85 replies to this topic

[medievil]

No problem, keep us updated, i allways look further then the issues of differened substances and look for ways around it.

[Sarif]

oh man...USPS misplaced my package!!! Now the only option for me is to get phenibut from a Chinese supplier via http://alibaba.com. 

 

In hope of finding a good supplier, I created another post http://www.longecity...ibabacomanyone/. Will keep you updated.

 

[Oracle Laboratories]

oh man...USPS misplaced my package!!! Now the only option for me is to get phenibut from a Chinese supplier via http://alibaba.com. 

 

In hope of finding a good supplier, I created another post http://www.longecity...ibabacomanyone/. Will keep you updated.

 

Sarif,

Liftmode is generally very good about sending free replacement products if there is some kind of loss in transit; I would contact them.  USPS has lost so many of my packages that now I spring for the three-day UPS shipping in the US for just about everything.  Contact USPS and see if the box was insured at all, or not.  Their flat-rate boxes are insured in the US for $50, although several of the overseas packages that I have shipped have been at least partially insured by the USPS for delivery to foreign customs.

[medievil]

What do you mean misplaced your package? does it have tracking? demand it to be send to the correct adress, phone them up saying it are important items from your grandma, with a extremely eig emotional value, keep on going on how upset she will be if its lost etc, this shit got me stuff send to my closed po box for example, the post office crew was looking out for it, or got me backpay in nhs money, basicly keep going on about something exhaust the other person.

 

also it should have tracking how else they know its misplaced?

[Oracle Laboratories]

medievil,

 

 

 

Since the GABAB agonism should be comparable, why is phenibut addictive and baclofen anti addictive? baclofen supresses da, so the drug is not associated with increased dopamine which makes a drug addictive, yet it looks like phenibut does increase da, is it possible the 

 

I think that you are a bit blurred regarding the difference in the psychopharmacological definitions of "dependence" versus "addiction".  Addiction of course being the psychological craving for the effects of a substance over one's "normal" waking consciousness; and dependence being a physical need for a exogenous substance in order for that biological mechanism to function in the same way that it did before the initial introduction of the exogenous substance.

 

Whereas you are correct in that most drugs of addiction (and many drugs that cause physical dependency) act by increasing synaptic dopamine levels, dopamine does not have to be involved in the physical, molecular dependency caused by a particular substance.  As I touched on in my previous post, many people are chemically dependent on drugs like beta-blockers to maintain normal cardiac rhythm, but they are certainly not addicted to those drugs. People even develop dependence, and in very rare cases, even an actual psychological addiction to some anti-psychotic drugs that function as dopamine antagonists, and actually block the binding of dopamine, and thus the agonization of dopamine receptors.

 

Likewise, both Baclofen and Phenibut can and do cause some degree of dependence, simply due to the down-regulation of GABA -B Receptors, but it is really hard for me to justify calling either substance truly "addictive" compared to most drugs of “abuse”.  As I stated, I have never heard of a group of high school kids rounding up all of their buddies to gather around and "get high" on Phenibut.  I understand the point that some people find the effects of Phenibut enjoyable (potentially due in some part to it's in-direct affect on dopamine release), and in that sense you could start to lean towards the definition of "addiction", but then again, as previously stated, Baclofen has almost no noteworthy influence on synaptic dopamine level increase, and Baclofen is abused also - simply because of it's sedating or "intoxicating" effects.  Drugs like ethanol and benzodiazepines can be both addictive and cause dependency, but neither have any pharmacologically noteworthy effect as an agonist at any of the dopamine receptors, nor any noteworthy affect on dopamine release or reuptake.  

 

So assuming that addiction (or dependency) always correlates to dopamine transmission is flawed.  In the case of many substances, yes, it is the increase in neuronal and synaptic dopamine levels (at least in part) that stimulates the reward centers of the hypothalumus and nucleus accumbens and causes the subject to continue seeking that stimulation, causing addiction.  However, addiction (and certainly dependency) does occur in mammals, with exogenous substances that affect other neurotransmitter systems. For example, addiction to amphetamines occurs because of the large influx in dopamine release (and serotonin release to a lesser extent), but dependency to the TAAR1 (Trace Amine-Associated Receptor) that amphetamine directly binds to, does not occur.  While on the contrary, both addiction and dependency to benzodiazepines is based almost entirely on the direct agonism of the GABA -A Receptors themselves.

 

This brings to mind the other topic that has sprung up in this thread regarding the use of NMDA Receptor antagonists to combat the effects of tolerance to particular substances. The NMDA Receptors also play a very important role in the case of true, psychological “addiction” as well, by blocking the association of those “reward center” memories from the hypothalumus and nucleus accumbens, with our sensory input. (ie, Things like “needle fixation”, in which cases some ex IV drug users will inject water when they get a craving, simply because the brain still associates the “ritual” act of injecting with a pleasurable reward sensation). Because NMDA Receptor antagonism blocks the formation of chloride channel-mediated substance/receptor associations, as well as increases activity in the locus coeruleus (the group of neuronal cells associated with our sense of “novelty”), NMDA Receptor modulator drugs are proving to even more and more viable and refined in developing treatments for tolerance associated with receptor down-regulation, as well as addiction by inhibiting the formation of pleasure/reward associations with habitual drug use.  One of the compounds that my team stumbled upon last year appears to act as a highly selective Dopamine Reuptake Inhibitor, as well as a potent NMDA Receptor activity inhibitor, acting as an antagonist at Glun1 subunits, and an inverse-agonist at GluN2 subunits.  One of it’s structural analogues appears to act purely on the NMDA and Glutamate Receptor complex, and may provide promising insights into inhibiting the development of tolerance and/or treating certain addictions. So far it hasn’t been developed further, but I intend to revisit it in time.

 

There is unfortunately a lot of unintentional (and intentional) misinformation, misconception, and plain wild speculation available on topics in this field on the internet, even sometimes from fairly reliable sources. I joined here at the request of a few members who I had contact with elsewhere online, to try and clarify some of these topics, and separate a lot of the speculation and misinformation from the actual pharmacokinetics of the use of these psychotropic substances. I will say that a few of you have some fairly odd interpretations and assumptions about a few of the off-topic biomechanisms here, but to each his own, I suppose.  Unfortunately, being a new member, I can only make a limited number of posts, so I can’t comment on everything.

 

jaiho,

 

Unfortunately, anhedonia is a very broadly-encompassing disorder in terms of pre-synaptic neurotransmitter systems, and is also highly variable among individuals. So, there isn’t really a good catch-all class of drugs that can be recommended for everyone. Early trials with mixed monoamine/catecholamine reuptake inhibitors (particularly the “Triple Reuptake Inhibitors”). That inhibit Serotonin, Dopamine, and Norepinephrine reuptake work for a large majority, but the effective dosages often have to be continually increased due to the development of tolerance to the main monoamine neurotransmitter receptor sites. Other patients respond to some acetylcholine receptor agonists, glutamate modulators, and even cannabinoids.  Unfortunately, it really comes down to working with the patient in question, one-on-one to find something that works, long-term. If you’d like to send me a private message, I can advise you on some easy-to-acquire options to test out, based on your personal responses to treatment.

 

 

Sarif,

 

Having a benzodiazepine drug with a long halflife around (such as as diazepam or clonazepam suggested) could’nt hurt, but I certainly would not advise using ANY GABA -A Receptor agonist to discontinue Phenibut use unless you absolutely had to (which you really never should, if you wean down your dose gradually enough), or in very small doses. Since you already stated that you have bad impulse control in your original post, quitting Phenibut by using a benzodiazepine could potentially be substituting a mild “addiction” for a potentially much more dangerous one.  I certainly would not use a week’s supply of a long-acting benzodiazepine like the suggested diazepam to discontinue Phenibut use.  If you wean your dose down gradually enough for your receptors to up-regulate sufficiently (even weaning over the course of a month or two, in the most extreme cases) then you shouldn’t notice anything like the horrendous Phenibut withdrawal stories that pollute the internet. If you were to stop using Phenibut with a benzodiazepine drug, and then decided that you liked the effects of the benzodiazepine, you could be substituting dependency to a GABA -B agonist (Phenibut) to a much more severe GABA -A Receptor agonist. While Phenibut withdrawal can be very unpleasant if done abruptly, Benzodiazepine Withdrawal Syndrome can be a medical emergency, inducing Tonic Clonic, Opclonic, and Grand Mal seizures, dangerous abrupt shifts in blood-pressure, and cardiac arrhythmia. You mentioned having a difficult time with impulse control, so this is just something to keep in mind.

 

Interestingly, I have used Baclofen for Phenibut withdrawal, and considered mentioning it in my original post - however, even though Baclofen does agonize the GABA -B Receptor and suppresses much of the actual withdrawal, as mentioned, it is not nearly as effective as Phenibut as an anxiolytic in most people and therefore does not fully suppress the rebound anxiety that one may experience when discontinuing Phenibut.  Now, I do fully understand where medievil is coming from in regard to using a GABA -A agonist benzodiazepine drug like diazepam or clonazepam to suppress both the withdrawal from Phenibut, and the rebound anxiety. As medievil recommended, long-acting benzodiazepines are definitely the way to go if you must do this. Some short-acting benzodiazepines, like alprazolam (Xanax) are incredibly effective for fast rescue treatment of Panic Attacks, but they have short halflives in the body, and build tolerance much faster. The idea is that although the GABA -B Receptors will be rapidly up-regulating in the absence of Phenibut causing withdrawals, the GABA -A acting benzodiazepine will suppress just about every symptom of withdrawal, as well as act with much more pronounced anxiolytic effect than Phenibut or Baclofen, effectively suppressing the rebound anxiety.  The issue I have in recommending this route to many people on forums like this one, however, is that many posters do have addictive personalities and/or difficulty in using the benzodiazepine drug only to suppress withdrawal (in the smallest effective dose, for the shortest required period of time). If you are using the benzodiazepine to suppress withdrawals because you “got in too deep” using Phenibut in extreme excess, or for “pseudo-therapeutic purposes” and are one of the individuals that responds to the dopamine influx and may misuse or overuse Phenibut, then introducing a potentially much more dangerous drug to misuse habitually is not the way to go.  With that being said, if you simply use reasonable amounts of Phenibut for therapeutic purposes, and are one of the individuals that experiences excessive rebound anxiety, even when weaning of Phenibut gradually, and can control your use of the benzodiazepaine, then a week of using a long-acting benzodiapeine like diazepam or clonazepam (just as much as is needed to suppress withdrawals and ensure sleep) can be a very effective way discontinue regular use of Phenibut.  Using a benzodiazepine with a half life like diazepam’s or clonazepam’s (other examples include temazepam, nitrazepam, flurazepam, etc) for a week or so, generally doesn’t cause issues of dependence, as long as you have good self-control, as it takes a decent bit of use to actually become dependent on a benzo such as those mentioned. The issue arises in people with impulse trouble, when the user enjoys the effects, and simply substitutes the Phenibut use for benzodiazepine use (using more than is necessary to suppress Phenibut withdrawals, for longer than needed).

 

I will not condemn the short-term use of benzodiazepines for discontinuing Phenibut, as it can be a very practical and effective option if done correctly, the issue arises in advising posters on forums like this, that have already gotten into some difficulty with Phenibut, potentially substituting a rather benign GABA -B Receptor agonist for a potentially much more dangerous GABA -A Receptor agonist, benzodiazepine drug in the case of abrupt discontinuation of habitual use. Just keep that in mind. Just about every psychiatrist and pharmacologist has their preference, but personally I recommend clonazepam (brand name Klonopin, etc) as probably the best example of a benzodiazepine drug for this purpose. Although the additional length in the half life of diazepam and it’s metabolites may benefit some people more, clonazepam has (in my opinion) the perfect strength as an agonist with perfect sedative/anxiolytic properties, as well as the perfect metabolic half-life, having a duration of action from 6 - 12 hours, and a metabolic half-life between 18 - 50 hours.

 

 

 

 

-J. Gona

Psychopharmacologist,

Psychotropic / Nootropic Treatment Specialist

 

Oracle Laboratories

NeuroPsych Institute

 

 

 

 

[medievil]

 

I think that you are a bit blurred regarding the difference in the psychopharmacological definitions of "dependence" versus "addiction".  Addiction of course being the psychological craving for the effects of a substance over one's "normal" waking consciousness; and dependence being a physical need for a exogenous substance in order for that biological mechanism to function in the same way that it did before the initial introduction of the exogenous substance.

 

I said baclofen is not addictive, which it isnt, im aware i can cause dependency, theres noone that craves baclofen, but im aware it causes withdrawals

[medievil]

I disagree that baclofen is abused, it may have relaxing have effects but its pretty much enheared off, that said benzos do increase dopamine in reward related pathways and is abused, the same is true for alcohol.

]

 

 

 As I stated, I have never heard of a group of high school kids rounding up all of their buddies to gather around and "get high" on Phenibut.

That is because its a very weak drug, it does cause a high tough but kids going to school look for more potent stuff

[medievil]

I disagree that baclofen is abused, it may have relaxing have effects but its pretty much enheared off, that said benzos do increase dopamine in reward related pathways and is abused, the same is true for alcohol.

]

 

 

 As I stated, I have never heard of a group of high school kids rounding up all of their buddies to gather around and "get high" on Phenibut.

That is because its a very weak drug, it does cause a high tough but kids going to school look for more potent stuff

 

 

While on the contrary, both addiction and dependency to benzodiazepines is based almost entirely on the direct agonism of the GABA -A Receptors themselves.

I disagree entirely, addiction and abuse is entirely caused by their dopaminergic effects

[medievil]

 

 

The NMDA Receptors also play a very important role in the case of true, psychological “addiction” as well, by blocking the association of those “reward center” memories from the hypothalumus and nucleus accumbens, with our sensory input. (ie, Things like “needle fixation”, in which cases some ex IV drug users will inject water when they get a craving, simply because the brain still associates the “ritual” act of injecting with a pleasurable reward sensation). Because NMDA Receptor antagonism blocks the formation of chloride channel-mediated substance/receptor associations, as well as increases activity in the locus coeruleus (the group of neuronal cells associated with our sense of “novelty”), NMDA Receptor modulator drugs are proving to even more and more viable and refined in developing treatments for tolerance associated with receptor down-regulation, as well as addiction by inhibiting the formation of pleasure/reward associations with habitual drug use.

Evidence for this? NMDA antagonists work for tolerance and addiction because the nmda pathway (following nitric oxide) causes changes in the receptors certain drugs act on, addiction occurs because drugs program themselves in the brain trough the nmda pathway, first sensitisation occurs making the brain sensitised to particular drugs, as most ppl notice the first time someone uses a drug they wont notice anything while the next times the effects become apparent, after that receptor downregulation occurs, addiction occuring because of association with the rewarding effects only plays a minimal role 

[medievil]

 

 

 

jaiho,

 

Unfortunately, anhedonia is a very broadly-encompassing disorder in terms of pre-synaptic neurotransmitter systems, and is also highly variable among individuals. So, there isn’t really a good catch-all class of drugs that can be recommended for everyone. Early trials with mixed monoamine/catecholamine reuptake inhibitors (particularly the “Triple Reuptake Inhibitors”). That inhibit Serotonin, Dopamine, and Norepinephrine reuptake work for a large majority, but the effective dosages often have to be continually increased due to the development of tolerance to the main monoamine neurotransmitter receptor sites. Other patients respond to some acetylcholine receptor agonists, glutamate modulators, and even cannabinoids.  Unfortunately, it really comes down to working with the patient in question, one-on-one to find something that works, long-term. If you’d like to send me a private message, I can advise you on some easy-to-acquire options to test out, based on your personal responses to treatment.

Exactly, im highly educated on anhedonia and as said here the treatment is highly individual, i can also provide information on effective treatments if you contact me

[medievil]

 

Sarif,

 

Having a benzodiazepine drug with a long halflife around (such as as diazepam or clonazepam suggested) could’nt hurt, but I certainly would not advise using ANY GABA -A Receptor agonist to discontinue Phenibut use unless you absolutely had to (which you really never should, if you wean down your dose gradually enough), or in very small doses. Since you already stated that you have bad impulse control in your original post, quitting Phenibut by using a benzodiazepine could potentially be substituting a mild “addiction” for a potentially much more dangerous one.  I certainly would not use a week’s supply of a long-acting benzodiazepine like the suggested diazepam to discontinue Phenibut use.  If you wean your dose down gradually enough for your receptors to up-regulate sufficiently (even weaning over the course of a month or two, in the most extreme cases) then you shouldn’t notice anything like the horrendous Phenibut withdrawal stories that pollute the internet. If you were to stop using Phenibut with a benzodiazepine drug, and then decided that you liked the effects of the benzodiazepine, you could be substituting dependency to a GABA -B agonist (Phenibut) to a much more severe GABA -A Receptor agonist. While Phenibut withdrawal can be very unpleasant if done abruptly, Benzodiazepine Withdrawal Syndrome can be a medical emergency, inducing Tonic Clonic, Opclonic, and Grand Mal seizures, dangerous abrupt shifts in blood-pressure, and cardiac arrhythmia. You mentioned having a difficult time with impulse control, so this is just something to keep in mind.

Stopping phenibut adddiction by gradually reducing the dose is hard, while you can easily do it the easy way,getting addicted to benzos by using them for withdrawal extremely unlikely, benzos are weak crap and deciding youd like them and getting addicted to them instead is laughable imo, like benzo withdrawal so is phenibut withdrawal a medical emergency, it can such as benzos cause life treatening seizures. I am very impulsive and have a extremely addictive personality and short term use of benzos is absolutely no issue, its highly unlikely that someone addicted to phenibut would get addicted to benzos as those are pretty much useless reward free drugs.

 

Saying that phenibut addiction is benign compared to benzos is extremely ignorant, withdrawal from phenibut is dangerous and life treatening simular to GHB addiction.

 

I would say that withdrawing of phenibut by dose reduction is too hard to be practical

I would second the suggestion of clonazepam, like diazepam its a extremely good benzo for withdrawals

 

[Oracle Laboratories]

medievil,
 

Lets get one thing sorted out from the start - we are all unique animals with unique “tastes”. I see a whole lot of your personal “tastes” in the lasts few posts (stating that benzodiazepines are “weak crap”), but very little reflection of actual clinical study data representing addiction or dependence in the majority of the population. Surely you know why benzodiazepine drugs like flunitrazepam are not used nearly as often clinically anymore (due to such high incidents of abuse and dependent regular users), and why many short-acting benzodiazepines such as alprazolam are prescribed much more infrequently than they once were. There are many who absolutely crave and have a strong desire to chase the “dreamy” anxiolysis that hypnotic benzodiazepine drugs induce. (Just search any of the clinical study cited publications at the bottom of the Wikipedia pages for any given benzodiazepine drug). Dopamine being an excitatory neurotransmitter, and not an inhibitory neurotransmitter (like GABA) - any minuscule dopaminergic activity that occurs as a consequence of a benzodiazepine’s action (not a direct mechanism-of-action) is certainly not what these individuals are chasing.

 

 

Eating a cookie (or anything for that matter) causes a dopamine influx, but does that mean that cookies should be classified as dopamine-releasing agents? Of course not. Do benzodiazepines have some in-direct action on increasing synaptic dopamine levels, sure, but it is not a primary mechanism-of-action of benzodiazepines. It occurs as an in-direct consequence of agonism at the Benzodiazepine Binding Site on the GABA -A Receptor, but is minuscule, and is not involved in the general pharmacological mechanism-of-action of benzodiazepines - and I don’t know anybody qualified who would press that point to the contrary. Take any one given psychoactive compound. Methylenedioxymethamphetamine (MDMA) is a great example. It presents specific action at over 18 distinct receptor types, but the effects that we associate with it’s psychoactive mechanism-of-action are fairly specific (being primarily 5HT serotonergic binding sites) - another big drug of abuse and psychological addiction that does have some effect on neuronal dopamine release, but that not being the primary reason the addiction occurs. (The actual mechanisms being primarily serotonergic, not dopaminergic).

 

Physical dependence in many cases has absolutely nothing to do with dopamine. Again, you can become dependent to dopamine antagonist anti-psychotic drugs (and compounds such as Baclofen), and even though many drugs that cause dopamine release (or inhibit it’s reuptake) are addictive in the accurate sense of the definition - the dopamine is not necessarily the mechanism-of-action that causes physical dependence, nor does it have to be involved in a psychologically “addictive” substance at all.  Although I do agree that most drugs of abuse are just that, because they cause synaptic increase in dopamine levels in the reward centers of the hypothalumus and nucleus accumbens, this action is not a requirement for a substance to be either addictive, or to cause physical dependence.  Simply because you personally only find substances that dramatically increase synaptic dopamine concentrations addictive, does not mean that everybody requires a noteworthy dopamine influx to become psychologically addicted to a compound. (And this is certainly not a requirement for physical dependence). - Again I reference benzodiazepines, MDMA, and drugs like ketamine.

 

According to your reasoning (dopamine influx being a requirement for psychological addiction, and the only mechanism by which addiction occurs) then drugs like the Dopamine/Norepinephrine Reuptake Inhibitors (such as drugs like the antidepressant Bupropion and the Tricyclic Antidepressant Amineptine), as well as the potent Dopamine Agonist anti-psychotic/antidepressant drugs like Aripiprazole and Brexpiprazole should be considerably addictive, but they aren’t. .Additionally, referring back to many GABA -A Receptor agonists (barbituates, meprobamate, methaqualone, benzodiazepines), MDMA, and Ketamine all cause habitual use in many people. I can even bring opiate/opioid agonist drugs into the equation. Yes, a big part of the addictive nature of opioids is their effect on neuronal dopamine release, but the direct mechamism-of-action that causes both addiction and dependence is the agonism of mu-Opioid Receptor (and Delta Opioid Receptors, to a lesser extent). These are the same receptors that the human endorphins bind to, which directly cause the sedation and some of the euphoria associated with the opioid high. (And also by directly causing neuronal dopamine release in the hypothalumus), however the dopaminergic action is only part of the addictive aspect of opioids - since if dopamine were the only mechanism that were responsible for the development of addiction, then the potent Dopamine Agonists Aripiprazole and Brexpiprazole should have an even potentially greater addictive quality, but as we know, they do not. (Also, were the dopaminergic action the only mechanism by which the psychological addiction (and physical dependence) to opioids occurs, then stimulatory dopamine-releasing agents (ie., amphetamine) and reuptake inhibitors (ie., methylphenidate, cocaine, etc) would substitute for opioids in addicted subjects. (Which we know, do not). 

 

 

" While on the contrary, both addiction and dependency to benzodiazepines is based almost entirely on the direct agonism of the GABA -A Receptors themselves. "

         " I disagree entirely, addiction and abuse is entirely caused by their dopaminergic effects "

That’s ridiculous. The Dopamine/Norepinephrine Reuptake Inhibitor antidepressants Bupropion and some tricyclics like Amineptine produce much greater synaptic dopamine influx than benzodiazepines or Phenibut, yet I have never heard any confirmed or sustained cases of anyone abusing or reporting a “high” from these compounds. Additionally, the indirect dopamine influx that is caused by indirect a2Ca-subunit Sodium Channel Activity as a consequence of Benzodiazepine Binding Site agonism occurs almost entirely in the prefrontal cortex, in the frontal and parietal lobes, while the dopamine reuptake inhibition that occurs due to the action of drugs like Amineptine is more widespread - even reaching some regions of the nucleus accumbens, yet no “high” or reward pathway association is associated with these drugs.

 

 

 

" The NMDA Receptors also play a very important role in the case of true, psychological “addiction” as well, by blocking the association of those “reward center” memories from the hypothalumus and nucleus accumbens, with our sensory input. (ie, Things like “needle fixation”, in which cases some ex IV drug users will inject water when they get a craving, simply because the brain still associates the “ritual” act of injecting with a pleasurable reward sensation). Because NMDA Receptor antagonism blocks the formation of chloride channel-mediated substance/receptor associations, as well as increases activity in the locus coeruleus (the group of neuronal cells associated with our sense of “novelty”), NMDA Receptor modulator drugs are proving to even more and more viable and refined in developing treatments for tolerance associated with receptor down-regulation, as well as addiction by inhibiting the formation of pleasure/reward associations with habitual drug use. "

     " Evidence for this? NMDA antagonists work for tolerance and addiction because the nmda pathway (following nitric oxide) causes changes in the receptors certain drugs act              on, addiction occurs because drugs program themselves in the brain trough the nmda pathway, first sensitisation occurs making the brain sensitised to particular drugs, as                  most ppl notice the first time someone uses a drug they wont notice anything while the next times the effects become apparent, after that receptor downregulation occurs,                    addiction occuring because of association with the rewarding effects only plays a minimal role "

Sure, (Baird & Crousse 1997; Eckhert et al 2001, etc). I also point to several of the publications of Alan Reirdon and David Nichols. This is well established. For an example that I happen to have handy, look at Methadone and the cited references from the Wikipedia page:

 

Levomethadone is a full µ-opioid agonist Dextromethadone does not affect opioid receptors but binds to the glutamatergic NMDA (N-methyl-D-aspartate) receptor, and thus acts as a receptor antagonist against glutamate. Methadone has been shown to reduce neuropathic pain in rat models, primarily through NMDA antagonism. Glutamate is the primary excitatory neurotransmitter in the CNS. NMDA receptors have a very important role in modulating long term excitation and memory formation. NMDA antagonists such as dextromethorphan (DXM), ketamine (a dissociative anaesthetic, also M.O.A+.), tiletamine (a veterinary anaesthetic) and ibogaine (from the African tree Tabernanthe iboga, also M.O.A+.) are being studied for their role in decreasing the development of tolerance to opioids and as possible for eliminating addiction/tolerance/withdrawal, possibly by disrupting memory circuitry. Acting as an NMDA antagonist may be one mechanism by which methadone decreases craving for opioids and tolerance, and has been proposed as a possible mechanism for its distinguished efficacy regarding the treatment of neuropathic pain. The dextrorotary form (d-methadone) acts as an NMDA antagonist and is devoid of opioid activity: it has been shown to produce analgesia in experimental models of chronic pain. Methadone also acted as a potent, noncompetitive α3β4 neuronal nicotinic acetylcholine receptor antagonist in rat receptors, expressed in human embryonic kidney cell lines.[47]

                    ^ From the Methadone Wikipedia page, under the pharmacology section.

 

I will try to summarize the role of the glutaminergic NMDA Receptors in the development of tolerance and addiction as best yet briefly as I can here.  Glutamate Receptor agonism is responsible for the formation of new memories, the transfer of short-term memories from the pre-frontal lobe to the long-term storage of memory in hippocampus, as well as being the brain’s way of keeping track of brain chemistry (in order to regulate voltage-gated sodium, calcium, and potassium nerve channel transmission and rebalance brain chemistry).  Glutamate Receptor excitation is responsible for the formation of new memory, and it is also the brain’s way of storing the data responsible for keeping track of the specific brain chemistry at any one given time.  When a new drug enters the brain and binds at it’s target receptor(s), simultaneously, glutamate receptors (and specifically the N-methyl-D-aspartate (NMDA) receptors) are being agonized by the neurotransmitter glutamate. During this time, memories and “snap-shots” of brain chemistry are being stored into subconscious memory by the NMDA pathway.  This way, the brain stores the data that tells it how much a particular foreign compound is agonizing a specific receptor complex. With this data, the brain can begin to fight back against the foreign exogenous substance, and can then begin to down-regulate the target receptor(s) that the foreign compound is activating, by suppressing the amount that that particular drug’s agonism is exciting the sodium, potassium, or calcium channel’s (depending on the receptor type in question) transmission within that particular neuron. - With this data, the brain can begin to down-regulate the target receptor(s) that the foreign exogenous drug is agonizing, by limiting the amount that a particular strength receptor agonist can excite the voltage gated (sodium, potassium, and calcium) channels within a specific neuron. By using an NMDA Receptor antagonist when a drug is administered, glutamate receptor agonism is blocked at the NMDA receptor, and the data that is stored in the brain, which tells the brain how to “fight back” against the effects of the foreign compound, is never committed to brain storage. Obviously, this can in some cases, significantly delay the development of tolerance.  Additionally, all of the psychological “ritual” that goes along with the procurement and preparation that goes into preparing drugs for use, are also stored by Glun1, Glun2, and NMDA Receptor pathways into memory.  This is why people begin to get antsy while going to get drugs (before even taking them) and this is also why ex-intravenous opiate/opioid users often still associate the use of a syringe with feeling good (even if they aren’t under the influence of the IV drug itself). - This is the reason that many ex-opioid addicts will inject water when they get a graving, as it’s not the drug that makes them feel better, but the ritual of shooting up - with which they still associate with the effects of the drug and feeling good.

 

A good friend of mine used opiate/opioid drugs orally and via insuflation (snorting) almost all of his life.  He then briefly starting injecting street Diacetylmorphine (Heroin) intravenously, and maybe did so 30 times before starting Suboxone treatment (a combination of buprenorphine and naloxone), which is used for opioid detox and maintenance. Bupreorphine has a very strong binding affinity for the mu-Opioid Receptor yet it only acts as a partial opioid receptor agonist. (Meaning that is only partially activates the opioid receptors, meaning that if the user is tolerant to traditional, full agonist opioids, then regular use of buprenorphine will not produce any kind of high). Even though he received no “high” from the buprenorphine, he continued to inject it for close to two years - even though the intravenous route-of-administration produced no different effect than simply taking the buprenorphine strips as prescribed - sublingually (under the tongue).  So, why did he continue to inject the buprenorphine even though the act of injecting it did not produce any high or pleasurable effect? - Simply because his brain still associated the act of injecting with a pleasurable experienced, from the brief time that he used IV Heroin.  And, every time he injected the buprenorphine (even though it did not produce any pleasurable effects), it reinforced the psychological sensation that his brain associated with the act of “shooting up” with a pleasurable sensation. (This is the same with ex-smokers chewing tooth picks, chewing gum, or keeping unlit cigarettes in their mouths, to occupy their mouths with something in place of a cigarette, as even though they are no longer receiving nicotine, they still associate the act of occupying their mouths with the pleasurable sensation of nicotine from cigarettes).  Therefore, by using an NMDA Receptor antagonist while using an exogenous drugs, not only does this slow down the development of tolerance, but it also breaks some of the stored association with the act of using drugs with feeling good, and this can help to break the compulsion to continue using - and, in some extreme cases, such as in NMDA Receptor inverse agonists such as ibogaine, the addictive memory-association that is generated by glutamate binding at NMDA Receptors, can even be partially reversed. 

 

" NMDA antagonists work for tolerance and addiction because the nmda pathway (following nitric oxide) causes changes in the receptors certain drugs act on, addiction occurs because drugs program themselves in the brain trough the nmda pathway, first sensitisation occurs making the brain sensitised to particular drugs, as most ppl notice the first time someone uses a drug they wont notice anything while the next times the effects become apparent, after that receptor downregulation occurs, addiction occuring because of association with the rewarding effects only plays a minimal role "

The above statements are very vague and unclear. In all honesty, I don't even know which specific mechanism you are referencing. (Perhaps if you elaborated a bit more).  It sounds to me like you are stating that all psychoactive drugs have some binding affinity for, and action at, NMDA Receptors, before binding to their target receptors. ?..  This is not true at all, and in fact, most psychoactive drugs have no affinity for, or action at the NMDA Receptors at all, yet many of those same drugs' development of tolerance and addiction can be slowed and deterred by the use of an NMDA Receptor antagonist.
 

Stating that many drugs (who have no affinity for, or action action at, NMDA Receptors) “change the receptors that certain drugs bind at” is ridiculous and is seriously confusing to me why anybody would have told you that, or what you read to lead to that interpretation. The agonism of one receptor in no way shape or form can alter the morphology of a completely unrelated receptor type.  No drugs (except for very few highly neurotoxic agents) chemically damage the actual morphology of a receptor type. Additionally, a drug that has an affinity at the NMDA Receptor complex certainly does not alter the morphology of a completely unrelated receptor complex type. Take several GABA -A Receptor agonists like Meprobamate or Methaqualone, or synthetic opioid agonists like Fentanyl - all of which have no known affinity for NMDA Receptors whatsoever, yet all who’s pharmacological effect as far as the development of tolerance (and to a lesser extent, addiction) can be slowed by the use of NMDA Receptor antagonists that are administered at the same time that the exogenous drug in question is administered.  This is because the use of an NMDA Receptor antagonist at the same time that a recreational or therapeutic exogenous drug is introduced to the brain, blocks the formation of association memories (that are produced by glutamate binding) (which to some degree hinders the development of addiction), and blocks the saving of the data that tells the brain how much that a particular drug is activating it’s target receptor(s) initially. By using an NMDA antagonist and blocking the saving of this data, the brain never saves it’s stored “set point” from which it can begin to down-regulate the target receptor(s) that the exogenous drug in question is agonising, following habitual use. When an exogenous drug is administered, the glutamate transmission that binds to NMDA Receptors stores data that tells the brain how much the exogenous drug in question is activating it target receptor(s) and how much that agonization is affecting the transmission of voltage-gated calcium, potassium, and sodium channels within those neurons. With this data, the brain can then begin to “fight back” against the foreign drug, in an attempt to rebalance brain chemistry, by down-regulating the target receptors that the particular exogenous drug is binding at - in one way by lessening the effect that a particular strength agonist can excite sodium, calcium, or potassium channels in those neurons, and by deactivating other receptors of the same type, to ensure that the brain is not overloaded by the neurotransmission of one particular neurotransmitter type. (This may be what you mean by “change the receptors that certain drugs bind at”). The actual morphological structure of the target receptor(s) is not changed, but the Voltage-Gated Na, Ca, and/or K coupling, that allows a particular strength agonist to excite of inhibit those Na, Ca, or K channels can be diminished, as a consequence of down-regulation (or up-regulation, depending on the drug and neurotransmitter system in question).

 

There are many proposed theories regarding how influxes or suppression in Voltaged-Gated Calcium Channel transmission affect the NMDA Receptors in regard to tolerance and addiction to other receptor complexes, but this mechanism is so far, the only one that we have actual scientific proof of. I don’t know what the rules are here about posting links to outside websites, but if you want references, just search Google with the key words “Role of NMDA Receptors in addiction” or “Role of NMDA Receptors in tolerance”. Also look over the cited material on the Methadone Wikipedia page regarding NMDA Receptor cross-reactivity. I do fully understand how this is a difficult concept for many casual researchers to grasp, no matter how well researched. There surely is a lot of information out there regarding the use of NMDA Receptor antagonists corresponding to lessened effects on tolerance and addiction to various drugs, however the vast majority of them provide only anecdotal clinical evidence, but do not make an attempt to try and speculate or test why NMDA Receptor antagonism produces these effects. If you’re interested, I can put you in touch with Roger Hutton (a colleague of mine from The Indiana Neural Research Center) who has taken this hypothesis further than probably anyone else alive has. Following his work, my team is working on an MDMA / AMPA Allosteric Modulator that could be combined with a drug like a long-acting opioid pain killer, into a single medication, to hopefully significantly negate the development of tolerance to the analgesic effect of the opioid, and slow or even partially deter the development of the strong reinforcement behavior to continue using, that other traditional opioid agonists produce.

 

 

" Stopping phenibut adddiction by gradually reducing the dose is hard, while you can easily do it the easy way,getting addicted to benzos by using them for withdrawal extremely unlikely, benzos are weak crap and deciding youd like them and getting addicted to them instead is laughable imo, like benzo withdrawal so is phenibut withdrawal a medical emergency, it can such as benzos cause life treatening seizures. I am very impulsive and have a extremely addictive personality and short term use of benzos is absolutely no issue, its highly unlikely that someone addicted to phenibut would get addicted to benzos as those are pretty much useless reward free drugs.

 

Saying that phenibut addiction is benign compared to benzos is extremely ignorant, withdrawal from phenibut is dangerous and life treatening simular to GHB addiction.

 

I would say that withdrawing of phenibut by dose reduction is too hard to be practical

I would second the suggestion of clonazepam, like diazepam its a extremely good benzo for withdrawals "

A little over a year ago, we analyzed a meta-analysis of 180 subjects all using standard therapeutic doses (500mg up to 2000mg daily) of Phenibut, specifically for Situational Anxiety and/or Panic Attack Disorder.  All of these participants were under the supervision of qualified psychiatrists or pharmacologists that are highly trained to spot potential problems during treatment. Out of all participants, not one experienced any significant difficultly in gradually weaning down their dose after the duration of the study. Now, I am absolutely aware that some people (particularly those who order large supplies from the internet) have a difficult time stopping Phenibut, particularly when they use much more than is required to chase that tiny dopamine influx. However, if not one of our study participants experienced any significant withdrawal syndrome upon gradually discontinuing Phenibut in doses from 500mg - 2000mg, than I am certain that many of the people who post in these forums with the crazy Phenibut withdrawal horror stories could do the same, as long as they exercised good self-control, and stick to a logical dose-reduction regimen. Now, I agree; some people are simply too impulsive to do this, and have addictive personalities through no fault of their own. However, although Phenibut’s GABA -B Receptor agonism, and it’s action as a gabapentinoid blocker at a2o-subunit containing Voltage-Gated Ca+ Channels do produce mild physical dependence, I still can’t justify calling Phenibut a serious drug of addiction. Not all that long ago, Phenibut was a well-kept secret, that many had to either synthesize it themselves, or contact a foreign lab to produce it. It may be that because it has become cheaper and more widely available that many internet order users are reporting having just a hard time “kicking it”, and although it may produce a mild mood boost, I can’t see many people actually “craving a hit of Phenibut”, just like you stating that nobody “craves” Baclofen. I have been doing this for years, and although I agree with you that 98% of the population that is exposed to Baclofen will not crave it’s effects, there are those few out there that do. (Just like the very small minority that abuse dopamine and serotonin antagonists like Chlorpromazine or Tramadol, which make the majority of people feel like shit). 

 

The subjects in our Phenibut meta-analysis (in particular those of the highest therapeutic doses) had their doses gradually weaned down by 10% every week for ten weeks until they were completely discontinued from Phenibut treatment. And, in all honesty, they probably could have been withdrawn from treatment a bit more rapidly, but because of their psychiatric conditions, our goal was to avoid any rebound anxiety as a result of ceasing treatment too quickly. 

" Stopping phenibut adddiction by gradually reducing the dose is hard, while you can easily do it the easy way,getting addicted to benzos by using them for withdrawal extremely unlikely, benzos are weak crap and deciding youd like them and getting addicted to them instead is laughable imo, like benzo withdrawal so is phenibut withdrawal a medical emergency, it can such as benzos cause life treatening seizures. I am very impulsive and have a extremely addictive personality and short term use of benzos is absolutely no issue, its highly unlikely that someone addicted to phenibut would get addicted to benzos as those are pretty much useless reward free drugs.

 

Saying that phenibut addiction is benign compared to benzos is extremely ignorant, withdrawal from phenibut is dangerous and life treatening simular to GHB addiction.

 

I would say that withdrawing of phenibut by dose reduction is too hard to be practical

I would second the suggestion of clonazepam, like diazepam its a extremely good benzo for withdrawals "

 

Another clinical study that my team conducted was observing the actual physical re-balancing of Ca+ channel neurotransmission following Phenibut (and a few related compounds that we developed) withdrawal in healthy volunteers, who were purposely (and consensually) dosed with Phenibut for and extended amount of time, then abruptly stopped .  Whereas GABA -A Receptors and GHB Receptors are ionotropic, GABA -B Receptors are metabotropic, and rely on secondary messenger kinases within the receptor coupling to the ligand gate that opens ion flow into the Voltage-Gated K+ and Ca+ channels. - They do not directly open ion flow from binding of a neurotransmitter from it’s synaptic vesicle in the pre-synaptic neuron, like an ionotropic receptor does.

 

In all of my experience, I have not come across a single incident of a confirmed Grand Mal, Absence, or Myoclonic seizure that has been properly medically verified, and can legitimately be tied to Phenibut withdrawal alone. (If you have an actual medical case-study report to the contrary, I would love to see it). Now, that is not to say that people with preexisting epilepsy, acetylcholine deficiencies, or those who are taking medications that significantly lower the seizure threshold can’t experience convulsions during abrupt Phenibut withdrawal, but it is very rare, and is of almost no concern to the majority of Phenibut users. It certainly cannot be compared with ionotropic GABA -A or GHB receptor agonist withdrawal, as far a being a life-threatening medical emergency. It may be extremely unpleasant, and in some cases the rebound anxiety panic attacks can one feel like they’re dying (acute Panic Attack Disorder is described by most as feeling like a heart-attack), but once Ca+ channel neurotransmission normalizes in the GABA -B Receptor complex, those symptoms will eventually subside. (In my experience, it is not the desire to “get high” on Phenibut that keeps people using, but the unpleasantness of the rebound anxiety that prevents them from stopping). In this sense, Phenibut withdrawal can be somewhat comparable to opiate withdrawal - you may feel like dying, but you generally are not in any direct medical danger, aside from heightened blood pressure and (in some cases) irregular cardiac rhythms (which in some individuals can be serious), the vast majority of healthy users are at no real significant medical risk. Anybody with epilepsy, acetylcholine deficiencies, are on medications that significantly lower the seizure threshold, or those with severe hypertension or certain cardiac arrhythmia are at greater risk for adverse medical conditions following Phenibut withdrawal, and in those cases should consult their physicians before discontinuing their Phenibut dose. The vast majority of healthy individuals, are at no real significant medical risk. (Aside from anxiety, insomnia, weakness, and flu-like symptoms). If Phenibut withdrawal were as medically serious as you claim, it would have long been scheduled as a controlled drug in many countries. (In some countries, like the US it will likely soon be banned from dietary supplements, since it is a man-made drug, and does not occur in nature, therefore not meeting the definition of a dietary supplement. However, as long as marked “not for human consumption”, it will be be allowed to be sold).

 

So, in extreme cases (such as those with severe preexisting anxiety disorders, or who are using massive doses of Phenibut, or for very long periods of time ) in those who experience unbearable rebound anxiety following Phenibut discontinuation, then benzodiazepine use during withdrawal is viable. However, I still have to insist on erring on the side of caution, here. First off, it should be noted that many people start using Phenibut to avoid becoming dependent on a benzodiazepine in the first place. Also, just because you refer to benzodiazepines as”weak crap”, and state that “deciding you’d like them and getting addicted to them instead is laughable imo” says a lot about your personal taste in drugs, but does not reflect the actual abuse and addiction rate within the majority of the population. To say that it is easy to become addicted, and hard to wean off of a very weak, and simple amino acid like Phenibut, that’s effect on dopamine influx in minimal; but becoming addicted to a ridiculously potent (compared to Phenibut) ionotropic GABA -A agonist benzodiazepine is “highly unlikely” is a very odd statement to me. You may not personally be fond enough of benzodiazepines to become significantly dependent or addicted to them, but many of the members on forums like these certainly are, and it happens much more frequently that you’d think. The member that started this thread has already stated having a problem with impulse control. - And, benzodiazepine addiction and physical dependence is much more prevalent than Phenibut dependence (even within the same amount of users of each substance) - and acute withdrawal from an ionotropic GABA -A Receptor can and often is a severe medical emergency due to the development of Grand Mal and Myoclonic seizures, which, if not treated promptly and properly, can lead to swelling and bleeding in the brain, leading to permanent brain damage, and even death.

 

One other drug that can be used in place of benzodiazepines for Phenibut withdrawal (if absolutely necessary) is the Skeletal-Muscle-Relaxant drug Carisoprodol.  In the US and much of Europe, it goes by the brand name Soma.  Carisoprodol itself has barely any pharmacological activity, but it acts as a prodrug to Meprobamate, which it produces as it's active metabolite.  Although Meprobamate is not all that commonly used anymore (it was indicated for anxiety), Carisoprodol is still fairly commonly used, and is metabolized into meprobamate by the body, which binds to the GABA -A Receptor (but not at the Benzodiazepine Binding Site, but rather at the vetrosteric GABA Binding Site).  In normal therapeutic doses, Carisoprodol does not produce cognitive impairment, but can produce symptoms just as drowsiness and sedation, similar to bezodiazepines or barbituates.  For some people, Carisoprodol is not as habit-forming as benzodiazepines, but for others (in high doses), it can be even more so, and can produce sedation that is even more "sloppy" than benzodiazepine intoxication - more reminiscent of barbituate intoxication.  Also, it too can cause life-threatening withdrawal syndrome if discontinued too abruptly after regular use.

So, although there are GABA -A agonist drugs, such as the benzodiazepines and drugs like Meprobamate and Carisoprodol, care should always be taken if using them to make it through the withdrawals of regular Phenibut use. Remember, if you have an addictive enough personality to become addicted to a very weak, metabotropic, GABA -B Receptor agonist, amino acid - you a substituting that amino acid (Phenibut) for a ridiculously much more potent, ionotropic, GABA -A Receptor agonist, who’s addiction profile is much higher, and who’s withdrawals are much more serious, medically. I am not saying that this is true for everybody, but it is certainly true for a large portion of the population. Personally, I’m very surprised that medievil seems to have become dependent on Phenibut (needing a benzodiazepine to stop using it), yet regards benzodiazepines as no big deal as far as addictive tendencies, or physical dependence. That is a good thing for him (and I personally am very similar), but I must urge on the side of caution, and advise other posters here to at least try to stop using Phenibut by gradually reducing their dose. As I previously stated, out of the 180 participants in our last meta-analysis of therapeutic Phenibut use, none of the patients had any significant withdrawal syndrome by reducing their therapeutic dose by 10% for ten weeks time. Many patients can wean faster, but this is what I recommend for those using Phenibut for legitimate anxiety disorders.

 

If you are part of the small percentage that experiences unbearable rebound anxiety, even while weaning down your dose, and you absolutely must use a benzodiazepine, or a drug like Carisoprodol, to control the withdrawal syndrome and rebound anxiety, use the smallest dose of the benzodiazepine drug that is effective for suppressing the withdrawal syndrome, rebound anxiety, and insomnia, for the shortest amount of time necessary. If you are somebody with impulse control issues, or somebody who has had prior abuse issues with alcohol, barbituates, of benzodiazepines, consider giving the supply of the benzodiazepine drug that you will be using for the withdrawal syndrome to a trusted friend or family member, so that they can dispense them to you, only as many and as often as needed. 

 

medievil,

 

In summary, there were a lot of good points brought up in this thread. After being contacted by a few of the members here, I played around with the idea of volunteering here, and after some thought, decided to check out the site. I must say, I am pleasantly surprised by some of the topics addressed here, and some of the posters’ recommendations. In some ways, it reminds me of an amateur version of our peer-review board, which is very refreshing to see. As I stated earlier, I came here at the request of a few members that had interacted with me elsewhere online, to help clarify some of the misinformation, misconceptions, and misinterpretations of published works, and to advise the membership here based on confirmed and factual scientific data. I always welcome any good debate. My only concern in this thread is that some posters not familiar with the effects of benzodiazepine drugs, may read your comments, assume that benzos carry no harm or addiction liability, and wind up dependent on a much more potent (and dangerous in the case of withdrawal) drug, than a simple weak amino acid, such as Phenibut. Just because individuals like you and I, do not find extended use of benzodiazepines to cause significant physical dependence and/or addiction, does not mean that a large portion of the population doesn’t find them very habit-forming. That is just something to keep in mind.

 

 

 

-J. Gona

Psychopharmacologist,

Psychotropic Treatment Specialist

Oracle Laboratories
NeuroPsych Institute

 

 

Edited by Oracle Laboratories, 14 March 2016 - 07:04 PM.

[stan08]

J. Gona,

 

Thank you for taking the time to provide such a well written and informative response.  I've often considered trying low doses of phenibut (<600 mg/day) to help with pretty severe social anxiety and mild depression but haven't yet due to all the horror stories I've read online about tolerance and addiction to the substance.  Based on the information you've provided, it would appear low daily doses (<2g/day) shouldn't be a problem as long as a person slowly tapers down their dosage if/when deciding to discontinue use. While I may not understand everything you wrote, I look forward to reading (and learning from) your future contributions to this site.  

[toto75015]

Hi there,

 

I always refused to test phenibut because its deregulation of GABA-B receptors, and all the horrors stories heard on the internet, and the fast tolerance.

 

I have strong social anxiety, and successfully tried Kava in the past. Only problem with Kava: the taste is strong, and it takes some time to prepare.

 

Also Kava cost more per dose than phenibut.

 

The advantage of Kava: no tolerance, a reverse tolerance instead where you become more sensitive to the kavalactones the more often you consume.

 

However Phenibut is still in my watch list, and recently I noticed this thread on reddit: https://www.reddit.c...essions_report/

 

So it seems that F-Phenibut is somewhere in between Baclofen and Phenibut in regards of effects and tolerance/potency.

 

If this compound is as effective as Phenibut as making you a social butterfly, and has low tolerance and low addiction potential, this could become the silver bullet in term of anxiety control.

 

But for the moment it's still a research chemical, so who knows the safety and side effects?

[BlueCloud]

....

If you’re interested, I can put you in touch with Roger Hutton (a colleague of mine from The Indiana Neural Research Center)

......

 

-J. Gona

Psychopharmacologist,

Psychotropic Treatment Specialist

Oracle Laboratories
NeuroPsych Institute

 

 

 

Odd...    

 

For such a prominent biochemist and drug developer , I cannot find a SINGLE trace on the net of a John Gona ( except for a programmer in Indiana), of an Oracle Laboratories ( except for the health department affairs of the well known Oracle database corporation, wich seems totally unrelated to this ) , absolutely no trace of "Oracle Laboratories Journal of Applied and Investigative Pharmacology, and The NeuroPsych Journal of Psychopharmacology" or "NeuroPsych Laboratory Press"

 

Zero references on the net of the "Indiana Neural Research Center"  or Roger Hutton...

 

Care to enlighten us, "John " ?

Edited by BlueCloud, 15 March 2016 - 09:21 PM.

[pinnacle]

I'd quite like to try the pure 'R' isomer of Phenibut someday.

 

R-phenibut binds to the α₂–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects

 

Highlights

• R-phenibut binds to the α₂–δ subunit of the voltage-dependent calcium channel (VDCC).

• The binding affinity of R-phenibut for the α₂–δ subunit of the VDCC is 5 times higher than that for GABA_B receptor.

• R-phenibut exerts gabapentin-like anti-nociceptive effects in the formalin-induced paw-licking and CCI tests.

• The anti-nociceptive effects of R-phenibut are not mediated through GABA_Breceptor

Also quite noteworthy:

R-phenibut is responsible for the pharmacological activity of racemic phenibut, and this activity correlates with its binding affinity for GABA_B receptors. In contrast, S-phenibut does not bind to GABA_B receptors.

 

 

http://www.sciencedi...09130571530037X

[Oracle Laboratories]

 

....

If you’re interested, I can put you in touch with Roger Hutton (a colleague of mine from The Indiana Neural Research Center)

......

 

-J. Gona

Psychopharmacologist,

Psychotropic Treatment Specialist

Oracle Laboratories
NeuroPsych Institute

 

 

 

Odd...    

 

For such a prominent biochemist and drug developer , I cannot find a SINGLE trace on the net of a John Gona ( except for a programmer in Indiana), of an Oracle Laboratories ( except for the health department affairs of the well known Oracle database corporation, wich seems totally unrelated to this ) , absolutely no trace of "Oracle Laboratories Journal of Applied and Investigative Pharmacology, and The NeuroPsych Journal of Psychopharmacology" or "NeuroPsych Laboratory Press"

 

Zero references on the net of the "Indiana Neural Research Center"  or Roger Hutton...

 

Care to enlighten us, "John " ?

 

 

Well, I certainly do not claim to be a "prominent biochemist and drug developer" compared to many university academic or government institution researchers.  I am simply one of many independent pharmacologists operating biochemical and/or analytical laboratories, not affiliated with a government institution or a state university, like almost all researchers and facilities associated with Oracle Laboratory Institute (under the umbrella of Orial NeuroPsych Institute) - a network of independent facilities and researchers.  No, Oracle Database Corporation is completely unrelated.  Our Journal of Applied and Investigative Pharmacology (a publication of NeuroPsych Laboratory Press) covers findings related to the research undertaken by the researchers and facilities affiliated with Oracle Laboratory Institute.  Unfortunately our main website is down for renovation, and the stored back-up version is incomplete (and was long ago abandoned to complete our main site).  Once everything is back online, I had already intended to share pertinent publications with the membership here.  (Although I was advised by the moderation team that in order to share our website links here, I would need to contact the site to setup banner ads).

Indiana Neural Research Center, as far as I know is a post-graduate organization of Indiana University / Purdue University of Indianapolis.  I am not entirely sure what Roger's official affiliation is as far as Purdue anymore, but I will attempt to dig up his NMDA Receptor Modeling work and post a link here, so long as is does not violate the pay-gate agreement with the publisher.

Unfortunately, as a new member, I can only make a limited number of posts, so I cannot possibly to respond to everything that I would like to.  In good time.



-J. Gona
 

[Oracle Laboratories]

(Accidental post, cannot delete)..

 

 

Edited by Oracle Laboratories, 16 March 2016 - 12:28 PM.

[BlueCloud]

 

 Oracle Laboratory Institute (under the umbrella of Orial NeuroPsych Institute) - a network of independent facilities and researchers. 

 

 

 

I just find it very odd that no search engine ( I tried Google and Bing ) is able to come up with even a SINGLE direct or indirect link or reference to any of these characters ( John Gona, Robert Hutton) or institutes or laboratories ( except for Indiana university, on wich a search on their own website doesn't show any Neural research Center or Robert Hutton ).... 

 

But perhaps your work, as well as your laboratories and institutes,  are super-secret and confidential, to the point of becoming invisible and leaving no trace whatsoever on the World Wide Web...Very hard in this day and age. I'm quite...uuh... impressed. 

Edited by BlueCloud, 16 March 2016 - 12:43 PM.

[BlueCloud]

 

My name is John Gona, and I am the founder of Oracle Laboratory Institute and NeuroPsych Laboratory Press (which encompasses Oracle Laboratories Journal of Applied and Investigative Pharmacology, and The NeuroPsych Journal of Psychopharmacology.  I am a biochemist and drug developer. My actual title is Phsychopharmacologist, and Psychotropic / Nootropic Treatment Specialist.

....

 

My research has led to the development of dozens of novel drugs, and even more derivatives and intermediate compounds.......

I have also helped to develop and improve various laboratory analytical instruments at our facilities and associate's facilities, such as Scanning Electron Microscopes; High-Performance Liquid & Gas Chromatographers; Polarimeters;.....

In addition to my laboratory research work, I also act as a pharmaceutical consultant for many pharmacological institutions, psychiatrists, neurologists, medical doctors, and work alongside these institutions, helping to develop custom-tailored treatment plans for their patients.

A more extensive background of my research experience, novel compound developments, publications, technological patent applications, and collaborative institutions can be provided upon request.

 

Wow... truly impressive achievements. Even more impressive to achieve all this while keeping your name, your work and your "laboratories" completely hidden from public eyes, Internet, and search engines. Probably an even greater achievement than your scientific and technological innovations.  My hat is off to you sir 

 

 

 

Now, let's be serious for a minute. You obviously possess a certain amount of serious scientific knowledge. So, why this whole masquerade and this whole fictitious persona  and world you invented ? What is exactly the point ??? Perhaps an experiment in how easy it is to fool adult rational people ?

 

Seriously, I'm curious.

Edited by BlueCloud, 16 March 2016 - 01:52 PM.

[Oracle Laboratories]

Look, I do not know you, and have had absolutely no contact with other than the numerous posts of mine that you are trolling on this website. (Certainly no intellectual communication). I came to this site at the request of several existing members, to volunteer my time and offer my expertise to the general membership here, to clear up misinformation, misconceptions, and misinterpretations of published material that seem to be oh so prevalent online in this particular field.  I came to this site as a courtesy, to volunteer some of my spare time, and I have absolutely no desire to argue with any internet poster who happens to be trolling posts that I have made here.

Aside from the large pharmacological publishers, and state university and government agency researchers that have large online collections of material, there are an equal if not greater number of independent researchers in the private sector, running privately-owned biochemical and analytical laboratories.  The great part about the US is that we have the right to assemble - that means that if you are so inclined, have to necessary background education, the equipment, and the organizational skills, you can form any sort of organization that you want to.  And, like myself, if you are so inclined, you can even establish a non-profit pharmacological institute. - All that is required is a group of like-minded individuals with the right skill-set and resources to pull it off.  I have no desire to (and in fact, I refuse to) argue with you and defend my work on thread after thread on a website such as this.  You DID bring up a valid question about our journal and online presence, and I answered it.  Had you searched the same keywords that you mentioned in the threads that you are currently flaming in, you would have been directed to the main Oracle Laboratory Institute and NeuroPsych Institute website through Google, before our domain and database crashed, and all of our membership accounts, forum posts, and articles were lost.  We are currently in the process of rebuilding the main site, and reactivating the main domain name.

However, perhaps it is worth giving you a bit of a brief history of Oracle Laboratory Institute..  The VAST majority of pharmacological research that is conducted in the US (and most of the established world, for that matter) is done either by private pharmaceutical company labs, or by state university journals - in conjunction with pharmaceutical companies, for the development of new commercial pharmaceutical patents.  Very few truly novel and noteworthy drugs get the funding for the research required to evaluate their specific pharmacology and pharmacokinetics, without some potential for a large commercial gain as a result of the development of said compound.  It is just a sad fact of life that many very interesting psychopharmacological ideas never get off the ground by mainstream university or pharmaceutical company labs, due to lack of funding, unless there is some potential for a significant monetary commercial gain as a result of the work.

Many of my personal heroes are men like Dr. Alexander Shulgin, who, after being shunned by the more established pharmaceutical companies, decided to fund and explore his own avenues of research interest.  I do not know if you are new to forums like this one, but if you search across all of the nootropic and psychopharmacological forums online, you will become aware of dozens and dozens of very talented biochemists and microbiologists, who without being officially affiliated with a university or government institution, have still made huge developments in many areas of biochemistry, microbiology, genetic research, etc., all independently in their home labs, and many of these people's accomplishments are now very well-referenced discoveries, even by the mainstream university, pharmaceutical developer, and government institution pharmacologists of today.

Several years ago, I approached many of these independent chemists and microbiologists that I have met along the way, and together we founded what has now become NeuroPsych Institute to facilitate the documentation and dissemination of psychopharmaceutical discoveries made in the private sector, and the network of researchers and private facilities that collaboratively follow our institute’s constitution and publish via our Journal of Applied and Investigational Pharmacology (via NeuroPsych Laboratory Press) is known as the Oracle Laboratory Institute network.

I in no way ever claimed to be a doctoral professor of a major US university, or the CEO of some Fortune 500 pharmaceutical company, but rather I accurately represented the nature of mine and my team’s work.  And, anybody that has the proper background, who is so inclined, and has access to the necessary resources, can found their own organization, compose their own peer-review journal, and do the exact same thing that we are doing if they are so inclined and motivated enough.  We are funded through the analytical work that we do on compounds and supplement quality analysis for various chemical suppliers, are privately and to some degree self-funded, and are also funded by the in-vivo and in-vitro pharmacological analyses that we do for other institutions, and the consultation work that I do for various patients on psychotropic medications, and in conjunction with several psychiatric centers and private practice psychiatrists.  I do not know where you got the idea that you have to be some kind of god to do the kind of work that I do - when all that is required is the proper background knowledge, organizational skills, and access to the necessary resources.  (That is not to say that I don’t have many friends who work in community college or university or medical labs, that I sometimes recruit to help us on some projects, such as in gaining access to the newer, high-resolution Nuclear-Magnetic-Resonance Imagers and Radioisotope Brain Imaging Systems on occasion, when our own equipment is not quite enough for a particular task).

I can name dozens of independent researchers from dozens of independent labs, who publish through their own local press journals, and who are not affiliated with large-scale universities, pharmaceutical companies, or government institutions, that likely do not have much of an online footprint, or publish in large-scale pharmacological journals that are associated with such universities, pharmaceutical companies, or government laboratories.  Like I said, you DID bring up a valid point in looking for our work via online search engines, and I answered that question.  I will NOT, however, continue to answer it over and over again.  As I said, if you were to have searched Google for the same keywords three months ago, you would have been directly forwarded to the NeuroPsych Institute domain, and subsequently, the Oracle Laboratories Institute’s main website.  After our domain went down, and our database was lost, the only version of our site that is still accessible is a free-hosted draft version, void of all of our membership accounts, forum posts, and our publication files, clinical surveys, and articles that were lost.  Hopefully, within a month’s time, you will again be able to visit our main domain and read everything about our inception, history, and research work to your heart’s content.  However, to simply claim that I am some fictional character, who just likes to post on forums an mislead people for the hell of it, is extremely ignorant, foolish, an illogical.  What would I gain by doing that; really?

To make blatant, bogus claims such as that our journal does not exist is pretty damn confident in outright fabricated “facts” of which you really don’t know what you’re talking about.  It is statements like that, that can end up making someone looking very foolish.

You stated “You obviously possess a certain amount of serious scientific knowledge.” - Well, I sure as hell didn’t obtain that knowledge by reading the back of a cereal box - I did so by conducting in in-vitro and in-vivo pharmacological work, first-hand, and in conjunction with my team.


As stated, our main website and publication database is a mess, but for something tangible that I happen to have handy on the hard drive of my laptop that we recently published, have at it:

http://oracle-labs.w...-submission.pdf

Phenigabine is one of the experimental cyclic phenyl ring GABA/Phenibut derivatives that I mentioned in my above post. (Note, that this is not the final publication on the pharmacological profile of Phenigabine, or it’s clinical review; it is simply a summary draft of it's general pharmacological effects that was submitted for publication via our journal).

As I said, hopefully, within a month’s time, when our main domain name is back online, and our main website’s database is restored, you can read all about our history and work, to your heart’s content.  For the mean time, as I stated, I can only make a limited amount of posts per day, and I certainly am not going to keep re-posting the same statements again and again, when I decided to volunteer my time sat this site as a courtesy to some of the membership, in the first place.  So, can we end the trolling now..?



 

[maxwatt]

It would help credibility to name the members who asked you to join.  You can PM if not wishing to post names publicly.

[sativa]

It would help credibility to name the members who asked you to join. You can PM if not wishing to post names publicly.

Come on...! Now I can understand the skepticism but, for a moment just stop and read the indepth and detailed pharmacological information that Oracle Laboratories has written.

Regardless of his credentials (what would he/she benefit from lying anyway??) the neuroscience information is quite top notch and clarifies many things. (thanks Oracle Laboratories)

[Sarif]

I don’t really understand this. It’s quite rare to come across people with the vast amount of knowledge like John Gona in longecity. Instead of criticizing him we should be thankful to him for taking the time to write the detail explanations.

 

Trolling is one of the main reasons serious researchers stay away from public forums like this.

 

I don’t know about you guys, but I for one is following his advice. 

[BlueCloud]

 

Regardless of his credentials (what would he/she benefit from lying anyway??) 

 

Well, there are a few explainations, of wich I'll refrain from posting, for now ...

 

Let's say we're wrong : All "John Gona from Oracle Laboratories" has to do is answer to Maxwatt's request. No big deal , right ? I mean, he even offers "A more extensive background of my research experience, novel compound developments, publications, technological patent applications, and collaborative institutions can be provided upon request."  This is from his bio on his profile page on the forum. All the moderator is asking for is to PM him wich "several" members of this forum have repeatedly invited him  , as he said.

 

This will settle the matters once and for all and we'll all move on and benefit from his posts. 

 

As far as I know, he still haven't answered to Maxwatt's request.

Edited by BlueCloud, 17 March 2016 - 02:15 PM.

[maxwatt]

FWIW, my daughter is a neuroscience PhD candidate at a top tier university, already has a  masters degrees in the subject and will have five more masters or equivalents in related fields when she finishes the program..  She has done extensive research with GABA receptors. If she can spare the time to look at Oracle Labs and John Gona's papers, I will post her impression and any remarks. 

 

Another moderator, niner, is a pharmacologist.  He can offer an evaluation as well.

Edited by maxwatt, 17 March 2016 - 02:49 PM.

[niner]

John / Oracle Laboratories, I had a look at your Phenigabine paper.  Who synthesized the analogs?  Did you guys also do the PK measurements, drawing blood at various timepoints and analyzing for phenigabine at different dose levels, salt forms, and fed/fasted status?  That's a lot of work.  If this is representative of stuff you guys can do, there are people in our community who might want to talk to you.  We're particularly interested in people who have access to analytical instrumentation and know how to use it. 

[maxwatt]

 

It would help credibility to name the members who asked you to join. You can PM if not wishing to post names publicly.

Come on...! Now I can understand the skepticism but, for a moment just stop and read the indepth and detailed pharmacological information that Oracle Laboratories has written.

Regardless of his credentials (what would he/she benefit from lying anyway??) the neuroscience information is quite top notch and clarifies many things. (thanks Oracle Laboratories)

 

 

John/Oracle Labs has provided several names, he has been active elsewhere and there is some member overlap.  Niner has looked at their paper and found it interesting, knowledgeable if perhaps nonconforming as to terminology in some areas.  My impression, maybe the work of a brilliant autodidact? .  It's certainly worth a good look.  

 

(As it happens, GABA blockers and agonists are an interest of mine.)

[BlueCloud]

John/Oracle Labs has provided several names, he has been active elsewhere and there is some member overlap.  

 

 

Did the longecity members confirm that they know him and  invited him here ?

 

If he and his labs and his team and journals are all real, I'd really love to know how they managed to publish, "patent technological innovations", "collaborate with various other institutions" ( his terms) ,  consult for so many people and corporations, and still manage to remain completely hidden from all internet search engines, never appear on any patent database ( despite patenting so many things), never be linked to or be cited in any external website ( other than his ), no traces from the past left in the cache of any search engine, etc..

 

To anyone familiar with how search engines work, that is , hands down, a FAR more impressive technological achievement than any pharmaceutical compound he and his team could ever create. Only the best minds at the NSA, or some brilliant hackers,  could probably achieve a similar thing.

Edited by BlueCloud, 18 March 2016 - 01:16 PM.

[YOLF]

While there is reason for concern with OL, I think we should be kinder in requesting that he validate some of his claims or admit that he's just a talented and/or opinionated self taught individual. If it's the case that you don't wish to divulge your identity for reason of the topics you're discussing we'd be happy to validate your identity and keep it private.

 

If you're self taught, they'll go pretty easy on you. I don't have any scientific credentials, nor am I as knowledgeable as you appear to be and while people frequently challenge me, I deal with it and have earned more positive reputation than negative and feel like I'm contributing and heard here for the most part. I'm a member of management after all...