Archive for Februar, 2010


Opiate addiction involves the development of chronic adaptive
changes in l-opioid receptors and associated pathways (e.g.
cAMP signalling) which lead to neuronal plasticity in the brain.
This study assessed the status of cAMP and mitogen-activated
protein kinase (MAPK) pathways in brains (pre-frontal
cortex) of chronic opiate addicts. In these subjects (n ¼ 24),
the immunodensities of adenylyl cyclase-I, PKA Ca, total and
phosphorylated CREB were not different from those in sex-,
age- and PMD-matched controls. Moreover, the ratio pCREB/
tCREB was similar in opiate addicts (0.74) and controls (0.76),
further indicating that opiate addiction in humans is not
associated with an upregulation of several key components of
cAMP signalling in the pre-frontal cortex. In contrast, the
components of MAPK cascade (Ras/c-Raf-1/MEK/ERK) were
decreased in the same brains. Notably, pronounced downregulations
of phosphorylated MEK (85%) and ERK1/2
(pERK1: 81%; pERK2: 80%) were quantitated in brains of
opiate addicts. Chronic morphine treatment in rats (10–
100 mg/kg for 5 days) was also associated with decreases of
pERK1/2 (59–68%) in the cortex. In SH-SY5Y cells, morphine
also stimulated the activity of pERK1/2 (2.5-fold) and the MEK
inhibitor PD98059 blocked this effect (90%). The abnormalities
of MAPK signalling might have important consequences in
the long term development of various forms of neural plasticity
associated with opiate addiction in humans.

Read more:Long-term_regulation_of_signalling_components_of_adenylyl_cyclase_and_mitogen-activated_protein_kinase_in_the_pre-frontal_cortex_of_human_opiate_addicts

(das ganze ist sehr schwierig und bedarf den Willen das ganze via Sroogle nachzubauen,

ist ne Knabberarbeit)

Werbeanzeigen

Abstract Relapse is a major clinical problem and
remains a major challenge in the treatment of addictions. A
goal of current research is to gain a greater understanding
of the neurochemistry underlying relapse to opiate use.
Factors which trigger relapse in humans such as stress,
exposure to opiates and/or drug-associated cues, can also
trigger opiate-seeking in animals. This review will overview
preclinical studies relating to the neurochemistry of
opiate-seeking with a focus on studies published from 2005
to present.

Read more:

Neurochemistry_underlying_relapse_to_opiate_seeking_behavior

Ist ne Doktorarbeit, gibt aber statistische Auswertungen von ueber 300 Befragten wider!

1. Bewaeltigungsforschung

2. wie reagieren Drogenabhaengige auf Stress

3. Ihre Strategien

4. Hypothesen und Loesungen

Read more (auf Deutsch):bewaeltigungsverhalten

The first few minutes are in dutch, but the rest is in english. The war on drugs has been going on for more than three decades. Today, nearly 500,000 Americans are imprisoned on drug charges. In 1980 the number was 50,000. Last year $40 billion in taxpayer dollars were spent in fighting the war on drugs. As a result of the incarceration obsession, the United States operates the largest prison system on the planet, and the U.S. nonviolent prisoner population is larger than the combined populations of Wyoming and Alaska. Try to imagine the Drug Enforcement Administration erecting razor wire barricades around two states to control crime and you’ll get the picture. According to the U.S. Dept of Justice, the number of offenders under age 18 imprisoned for drug offenses increased twelvefold from 1985 to 1997. The group most affected by this propensity for incarceration is African-Americans. From 1985 to 1997, the percentage of African-American young people put in prison increased from 53 to 62 percent. Today, 89 percent of police departments have paramilitary units, and 46 percent have been trained by active duty armed forces. The most common use of paramilitary units is serving drug-related search warrants, which usually involve no-knock entries into private homes.

The WAGER Vol. 9(11) – Attribution, Addiction, and Gambling: Series Conclusion

Series Special Editor: Sarah E. Nelson

Attributions play a role in all aspects of addiction. Attributions for wins and losses can influence the development of gambling problems (see WAGER 9(6)); attributions about peers’ drinking behavior can affect a person’s own drinking behavior (see WAGER 9(7)); being labeled as a heavy smoker can alter people’s attributions about their smoking (see WAGER 9(8)); people’s attributions about their own addictive behavior differ in predictable ways from attributions they make about others’ addictive behaviors (see WAGER 9(9)); and the attributions people make about their addictions can predict their own chances for recovery or likelihood of relapse (see WAGER 9(10)). This week’s WAGER reviews an article that attempts to model the way attributions change across the course of addiction (Davies, 1996).
Davies’ theory of attribution change rests on the idea that the explanations people make for their behaviors are functional: people make different attributions for the same  event in different contexts (i.e., depending on the setting and the goals of the interaction) (Davies, 1996; Schlenker & Weigold, 1992; Tedeschi & Reiss, 1981). For example, in a group of heroin users, Davies found that subjects made different attributions for their own heroin use to an interviewer who substance using habits were unknown than they did to a fellow heroin user (Davies & Baker, 1987). When it comes to explaining our own behavior, the attributions we make often reflect an ego-defensive bias: that is, attributions about the self serve to protect self esteem, meet self-presentational goals, and preserve self-concept (Schlenker, Weigold, & Hallam, 1990). Davies’ model reflects how attributions might serve this self-protective function in relation to an addiction.

In several different studies, Davies and his colleagues conducted interviews in Scotland with drug and alcohol users both in and out of treatment. Based loosely on these interviews, Davies outlined five attributional stages through which a person might progress as an addiction develops. Each stage is marked by a different attribution style for substance-using behavior. In Davies’ model, attributions can vary in terms of purposiveness (i.e., how intentional the behavior is portrayed), hedonism (i.e., how positively the behavior is described), contradictoriness (i.e., whether attributions contradict across the course of the interview), and the inclusion of addicted self-ascription (i.e., whether attributions make use of the concept of addiction as an explanation for behavior). (1)

During the first stage, presumably before the substance using behaviors become a problem, subjects’ attributions for their drug or alcohol use are high on purposiveness and hedonism – people enjoy using the substance and consider it under their control. During stage two, as problems begin to surface, subjects’ discourse becomes contradictory, varying from context to context between the positive and negative aspects of drug use, and the controlled and uncontrolled aspects of their using behavior. These attributions reflect the ambivalence that emerges during the development of addiction (e.g., Shaffer, 1997). During stage three, people refer to themselves as addicted, explain their substance use as out of their control, and view it as negative. At stage four, people begin to reject the usefulness of the concept of addiction in explaining their behavior and their discourse again becomes mixed and contradictory. Finally, people are able to proceed to a fifth stage that is either positive or negative. In either version, their attributions are relatively stable (i.e., the attributions don’t contradict from one context to another) and do not refer to substance using behavior in terms of addiction. In the positive version, people might have given up drugs or alcohol, but return to a view of their past behavior as controllable and a description of their use that highlights both the positive and negative aspects of that behavior. In the negative version, although the concept of addiction has been dropped, people continue to use substances and see themselves as “down and out” – their behavior is uncontrollable and their substance use is negative. Although these stages tend to relate to the progression of an addiction, people can move back and forth between stages. The one exception to this, according to Davies, is an irreversible transition from stage two to stage 3, which often occurs when subjects enter treatment and may persist long after; consider the Alcoholics Anonymous practice of participants introducing themselves, “Hi, my name is X and I’m an alcoholic.” .

Wager911table1

To test this model of attributions, interviews with drug and alcohol users were transcribed and coders rated the attributions given in each interview in terms of the dimensions outlined in the model. The investigators assigned each respondent to one of the six stages based upon those ratings. Consensus between four judges rating the same twenty subjects was good: average agreement between the judges was 71% (.’s ranged from .49 to .75). In all cases, the judges never disagreed by more than one stage.
Although Davies demonstrated the reliability of his model (i.e., ability of coders to identify the attribution patterns associated with each stage) and stated that these stages related to the stages of an addiction, he did not provide information about hwo the attributional stages correspond to the actual temporal progression of addiction in his interviewees (e.g., whether the majority of subjects classified as stage 3 were in treatment at the time of the interview). Given his claim that movement between at least two of the stages is irreversible (a claim that contradicts established research on addiction stages — see Prochaska, Norcross, & DiClemente, 1994; Shaffer, 1997), this research is needed to verify the model. Also, although he developed his model based on years of observations and interviews of substance users, in this paper he only tests it on twenty interviewees. Given the theoretical basis of the model (i.e., that attributions vary according to context), it is important to test this model and its stages in different samples of substance users and different settings.

Davies’ model of attribution change needs to be validated, but is important for the questions it raises. How do these attributional stages relate to the stages of change described in more well-studied models (e.g., precontemplation, contemplation, preparation or determination, action, maintenance, and termination; Prochaska, Norcross, & DiClemente, 1994)? If these attributional patterns do reliably correspond to different stages of an addiction, it is important to determine

whether these attributions predict change (e.g., provide explanations that refer to being addicted as precursors of treatment-seeking behavior) or reflect change (e.g., provide explanations that refer to being addicted as an attempt to understand and explain past behavior within the treatment context). Both possibilities (i.e., predictive and reflective) and the research reviewed in this WAGER series stress the importance of people’s subjective understanding and interpretation of behavior in guiding future behavior. This attribution-behavior cycle is a crucial, often neglected piece of the study of addictions.

ABSTRACT. Hedonism and the desire-satisfaction theory of welfare
(‘‘desire satisfactionism’’) are typically seen as archrivals in the contest over
identifying what makes one’s life go best. It is surprising, then, that the most
plausible form of hedonism just is the most plausible form of desire satisfactionism.
How can a single theory of welfare be a version of both hedonism
and desire satisfactionism? The answer lies in what pleasure is: pleasure
is, in my view, the subjective satisfaction of desire. This thesis about pleasure
is clarified and defended only after we proceed through the dialectics that get
us to the most plausible forms of hedonism and desire satisfactionism.

Read more: DSH 22.02.22

The functioning of reward in drug addicts is a major issue both in terms of
pathophysiology and in a rehabilitative view. We used a PET imaging device
to assess the hedonic functioning of methadone maintained heroin addicts,
compared to control subjects, by two modalities: 1) the elicitation of interest by
anticipated monetary reward; 2) the neuroimaging correlates of visually elicited
pleasure. In heroin addicts fewer brain regions showed activated during tasks
implying known monetary reward in comparison to tasks without any reward.
On the other hand, the processing of subjectively pleasant videoclips resorted to
different brain pathways in heroin addicts. Heroin addicts seem to show a lower
level of anticipatory sensitivity to monetary reward, whereas the topography of
pleasure-feeling seems to be different from normal subjects’. Such results show
a different reward-seeking and reward-feeling status of methadone maintained
heroin addicts, although it is to be clarified whether such a status was also forerunning
heroin use, or developed as a correlate of addiction

Read more:Martin-Soelch 8(2)2006

Howard Lotsof Dies at 66; Saw Drug Cure in a Plant

Howard Lotsof was 19, addicted to heroin and searching for a new high in 1962 when he swallowed a bitter-tasting white powder taken from an exotic West African shrub.
right align image
“The next thing I knew,” he told The New York Times in 1994, “I was straight.”

The substance was ibogaine, an extract of Tabernanthe iboga, a perennial rain-forest plant found primarily in Gabon. In the Bwiti religion it is used in puberty initiation rites, inducing a powerful altered state for at least 48 hours during which young people are said to come into contact with a universal ancestor.

By Mr. Lotsof’s account, when he and six friends who were also addicted tried ibogaine, five of them immediately quit, saying their desire for heroin had been extinguished.

It was the start of a lifelong campaign for Mr. Lotsof. And now thousands of former addicts around the world and some scientists contend that ibogaine should be scientifically tested for its ability to halt heroin and cocaine cravings and even end addiction. Ibogaine is used in drug treatment clinics in many countries, but is banned in the United States.

Mr. Lotsof, who was 66, died on Jan. 31 at a hospital near his home on Staten Island. The cause was liver cancer, his wife, Norma said.

Virtually from that day 48 years ago when he first tried ibogaine, Mr. Lotsof became perhaps its leading advocate, lobbying public officials, pharmaceutical companies and independent researchers to investigate its efficacy. In the mid-1980s, he persuaded a Belgian company to manufacture ibogaine in capsule form and begin offering it to addicts in the Netherlands.

By then he had started the Dora Weiner Foundation, named for his grandmother, to develop ibogaine as a medication, to disseminate information about chemical dependence and to refer people to treatment. Mr. Lotsof ran the foundation.

In 1986 he received a patent for the use of ibogaine as a remedy for heroin and cocaine addiction. Five years later, he began working with Jan Bastiaans, a Dutch psychiatrist who had gained renown by using LSD therapy for Holocaust survivors.

They treated 30 addicts from around the world, two-thirds of whom stopped using drugs for periods ranging from four months to four years. With 75 percent of addicts typically relapsing within six months of conventional care, the results spurred scientific interest.

“His great achievement,” said Kenneth Alper, an associate professor of psychiatry and neurology at the New York University School of Medicine, “was in inducing the National Institute on Drug Abuse to undertake a research project on ibogaine that produced scores of peer-reviewed publications and paved the way for F.D.A. approval of a clinical trial.”

The Food and Drug Administration did approve the trial, Dr. Alper said, but it was never completed because of contractual disputes and lack of financing. Ibogaine remains banned by the federal government.

“In the uncontrolled environments in which ibogaine is typically used, clinics or nonmedical settings,” Dr. Alper said, “the observations indicate that there is a resolution of withdrawal, meaning the addict is detoxified and no longer has withdrawal symptoms and is no longer physically dependent.” Scientifically controlled testing is needed, he said.

Herbert D. Kleber, director of the division on substance abuse at the New York State Psychiatric Institute at Columbia University, said he was skeptical about the efficacy of ibogaine in treating substance abusers, including those addicted to opium-based drugs like heroin.

“At various times ibogaine has been proposed to treat opioid withdrawal as a cure for opioid dependence and as a cure for cocaine dependence,” Dr. Kleber said. “But there is a lack of controlled scientific studies to back those beliefs.

“A number of deaths have been associated with its use, especially to treat opioid withdrawal and dependence,” Dr. Kleber continued. “I therefore do not feel it is something that should be used in the absence of such evidence.”

Howard Stephen Lotsof (pronounced LOTS-uv) was born in the Bronx on March 1, 1943, the only child of Abner and Lillian Weiner Lotsof. Besides his wife, the former Norma Alexander, he is survived by two sisters, Rosalie Falato and Holly Weiland.

Mr. Lotsof, who dropped out of Fairleigh Dickinson University in the 1960s, graduated from N.Y.U. in 1976. Over the years he wrote or co-wrote scientific papers on ibogaine that were published in respected academic journals, including The Journal of Ethnopharmacology and The American Journal on Addictions.

“These accomplishments are all the more extraordinary,” Dr. Alper said, “in view of the fact that Mr. Lotsof, a graduate of New York University who majored in film, was without a doctoral-level degree.”

By DENNIS HEVESI
February 17, 2010
NY Times

Abstract
Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication.

We provide an overview of the factors liable
to influence opioid action in the elderly population.
A major challenge for the physician prescribing opioids in the elderly is their greater risk of medication-associated problems.
Thus, older patients suffer increased vulnerability to adverse drug effects and interactions, higher rates of polypharmacy, and more comorbidity. These problems are compounded by a relative lack of definitive published information. There is clearly a need for more research in this area.
Aging affects opioid pharmacokinetics via altered body composition (distribution volumes) and organ function (liver = metabolism,
kidney = excretion). Pharmacodynamics is affected via impaired neurotransmitter/peptide production and changed receptor affinities/populations. Older women may need less morphine analgesia postoperatively, while pain sensitivity tends to increase particularly in older men. However, the net effects of changes in opioid pharmacology with age on clinical opioid analgesia remain unclear, probably due to the significantly greater variability in body function with increasing age.
Practical recommendations for opioid prescription in the elderly include meticulous review of indication for opioid use, not only initially but also at regular intervals thereafter. A policy of careful titration should be followed, with conservative choice of dosage on starting. Dosing intervals may need to be lengthened subsequently. Finally, it should be remembered that old persons do not necessarily need less opioid than younger ones.

Read more: OpioidsElderly feb. 2010

and as well here: 842 feb 2010 eldery

ABSTRACT
The present article documents an authentic process of heroin manufacturing
in Afghanistan: white heroin hydrochloride produced using simple equipment and
a small quantity of chemicals. The quantities of chemicals actually used corresponded
to the minimum needed for manufacturing heroin. The only organic solvent
used was acetone, and only a very small quantity of it was used.
Because the chemicals used in the demonstration were from actual seizures
in Afghanistan, some of the chemicals had been disguised or repackaged by
smugglers. Others had been put into labelled containers that proved to be counterfeit,
and some glass containers used were not the original containers of the
manufacturer displayed on the label.
The brown heroin base prepared as an intermediate step in the process shares
some of the characteristics of the South-West Asia type of heroin preparations
often seized in Germany. The final product of the documented heroin manufacturing
process was white heroin hydrochloride, which shares the key characteristics
of the white heroin occasionally seized in Germany and other countries in Western
Europe since 2000. The present article demonstrates that this kind of heroin can
be produced in Afghanistan.

Documentation_of_a_heroin_manufacturing_process_in_Afghanistan

(Vielleicht bewegt dieser Artikel ja den ein oder anderen „einzusehen“ wie ekelig das Strassen Heroin in deutschsprachigen Raum wirklich ist, dieser Artikel ist keine perfekte Synthese Anleitung, aber er hilft mit vielen „Urban legends“ aufzuraeumen)

Background:

In vitro experiments suggest that circulating metabolites of oxycodoneare opioid receptor agonists.
Clinical and animal studies to date have failed to demonstrate a significant contribution of the O-demethylated
metabolite oxymorphone toward the clinical effects of the parent drug, but the role of other putative circulating
active metabolites in oxycodone pharmacodynamics remains to be examined.
Methods: Pharmacokinetics and pharmacodynamics of oxycodone were investigated in healthy human volunteers;
measurements included the time course of plasma concentrations and urinary excretion of metabolites derived
from N-demethylation, O-demethylation, and 6-keto-reduction, along with the time course of miosis and subjective
opioid side effects. The contribution of circulating metabolites to oxycodone pharmacodynamics was
analyzed by pharmacokinetic-pharmacodynamic modeling. The human study was complemented by in vitro
measurements of opioid receptor binding and activation studies, as well as in vivo studies of the brain distribution
of oxycodone and its metabolites in rats.
Results: Urinary metabolites derived from cytochrome P450 (CYP) 3A–mediatedN-demethylation of oxycodone
(noroxycodone, noroxymorphone, and - and -noroxycodol) accounted for 45%  21% of the dose, whereas
CYP2D6-mediated O-demethylation (oxymorphone and - and -oxymorphol) and 6-keto-reduction (- and
-oxycodol) accounted for 11%6% and 8%6% of the dose, respectively. Noroxycodone and noroxymorphone
were the major metabolites in circulation with elimination half-lives longer than that of oxycodone, but their
uptake into the rat brain was significantly lower compared with that of the parent drug. Pharmacokineticpharmacodynamic
modeling indicated that the time course of pupil constriction is fully explained by the plasma
concentration of the parent drug, oxycodone, alone. The metabolites do not contribute to the central effects,
either because of their low potency or low abundance in circulation or as a result of their poor uptake into the
brain.

oxycodone_pharmacokinetics

Abstract Oxycodone has become
one of the most popular opioids in
the United States. It is superior to
morphine in oral absorption and bioavailability,
and similar in terms of
protein binding and lipophilicity.
Gender more than age influences
oxycodone elimination. Unlike morphine,
oxycodone is metabolized by
the cytochrome isoenzyme CYP2D6,
which is severely impaired by liver
dysfunction. Controlled-release (CR)
oxycodone has become one of the
most frequently utilized sustainedrelease
opioids in the United States.
Both its analgesic benefits and its
side effects are similar to those of
CR morphine. CR oxycodone is similar
to morphine and other opioids in
its abuse potential. Deaths attributable
to oxycodone are usually associated
with polysubstance abuse in
which oxycodone is combined with
psychostimulants, other opioids,
benzodiazepines or alcohol. Oxycodone’s
kappa receptor binding has
little role in abuse or addiction. The
cost of CR oxycodone is prohibitive
for most American hospices.

Normal-release_and_controlled-release_oxycodone

Pain Therapeutics, Inc. (Nasdaq: PTIE) today announced the initiation of a Phase III study with Oxytrex, an investigational drug. Oxytrex is a unique oral painkiller for patients who suffer from persistent severe chronic pain. The Company believes Oxytrex offers less physical dependence/withdrawal than oxycodone, an 80-year-old prescription painkiller still widely used today to treat persistent severe chronic pain.

„We remain encouraged by the strong science around Oxytrex published in several top journals, including a recent article in Journal of Neurobiology that further elucidates the unique attributes of ultra-low-dose opioid antagonists,“ said Remi Barbier, president and chief executive officer.

This study is being referred to as the „Extreme Study“ in deference to patients who depend on extremely high daily doses of oxycodone (greater than or equal to 120 mg per day) to treat severe chronic pain. The Company believes this sub-population of patients is prone to physical dependence/withdrawal.

In the second half of 2007, Pain Therapeutics plans to initiate a large study with Oxytrex in a broad patient population.

„Extreme Study“ Design

This clinical study is randomized, double-blinded, multi-center and placebo-controlled. The study will enroll approximately 120 patients who have each been taking greater than or equal to 120 mg of oxycodone per patient per day for over a year. Patients who meet this and all other eligibility requirements are randomized to receive twice-daily doses of 100 nanograms (i.e., 0.0001 mg) ultra-low-dose naltrexone or matching placebo for two weeks. At the conclusion of the treatment period, patients check into a clinic and receive an injection of a high-dose opioid antagonist to precipitate withdrawal. During the withdrawal phase of the study, patients are closely monitored and measured for signs and symptoms of physical dependence/withdrawal using the Subjective Opiate Withdrawal Scale. The study’s primary endpoint is prospectively defined as physical dependence/withdrawal scores in the treated arm compared to placebo. For ethical and other reasons, the study protocol allows an interim analysis.

About Oxytrex

Pain Therapeutics owns commercial rights to Oxytrex, a unique oral painkiller that preferentially inhibits an excitatory effect of opioid receptors. This excitatory effect is believed to counteract analgesia (pain relief) and cause tolerance. Its inhibition enhances pain relief and minimizes opioid tolerance. The FDA has not yet evaluated the merits, safety or efficacy of Oxytrex.

http://www.medicalnewstoday.com/articles/58973.php

Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

PMID: 17685875 [PubMed – indexed for MEDLINE]

Achieving effective, durable, and safe pain relief, especially
in patients with chronic and/or severe pain conditions,
can be a clinical challenge. For many types of pain, prescription
opioids are among the most effective analgesics [Fine
and Portenoy 2004]. However, there could be concerns about the
development of opioid tolerance or adverse effects, and in some
cases opioids seem to worsen pain (eg, hyperalgesia) [Compton
2008; DuPen et al. 2007; Stein et al. 2003]. For certain difficult
conditions, such as fibromyalgia or neuropathies, opioids alone are
sometimes considered of limited effectiveness [Chou et al. 2009].
Healthcare providers interested in pain management must be
alert to new or novel approaches that help to overcome deficiencies
of opioids, such as treatment-limiting side effects, and as aids
in relieving difficult-to-treat pain conditions. In this regard, there is
a growing body of evidence suggesting potential benefits of opioid
antagonists.
Opioid antagonists — in particular, naloxone and naltrexone —
have been available and studied for decades as agents that displace
opioid molecules from their neuroreceptors, and block
opioids from attaching to and activating those receptors. Such
qualities can be of important benefit, as short-acting antagonists
like naloxone are used effectively to quickly reverse toxic effects of
opioid overmedication or overdose.
Laboratory research and clinical trials have demonstrated the
unexpected, paradoxical effects of opioid antagonists as adjuvants
for enhancing rather than attenuating analgesic effects of opioids
like morphine, oxycodone, and others. Further benefits of opioid
antagonists, as monotherapy, for better managing certain chronic
pain conditions also have been discovered.

OpioidAntagonistsForPain

Pain and addiction share some common physiologic pathways
in the brain, especially those involving opioids, and each may
affect the other. That is, the presence of pain may influence the
development and course of opioid addiction, and vice versa
(Compton and Gebhart 2003).
These interactions may complicate therapy for opioid addiction.
For example, opioid-addicted persons appear to have lower tolerance
for and greater sensitivity to pain, and this may continue during
addiction treatment. Sleep disorders and psychiatric illness often
associated with addiction may increase the experience of pain
and decrease the effectiveness of pain-relief interventions. Furthermore, opioid medications
may lose their analgesic potency in many of these patients, so the management of their pain
can be challenging (Compton and Gebhart 2003).

Read more:

Pain_Addiction_Addiction_Tx

More than half of adults in the United States experienced chronic or recurrent pain in 2003 (Peter D. Hart Research
Associates 2003). Effective management of pain not only reduces suffering, but also improves sleep, reduces affective
stress, and increases levels of daily functioning (Roper Public Affairs & Media 2004; Schneider 2005). This publication
will assist healthcare providers in understanding that opioid medications can effectively manage pain, distinguishing
between physical and psychological dependence, and reducing their patients’ risk of psychological dependence on
opioids during pain management

Read more:

SAMHSA-PainMgmt-WithoutAddiction

Pain and substance abuse co-occur frequently, and each can make the other more difficult to treat. A knowledge of pain and its interrelationships with addiction enhances the addiction specialist’s efficacy with many patients, both in the substance abuse setting and in collaboration with pain specialists. This article discusses the neurobiology and clinical presentation of pain and its synergies with substance use disorders, presents methodical approaches to the evaluation and treatment of pain that co-occurs with substance use disorders, and provides practical guidelines for the use of opioids to treat pain in individuals with histories of addiction. The authors consider that every pain complaint deserves careful investigation and every patient in pain has a right to effective treatment.

Read more:

Challenges

The present review aims to clear up the issue of the neurological processes underlying the personality changes induced by chronic opioid use. The effects of methadone treatment on brain functions have been analyzed, too. Brain disintegration becomes evident very soon after an onset of chronic heroin abuse and continues throughout the period of drug consumption. A considerable proportion of opioid addicts are characterized by conspicuous neuropsychological deficits, which preclude the maintenance of complete opioid abstinence in this patient subgroup. At present, there are no data to testify that the effects of methadone maintenance on brain functions exceed the adverse neurological effects of chronic heroin use.

Polunina_9(2)2007 02.10.

Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during
adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC)
exposure during postnatal days 35–49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects
of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference
and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and
m-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an
increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the
nucleus accumbens and the caudate–putamen nucleus, without any modification for preference to oral morphine consumption. In
contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to
morphine conditioning. CB1 and m-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all
groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine
on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups
of individuals subjected to adverse postnatal environment.

02.10

Eine kleine Einfuehrung!

opiumrevisited

The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction.
NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of
drug abuse, including:
• genetic and social determinants of vulnerability and response to drugs;
• short- and long-term effects of drugs on the brain, including addiction;
• other health and social impacts of drug abuse, including infectious diseases and economic costs;
• development and testing of medication and behavioral treatments for abuse and addiction; and
• development and evaluation of effective messages to deter young people, in particular, from abusing drugs.
Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter,
NIDA Notes. Six times per year, NIDA Notes reports on important highlights from NIDA-sponsored research,
in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended to remind regular NIDA Notes readers and inform other readers of important research discoveries during the periods they cover.

.A_Collection_of_Articles_That_Address_Heroin_Prevention,_Treatment_and_Research

Over the 75-year lifetime of the British Pharmacological Society there has been an enormous
expansion in our understanding of how opioid drugs act on the nervous system, with much of this
effort aimed at developing powerful analgesic drugs devoid of the side effects associated with
morphine – the Holy Grail of opioid research. At the molecular and cellular level multiple opioid
receptors have been cloned and characterised, their potential for oligomerisation determined, a large
family of endogenous opioid agonists has been discovered, multiple second messengers identified and
our understanding of the adaptive changes to prolonged exposure to opioid drugs (tolerance and
physical dependence) enhanced. In addition, we now have greater understanding of the processes by
which opioids produce the euphoria that gives rise to the intense craving for these drugs in opioid
addicts. In this article, we review the historical pathway of opioid research that has led to our current
state of knowledge.
British Journal of Pharmacology (2006) 147, S153–S162. doi:10.1038/sj.bjp.0706435

holy_grail_of_opiates Feb 2010

Concern about abuse/dependence in chronic pain patients taking opioid analgesics may lead
to undertreatment of pain, yet little is known about the prevalence of abuse/dependence in
these patients and how it differs among analgesic agents. The objective of this study was to
assess the prevalence of tramadol abuse compared to nonsteroidal anti-inflammatory drugs
(NSAIDs) and hydrocodone-containing analgesics in patients with chronic noncancer pain
(CNP). The study had three arms. The first arm consisted of subjects prescribed tramadol
alone; the second of subjects randomized to either NSAIDs or tramadol; and the third of
subjects randomized to hydrocodone or tramadol. Each investigator received two boxes of
prescriptions randomized so that one in every four prescriptions was for tramadol. Upon
deciding on the therapeutically appropriate arm, the physician selected the appropriate box,
opened the next envelope and completed the enclosed prescription. After the initial
randomization, physicians could prescribe whatever medication was therapeutically
appropriate. A total of 11,352 subjects were enrolled. Up to nine interviews using
a structured questionnaire were conducted over a 12-month period. An algorithm called the
‘‘Abuse Index’’ was developed to identify subjects who were abusing the drug. The primary
components of the index were increasing dose without physician approval, use for purposes
other than intended, inability to stop its use, and withdrawal.

CiceroJPain2006 2010 feb