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").

Sunday, October 30, 2011

Racemorphan: Evidence Based Overview

Who else would love to try this? I wonder what type of rush it would give when injected via IV route...

Synthetic opioid of the morphinan type. Chiral mixture of both levorphanol and dextrorphanol. Also referred to as morphanol.

Multiple modes of action as a narcotic mu agonist, NMDA antagonist, sigma agonist, and a serotonin & norepinephrine reuptake inhibitor.

Roughly half as potent as levorphanol, or about 2 - 2.5x as potent as morphine. 4-5mg intravenously is equianalgesic to 2mg levorphanol and 10mg morphine (IV route). 8 - 10mg orally is comparable to 30mg morphine.

Can be (and has been) given by almost any route: oral, rectal, SC, IM, IV.

Very effective pain reliever. May be superior to morphine in cancer and neuropathic pain. Single doses of 5mg parenterally (IV or IM) have generally speaking, been effective for almost any type of pain - to include cancer and post-operative pain. Suppression of severe cough can be achieved with 2 - 4mg subcutaneously.

Longer acting than morphine with effects which range 6 - 12 hours, depending on dosage and ROA. Even parenteral doses have provided effects for up to 12 hours, or up to 18 hours post operatively when given intravenously as a supplement to nitrous oxide anaesthesia.

Has been observed to have strong sedative tendencies in some cases, due in part to NMDA blocking activity.

Side effect profile is similar to morphine. No significant difference in respiratory depression. May cause less itching and constipation than morphine.

Tolerance development is slower than that of morphine in most cases - comparable with levorphanol, methadone, or other long acting, NMDA active opioids.

Substitutes completely in morphine addicts and fully suppresses morphine abstinence symptoms. Dependence potential is high.

Subjective effects are similar to those of other mu agonists. Injections in post-morphine addicts produced morphine-like euphoria, sedation, relaxation, and requests for more of the drug. One author reported 7.5mg racemorphan produced subjective effects comparable to 30mg morphine, both parenterally. Euphoria is most pronounced by the IV route, onset is slightly delayed compared with morphine.

Tuesday, October 25, 2011

Is Opiate Addiction Really an Epidemic?

How do you define "epidemic"?

The bubonic plague wiped out (killed) 25 million people - One-third of Europe’s population.

The Irish famine of the 1800's led to the death of roughly one million people out of a population of eight million; for those who can't do the math, that's 1/8th of the country's population, wiped off the face of the earth (as opposed to 1/16,735th of the population struggling with a bad habit, which seems to be an appealing alternative).

Over 40 million people around the world are currently HIV positive. In the year 2003, 5 million people became infected with AIDS.

All would most likely be considered epidemics by most standards; especially considering our popular definitions for the term, as follows...

"A widespread occurrence of an infectious disease in a community at a particular time"

"An outbreak of a contagious disease that spreads rapidly and widely"

"Spreading rapidly and extensively by infection and affecting many individuals in an area or a population at the same time"

Now in regard to opioid addiction and abuse --

This phenomenon is not contagious, does not catch the affected individual off gaurd, does not inevitably sicken, harm, or kill anyone (as does influenza or smallpox), and most importantly, is not in itself a pathology but a deliberate and consentual behavior in which participation is completely up to the affected user. Furthermore, it is reported that about 1 to 3 out of 100 individuals become opioid dependent solely as a result of prescription use. It has also been observed that 80 percent of OxyContin abusers have a previous history of cocaine abuse, and that less than 2 percent of americans report using heroin at any point in their lifetime.

Considering the proper definition of a true "epidemic", and considering the aforementioned statistics, I feel strongly that those who insist that the current trend in narcotic addiction constitutes a disease epidemic, are distorting reality when they speak so hyperbolically. Only an alarmist with an agenda would suggest such a thing. Only "recovery" industry capitalists, underfunded law enforcement bureaucracies, and self deceiving drug users would embrace and such a perception. Conceptualizing narcotic drugs as if they were living baccili while treating their use as an infection which someone somehow "catches" and is hopeless to control or change has created an ideological platform in which self autonomy and personal responsibility are ignored and abandoned, with counterproductive consequences.

One could assume a contributing factor to the high rate of actual narcotic addiction in our present time is the very removal of social stigma towards casual drug use. The failure of the addicted individual to take drugs moderately and responsibly is no longer considered a poor choice to be changed, but rather a chronic illness to "surrender" to and have treated by others - essentially putting the addicted in the position of powerless, hapless medical victim. Compound this with the law of self-fulfilling prophecy, and the learned helplessness instilled by the mainstream approach to "recovery"; and you're likely to see greater rates of problematic opioid use, with characteristic overdoses, and self-indulgent binging by those who have been conveniently absolved of all perceived accountability and self-empowerment, having been convinced that "those ill-intentioned drugs" or "the disease" made them do it.

This indeed might ameliorate a large degree of guilt and shame - I myself have dealt with my own problematic habits and can surely understand the relief one might feel by abandonding all sense of responsibility or power to change, and becoming a medical 'victim'. But this surely is not the case.

What we have here is not an opiate addiction epidemic, but rather an epidemic of social misguidance and mass scale rationalization. Perhaps we fight the drug problem by empowering individuals to make positive choices and better control their own lives; and by rethinking our perspective on the very nature of drugs, drug use, and addiction.

Just my thoughts. What are yours?

Monday, October 24, 2011

The RX Drug Epidemic: Putting It Into Perspective

US Population in 2007: 301,231,207

Overdose Deaths for All Drugs in 2007: 27,600 (Over 1/2 from opioid RX drugs)

To overestimate and assume 2/3 these deaths were from prescription opioids, the grand total for annual RX opioid deaths comes to 18,400. So considering the following...

That 1 in 16,371 died from an RX opioid overdose, and 1 in 10,914 died from a drug overdose;

...One would have to conclude that creating mass public hysteria by claiming that overdose deaths due to opioids, or any drug for that matter, is a national crisis, is nothing short of alarmist and delibrately misleading.

And interestingly enough, seeing that americans consume 80% of the world's pharmaceutical opioid supply, we're actually seeing the very worst of the issue.

I'm not suggesting that opiate related harm such as addiction and death is not a problem, it certainly is. I'm simply suggesting we set our perception of the issue straight, that we avoid a disproportionate social response which might create and worsen more problems than it sets to attenuate.

Let's compare some other deaths from 2007, also related to lifestyle risks:

Heart disease: 616,067 (Most caused by eating habits, i.e. food addiction)

Chronic lower respiratory diseases: 127,924 (Smoking causes many cases)

Cancer: 562,875 (Often largely brought on by various carcinogens present in foods, sunlight, smoke, preservatives)

(Compared to 27,600 drug overdose deaths & 18,400 of these related to opioids)

All overwhelmingly outnumber opioid abuse related deaths. If we were to legislate away lifestyle risk associated with these conditions; fast food, high fat food and smoking would be illegal.

The mass hysteria and bureaucratic crackdown seem yet further obsurd when considering that the vast, vast, majority of these opioid deaths are a result of delibrate & grossly negligent, or non-therapeutic opioid use; Furthermore, a majority of these opioid related cases are not even caused solely by opioid use, but rather by the concurrent abuse of alcohol, benzodiazepines, illicit drugs, and other intoxicants. Deaths caused by opioids alone, not to mention deaths involving medically sanctioned opioid use for the treatment of pain, are far less common than most alarmists would have us believe.

The entire notion that opioid abuse, addiction and overdose has become an epidemic is largely reliant on the assertion that opioid abuse and addiction, like heart disease or the bubonic plague, is involuntary. And to those perpetuating the pseudoscientific claim that opioid abusers are victims and can not help themselves; such mindless rhetoric has been adressed many times here before, and is not even worthy of being acknowledged. The notion that "drugs themselves addict users" and addicts cannot control their behavior is nothing more than the product of religious propaganda, age old superstitions & voodoo pharmacology.

Drugs are inanimate & insentient entities.

They are neither good nor evil. They do not inevitably cause harm. Drugs are not contagious. Drugs cannot destroy will power or decision making ability. Drugs have no inherent willful powers and are incapable of acting on their own. Drugs do not attack, destroy, or infect individuals and drugs do not infect communities.

Some try to reason: "No one as a child ever aspired to become addicted to drugs, therefore addiction is a disease, it's something they catch from drugs, they must be helpless and unable to control themselves"

To this I say: No one as a child aspires to become a janitor; this does not mean they don't make the choice to accept the job, and does not make "janitorialism" a disease. No one as a child dreams of becoming obese; this does not mean they don't choose to overindulge in food, nor does it make gluttony a disease. No one as a child aspires to becoming a felon; this does not mean they couldn't help but rob, steal, or kill.

We should be approaching this problem with truthful education. We must 'rebuild and maintain' rather than limit, our allowance of individual choice, while emphasizing individual responsibility and good decision making.

Data Source: http://www.cdc.gov/nchs/fastats/lcod.htm

Food For Thought: The Parallels of Drug Policy & Social Climate

In analyzing the history of US drug policy we can see that the past and current patterns of drug legislation are very much reflective of the current social and political climates of our country. Looking back at some of the landmark "acheivments" in drug prohibition - such as the Harrison Act, the Marijuana Tax Act, the Rockafeller statutes and the Controlled Substances Act - drug policy patterns are consistent with the current fears, insecurities, cultural or racial tensions, and hostilities of the commonfolk.

Sunday, October 23, 2011

Drug History Timeline Pt 1 (Opium War Era)


Opium first arrives in China


Britain dominates the opium trade - Most of Britain's opium originates from British colonial plantations in India.

Period of widespread opium use & habituation in China

Morphine is first isolated from opium (1804)

Slavery ends in the Northern US (1804)


Romantic writers sensationalize opium through dramatic poetry & literature (1820's)

Thomas DeQuincey publishes a romanticized account of his opium use when he publishes "Confessions of An English Opium Eater" (1821)

Merck of Germany begins marketing morphine (1827)


Codeine isolated in Europe by French chemist, brought to market as a mild antitussive & analgesic with less dependence producing properties than morphine (1832)


Chinese/British Opium War (1839-1842)

Invention of the hypodermic needle (i.e. syringe), represents a major breakthrough in medicine and drug administration. (1840's)

A Doctor in Edinburgh discovers the efficacy of injecting morphine directly into the bloodstream, using the newly invented syringe. This will change the way morphine is used for therapeutic and casual purposes. (1843)

Next Section Here (Yellow Peril Era)

Origins of the Alcoholic & Addictive Disease Myth

The disease concept of addiction originated with the temperance movement during the 19th century with a man named Dr. Benjamin Rush. Rush had speculated that those who drank alcohol excessively were 'diseased'. Dr Rush - whose deep anti-drug sentiments would eventually lead him on a passionate anti-alcohol crusade - used his disease idea to promote a prohibitionist political campaign. Interestingly enough, this very same Dr. Rush had also characterized several other medical disorders or diseases, including dishonesty, political dissent, and 'african-americanism' (i.e. being black).

The disease propaganda grew, and was endorsed by the newly established religious cult of A.A; which interpreted its 12-steps from the Oxford religious Group which had actually created this very same series of 'steps' for becoming free of sin.

The disease theory was heavily pushed by a devout 12-stepper named Marty Mann and backed by a dubious scientist by the name of E.M. Jellinek, who was happy to falsify research using a group of drunks who had been handpicked by Mann (the 12 stepper). He was later asked by officials of Yale University to refute these findings which had not stood up whatsoever to scientific scrutiny. However not before the disease theory was eagerly capitalized upon by the American Medical Association (AMA), setting the stage for what would become, and to this day remain, the multibillion dollar annual "treatment" industry.

To this day, the disease concept of addiction has not been supported by any factual research, and remains recognized by the DSM owing to the progressive semantic elasticity of major medical & public health organizations.

For more on the origins of the Dr. Rush's disease rhetoric & the multibillion dollar recovery industry, check out the following article:

Wednesday, October 19, 2011

MDMA (Ecstasy) Vault


MDMA is one of the most widely popular recreational drugs in the world. It is an amphetamine derivative with stimulant and enactogen properties.


MDMA was origninally synthesized in 1912 by Merck, the German pharmaceutical firm. The pharmacological properties of MDMA were initially overlooked, as it had been specifically patented as an intermediate in the production of a haemostatic drug called methylhydrastinine.

In the 1920's it was observed that MDMA had effects on blood sugar and smooth muscle tissue that were similar to those of ephedrine, while in the 1950's, the US Army conducted toxicity and behavioral studies on animals injected with mescaline and MDMA.

The US government experimented with MDMA, among other drugs (including LSD) and sensory deprivation techniques, as an interrogation tool in Project MKUltra. The findings of these investigations were eventually declassified and made public in 1973.

In the US, MDMA was being taken recreationally in the early 1970's. In the mid 1970's, psychopharmacologist and drug chemist Alexander Shulgin synthesized MDMA and used the drug himself. He later published a paper with David E. Nichols documenting the psychoactive effects of the drug in humans.

In his process of advocating for the use of MDMA, Alexander Shulgin introduced the drug to a psychotherapist colleague named Leo Zeff. Zeff was intrigued with the tendency of the drug to promote open communication and empathy in patients during therapy sessions, and later came to popularize its use as a psychotherapy tool.

It was in the 1980's that MDMA became a popular drug in the nightclub scene and rave culture. It was sometimes referred to as "Adam", while its N-ethyl substituted homologue MDEA (methylenedioxyethylamphetamine) was referred to as "Eve". By the mid 1980's its casual use had become mainstream - the DEA responded by proposing its inclusion among other illicit drugs as a schedule I controlled substance, with no exception for clinical use.

The BBC reported in 2010 that MDMA use in the United Kingdom had declined in recent years. This could be due to substitution with other substances misrepresented as MDMA, or also due to the availability of newer analogous chemicals such as methylone, mephedrone, and 2C-I.


MDMA is a shortened abbreviation for the chemical name methylenedioxymethamphetamine. MDMA is closely related to methamphetamine. MDMA differs from methamphetamine at the molecular level with the presence of 2 oxygen atoms (conncected to positions 3 and 4 of the benzene ring) which are bound together by a methylene bridge (a carbon atom bount with 2 hydrogen atoms and connected by two single bonds with two distinct atoms, in this case being oxygen atoms).

A popular method of MDMA manufacture utilizes a compound called safrole as a precursor - safrole is derived from the root-bark or the fruit of sassafras plants, and contains the methylenedioxyphenyl backbone used as a starting point to produce MDMA.

Most available MDMA is the racemic mixture containing both dextrorotatory and laevorotatory enantiomers. The dextrorotatory enantiomer is slightly less active than the laevorotatory enantiomer; showing a weaker effect on dopamine release, but with a somewhat longer half life. 

Most MDMA is supplied through illicit channels and has been manufactured in the clandestine setting. Illicit
MDMA is often sold as a pill or powder. The compressed, tablet form of the drug is often referred to as ecstasy, X, or E. When in the form of a pure powder or capsulized powder, it is often referred to as molly, or M.

MDMA remains one of the more frequently used recreational drugs in the US (and in the rest of the world). A 2008 survey by the UN estimated a similar number of past year MDMA users as cocaine and opioid users, however this number was dwarfed by that for past-year marijuana users.

MDMA is taken in the casual setting as well as the social setting, and is often distributed at music festivals and raves alongside other enactogens, psychedelics, or dissociatives, which may include 2C-I, LSD, and ketamine.

MDMA is criminalized in many countries, under the UN's Convention on Psychotropic Substances. It is also, in most cases, illegal even for clinical use. However, there are some private therapists who administer MDMA to their patients in a clandestine setting (such as their office at home). Also, MDMA is being investigated for clinical use as a treatment for post traumatic stress disorder and other anxious conditions.

In the recreational setting, MDMA is usually available in tablet, encapsulized powder, or free powder form. It is usually taken by the oral route. It is less commonly adinistered by intranasal, rectal, and intravenous routes.

Effects are apparent around 30-90 minutes after oral administration and last a few hours to several hours, with after-effects lasting up to 24 hours. Typical doses range from 100-200mg when the drug is taken orally. Erowid.org lists a threshold dose of about 30mg, with a "heavy" dose being 200mg or higher.

Mode of Action:

Effects of MDMA are most likely due to increases in synaptic dopamine, norepinephrine and serotonin activity. MDMA promotes the "release" of these neurotransmitters and inhibits their reuptake by reversing the flow of monoamine transporters (i.e. reuptake pumps) - this reversal of transporter function is a process known as phosphorylation. MDMA elicits weak agonist activity at serotonin receptors and also at the Trace Amine-Associated (TAAR-1) Receptor; which is involved in monoamine transporter regulation. The major active metabolite MDA contributes to the effects of MDMA, particularly as a serotonin (subtype 1 and 2) receptor agonist.

Its empathogenic properties are aossociated with its action as a serotonin-releasing agent, and have been hypothesized to be linked in part with 5HT-induced oxytocin release, the latter of which serves as a hormone involved in the hard-wiring of emotional attatchments between a mother and fetus during pregnancy & childbirth.

Racemic MDMA has a half life of about 8-hours.


Psychological effects include a euphoric state or mood lift, enhanced tactile perception (i.e. perception of touch), altered visual perception (i.e. enhanced sense of color, etc), CNS stimulation (feeling "speedy"), social disinhibition, stronger empathetic tendencies, changes in ego, enhanced appreciation for music, increased motivation, grandiosity, analgesia (i.e. reduced pain perception).

Physiological effects include increased heart rate, thermal dysregulation, involuntary eye movements, dilated pupils, jaw clenching or grinding, perspiration, dehydration, nausea & vomiting, headache, dizziness, shortness of breath, erectile dysfunction, and trouble acheiving orgasm.

Adverse side effects may include depression, anxiety, paranoia or fear, amphetamine-psychosis, serotonin syndrome, neurotoxicity, cardiac arrhythmias, cardiac arrest, and seizures.

Related Compounds:

MDMA is just one compound of a larger series of methylenedioxy substituted amphetamines and cathinones which have been sold as grey market research chemicals and designer drugs. Drugs of this series include MDEA ("Eve"), methylone, ethylone, butylone, and MDPV.

Monday, October 17, 2011

A Tribute to L-Dromoran

Levorphanol is known by the chemical name (L)-3-hydroxy-N-Methylmorphinan, or its generic name Levo-Dromoran. L-Dromoran is a member of the morphinan family. It is a fully synthetic analogue of morphine - containing the structural characteristics essential for morphine-like action (i.e. the N-methyl & 3-HO) - but omitting a number of morphine's other features. Levorphanol is only one modification away from the bare bones morphinan structure (N-methylmorphinan, off of which its entire class is based); this modification being specifically, the addition of the phenolic hydroxyl, which is essential for morphine activity. Its closest morphine derived relative is actually desomorphine, which is slightly more potent than levorphanol itself, and differs only with the presence of an oxygen bridge (i.e. the root of the prefix epoxy, in 'epoxymorphinan'). This is the key difference which sets the morphinans apart from the classical morphine-codeine family.

Levorphanol was originally marketed as an alternative to morphine for severe pain, and was a succesful painkiller during its era (1950's thru 1970's), and was utilized in the original research which led to the discovery of opioid receptors in the 1970's. With the release of newer opioids to market, the increased use of methadone for pain, and the introduction of sustained release preparations of existing opioids; much attention was fixed upon the newer products, leading to a decrease in its popularity. Once the brand name was discontinued, levorphanol became (and has remained) relatively obscure up to present.

The drug is still available generically, currently as the oral form only. But while research has shifted toward atypical analgesics and more of a novel approach to pain, a narcotic with multiple modes of action is a prime candidate. Levorphanol has been around for a while, but many are rediscovering its value as a painkiller and euphoriant - this includes doctors, researchers, patients & users, even clandestine hobby chemists, who acknowledge the relatively practical/rudimentary nature of synthesis, for this class of synthetics.

One might speculate that L-Dromoran is superior to morphine in the following respects:

A low(er) capacity to induce tolerance

An enhanced action on descending inhibitory pathways

Its multi-modal synergystic properties

Actions against hyperalgesia

Its unique applicability to severe chronic pain including cancer-related and neuropathic pain.

Its long duration of action and accumulative phartmacokinetic properties; when dosed correctly this accumulation allows chronic doses to be reduced to as little as half the induction dose.

Often better tolerated than morphine, with less nausea & vomiting, pruritis, constipation, and very little to no clouding or sedation.

Its Pharmacodynamic Mechanisms of Action (A lower numerical value indicates a higher binding affinity for a particular site)

Very high affinity mu agonist - 0.21nM

High affinity kappa agonist - 2.3nM

Moderate affinity delta agonist - 4.2nM

High affinity NMDA antagonist - 0.6uM (methadone is 6.0uM, ketamine is 0.8uM)

5HT (i.e. serotonin) reuptake inhibitor

Norepinephrine reuptake inhibitor
For Some Good Literature on Levorphanol Tartrate:

Saturday, October 15, 2011

All About the Bentley Compounds

It may not seem like much, but trust me, I've worked many hours to piece together enough information for a relatively minor overview of the Bentley family of opioids; specifically focusing on Etorphine, Buprenorphine & Dihydroetorphine. Short of scouring the depths of the web for days (with dozens of sources), you won't find much of this information so conveniently summarized - anywhere else. Consider it a few steps up from Wiki. Any sources I've used relating to the Bentley's are listed on my reference & further reading page.

The Bentley Compounds

Opioid analgesics were a major focus of research during the late 1950's and early 60's. Several years before Paul Janssen and his colleagues would discover the fentanyl family, Kenneth Bentley and his team identified some 200 compounds derived from thebaine, known as the orvinols. The orvinols are popularly referred to as the bentley compounds. The bentley's are built off of the O-demethylated product of thebaine - oripavine. Oripavine occurs naturally in poppy straw concentrate, as a degradation product of thebaine.

From Thebaine to Oripavine (Top)
Oripavine plus C-Bridge (Bottom)

Chemically, bentley compounds are 'diels alder' reacted adducts of thebaine, also derived from oripavine, the compound off which the orvinols are chemically built. They are molecularly known as the endoetheno-tetrahydro-oripavines. It is important to note that both thebaine and oripavine are phenanthrene opiate alkaloids of the epoxymorphinan type, with a similar structure to morphine and are considered semi-synthetic morphine-type opiates. However, they are unique from morphine in that they have an endoetheno bridge at the C-ring, and any one of a number of alcoholic substituents branching from C-7.

The bentley's include over 200 identified compounds, each with varying potency and activity. The more common compounds range in potency from several to several thousand times stronger than morphine. The intermediate orvinol structure differs from oripavine only with the addition of the C-bridge - it is roughly 40x more potent than morphine; and the addition of a C-7 substituent further increases its potency.

As with other morphinan opioids, a methyl group off of the tertiary nitrogen is ideal for mu-opioid efficacy. Most other nitrogen substitutions elicit major changes in intrinsic activity or binding affinity; changes include reduced agonist activity, zero agonist activity, partial agonist activity, or mixed agonist/antagonist activity.

Etorphine (Fact Overview)

Discovered in the early 1960's.

Effects similar to morphine. Analgesia, catatonia, constipation, respiratory depression, initial excitement, and sedation.

Takes effect within minutes of injection, peaks after 15 to 30 minutes. Analgesia and sedation last 30 to 60 minutes in animals.

Produces euphoria & reward. Presumed to have a high abuse & addiction liability in humans.

Very effective as a painkiller. 1,000 to 4,000x more potent than morphine as an analgesic, depending upon the clinical setting. A dose of 0.0025 to 0.01 mg (or 2.5ug to 10ug i.e. micrograms) would be roughly as active as 10mg morphine by injection. Lethal dose for an adult human will range from 30ug to 120ug.

One of the least subtype-selective opioid agonists in use.

High affinity for mu and kappa receptors, moderate affinity for delta receptor; agonist at all three.

Also referred to as 'M-99' or Immobilon in the veterinary setting. Used on large game animals as a tranquilizer and anaesthetic.

Because of its potency, M-99 is always supplied alongside its antidote, diprenorphine (or Revivon), an ultra potent opiate antagonist, and also a bentley compound. In case of human exposure, diprenorphine reverses an overdose.

International legislation barred etorphine for use in humans unfortunately. Its 7,8 dihydro derivative is currently used in humans, and is several times more potent. John Lewis, a former researcher with Bentley, has speculated that etorphine may have had success as a human product, had it been marketed differently:

Immobilon (i.e. Etorphine Hydrochloride)
"The popular scientific press were excited by news that doses of a few milligrams of etorphine could immobilize an elephant or rhinoceros. This turned out to be very bad publicity for etorphine for it convinced the World Health Organization (WHO) that etorphine was extremely dangerous and therefore should be controlled in Schedule 4 of the Single Convention, the most restrictive level of control. At about that time, fentanyl, a synthetic opiate of not dissimilar potency to etorphine was being developed by Paul Jannsen as an intravenous anesthetic for human use. Fentanyl and its analogs have been huge commercial successes whereas etorphine, which I’m sure could have been an equally successful clinical anesthetic, has had very modest sales as a veterinary anesthetic. I think we must conclude that etorphine arrived too early for the consumer marketing people of Reckitt to appreciate how it should be commercialized."

J. Lewis - Former Researcher with K W Bentley's Team - From his lecture at the 'Nathan B Eddy Award Ceremony' explaining the history of the Orvinols, i.e. Bentley Compounds

Dihydroetorphine (Fact Overview)

Ultra potent opioid agonist. Reletatively selective for the mu receptor, with high affinity and efficacy. 1,000 to 12,000x more potent than morphine and 2 to 13x more potent than etorphine, depending on the method of measure.

Elimination half life of 30-40 minutes (~38min); analgesia lasts 1-2 hours depending on ROA and dose - requiring dosing intervals of 1 to 3 hours when given in its traditional form.

Used as an analgesic in humans in China. Like bupe, DHE is poorly absorbed orally. It is given by injection, sublingual or buccally, or transdermally. Sublingual doses of 20 to 180 ug are fully analgesic and produce relatively mild side effects. DHE in a long acting transdermal patch has been shown to relieve pain for up to 32 hours with minimal side effects.

Produced potent reward & reinforcement in studies, but is believed to produce a lesser ratio of euphoria to analgesia than does morphine or heroin. Though it is obviously a more potent euphoriant than morphine by weight, it may carry a lower addiction liability in equivalent doses.

Reportedly has been used in opiate substitution therapy, with positive results.

Available in sublingual tablets of 20ug or 40ug. Or as solution for injection containing 20ug/ml dihydroetorphine hydrochloride. Transdermal patches available (dose range??)


In 1966, researchers had synthesized a compound which was reserved the name M6029. M6029 was an N-subtituted orvinol which would later become known as buprenorphine (i.e. bupe). Bupe was a typical bentley opioid, similar in structure to etorphine, but was substituted with a nitrogen-cyclopropylmethyl as opposed to the methyl. None the less, it produced potent antinociceptive effects, 33x stronger than morphine.

As it turned out, the CPM group of bupe created a mixed agonist antagonist - with partial agonist activity at the mu receptor, antagonist activity at the kappa receptor. Unlike other mixed agonist antagonists at the time, buprenorphine produced no dysphoria - while drugs such as pentazocine and butorphanol were agonists at the kappa receptor and thus likely to produce dysphoria, bupe was an antagonist at kappa receptors.

Also, being a bentley compound, bupe retained a significant deal of potency even with the N-CPM substituent. As a potent mu-receptor partial agonist; It activated the mu receptor in relatively miniscule doses, until reaching a plateau in dose-effect. In doses below the ceiling, it acted just as any potent full agonist would, but did so at a microgram dose. Only 0.3mg of IV bupe was equal to 10.0mg IV morphine in its pain relievieffectng . More recently it has been found that the ceiling for analgesia occurs at around 2 to 4mg of sublingual buprenorphine (or roughly 0.6 to 1.2mg IV). The ceiling for other agonist type subjective effects (euphoria, narcosis) occurs higher, ranging between 4mg and 32mg.

Friday, October 14, 2011

"Why Medicate Pain?"

Many who crusade against the practice of chronic opioid therapy are suggesting that people in pain can and should simply come to terms with suffering. And even go so far as to suggest it may be "good for them" or "good for the healing process".

Religions and subcultural groups throughout history have often objected to palliative-oriented treatments which were aimed at treating symptoms rather than a cause; even when the latter was not possible. Some believed that pain was a crucial part of the body's healing process, while others believed pain was god's way of sending a message or punishment.

There is an anti-narco attitude which is prevalent throughout the christian community and was/is likely rooted in the judeo-christian notion that suffering or pain was a testing of one's faith, or was symbolic of the pain and sacrifice of jesus christ; That to avoid pain was an act of cowardice or sin, a lack of faith, an act of disrespect to god. Pain aside, this idea applied to any form of aversive experience, physical or emotional.

To this day there remains the puritan belief that there is something inherently wrong or immoral about altering one's consciousness, to supress negative experience with a drug. This is all too apparent in society's attitude toward not only illicit drug use, but also the use of antidepressants, antipsychotics, and other psychotrophic prescription drugs. It is perhaps most apparent with society's degenerative attitude toward the opioids.

"How long will we set aside while our family told these lies that they can't deal with a little pain? You have to give yourself time to heal, not dope it up so you don't feel!" ~Anti Opioid Crusader (grammatical errors are left unchanged to help characterize the credibility of the source)

Such statements demonstrate the scientific illiteracy of such an attitude. Such individuals are speaking purely from superstition or ignorance; as they have no actual understanding of how pain and the human nervous system works. So, why do we treat the symptom of pain in itself?

Pain retards the body's healing process. Pain itself elicits additional pain. When pain over an extended period is not supressed (and instead is simply 'dealt with'), pain circuits of the sensory nervous system undergo an adaptive neuroplastic process of potentiation, causing the pain-flow to continue even after the source of the pain has healed. At this point, the pain has become a serious chronic disorder of the central nervous system; Researchers now classify this as a disease state, which by this time has become completely unrelated to the original condition or injury.

Untreated chronic pain is likely to cause depressive disorders, hypertension, aneurysm, stroke, heart attack, and premature death - take Sean Reynolds for instance (google it). Opioids prevent acute pain from becoming a chronic condition, and facilitate the body's natural healing process.

Opioid treatment on a long term basis is not simply a means of "covering up the pain"; but serves multiple purposes. Aside from blunting the perception of pain, which - by the time they are initiated - has become a self-perpetuating chronic condition, opioids achieve the following:

Restoring mobility, physical function & employability (and thus independence)

Improving mood and cognitive function

Restoring balance in mood, sleep, and eating patterns

Improving the daily quality of life for the user or patient

Evidence Continues to Shatter the Accidental Addict Myth

A recent piece of literature states:

"Less than 3 percent of painkiller addicts initially become addicted from their medical prescription for legitimate pain."

"80 percent of OxyContin addicts have previously taken cocaine."

This here further serves to further discredit the "accidental addict" myth - the tale of jack or jane who has never so much as taken alcohol, who develops a painful condition and "gets addicted" (as if it's something that one just catches from a drug) due to pressure from a pill pushing doctor (which doesn't even make sense seeing as with the exception of Florida, most physicians are increasingly apprehensive to prescribe even codeine, and even in the case of Florida, not even the most unscrupulous doctor is "pushing" anything on the patient, who generally seeks out the drug deliberately).

I'll say it again - In patients without a history of recreational drug use or addiction, the vast majority of those who begin opioid therapy secondary to an injury do not become "drug addicts" through narcotherapy, whether acute or long term.

Most addicted prescription opioid users have had histories of illicit or casual drug use prior to beginning  opioids - Which we can speculate is in large part because it is primarily these same casual drug users who seek a supply through pseudo-legitimate means (i.e. legal means).

Might I add that recently, propagandist & anti-drug crusader Larry Golbom cited this aforementioned statistic on his radio show in a way which implied that the 3% figure is actually alarming - which if you ask me is simply an instance of flash and trash propaganda - which is basically, the use of figures or statistics presented to an audience of lay-people, conveyed in a manner which allows the propagandist to conceptualize the figure in whichever manner supports his rhetoric (even to mean the opposite of what it actually means); To put it simple; an instance of flash & trash might be a speaker (Larry G) who presents what is actually a very low figure (3%), but articulates it in a way in which to convince the audience that it's a shockingly high figure (i.e. epidemic proportions); thus worthy of a great deal of concern, and therefore adding an illusion of credibility or supporting evidence for his cause.

Tuesday, October 11, 2011

Buprenorphine Vault (Subutex, Suboxone, Buprenex)


Buprenorphine also known as Bupe, is a semi synthetic opioid analgesic. It may be produced from thebaine, but is typically derived from a similar opium alkaloid, oripavine.

Having not been well known as an analgesic in the US, buprenorphine in recent years has gained popularity for its newly approved use in detox and substitution treatment of narcotic dependence.


Buprenorphine's classic role has been as a strong analgesic for both inpatient and outpatient use. It is used by parenteral routes (primarily IV/IM), as well as the transdermal (patch), or sublingual route (tablet), - The typical dose being 200 to 400ug sublingually, and 100-300ug IV/IM.

For fast acting "as needed" management of pain for the outpatient, the drug is supplied as a solution for IV/IM injection in 0.3mg single dose vials - by the brand name Buprenex. Or by 0.2mg or 0.4mg sublingual tablets - by the brand Temgesic. The short acting products are not commonly encountered on the 'unapproved' market, but are commonly used as a breakthrough medication in chronic cases of moderate to severe pain, malignant or non - physicians & certain patients may prefer buprenorphine due to its limited side effects and low-dependence liability, and its efficacy in resistant or atypical types of pain; including migraines and possibly neuropathic pain.

TransTec - buprenorphine dermal patch
(used in Europe for treating chronic pain)
Buprenorphine has become recently available in the form of a long acting transdermal patch, marketed by Purdue Pharma as "BuTrans". The butrans patch is applied dermally and provides a steady flow of buprenorphine for 7 days. The patch is available in 3 doses; engineered to realease buprenorphine at rates of 5ug/hour, 10ug/hour, and 20ug/hour. These doses are relatively low compared to the european equivalent, which is available in doses up to 70ug/hour. This could be seen as overly cautious on the part of the manufacturer and/or nanny-state regulatory agencies. BuTrans is indicated for the treatment of moderate to severe chronic pain in cases that an opioid is appropriate, and may be supplemented with atypical analgesics and fast acting buprenorphine for breakthrough pain. BuTrans may be safely used in opioid naiive individuals.

For individuals switching from opioid full agonists such as morphine; a waiting period of 24 hours (allowing for moderate withdrawal), may be reccomended before beginning higher doses of buprenorphine, specifically doses greater than 1-2mg (which may rarely be used in the treatment of pain).

In recent years, high dose buprenorphine has become popular for its efficacy as a casual office based maintenance treatment for opioid dependent individuals. It offers a convenient alternative to methadone maintenance due to its ability to be prescribed for outpatient use by any registered physician. The drug is marketed in a high dose (milligram) product and is available in various formulations. Subutex contains buprenorphine alone, as a sublingual tablet in doses of 2mg or 8mg. Suboxone contains both buprenorphine and the opioid antagonist naloxone, in a 4 to 1 ratio, as both sublingual tablet or a fast dissolving film-strip - in doses of 2mg buprenorphine w/ 0.5mg naloxone, or 8mg buprenorphine w/ 2mg naloxone. The addition of the opioid antagonist is intended as a deterrent to IV misuse of the product - Evidence suggests buprenorphine with naloxone in a 4/1 ratio produces less desired effect than buprenorphine alone when injected. The Suboxone formulation is therefore preferred by most providers.

Buprenorphine is frequently used in opioid "detox" protocols. The idea is simple; rather than abrupt withdrawal, a long acting opioid (buprenorphine) is taken in gradually receeding doses over a period of anywhere from 7 days to 3 months. For temporary detox purposes, a 5 to 7 day taper is highly reccomended; allowing the buprenorphine to be discontinued before any real degree of dependence develops. Using buprenorphine short term, the worst of withdrawal is mitigated, allowing a patient to return home or receive "rehabilitative care".

The idea of buprenorphine maintenance treatment is similar to that of methadone maintenance; and both are best exlained as harm reduction based approaches to addiction. With access to a legal alternative opioid, addicted individuals are relieved of the financial, social, and legal burdens of an illicit habit, not to mention the health risks involved with such a lifestyle. By providing a pharmaceutically pure, long acting opioid that is taken once or twice daily, the addicted person's drug habit will makes profoundly less of an impact on their daily lives; becoming a no more remarkable or significant part of their lives than the regular cup of coffee is to the lives of others. The physical dependence on opioids is rendered irrelevant so long as the medication is taken consistently. The less frequent dosing offered by buprenorphine provides the additional benefit of lessening the consistency of 'dosing behavior', perhaps leading to a lesser fixation on drug-taking and promoting a change in associated habits.

Buprenorphine, like methadone, maintains the user in a stable physiological & psychological state due to its extended duration; by preventing the occurence of opioid withdrawal syndrome and providing a level of reinforcement, which promotes compliance and satisfies users with this treatment (reducing likelihood of "treatment retention" or failure). Once stabilized on buprenorphine, opioid users are far more likely to function as socially engaged and productive individuals. One will more easily maintain employment, continue education, repair fincanial status or credit, address underlying depression or anxiety, maintain a healthy diet and appearance, fulfill family roles and obligations, and devote time to long lost or new found passions or goals.

Maintenance with buprenorphine may last for several months or several years, and in some cases indefinitely. It is a corrective treatment rather than a curative treatment, and should ideally be available to an individual for as long as one desires. The eventual course and duration of maintenance treatment is mutually considered and discussed by both a physician and the patient.

Buprenorphine has some value in other areas of therapy, which generally fall under the scope of "off label" use;

A study at Harvard has demonstrated efficacy of buprenorphine in treating refractory major depressive disorders. Both clinical and anecdotal experience supports its use as an antidepressant agent - aside from the promotion of lymbic activity via its partial mu-agonist properties, many have speculated its kappa antagonist properties to play a role in its unique efficacy.

Other opioids which have shown clinical value in depression include oxymorphone & oxycodone; a small scale case study is available which documents their successful use in a small psychiatry practice for a number of individual patients.

Buprenorphine has been successfully used as an adjunct to spinal anaesthesia, given along with bupivicaine (a local anaesthetic).


The pharmacological properties of buprenorphine are uniquely complex, the current scientific understanding of this compound is yet in its infancy and has yet to grow.

The molecular properties of buprenorphine have been extensively documented (in part through a series of related compounds). Buprenorphine is one of a series of adducts of thebaine (often derived from thebaine's O-demethylation product, oripavine), popularly known as the bentley compounds, named after researcher Kenneth Bentley. They may be referred to as the orvinols, or the ethenooripavines. All have an etheno bridge at C 6 & 14, and varying alcoholic substituents at C 7.

Buprenorphine is a semi-synthetic phenanthrene based opioid (and may properly be considered an 'opiate' as well). It posesses the morphine core structure and is molecularly related to the potent veterinary painkiller etorphine (also a bentley opioid). It's An N-substitution gives buprenorphine its mixed agonist/antagonist properties. It is generally manufactured from commercial thebaine or thebaine's derivative, oripavine.

Buprenorphine shows binding affinity for multiple opioid receptors - specifically mu, delta, kappa, and ORL1 (nociceptin) sites, though its primary actions involve its interaction with mu and kappa sites. It is a partial agonist for the mu (i.e. morphine) receptor and an antagonist at the kappa receptor. Due to its extremely high affinity for the mu receptor, it is capable of competitive displacement (or antagonism) of most available opioids, including morphine, hydromorphone, and fentanyl - It behaves similar to naloxone in this respect, but has an even greater binding affinity. When bound at the mu receptor, buprenorphine induces a similar cellular response to agonists such as morphine, only to a lesser extent.

There are many properties of buprenorphine to which we have a vague understanding. However we know the following to be true:

Buprenorphine is a potent opioid analgesic with effects qualitatively similar to morphine - it is a little over 30x the potency of morphine as an analgesic, with 0.3mg buprenorphine being equivalent to 10mg morphine parenterally. Buprenorphine binds with very high affinity (~0.08nm) to mu opioid receptors, and behaves as a partial agonist, with a limit to its morphinomimetic activity (its mu receptor mediated activity).

Buprenorphine activates the morphine (mu) receptor only to about 30-40% of its maximum potential.

Buprenorphine has an affinity for delta receptors, though its action at this receptor is believed to range from mild agonist activity to only receptor-blocking (i.e. antagonist) activity. It is also a high efficacy partial agonist at the ORL1 nociceptin receptor (opioid like receptor 1).

Buprenorphine exhibits potent antihyperalgesic properties (possibly associated with its kappaminergic as well as its nociceptoid action). In other words, it prevents long term neuroplastic excitation (i.e. central sensitization) in cases of chronic pain. For this reason, bupe is useful for complicated cases of treatment-resistant pain (including neuropathic pain). Its antihyperalgesic potency exceeds its analgesic potency.

Buprenorphine undergoes glucuronidation, and N-dealkalation to the active metabolite norbuprenorphine; both via UGT and P40 (cytochrome) enzymes respectively. Buprenorphine is metabolized hepatically, it's excretion is via renal (kidneys through urine) and biliary (through the bile) routes. Norbuprenorphine, its active metabolite, is a partial or full agonist at mu, delta, and ORL-1 receptors, and a partial agonist at kappa receptors. It is unknown to what extent norbuprenorphine contributes to buprenorphine's effects, however, NORbupe has been observed to be present in higher plasma levels than the parent drug in those regularly taking sublingual buprenorphine. Buprenorphine is a hydrophobic and highly lipophilic opioid, with an average half life of 37 hours.

Buprenorphine will displace (or antagonize) typical agonists at mu-receptors, and cause precipitated withdrawal in full agonist dependent individuals. Likewise, buprenorphine is not easily displaced from mu-binding sites. Buprenorphine overdose requires high dose infusions of naloxone, or a more potent antagonist
When given as an analgesic, buprenorphine demonstrates a typical agonist-like dose-response curve with doses up to at least 7mg; each increase in dose produces a proportionate increase in response.

Buprenorphine has been shown to demonstrate a bell-shape dose response curve in certain animals. This phenomena is currently being clinically investigated in humans.

Buprenorphine produces analgesia and respiratory depression at the microgram level which is similar to morphine. Its respiratory depressant properties are limited by a ceiling at around 4mg.

Buprenorphine's euphorigenic and narcotizing effects (mediated through mu receptors) are limited by a ceiling in response. Research demonstrates that in opioid experienced non dependent subjects, typical opioid agonist effects of buprenorphine reach a ceiling at 8mg to 16mg. Higher doses of 8mg to 32 mg were shown to extend the duration of this effect to 48 hours or more.

Tolerance to the subjective agonist effects develops quickly in maintenance patients, making buprenorphine ideal for "addiction" or maintenaince therapy.

Clinical tolerance to buprenorphine does not progress in high dose patients once one has reached steady state levels and is stabilized at an optimal dose. Physical dependence in buprenorphine users is limited by its intrinsic ceiling on morphine-like response.

Buprenorphine has been known to produce intense narcosis in users with limited opiate tolerance, such as recreational users and post-detox opioid "addicts". It is a popular recreational opioid in many areas, and used in the same fashion as other narcotics.

The Suboxone combination product (burenorphine and naloxone) has been demonstrated to produce less pleasure when injected than the Subutex formulation (buprenorphine alone), this however does not prevent an opioid naiive individual from experiencing intense subjective effects. Suboxone, when injected intravenously, does not precipitate withdrawal in subjects maintained solely on buprenorphine products.

High dose buprenorphine inhibits opioid withdrawal for up to 24 hours or longer. When taken in maintenance doses of 8 to 32mg, duration is generally no less than 48 hours.

Buprenorphine is relatively fast acting and is more lipophilic than morphine (penetrates the brain more quickly). Effects are felt about 5 minutes after an IV dose and about 15 minutes following an IM dose.

In most settings, buprenorphine is as effective as morphine as an analgesic. It has been succesfully used for this purpose by the following routes: intravenous, intramuscular, or subcutaneous injections. Epidural and intrathecal injections. Transdermal, buccal, and sublingual routes. It is poorly absorbed by the gut, with an oral bioavailability similar to oxymorphone (~10%).

Because of its high lipophilicity, buprenorphine has been prepared for dermal administration, in the form of a transdermal patch (similar to the fentanyl patch) which releases the drug over an extended period. Transdermal buprenorphine takes effect about 12-24 hours following application of the patch, and lasts 3 days or one week, depending on the product.

Effects & Side Effects:

Effects produced via buprenorphine are experienced at varying levels depending on one's tolerance to the drug; this indeed applies to the effects of all opioids. The only real significant difference in buprenorphine is its disparate dose-response curve.

In the scope of side effects, buprenorphine may produce those which could be expected from a mu-agonist.

Side effects of buprenorphine are generally experienced to a lesser extent than morphine and other opioids, especially in analgesic doses. They however can include nausea & vomiting in opioid naiive individuals, pruritis & itching, miosis, constipation, urinary retention, muscle rigidity, myoclonus, orthostatic hypotension, and limited respiratory depression. Buprenorphine on its own shows a threshhold for respiratory depression.

When taken in acute excess by an opioid naiive individual, or with the addition of sedatives & other CNS depressants in subjects with a tolerance to neither opioids nor the additional sedative.

Subjective effects of buprenorphine are of the morphine origin, with the exception of situations involving the precipitation of withdrawal (which may be avoided with common sense precautions), and may range from overwhelming in intensity to subtle, depending on the tolerance or dependence level of the user. The effects are morphine like across the board, with the only variable being the subjective intensity.

Effects of sublingually administered buprenorphine come on gradually and peak after several hours, very similar to the onset of methadone. include analgesia, anxiolysis, inhibition of stress & worries, euphoric state of well being, positive mood, contentment, increased sociability, empathetic tendencies, motivation & productivity, a sense of warmth, and a dreamlike psuedo-somnolent state or 'nod'. Casual opioid users who are currently 'clean' find effects quite pleasant & pronounced, while opioid naiive individuals often experience the nodding and vivid waking dreams, with intermittent bouts of nausea. The effects of buprenorphine to post-detox narcotic users may be indistinguishable from methadone - studies have shown IV administration of the drug in this same population produced effects which could not be distinguished from full agonists; with a number of subjects identifying the drug as heroin. Indeed, buprenorphine is an opioid of choice for some casual narcotic users (or chippers).

In the high dose maintenance population; the euphorigenic effects of buprenorphine vary, depending on dose, timing of dose, and route of administration. Those who maintain on microgram level doses (tolerance permitting) are able to avoid reaching buprenorphine's threshhold for such effects; with blood levels below a certain level, high points and low points are all subjectively pronounced, similar to those maintained on a full agonist such as methadone or long acting morphine.

Those who are at the level of clinically reccomended maintenance doses may feel subtle effect upon daily administation, or no noticeable increase, depending on dose level and interval. Those consistently maintained at the clinically "intended" level, will be at a point where blood level is consistently 'just above' the maximum effective concentration, even at the end of each dose-interval (the point of lowest concentration). After one at this level has developed a tolerance to buprenorphine's euphoric effects, there will be no change in subjective effect with each dose. One way around this is to wait an extended period until taking the next dose (rather than 24, wait 48), blood levels will at some point taper to a level below the maximal effective concentration, resulting in a pronounced decrease in subjective effects; marked by mild withdrawal - if one waits until this point to dose, the pleasant subjective effects are acheived, due to the 'sub-threshhold' low point in blood level causing a net decrease in narcosis, thus allowing for a net increase which will actually be "felt" by the user.

Further Reading:

Idiot's Guide to Buprenorphine Maintenance Treatment
Buprenorphine - Fact VS Fiction
All About the Bentley Compounds
Abrupt Discontinuation of High Dose Buprenorphine: A Hellish Spring
Is Less Really More?

Friday, October 7, 2011

Reading List and Key References

Key References & Suggested Reading

How Do Opiates & Opioids Relieve Pain?

It's been covered here before; but not for a while. This is a condensed version summarizing the primary targets of opioid analgesia.

1) Ascending Inhibition (Dorsal Horn)

Mu receptor activity inhibits sensory afferent pathways, reducing the flow of noxious stimulus to the brain.

Presynaptic receptors: block the release of substance P.

Post synaptic receptors: desensitize the receiving neuron to excitatory stimulation.

2) Descending Modulation (PAG, Medulla, Spinal Cord)

PAG: Opioids inhibit GABA interneurons allowing excitatory transmission to the medulla.

Projections to the medulla activate descending interneurons which release serotonin & norepinephrine at the spinal level. Both act through a2 adrenergic and 5-HT receptors to modulate ascending pain pathways; potentiating the action of opioids at the spinal level.

3) Altered Emotional Perception (Limbic Pathways i.e. Pleasure Centers)

Mu receptors throughout the ventral tegmental area (VTA) inhibit GABA's inhibitory role; allowing a burst in the transmission of dopamine from the VTA. Dopamine pathways project to key areas of the brain involved in emotional processing, including the Nucleus Accumbens, producing a state of well being and reducing the emotional perception of pain.

4) Reduced Sympathetic Reaction (LC, Hypothalamic Pituitary Adrenal Axis)

Mu receptors mediate depression of the locus coeruleus (LC) and reduce sympathetic arousal. The LC plays a role in the body's physiological response to pain (i.e. fight or flight mode, adreno-response) and other stressors. LC inhibition produces sedation, relaxation & anxiolysis.

Wednesday, October 5, 2011

Some Much Needed Clarification on Morphine

It seems that some users have assumed the oral bioavailability is much lower than it actually is, leading many to snort their morphine; this is an amateur's mistake. As a traditional sulfate salt, morphine's intranasal b/a is extremely low (around the 10% range) but at least 3-4x that is absorbed systemically when swallowed. Early trials with MS Contin and other products found bioavailability at 40% orally. Substantially higher than hydromorphone and oxymorphone (The frequent 1 to 3 claim is an under estimate used for the sake of convenience when converting). All this to say; with pharmaceutical morphine; one is wisest either to "suck it up and swallow", or inject into a muscle or vein.

Morphine can be taken orally, rectally, or parenterally. Morphine can be smoked in the form of morphine base. Morphine in its crude form (as a base) can be readily prepared from opium latex, dried poppy seedpods, and bulk quantities of store bought poppy seed as well.

Morphine has an onset of about 60 to 90 minutes after dosing orally, and a rapid onset within minutes after injection (though when injected into a vein it produces effects almost immediately.) Morphine has a half life of 2 to 4 hours which varies with the route administered. Generally with any route, its effects last 3 to 4 hours - while in the case of modified release tablet formulations, effects last 8 to 12 hours.

Though partially absorbed by the bloodstream when taken orally, its bioavailability by this route is typically 40%.

Morphine is an ideal candidate for use in just about any context. It retains at least a portion of its efficacy across the board, meaning by most routes of administration. Some suggest that oral morphine is non euphoric, or "wasteful". As already mentioned, this is not really the case. Swallowing the drug is the next best option for those who don't inject and refuse to shove objects into their wet brown anus hole. The pleasant effects of poppy tea and opium are due mainly to morphine.

The stereotypic model for the effects of opioids (including heroin), is based on the effects of morphine. Such morphine-type effects are - anxiolysis, excitement/euphoria, nausea & vomiting, pruritis/itching, constipation, histamine release, peripheral vasodilation, miosis, myoclonus, smooth muscle rigidity, decrease in biliary secretions, dry mouth or nose, cough suppression, sedation, and respiratory depression.

Morphine is one of the top few alternatives for heroin users when heroin is unavailable. Of all available opioids, the effects of morphine share the greatest degree of similarity with heroin. Some clinical research has shown dependent heroin users may be unable to discriminate the two when given in similar doses; other research has shown that user are able to discriminate the two, but show no preference for one over the other. Though morphine is the next choice to heroin by default, some users prefer hydromorphone or oxymorphone as a second choice, often due to their intense onset and potency. Either way, there remains a great deal of loyalty among users, to the raw heavy high of morphine, with its accompanying warmth & itch (not to mention the overwhelming pins & needles rush during onset).

Morphine's place as the golden standard in narcotics may be due not only to its long history (200+ years) of use, but also due to its flexibility (i.e. its fair strength in several aspects rather than a remarkable strength in limited aspects) - It may be superior in most aspects to morphine derivatives when used orally; bioavailability of 30 to 40%, a relatively marked degree of physiological and subjective effects, and a solid duration of action. Its impressive duration is especially apparent in the case of poppy straw tea.