About

Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, August 31, 2011

Pharmacological Targets of Psychoactive Drugs by Class



Sedative Hypnotics: CNS depressants or "downers"
GABA Receptors - agonism or postive allosteric modulation
Glutamate Receptors (NMDA, AMPA) - antagonism or blockade
Cholinergic Receptors (nicotinic or muscarinic) - antagonist or blockade

Sympathomimetics: Psychostimulants or "uppers"
Catecholamine Transporters - blockade (reuptake inhibition)
Catecholamine Transporters - phosphorylation
Catecholaminergic Neurons - increased neurotransmitter firing
Catecholaminergic Receptors - agonism or positive allosteric modulation
Note: Catecholamines include dopamine and norepinephrine.

Dissociatives: Sometimes known as dissociative anaesthetics
NMDA Receptors: antagonism or blockade
Sigma Receptors: agonism

Classical Psychedelics: Popular term being "hallucinogens"
Serotonergic Receptors (5HT2A) - partial agonism
Kappa & Delta Opioid Receptors: agonism
Cannabinoid Receptors: agonism

Deleriants: Another form of psychedelic or "hallucinogen" 
Cholinergic Receptors (nACh) - antagonism or blockade
Kappa Opioid Receptors - agonism
Histaminergic Receptors - antagonism or blockade

Opioids: Narcotic analgesics or morphinomimetics
Opioid Receptors - agonism (mu, delta, kappa, epsilon, ORL1)

Tuesday, August 30, 2011

Adults Making Their Own Choices? What Blasphemy!

Former Bush Official Attacks Ron Paul on Drug Policy

image is the work of a political cartoonist and not my own

I recently came across an opinion piece that was written by a former Bush Administration Speechwriter, who was outraged following South Carolina's GOP Presidential debate in May of this year, where Ron Paul (along with one other candidate) intelligently spoke the truth regarding our fascist drug policy. Mr. Gerson was outraged by Ron Paul's suggestion that grown adults ought to be able to make their own lifestyle choices. Michael Gerson is a syndicated columnist for the washington post. So rather than feeding his paternalistic spew to the nation through Bush speeches, he now does so through a major news journal.

Mike Riggs at Reason magazine briefly discussed this piece, and so did David boaz in an article of The Free-Man. I would now like to add my remarks to this clearly misguided piece of propaganda.

Below in purple, is the opinion piece, paragraph by paragraph, with my responses in green text. Enjoy



Ron Paul favors legalizing heroin

Texas congressman deserves first-tier scrutiny.


Before last week's South Carolina Republican debate, Ron Paul supporters complained that their candidate was not getting the first-tier attention his polling and fundraising should bring. It is true that Paul has often been overlooked and dismissed, as one might treat a slightly dotty uncle. But perhaps some first-tier scrutiny is deserved.

After laboring through this piece, I've concluded that your nonsensical, paternalistic reporting deserves some first tier scrutiny; not so much the politics of Mr. Paul.

Paul was the only candidate at the debate to make news, calling for the repeal of laws against prostitution, cocaine and heroin. The freedom to use drugs, he argued, is equivalent to the freedom of people to “practice their religion and say their prayers.” Liberty must be defended “across the board.” “It is amazing that we want freedom to pick our future in a spiritual way,” he said, “but not when it comes to our personal habits.”

Not so much an 'arguement' as it is a truth. Just as individuals are free to pursue various faiths as a means of finding meaning in the human experience; individuals are likewise entitled to sovereignty over their minds & bodies, and are naturally free to regulate their personal perception of the human experience, through religion, meditation, or self medication (drug use).

This argument is strangely framed: If you tolerate Zoroastrianism, you must be able to buy heroin at the quickie mart. But it is an authentic application of libertarianism, which reduces the whole of political philosophy to a single slogan: Do what you will — pray or inject or turn a trick — as long as no one else gets hurt.

Just as your contrast of religion and drug use is irrationally framed. Must I point out the fact that you contrast the concept of a religious practice with your own terribly simplified & sensational version of the concept of the use of a pscyhoactive.. Going so far as to utilize blind assumptions with pop-culture slang in order to marginalize the relative merits of drug use in the reader's mind, you yourself have reduced the image of altering one's consciousness to a single ghetto-life stereotype.

Even by this permissive standard, drug legalization fails. The de facto decriminalization of drugs in some neighborhoods — say, in Washington, D.C. — has encouraged widespread addiction. Children, freed from the care of their addicted parents, have the liberty to play in parks decorated by used needles. Addicts are liberated into lives of prostitution and homelessness.

Here, you've taken your subjective perception of apparent social decay and irresponsible behaviors, which are prominent among the lower-class; blindly implying that drug use is the culprit behind a broad spectrum of lower-class behavioral traits. It seems all too common for manipulative journalists such as yourself to conveniently confuse cause-effect and correllative relationships where it serves your 'butthole-speak' agenda. It shouldn't take an anthropological genius to realize that the many behavioral & cultural traits of a particular demographic are much more the reflections of educational, socioeconomic, and character pre-sets, than they are of their collective intoxicant of choice. Furthermore, apathy causes addiction more than addiction causes apathy. The same could be said for criminal behavior. However, all that considered, this is not even the point; drugs have not been "decriminalized" in washington. As Mike Riggs of Reason Magazine puts it, "I want to know where in D.C. one can get away with slinging or using in front of a cop. The 2,874 people arrested by the MPD for narcotics violations between Jan. 1 and April 9 of this year would probably like to know, too." It is the prohibitionist policies of government and the societal marginalization which it has led to which continues to cause massive damage to the urban and suburban US.

But Paul had an answer to this criticism. “How many people here would use heroin if it were legal? I bet nobody would,” he said to applause and laughter. Paul was claiming that good people — people like the Republicans in the room — would not abuse their freedom, unlike those others who don't deserve our sympathy.

Or perhaps Mr. Paul was [symbolically] attempting to convey a much simpler point; the point being that the legalization of narcotics, (just like the legal availability of tobacco) is not a determinant of its use. Who is to say that the use of heroin is an "abuse" of freedom? Where is this arbitrary line that determines which neurochemically based pleasure is "good" vs which is "evil"? And why would one's overindulgence in heroin deserve our sympathy? Rather than deserving our envy? In fact, I find the acceptance of the poor choices of others to be far more "sympathetic" than your suggestion to criminalize & imprison them.
The problem, of course, is that even people in the room may have had sons or daughters who struggled with addiction. Or maybe even have personal experience with the freedom that comes from alcohol and drug abuse. One imagines they did not laugh or cheer.

The problem with emotional appeal is that it's not exactly conducive to sound reasoning or logic. Then again, neither is sensational journalism. And why do we constantly speak of overindulgent drug use as if it's something that "happened" to someone; using the terms "struggling", "battling", "victim" ... As if their behavior were involuntary.

Libertarians often cover their views with a powdered wig of 18th- and 19th-century philosophy. They cite Locke, Smith and Mill as advocates of a peaceable kingdom — a utopia of cooperation and spontaneous order. But the reality of libertarianism was on display in South Carolina. Paul concluded his answer by doing a jeering rendition of an addict's voice: “Oh yeah, I need the government to take care of me. I don't want to use heroin, so I need these laws.”

This interpretation of Paul's rendition, is of course completely subjective. Rather than the mean old politician mocking drug users, it is much more likely that this statement was used to support his point; that the legalization of narcotics does not represent "promotion of drug use", nor is it interpreted this way by any independent minded individual. Mr. Paul was in fact obviously mocking the idea of paternalism in government, and I can assure you, there is no drug user in this world who WANTS his government to protect him from the experience which he so eagerly seeks. As a side note; how does one find it necessarry to pollute concrete matters of  personal liberty with the mainstream "left vs right" party line rivalry? The fundumental philosophy of a constitutional republic is quite simple, and to even find it necessarry to establish a labeling system for the ever growing spectrum of government micromanagement ideologies simply goes to show how far we've gone astray from the intentions of our US founding fathers. I digress...
This is not “The Wealth of Nations” or the “Second Treatise on Government.” It is Social Darwinism. It is the arrogance of the strong. It is contempt for the vulnerable and suffering.

What you're implying is that to legalizate and regulate narcotics is to leave the overindulgent or "sick" for dead... As if it is an inherent duty of government to micro manage the personal habits of the hedonist, and as if leaving one the freedom and accountability of their own personal choices is tantamount to genocide. And some more realistic, less idealistic, individual might fail to see a problem in natural selection... Only in the last century have we found it necessarry to micromanage such petty behavioral traits. It is remarkable how paternalist figures like yourself can reach so far as to suggest that allowing other adults to make, and hold accountability for, their own decisions somehow constitutes "contempt"; yet you seem to find no contempt in persecuting and arresting these same adults for these personal choices. The paternalism of drug laws aside; all of the arresting and imprisoning in the world will not beat the darwinian law of natural selection.
The conservative alternative to libertarianism is necessarily more complex. It is the teaching of classical political philosophy and the Jewish and Christian traditions that true liberty must be appropriate to human nature. The freedom to enslave oneself with drugs is the freedom of the fish to live on land, or the freedom of birds to inhabit the ocean — which is to say, it is not freedom at all. Responsible, self-governing citizens do not grow wild like blackberries. They are cultivated in institutions — families, religious communities and decent, orderly neighborhoods. And government has a limited but important role in reinforcing social norms and expectations — including laws against drugs and against the exploitation of men and women in the sex trade.

Above is a perfect representation of a fundumental flaw in the popular perception of drug use. The "enslavement" rhetoric incorporates the science of the brain's instinctual reinforcement & reward mechanism and interprets the neurochemical workings behind drug use to represent drug addiction as an illness, and problem users as medical victims. The problem with this myth is that it completely disregards the higher functioning rational mind; which exerts control over all instinctual urges. Where as hedonist desire is an influential element to human nature, self control is a dominant element of human nature. I suppose however, in order to continue rationalizing the atrocity of arbitrarily prohibiting a drug of choice, one must rationalize the myth that narcotics, like viruses and bacilli, are capable of acting on individuals against their will, infecting the user with a "disease" which causes involuntary behaviors such as "crime and more drug use."

And call prostitution "exploitation" all you would like, it doesn't change the fact that it's consentual, SELF exploitation. Isn't there a degree of exploitation in all markets? Principles of marketing require it.

It was just 12 years ago — though it seems like a political lifetime — that a Republican presidential candidate visited a rural drug treatment center outside Des Moines, Iowa. Moved by the stories of recovering young addicts, Texas Gov. George W. Bush talked of his own struggles with alcohol. “I'm on a walk. And it's a never-ending walk as far as I'm concerned. ... I want you to know that your life's walk is shared by a lot of other people, even some who wear suits.”

In determining who is a “major” candidate for president, let's begin here. Those who support the legalization of heroin while mocking addicts are marginal. It is difficult to be a first-tier candidate while holding second-rate values.

Congratulations, you've demonstrated your inability to think intelligently, not to mention speak articulately, regarding drug use and "public policy". I suggest gaining some knowledge about that which you plan to critizice.. But then again, if one had any solid knowledge whatsoever regarding the science and sociology of drugs and their use, they wouln't be speaking out against legalization.

Fascist Colomnist Michael Gerson may be contacted by email: michaelgerson@washpost.com

Sunday, August 28, 2011

Changes & Disclaimer

To my readers; I have run this blog for a bit over a year now. In that time I have not exactly acheived as much substance as I would ideally like to in my posts. As a result of either my limited creative abilities, or perhaps just my style of though, much of this material has been limited thus far, to the concrete science of opium based drugs. Would I like to broaden the material of the blog? Of course. I'll work hard to do so over the coming weeks and months.

I'd like to 'attempt' to explore the social stigma of heroin, the opioids, and non opioids. I'd like to discuss the subjectivity of the neat little labels by which we arbitrarily attempt to categorize drug use. I'd also like to get into the history of opium and cannabis prohibition and the trends of both licit and illicit use over the last hundred years. There is much to cover, much to analyze, even when I have touched on these (or similar) topics, I have always managed only to scratch the surface.

In the meantime, I've begun restoring many popular areas of this site. Some of these were constructed quite some time ago, and I have unfortunately found some degree of error, bias, or "immaturity" in much I had written. Indeed, it may have been a year ago at most, however alot has changed in that year. I've developed a much greater understanding of society, history, and science since this site was started. I'm sure some might relate to that sense of self disgust or embarrasment one feels when looking back at your writing. It's humbling.

So, please hang in with me. There are many pages which I'm in the process of editing, improving, and restoring; as everyone is entitled to objective, evidence based, and realistic information regarding drugs.

Thanks for reading, stay safe
 
....and, fuck bureacrats, fuck our police state, fuck over reaching government, and fuck fear mongerers.

Saturday, August 20, 2011

Narcotics and Psychological Dependence

Primer on Dopamine & Mesolymbic Reward

Cocaine, methamphetamine, MDMA, alcohol, benzodiazepines, morphine or heroin; Nearly all psychoactive drugs have one major action in common; that is to directly or indirectly increase the firing of dopamine from the ventral tegmental area (or VTA) into the nucleus accumbens (an area known as a key pleasure center of the brain). These areas comprise 2 components of a functional system known as the brain's reward system, also known as the mesolimbic dopamine system.

Elevation in limbic dopamine is a natural, not to mention vital, function of the brain, and plays a major role in motivation, through positive reinforcement of certain behaviors such as eating or sex. Dopamine plays a dominant role in mediating our sense of motivation, urge, and desire.

To put it simply; synaptic transmission of dopamine is the brain's way of rewarding an individual for certain activities, which in many cases are evolutionarily essential components of survival - The brain rewards human behavior much like one rewards a dog with a bone. Just as a dog is eventually trained to "sit, shake, lie down", the brain is trained to depend on these rewarded behaviors; in turn we become motivated to eat, drink, excercise, have sex, pursue a partner or pursue a personal passion.

Cortical connections between reward and memory are formed over time through a process of synaptic adaptation, or, the strengthening of connections between neural pathways. These changes in the long term affect motivation & instinct. In essence, by the time a human has fully developed in most ways which are relevant, he/she has become psychologically dependent on a myriad of seemingly rudimentary, everyday tasks. Even our indulgent, non-essential personal habits or vices, whatever they may be; dancing, gambling, smoking, eating, spending, stealing, have become psychological dependencies which the instinctual drive often believes are necessary to survival (as the primitive limbic brain cannot distinguish want from need).

These habits may or may not be essential to survival, and may or may not be healthy or constructive. They may or may not have negative impacts on us socially, occupationally, financially, or behaviorally. Most individuals will maintain a level of good judgement and responsibility; however some individuals by nature or character tend to act impulsively, and without a great deal of regard for the potential impact of such behavior. This may often be referred to as a compulsive or "addictive" personality. This individual is more likely than others to develop a pattern of problematic or destructive behavior.

Are opioids addictive?

In some cases yes. Just as any other reinforcing activity is potentially "addictive". However, a compulsive habit does not develop overnight. To the contrary, it generally takes a great deal of work to develop an instinctual desire for opioids; and no one inadvertently finds themselves in this situation. As discussed earlier, opioids can be just as reinforcing to the brain as food, sex, or money. Additionally, their physiological and emotional effects are extremely pleasant to most users.

The psychological dependence liability of opioids, as with other drugs, is mediated by this very reinforcement mechanism; the limbic dopamine regions of the VTA & nucleus accumbens; the same circuitry which mediates much of the euphoric sense of well being provided by a mu opioid agonist.

When opioids are used habitually, and in excess doses, their rewarding & reinforcing effects prime the brain to prioritize this particular behavior, much as it would eating (see dopamine above). Cortical connections are eventually formed, incorporating drug taking as a 'prioritized behavior'. Opioid use becomes an instinctual urge much like love or sex, and in addicted individuals will often take precedence over these everyday tasks, including eating and self care. But while the brain craves the use of an opiate, the conscious or "rational" mind exhibits control over impulse, leaving one the choice to either resist or to satisfy the urge. Just as sexual desire may be hard to resist, most of us do not allow these urges to control our behavior; however, the pleasure of opioids much like the pleasure of sex, serve as sufficient motivation for some to continue habitual use despite negative results.

Is addiction involuntary?

Addiction is not a disease and addiction is certainly not involuntary. Likewise, the addict is not a victim. Despite an instinctual urge, continued use in this situation is a conscious choice. Many regular users (if not a majority) will likely simply choose to use narcotics, even when this choice is not in their current best interest. They are simply that pleasant, not to mention that reinforcing. As cortical connections of opioid use have made this behavior as high a priority as sex, money, or food - to simply give up narcotics may be no easier than giving up a heated relationship, or refusing a fat stack of cash. It is simly an instinctual insult, much like refusing to eat good tasting food, or to have ones dick sucked. Narcotic use is reinforcing in the same way as virtually any other vital or hedonistic behavior; in fact, if opioids did not produce reinforcement, the brain would not "learn" to transmit endogenous opioids (endorphins) in response to pain or injury, thus stripping the body's ability to naturally regulate pain.

The only involuntary component of habitual narcotic use is the biological reinforcement itself, which is merely a motivational factor. The behavior alone, like all other conscious behavior, is mediated completely by the higher functioning brain (i.e. the conscious mind). Simply put, drug use in an "addict" is a choice, mediated by ones own will. For an opioid addict to stop or reduce their use may not be an easy task, just as any reinforcing habit. However, it can be, and is, done by many people. Some may face an eventual crossroads, some may find something which provides greater fulfillment, and some may become tired of the social and financial hassle, while others may sacrifice their habit to the wishes of a loved one.

On the other hand, those who choose to indulge in narcotics have every right to that choice; but would be childish and delusional to play the role of medical "victim" in the face of repercussions of their own poor choices and incompetence. Must I state the obvious by saying that "addicts" use opiates because they find great pleasure in it? It should not be dissicult to grasp that; those who sacrifice much of their world for a drug habit, do so because they find comfort in narcotic induced elation & contentment. Is this news? Value is subjective; what the status quo dictates as meaningless, another will find of great importance. Just as much of the things which popular culture finds essential to life such as money, cars, love and reproducing, is of little to no value to the narcotic dependent.

Does a drug-related addiction last a lifetime?


The answer is much more complicated than a simple yes or no. Bearing in mind that addiction is not a disease, but a deeply reinforced behavioral pattern or habit, the act of habitual drug use can be broken by anyone who chooses to do so.

In terms of the brain - by linking specific behavioral, sensory and environmental stimuli to specific memory storage sites, and further linking emotional processing into the equation, the brain has the ability to form memories, passions, personal meanings and sentiments which remain written into the brain for years to a lifetime. A chronic habitual drug user will likely always have memories of cocaine use, along with their own feelings associated with such memories. Furthermore, their may even remain positive sentiments or passions associated with drug use. This is dependent on one's personal experience with drug use and their own interpretation of the subjective effects of a drug.

On the other hand; other circuitry of the brain has the remarkable ability to revert to its original state of function (i.e. ability to maintain homeostasis). This includes much of the "base brain" circuitry associated with reward, reinforcement and obsession or compulsion. Drug related "psychodependence" - the phenomena which leads one to reward seeking behavior - fades with drug moderation or a period of abstinence. The absence of this phenomenon allows the subsequent habit to be much more easily broken, just as any other obsessive or compulsive habit. Depending on the length of ones habit and ones level of attatchement & reliance upon a given drug, this can take anywhere from weeks to months.

Tuesday, August 2, 2011

Buprenorphine 'Web Forum' Myths


In compiling this entry, I had visualized a simple, user friendly Q&A type series. During the process of attempting to articulate, I've found that a brief, simple explanation is not possible, and I'm reminded of the complex nature of the drug. It's interesting to see how my understanding of buprenorphine has evolved over time; Just as our general understanding of drugs (particularly opioids) and pharmacology evolve over time with research, analysys, and experience. I've become cynical of the web based narcotic use or buprenorphine treatment forums; As there is a frequent patter of anectdote, speculation, and opinion being flaunted as fact. These myths are collectively formed by entire forum-communities and followed religiously - for example, the "less is more" myth which I've dedicated a number of entries to; this type of half truth or speculation is counterproductive to those seeking credible input off which to base a major decision regarding treatment. There is often what I would describe as a "booksmarts or science doesn't apply to real life" type attitude within these communities that the anecdotal or subjective "advice of a user is more credible than that of science or trained physicians". I can not fully express my frustration with such an attitude. I continue to do my best to offer as much credible information as possible regarding bupe treatment and all other narcotics, etc.. Below are some very common myths and half truths regarding buprenorphine, particularly Subutex & Suboxone, along with my response to these myths.

"Using other narcotics while regularly taking buprenorphine will precipitate (i.e. cause) withdrawal symptoms."

False. This is a common misconception by drug treatment clients and uninformed counselors. The commonly available opioids do not have a binding affinity sufficient to compete with buprenorphine at mu-receptors, and therefore will likely have no effect. In higher doses, buprenorphine simply blocks the binding of other opioids due to its high affinity. At doses of 8 to 16mg, mu receptors are near completely saturated.

However; using buprenorphine during a period of regular narcotic use and physical dependence WILL precipitate withdrawal. Buprenorphine's high binding affinity allows it to competitively displace other opioids from receptors, taking their place; when this happens in a subject physically dependent on regular agonists such as morphine or methadone, the limited intrinsic activity of buprenorphine is often lower than the opioid currently used, this net decrease in mu-receptor stimulation is experienced as acute withdrawal. Subjects dependent on high doses of morphine or other strong opioids have the near certainty of precipitating withdrawal if buprenorphine is taken alongside.

"The acute withdrawal phase of buprenorphine is worse than that of morphine, methadone, and other regular agonists"

Neither completely true nor completely false: Acute withdrawal from buprenorphine use is generally much longer in duration and in theory should be significantly less severe (painful) than the withdrawal experienced with other potent opioids. In part this is undoubtedly true, as narcotics with extended half life and slow dissociative properties have shown to produce a lesser intensity of withdrawal upon discontinuation, relative to short and intermediate acting opioids. The logic to this statement that one must keep in mind is that clinical tolerance to buprenorphine is limited by a ceiling or plateau - As intrinsic activity ceases to increase, one's tolerance ceases to progress past this point, and most significantly, physical dependence will not progress beyond this level, even when very high doses are taken. In contrast, clinical tolerance to regular agonists develops consistently with continued use and dose, and as these agents have no real limit to intrinsic activity will continue to grow perpetually.

Now in the case of a habitual user taking potent regular agonists such as morphine or heroin consistently, withdrawal from buprenorphine preceeded by a gradual dose reduction (taper) will be comparatively mild - considering that the minimal daily dose level reached at the end of any prudent buprenorphine taper may go as low as 250 ug of sublingual buprenorphine. A way to put it simply; jumping from buprenorphine at an equivalent dose to other opioids will indeed be relatively mild.

On the other hand, to those with a lower tolerance level, such as those taking lower daily doses of oxy or hydrocodone regularly, may find withdrawal from buprenorphine similarly uncomfortable; however, I have found that many of those who have reported suboxone/subutex withdrawal to be "pure hell", have typically jumped from a typical dose such as 2mg of bupe, often higher. Worse yet, many folks have been advised by a doctor not to bother, or not felt the need to even taper.

Many fail to realize the potency of buprenorphine - a straight jump from 8mg will result in perhaps weeks of intense discomfort; however, compared with jumping from 40mg of methadone the symptoms are relatively mild. This emphasis often put on the mild withdrawal profile of buprenorphine is too often misunderstood; and taken to mean that to simply "stop" taking the medication will pose little difficulty. Wrong.

Ever wonder why those switching from high dose methadone maintenance to buprenorphine must first lower their dose? This as well reflects the relatrively limited agonist activity of buprenorphine. Preceeded by a proper taper of dose, acute withdrawal from buprenorphine is generally quite limited in severity compared to symptoms experienced by a highly tolerant opioid agonist user; Also note that the physical severity of opioid withdrawal may be largely mediated psychosomatically - anxiety and stress related to withdrawal will commonly manifest physically. A negative interpretation or thought process during withdrawal, will excacerbate physiological symptoms; an objective attitude goes a long way.

"After months of regular use, acute withdrawal syndrome from buprenorphine will be substantially worse than with shorter term use."

Not completely true. Once one has reached a steady state blood level, developed a maximal tolerance, as well as physical dependence to buprenorphine, the length of time spent taking the drug will not have any significant effect on severity of withdrawal upon discontinuation. This is assuming that the dosage is at the clinically appropriate level (just above the ceiling, i.e. the leveling off of response to increasing dose)

The only situation in which time would play a role would be in the case that buprenorphine tolerance progressed perpetually with use, having no ceiling.

The only exception to this is the possibility of psychological dependence to the drug, which may develop over time - the psychological component of withdrawal may very well manifest physically.

"The naloxone present in suboxone will cause severe withdrawal symptoms if the drug is injected intravenously by maintenance patients."

Naloxone present in Suboxone only serves to reduce the effect of the concurrently injected buprenorphine, and only does so to an extent. Many often believe the addition of naloxone in suboxone represents a misjudgement on the part of the manufacturer, while others believe the naloxone was intended simply for deterrent rather than literal purposes. This is not the case; the naloxone was intended to reduce the "high" of the drug if injected, by counteracting much of the dose. Additionally, the amount of naloxone in one dose will not displace the high levels of buprenorphine already saturating the opioid receptors in regular users.

The sole purpose of naloxone in the drug is to significantly reduce the effects of and IV administered dose. Nothing more. Naloxone plays negligible role in the ability of suboxone to precipitate withdrawal in users dependent on regular opioids; injected or otherwise. It is buprenorphine which does this by antagonizing currently bound opioids to take their place (hence the label 'mixed agonist/antagonist); Acute withdrawal may therefore be caused due to its comparatively mild intrinsic activity. Use of the buprenorphine only product (subutex) by a currently opioid dependent individual will precipitate withdrawal the same as Suboxone will.

Despite a degree of interference from the naloxone, some individuals report experiencing a degree of agonist type subjective effects upon IV injection of suboxone, and are liable to experience respiratory depression along with all other side effects of opioid agonists. IV use of subutex in these same individuals will produce these effects as well, and most likely to a greater extent.

Naloxone present in suboxone may affect the activity of unbound concurrently administered buprenorphine to a degree, which explains the buprenorphine/naloxone combo providing less narcosis than buprenorphine alone in studies.