spinal slices from opiate-tolerant neonatal rats show an increase in miniature, spontaneous, and primary afferent-evoked EPSCs when compared with lamina I cells from opiate-naive rat spinal slices. This increased excitation can be blocked by the NMDA receptor (NMDAR) antagonist APV, apparently acting at NMDARs on primary afferents. Consistent with these results, electron microscopy demonstrates an increased incidence of NMDARs in substance P-containing spinal dorsal horn primary afferent terminals in opiate-tolerant rats. Moreover, superfusion of spinal slices from opiate-tolerant rats with NMDA produces a reversible increase in miniature EPSC (mEPSC) frequency in contrast to a decrease in mEPSC frequency produced by NMDA in opiate-naive slices. Finally, NMDAR antagonists inhibit the expression of opiate tolerance both in inhibiting EPSCs in spinal slices and in inhibiting behavioral nociceptive responses to heat. NMDAR antagonists have been reported in many studies to inhibit morphine analgesic tolerance. Our studies suggest that an increase in primary afferent NMDAR expression and activity mediates a hypersensitivity to noxious stimuli and causes the inhibition of opiate efficacy, which defines tolerance.





Title: Tolerance to morphine analgesia: evidence for stimulus intensity as a key factor and complete reversal by a glycine site-specific NMDA antagonist.
Author: Adam, Frederic; Bonnet, Francis; Le Bars, Daniel
Institution: Institut National de la Sante et de la Recherche Medicale (INSERM) U-713, 75013 Paris, France.
Appears In: Neuropharmacology. vol. 51, no. 2 (2006 Aug): 191-202.
Journal Info: Abbreviation: Neuropharmacology. Journal Subset: IM.. Country of Publication: England.
Abstract: N-methyl-D-aspartate (NMDA) receptors are widely involved in opioid tolerance. However, it is less clear whether NMDA receptor antagonists reverse already-established tolerance and whether the intensity of the nociceptive stimulus influences morphine tolerance. Three days after implantation of morphine or control pellets the effects of i.v. morphine and pre-administration of saline or (+)-HA966 (a glycine site-specific NMDA receptor antagonist), were studied on the C-fibre reflex elicited by a wide range of stimulus intensities. Morphine both increased the threshold and decreased the slope of the recruitment curve in the "non-tolerant" group of animals. In the "morphine-tolerant" group, the threshold did not change but the gain of the stimulus-response curve decreased. The expression of tolerance to morphine depended on the intensity of the stimulus, being maximal when threshold stimulus intensities were used but considerably less with supra-threshold stimulation. As expected, a single treatment with (+)-HA966, potentiated morphine antinociception in "non-tolerant" rats. However, in "morphine-tolerant" rats (+)-HA966 reversed established morphine tolerance and increased the antinociceptive effects of morphine. These results suggest that (+)-HA966 interfered with expression of morphine tolerance, and offered an encouraging therapeutic approach for pain management in opioid abusers.

[imyourlittlebare]

Title: Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence.
Author: Regunathan, Soundar
Institution: Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA. sregunathan@psychiatry.umsmed.edu
Appears In: The AAPS journal. vol. 8, no. 3 (2006): E479-84.
Journal Info: Abbreviation: AAPS J. Journal Subset: IM.. Country of Publication: United States.
Abstract: Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, alpha2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.




Title: Chronic morphine treatment alters expression of N-methyl-D-aspartate receptor subunits in the extended amygdala.
Author: Bajo, Michal; Crawford, Elena F; Roberto, Marisa; Madamba, Samuel G; Siggins, George Robert
Institution: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
Appears In: Journal of neuroscience research. vol. 83, no. 4 (2006 Mar): 532-7.
Journal Info: Abbreviation: J Neurosci Res. Journal Subset: IM.. Country of Publication: United States.
Date Revised: 20061115
Abstract: The nucleus accumbens (NAcc) and central amygdala (CeA) are parts of the extended amygdala, a complex that plays a key role in drug abuse and dependence. Our previous studies showed that opiates and ethanol alter glutamatergic transmission in these regions. N-methyl-D-aspartate (NMDA) receptors are key components of glutamatergic transmission likely involved in the development of opiate tolerance and dependence. In this study we examined the effects of chronic morphine administration on gene and protein expression of three major NMDA receptors subunits (NR1, NR2A, and NR2B) in NAcc and CeA. Real-time PCR showed no differences in mRNA levels of any of the subunits in the whole NAcc between naive and morphine-dependent rats. However, at the protein level, immunoblotting revealed that chronic morphine significantly increased levels of NR1 and NR2B subunits. In contrast to the case for NAcc, in CeA we found an increased mRNA level for the NR1 subunit only but unchanged protein levels of all three subunits in morphine-dependent rats. The altered expressions of NMDA receptor subunits, especially in NAcc, of morphine-dependent rats may represent a neuroadaptation to chronic morphine and suggest a mechanism for the changes of glutamatergic transmission found in the extended amygdala in dependent rats. In addition, our results indicate a region-specific response of NMDA receptor subunits to chronic morphine administration at the gene and protein levels. Copyright 2006 Wiley-Liss, Inc.




Title: The role of N-methyl-D-aspartate (NMDA) receptors in pain and morphine tolerance.
Author: Inturrisi, C E
Institution: Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA. ceintur@med.cornell.edu
Appears In: Minerva anestesiologica. vol. 71, no. 7-8 (2005 Jul-Aug): 401-3.
Journal Info: Abbreviation: Minerva Anestesiol. Journal Subset: IM.. Country of Publication: Italy.
Date Revised: 20061115
Abstract: To determine the importance of the N-methyl-D-aspartate (NMDA) receptor in pain hypersensitivity following injury, the NMDAR1 subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adeno-associated virus expressing the Cre recombinase into floxed NR1 mice. This procedure resulted in more than an 80% reduction in the expression of both NR1 mRNA and protein and a corresponding loss of NMDA, but not AMPA currents, in the lamina II neurons in the injected area. This spatially and temporally restricted knockout dramatically reduced the response to pain hypersensitivity resulting from the intraplantar injection of formalin but did not alter heat or cold paw withdrawal latencies, mechanical threshold, or motor function. Thus, the NMDA receptor in the spinal cord dorsal horn is essential for central sensitization, the central facilitation of pain transmission produced by peripheral injury. Agents that act on these spinal receptors may provide a therapeutic approach to ameliorate injury-induced pain.




Title: Morphine-induced changes of gene expression in the brain.
Author: Ammon-Treiber, Susanne; Hollt, Volker
Institution: Institute of Pharmacology and Toxicology, Otto-von-Guericke University, Magdeburg, Germany. susanne.ammon@medizin.uni-magdeburg.de
Appears In: Addiction biology. vol. 10, no. 1 (2005 Mar): 81-9.
Journal Info: Abbreviation: Addict Biol. Journal Subset: IM.. Country of Publication: England.
Date Revised: 20070327
Abstract: Repeated opiate administration alters gene expression in different brain regions of rodents, an effect which may contribute to plastic changes associated with addictive behaviour. There is increasing evidence that multiple transcription factors are induced in morphine tolerance, sensitization and during morphine withdrawal. Whereas morphine treatment does not lead to major alterations in the expression of mu-opioid receptors (MOR), there is transcriptional regulation of proteins involved in MOR trafficking such as GRK2 or beta arrestin 2 as well as altered expression of other receptors such as dopamine receptors, NMDA receptors, GABA(A) receptor and alpha(2A) adrenoceptor. Recent gene expression profiling studies reveal additional clusters of morphine-responsive genes: whereas single dose administration has been shown to predominantly reduce expression of genes involved in metabolic function, ascending morphine doses leading to morphine tolerance revealed induction of genes which alter patterns of synaptic connectivity such as arc or ania-3. These genes remained elevated after precipitated withdrawal, which also triggered the expression of several transcriptional activators and repressors. In addition, morphine has been shown to be a strong inducer of heat shock protein 70, a cell protective protein which might counter-regulate opiate-induced neurotoxicity. Temporal expression profiles during a chronic morphine application schedule revealed discrete and fluctuating expression of gene clusters such as transcription factors, G-protein-coupled receptors and neuropeptides. Prolonged abstinence seems to be characterized by up-regulation of several transcription factors and persistent down-regulation of ligand gated ion channels such as glutamatergic and GABA-ergic receptor subunits. These long-term changes in receptor expression suggest a persistent alteration of synaptic signalling after morphine treatment.




and i was right about both. if you read the story of the miraculous healing of the heroin addict by a hallucinogen, it was due to its effects on subtypes of nmda receptors



Title: Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors.
Author: Leal, Mirna Bainy; Michelin, Katia; Souza, Diogo Onofre; Elisabetsky, Elaine
Institution: Faculdade de Farmacia, Pontificia Universidade Catolica do Rio Grande do Sul, Rua da Republica 580/306, Cep: 90050-320, Porto Alegre, RS, Brazil. mirnabl@pucrs.br
Appears In: Progress in neuro-psychopharmacology & biological psychiatry. vol. 27, no. 5 (2003 Aug): 781-5.
Journal Info: Abbreviation: Prog Neuropsychopharmacol Biol Psychiatry. Journal Subset: IM.. Country of Publication: England.
Date Revised: 20031114
Abstract: Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a noncompetitive NMDA antagonist. The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. Jumping, a major behavioral expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK-801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine-dependent animals treated with IBO or MK-801. This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.
Subjects:

[imyourlittlebare]

When you start to develop tolerance and cravings, its due to LTP which is modulated by the nmda receptors. I hope this helps and helps you reevaluate your theories. Im glad you made me look it up though i hadnt read a good article on it in a while.

[imyourlittlebare]

and my non-scientific theory is. SSRIs work for some people but for the others that react badly and have intense weight gain, apathy, sleeplessness and extreme anxiety, they arent worth it and it happens more than not. Bunephorin, with its extremely long half life and agonist/antagonist abilities make it a great medicine for depression. Its milder in euphoria and cloudiness while still relieving immediate symptoms of depression. And in my mind, i believe the research is pointing towards depression being a model with problems in the opiate receptors. and with the kappa opiate receptor being part of this pathway and being involved with nmda receptors, this could account to why ketamine works as an antidepressent too. I just believe that bup can improve someones quality of life rather than destroy it. And this is a professional opinion with some research to back it up but there are many other approaches so i am not saying mine is best. Id love to debate what your ideas are and id love for you to share information.

[MrG]

5-Htp is supposed to work wonders for depression as it boosts serotonin levels.

Although you would have to first establish the cause of your depression because any treatment of symptoms would not fix the underlying cause and would likely mean constant medication otherwise you would relapse. Anyway, feeling depressed (sad) is not actual depression (mental illness) so you need to explain your symptoms a bit better.

[candy_kid]

^^ that 5-htp does, however 5-htp also eventually turns into melatonin which can end in some rather lengthy sleep periods and difficult wakeups also note that lengthy sleep periods can reduce exposure to daylight and in themselves cause a form of depression, use at one's caution (it does work though! they're swim's backup to syrian rue when he's been tasting things that would otherwise interact with a MAOI)

also on that note, keep in mind that there are two main neurotransmitters that can result in depression if low- one being serotonin and one being dopamine. Lower serotonin levels seem to more often involve a general sadness associated with guilt, poor self image and tiredness, low dopamine levels on the other hand seems to more often simply make the person feel there is nothing worth living for, or cause extreme boredom and irritability. Both can be at play btw but if one were to suspect dopamine being low, l-tyrosine, the precursor to dopamine and epinephrine may help ease the symptoms like 5-htp would for serotonin

btw, swiy should never mix either of these with syrian rue or any other MAIO; precursors to neurotransmitters along with many other drugs will cause reactions that wont get broken down which is very dangerous-- most definitely read up on syrian rue and what you need to avoid if swiy plans to use it.

edit : I just noticed that you were asking about legal highs that wouldn't effect depression, rather than legal highs that would cure depression it should be noted that any high will move one's brain chemistry around and could very well risk making things worse.. or better. I was originally recommending syrian rue to swiy as an antidepressant and although it can be used as a hallucinogen technically (at larger doses), I dont know if it would keep the brain chemistry looking good necessarily... The question is rather tricky and many drugs can and will both make depressions better and worse. My best advice is to not take anything addictive as swiy may become reliant on that drug to avoid depression (caffeine, alcohol, kratom etc). As for some other drugs, hallucinogens could renew a love for life, or enhance the depression times ten... they're somewhat risky methylone will completely kill the depression temporarily, the question for that one is though; will it give an afterglow or a hangover (which of course would make things much worse). Why doesn't swiy kill the depression first (work out demons, supplement brain chemistry, HAVE FUN, etc) and then start doing drugs without having to worry? drugs are something that if used at all should come at the end of the day when everything is taken care of- but it sounds like there are still things to work out for swiy

either way, good luck!

Reputation Comments on this post:

great post. considerate of him to want to help individual!

[imyourlittlebare]

Originally Posted by candy_kid

^^ that 5-htp does, however 5-htp also eventually turns into melatonin which can end in some rather lengthy sleep periods and difficult wakeups also note that lengthy sleep periods can reduce exposure to daylight and in themselves cause a form of depression, use at one's caution (it does work though! they're swim's backup to syrian rue when he's been tasting things that would otherwise interact with a MAOI)

also on that note, keep in mind that there are two main neurotransmitters that can result in depression if low- one being serotonin and one being dopamine. Lower serotonin levels seem to more often involve a general sadness associated with guilt, poor self image and tiredness, low dopamine levels on the other hand seems to more often simply make the person feel there is nothing worth living for, or cause extreme boredom and irritability. Both can be at play btw but if one were to suspect dopamine being low, l-tyrosine, the precursor to dopamine and epinephrine may help ease the symptoms like 5-htp would for serotonin

btw, swiy should never mix either of these with syrian rue or any other MAIO; precursors to neurotransmitters along with many other drugs will cause reactions that wont get broken down which is very dangerous-- most definitely read up on syrian rue and what you need to avoid if swiy plans to use it.

edit : I just noticed that you were asking about legal highs that wouldn't effect depression, rather than legal highs that would cure depression it should be noted that any high will move one's brain chemistry around and could very well risk making things worse.. or better. I was originally recommending syrian rue to swiy as an antidepressant and although it can be used as a hallucinogen technically (at larger doses), I dont know if it would keep the brain chemistry looking good necessarily... The question is rather tricky and many drugs can and will both make depressions better and worse. My best advice is to not take anything addictive as swiy may become reliant on that drug to avoid depression (caffeine, alcohol, kratom etc). As for some other drugs, hallucinogens could renew a love for life, or enhance the depression times ten... they're somewhat risky methylone will completely kill the depression temporarily, the question for that one is though; will it give an afterglow or a hangover (which of course would make things much worse). Why doesn't swiy kill the depression first (work out demons, supplement brain chemistry, HAVE FUN, etc) and then start doing drugs without having to worry? drugs are something that if used at all should come at the end of the day when everything is taken care of- but it sounds like there are still things to work out for swiy

either way, good luck!

just thought i would critique a little to fix things i was unsure about? please corrent me if im wrong with a source. first is 5-htp. i believe its a precursor to seritonin, which effects the sleep wake cycle. melatonin is another thing i belive or perhaps since it effects the swc, it effects melatonin.
2. I believe l-dopa is a precursor to dopamine
3. 3 main neurotransmitters theorized to effect depression- dopamine, seritonon and norepinephrine.
the theory is lower levels of seritonin are evolutionary markers of those depressed, those with lower status. however, when reading neuropsychopharmacology books, they state that increased seritonin might actually be a byproduct of depression and its just not seen in urine tests. its also responsible for food intake and the Neurotransmitter is mainly found in the digestive tract with 90% there and 10 percent in the brain for a fun fact. the book title is principles of neuropsychopharmacology by robert s feldman, jerrold s meyer and linda f quenzer. dopamine is therorized to be involved with motivation, attention, and mobility, however it tends to make depression worse because a bad side effect of treatments involving increased dopamine is anxiety. this is due to 5 different dopamine pathways and this pathway doesnt have to do with addiction or pleasure. It just has to do with epinepherine like you said and its involved in the fight or flight response.
norepinepherine is implicated in mobility and a few other things

great post though candyman. i just wanted to elaborate a few things i read i appreciate the post!

this goes to both of you the depresses and candyman

your very right about maoi. thats what st johns wort is so dont take it with 5htp or anything else without the consultation of a pharmacist. hallucinogenic drugs can kill. If you desire to use something else i believe slowly weaning yourself off of st johns wort to prevent a shock is in order. also, did you watch what you ate? certain foods react badly to st johns wort including wine and cheese and it decreases the effectiveness of oral drugs like birthcontrol and antibiotics by up to 30%. maybe do waht cany was saying. before trying drugs have you tried other alternatives? i find exercise after the first month helps, light exposure therapy helps as well as vitamins and having time to be carefree. before trying something addictive like kratom, perhaps try that or try kava first. kava can do wonders. i have literature if you want

[kratom_]

Originally Posted by candy_kid

^^ that 5-htp does, however 5-htp also eventually turns into melatonin which can end in some rather lengthy sleep periods and difficult wakeups !

thats good for somone kicking opiates, im gonna be depressed cuz im kickin and i wish i could get some valiums benzos work wonders for anxaity and all the wds u get. i will used kratom but really ur better off not using that cuz it will make u really depressed if u get hooked on that and the com downs suck and make u do more or feel bad.

i also believe medium-heavy kratom use will make you crazy, crazerier then opiate usage.

[wendel]

A good dose of San Pedro cactus took swim right out of a minor depression.

[bbdd]

thanks for info guys.over the years i have been treated for depression with meds mainly ssri's and they did not work for me. currently i am taking st johns wort, 1000 mgs. i would say that they are he helping me to sleep better but i actually feel more depressed. alcohol gives me a lift but i know it's not the solution. i might try kratom in the near future, any escape would be a blessing. if kratom did work for me i think it would give me a psychological boost.

[snapper]

Sorry SWIM didn't get back to this one sooner.
Here is one ref for ketamine-assisted analgesia. Since this thread is about herbal antidepressants, SWIM'll leave it at that. The articles that imyourlittlebare presented are interesting, but the hotplate and tail flick tests could represent synergy between opiate and NMDA antagonist. The betaAR-2 knockout mouse study is really interesting, though, and is the most convincing.
SWIM thinks these studies are really interesting and was not aware of this recent course of research. However, why have NMDA antagonists not been used to mitigate withdrawal in humans if they can do so in mice ? SWIM tried to use DXM on a heroin addicted friend and it did not help at all, though DXM is far less straightforward than ketamine and other pure NMDA antagonists. There is clearly more to this - either new more receptor specific ligands need to be developed, or decreased tolerance is in part being mistaken for synergy.
Here's one abstract illustrating SWIM's point. SWIM could post a list but does not have time. Thanks for the really useful info imyourlittlebare. It might be worth starting a new thread since it is not in context of this one, given the lack of natural NMDA antagonists. And don't worry, no one here wants to flame you for discussing things - that's what this forum is for.

Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty.

Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D.
Department of Anesthesia and INSERM E-332, Hôpital Ambroise Paré, Publique-Hôpitaux de Paris, 92100 Boulogne, France.
We designed this study to evaluate the effect of small-dose IV ketamine in combination with continuous femoral nerve block on postoperative pain and rehabilitation after total knee arthroplasty. Continuous femoral nerve block was started with 0.3 mL/kg of 0.75% ropivacaine before surgery and continued in the surgical ward for 48 h with 0.2% ropivacaine at a rate of 0.1 mL . kg(-1) . h(-1). Patients were randomly assigned to receive an initial bolus of 0.5 mg/kg ketamine followed by a continuous infusion of 3 mug . kg(-1) . min(-1) during surgery and 1.5 mug . kg(-1) . min(-1) for 48 h (ketamine group) or an equal volume of saline (control group). Additional postoperative analgesia was provided by patient-controlled IV morphine. Pain scores and morphine consumption were recorded over 48 h. The maximal degree of active knee flexion tolerated was recorded daily until hospital discharge. Follow-up was performed 6 wk and 3 mo after surgery. The ketamine group required significantly less morphine than the control group (45 +/- 20 mg versus 69 +/- 30 mg; P < 0.02). Patients in the ketamine group reached 90 degrees of active knee flexion more rapidly than those in the control group (at 7 [5-11] versus 12 [8-45] days, median [25%-75% interquartile range]; P < 0.03). Outcomes at 6 wk and 3 mo were similar in each group. These results confirm that ketamine is a useful analgesic adjuvant in perioperative multimodal analgesia with a positive impact on early knee mobilization. No patient in either group reported sedation, hallucinations, nightmares, or diplopia, and no differences were noted in the incidence of nausea and vomiting between the two groups.
PMID: 15673878 [PubMed - indexed for MEDLINE]

[imyourlittlebare]

Originally Posted by snapper

Sorry SWIM didn't get back to this one sooner.
Here is one ref for ketamine-assisted analgesia. Since this thread is about herbal antidepressants, SWIM'll leave it at that. The articles that imyourlittlebare presented are interesting, but the hotplate and tail flick tests could represent synergy between opiate and NMDA antagonist. The betaAR-2 knockout mouse study is really interesting, though, and is the most convincing.
SWIM thinks these studies are really interesting and was not aware of this recent course of research. However, why have NMDA antagonists not been used to mitigate withdrawal in humans if they can do so in mice ? SWIM tried to use DXM on a heroin addicted friend and it did not help at all, though DXM is far less straightforward than ketamine and other pure NMDA antagonists. There is clearly more to this - either new more receptor specific ligands need to be developed, or decreased tolerance is in part being mistaken for synergy.
Here's one abstract illustrating SWIM's point. SWIM could post a list but does not have time. Thanks for the really useful info imyourlittlebare. It might be worth starting a new thread since it is not in context of this one, given the lack of natural NMDA antagonists. And don't worry, no one here wants to flame you for discussing things - that's what this forum is for.

Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty.

Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D.
Department of Anesthesia and INSERM E-332, Hôpital Ambroise Paré, Publique-Hôpitaux de Paris, 92100 Boulogne, France.
We designed this study to evaluate the effect of small-dose IV ketamine in combination with continuous femoral nerve block on postoperative pain and rehabilitation after total knee arthroplasty. Continuous femoral nerve block was started with 0.3 mL/kg of 0.75% ropivacaine before surgery and continued in the surgical ward for 48 h with 0.2% ropivacaine at a rate of 0.1 mL . kg(-1) . h(-1). Patients were randomly assigned to receive an initial bolus of 0.5 mg/kg ketamine followed by a continuous infusion of 3 mug . kg(-1) . min(-1) during surgery and 1.5 mug . kg(-1) . min(-1) for 48 h (ketamine group) or an equal volume of saline (control group). Additional postoperative analgesia was provided by patient-controlled IV morphine. Pain scores and morphine consumption were recorded over 48 h. The maximal degree of active knee flexion tolerated was recorded daily until hospital discharge. Follow-up was performed 6 wk and 3 mo after surgery. The ketamine group required significantly less morphine than the control group (45 +/- 20 mg versus 69 +/- 30 mg; P < 0.02). Patients in the ketamine group reached 90 degrees of active knee flexion more rapidly than those in the control group (at 7 [5-11] versus 12 [8-45] days, median [25%-75% interquartile range]; P < 0.03). Outcomes at 6 wk and 3 mo were similar in each group. These results confirm that ketamine is a useful analgesic adjuvant in perioperative multimodal analgesia with a positive impact on early knee mobilization. No patient in either group reported sedation, hallucinations, nightmares, or diplopia, and no differences were noted in the incidence of nausea and vomiting between the two groups.
PMID: 15673878 [PubMed - indexed for MEDLINE]

yeah dxm effects different subtypes. there are many variables for nmda antagonists. which subtypes it effects, how strongly it binds, its half life, etc. dxm is not promising. ibogaine is. give that a read its interesting!

[candy_kid]

@imyourlittlebare - I'm about to pass out for 4 hours and write a test so I wont elaborate too much but hopefully this fills you in a touch as to my thought processes and whatnot

1) 5-htp is a precursor to serotonin correct which controls many bodily functions such as mood and pupil dilation, however, to quote Shulgin "A few words are needed here concerning the neurotransmitterserotonin. It is the immediate precursor to melatonin in the brain" - melatonin production occurs mostly at night and helps to induce sleep and regulate sleep/awake cycles among other things.

2) yes, l-dopa is a precursor to dopamine, however, typically it is only available through prescription (usually to Parkinson's patients) - l-tyrosine is the precursor to dopamine, norepinephrine and epinephrine among other things and is widely available at one's local health shop making it a bit more convenient. l-dopa would most definitely be favourable however.

3) I've also heard norepinephrine is related to depression- dopamine and serotonin seem to be theoretically more direct, but norepinephrine seems very likely involved as well from what I've read. norepinephrine helps stimulate dopamine release I believe also so I suppose the l-tyrosine would be a double whammy there! That's an interesting theory about serotonin btw, could it be that the reason its so prominent in the rest of the body be because its being expelled from the brain? I suppose large amounts could very well be a cause however as too large an increase in serotonin will cause a reduction in available dopamine which could cause problems involving lowered levels of dopamine (they tend to have a yin yang sort of effect on eachother) and thus the same could be said about too much dopamine- I suppose the key is balance

anyway, thx for taking the time to fact check- I do usually keep pretty close tabs on the things I post, but I've certainly made mistakes before check up on this stuff if you want, its fascinating !

Reputation Comments on this post:

Good informative posts, but please cut down on the smiley faces!

[imyourlittlebare]

[quote=candy_kid;317476]@imyourlittlebare - I'm about to pass out for 4 hours and write a test so I wont elaborate too much but hopefully this fills you in a touch as to my thought processes and whatnot

1) 5-htp is a precursor to serotonin correct which controls many bodily functions such as mood and pupil dilation, however, to quote Shulgin "A few words are needed here concerning the neurotransmitterserotonin. It is the immediate precursor to melatonin in the brain" - melatonin production occurs mostly at night and helps to induce sleep and regulate sleep/awake cycles among other things.

2) yes, l-dopa is a precursor to dopamine, however, typically it is only available through prescription (usually to Parkinson's patients) - l-tyrosine is the precursor to dopamine, norepinephrine and epinephrine among other things and is widely available at one's local health shop making it a bit more convenient. l-dopa would most definitely be favourable however.

3) I've also heard norepinephrine is related to depression- dopamine and serotonin seem to be theoretically more direct, but norepinephrine seems very likely involved as well from what I've read. norepinephrine helps stimulate dopamine release I believe also so I suppose the l-tyrosine would be a double whammy there! That's an interesting theory about serotonin btw, could it be that the reason its so prominent in the rest of the body be because its being expelled from the brain? I suppose large amounts could very well be a cause however as too large an increase in serotonin will cause a reduction in available dopamine which could cause problems involving lowered levels of dopamine (they tend to have a yin yang sort of effect on eachother) and thus the same could be said about too much dopamine- I suppose the key is balance

good luck on your test man! ill be sure to get back to your pm soon! thanks for ther seritonin info i didnt read up on that ever! and i found you are right about l tyrosine being a precursor. however, its a precurso to a precursor. it turns into l-dopa. at least in the U.S. you can buy l-dopa via internet. here is a blurp about l-tyrosine

[top]MECHANISM OF ACTION

The mechanism of L-tyrosine's putative antidepressant activity may be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.

and norepinephrerine comes directly from dopamine so i dont find it hard to believe it effects dopamine synthesis.

Reputation Comments on this post:

interesting info, I didn't know that- thanks!

[bbdd]

cut the bullshit guys! just give me a fix.