Buprenorphine May Not Be as Safe as You Think

Pediatrics. 2012 Nov 5. [Epub ahead of print]

Kim HK, Smiddy M, Hoffman RS, Nelson LS.

 

Abstract

Buprenorphine is a partial μ-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression.

Patterns of symptom reporting during pregnancy comparing opioid maintained and control women

J Addict Med. 2012 Dec;6(4):258-64. doi: 10.1097/ADM.0b013e31826b299d.

 

Gordon AL, Lopatko OV, Stacey H, Pearson V, Woods A, Fisk A, White JM.

methadone-maintained (MM) and buprenorphine-maintained (BM)
Methadone-maintained women reported significantly (P < 0.05) more symptoms than BM women compared to controls throughout pregnancy. Methadone-maintained women reported 8 and BM women reported 3 symptoms in the third trimester at rates greater than controls. Methadone-maintained women reported greater opioid withdrawal than controls; this did not occur in BM women.

Sudden Cardiac Arrest in a Patient on Chronic Methadone After the Addition of Azithromycin.

Am J Med Sci. 2012 Oct 25
http://www.ncbi.nlm.nih.gov/pubmed/23103438

sexual dysfunction methadone

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Aug;36(8):739-43. doi: 10.3969/j.issn.1672-7347.2011.08.007.

Sexual function of 612 male addicts treated by methadone.

Zhang Y, Wang P, Ma Z, Xu Z, Li Y.

alcohol gene fMRI

• rs3771863, rs3755459, and rs1106855 predicted BOLD activation in response to alcohol cues in those same reward and reinforcement brain areas, especially in the medial prefrontal cortex, striatum, and insula.
•  rs3771863 also predicted AD symptom count in the SAGE data set and BOLD activation in the mesocorticolimbic pathway response to alcohol cues.

TACR1 Genotypes Predict fMRI Response to Alcohol Cues and Level of Alcohol Dependence.
Blaine S, Claus E, Harlaar N, Hutchison K.
Alcohol Clin Exp Res. 2012 Oct 18. doi: 10.1111/j.1530-0277.2012.01923.x. [Epub ahead of print]

publish on scientific journal

• we report results from a large-scale survey of the submission process, covering 923 scientific journals from the biological sciences in years 2006–2008.
•  Manuscript flows among journals revealed a modular submission network, with high-impact journals preferentially attracting submissions. 
• About 75% of published articles were submitted first to the journal that would publish them, and high-impact journals published proportionally more articles that had been resubmitted from another journal. 
• Submission history affected postpublication impact: Resubmissions from other journals received significantly more citations than first-intent submissions, and resubmissions between different journal communities received significantly fewer citations.

Flows of Research Manuscripts Among Scientific Journals Reveal Hidden Submission Patterns
Science DOI: 10.1126/science.1227833

cocaine evoked synaptic potentiation

• We find that cocaine potentiates excitatory transmission in D1-receptor-expressing medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time course that parallels locomotor sensitization
•  Depotentiation of cortical nucleus accumbens inputs by optogenetic stimulation in vivo efficiently restored normal transmission and abolished cocaine-induced locomotor sensitization. 
• These findings establish synaptic potentiiation selectively in D1R-MSNs as a mechanism underlying a core component of addiction, probably by creating an imbalance between distinct populations of MSNs in the nucleus accumbens. 
• Our data also provide proof of principle that reversal of cocaine-evoke synaptic plasticity can treat behavioural alterations caused by addictive drugs and may inspire novel therapeutic approaches involving deep brain stimulation or transcranial magnetic stimulation.

Nature. 2011 Dec 7;481(7379):71-5. doi: 10.1038/nature10709.

Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour.

Heroin hepatitis

•  Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response.
•  87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24weeks.

Concurrent group treatment for hepatitis C: Implementation and outcomes in a methadone maintenance treatment program.

J Subst Abuse Treat. 2012 Oct 2. pii: S0740-5472(12)00142-0. doi: 10.1016/j.jsat.2012.08.007. [Epub ahead of print]

Drug abuse-related accidents

• During the study period, a total of 166 patients visited the EDs of one of the two study hospitals due to drug abuse-related accidents.
•  Opioids (41.1%) were the drugs most commonly abused by the patients, followed by benzodiazepines (32.1%).
• More than two-thirds of the patients (n=38, 67.9%) required hospitalization, and three patients died (5.4%).

Drug abuse-related accidents leading to emergency department visits at two medical centers.

J Chin Med Assoc. 2012 May;75(5):234-9. Epub 2012 Apr 28.

Why We Like to Drink

• Alcohol robustly activated striatal reward circuits while attenuating response to fearful stimuli in visual and limbic regions.
• Self-ratings of intoxication correlated with striatal activation, suggesting that activation in this area may contribute to subjective experience of pleasure and reward during intoxication.
• These results show that the acute pharmacological rewarding and anxiolytic effects of alcohol can be measured with fMRI.

Why We Like to Drink: A Functional Magnetic Resonance Imaging Study of the Rewarding and Anxiolytic Effects of Alcohol. The Journal of Neuroscience, April 30, 2008 • 28(18):4583– 4591 • 4583

Opioid itch

• μ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS)

Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids.

Cell. 2011 Oct 14;147(2):447-58.

Memory retrieval-extinction heroin craving relapse

• In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking.

• In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.

A memory retrieval-extinction procedure to prevent drug craving and relapse. Science. 2012 Apr 13;336(6078):241-5.

Methadone mortality Taiwan

Factors associated with mortality among heroin users after seeking treatment with

methadone: A population-based cohort study in Taiwan

• 1616 Taiwanese heroin users between October 2006 and December 2008, central Taiwan (National Taiwan University Hospital Yun-Lin Branch, St. Joseph's Hospital, China Medical University Beigang Hospital, and National Cheng Kung University Hospital Dou-Liou Branch),
• linkage with the National Death Certification Registry system
• Opiate Treatment Index (OTI),
• 26 (1.6%) people died, with an all-cause mortality rate per 100 person years of 3.42
• The primary cause of death  was
• accidents,
• suicide
• drug overdose
• Older age, HIV infection, psychiatric treatment history, and alcohol abuse/dependence were risk factors for all-cause mortality;
• remaining on MMT was protective for survival

Factors associated with mortality among heroin users after seeking treatment with methadone: A population-based cohort study in Taiwan. J Subst Abuse Treat. 2012 Sep 25. pii: S0740-5472(12)00138-9. doi: 10.1016/j.jsat.2012.08.003. [Epub ahead of print]


Charles Lung-Cheng Huang, M.D.a,b, Lee Chung-Wei, Master c
a Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan
b Department of Nursing, Chung-Hwa University of Medical Technology, Tainan, Taiwan
c Department of Psychiatry, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan

Heroin gene postmortem

Method: We evaluated singlenucleotide polymorphisms of key genes within these systems in three populations of opiate abusers and controls, totaling 489 individuals from Europe and the United States with postmortem tissue.
Conclusion: Genetically influenced interactions between glutamatergic and dopaminergic pathways in opiate abusers


Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels. Molecular Psychiatry (2012), 1–6

Methadone and perinatal outcomes

  A total of 117 pregnant women on methadone maintenance treatment recruited between July 2009 and July 2010.
 Information on concomitant drug use was recorded with the Addiction Severity
Index. Perinatal outcomes included pre-term birth (<37 weeks’ gestation), small-for-gestational-age (<10th centile) and neonatal unit admission. NAS outcomes included: incidence of medically treated NAS, peak Finnegan score, cumulative dose of NAS treatment and duration of hospitalization. Findings Of the 114 liveborn infants 11 (9.6%) were born pre-term, 49 (42.9%) were small-for-gestational-age, 56 (49.1%) had a neonatal unit admission and 29 (25.4%)were treated medically for NAS. Neonates exposed to methadone-only had a shorter hospitalization than those exposed to methadone and concomitant drugs (median 5.0 days versus 6.0 days, P = 0.03). Neonates exposed to methadone doses 80 mg required higher cumulative doses of morphine treatment for NAS (median 13.2 mg versus 19.3 mg,P = 0.03).The incidence and duration of NAS did not differ between the two dosage groups.
 Conclusions The incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose, but maternal opiate, benzodiazepine or cocaine use is associated with longer neonatal hospitalization

Methadone and perinatal outcomes: a prospective cohort study. Addiction. 2012 Aug;107(8):1482-92. doi: 10.1111/j.1360-0443.2012.03844.x. Epub 2012 May 8.

Nucleus Accumbens Surgery for Addiction

  Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow up study showed the 5 years non-relapse rate was 58% and the quality of life was significantly improved.

 

Nucleus Accumbens Surgery for Addiction. World Neurosurg. 2012 Oct 6. pii: S1878-8750(12)01106-0. doi: 10.1016/j.wneu.2012.10.007. [Epub ahead of print]