PubMed · 17089454
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Keath Wade. 2006. Why such a large discrepancy?. https://pubmed.ncbi.nlm.nih.gov/17089454/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Two psychonautic bioassays (self-experiments) in stepwise and abrupt cessation of long-term daily oral ingestion habits of 800 mg of codeine phosphate are presented. Concomitant administration of minute doses (about 0.5 mcg) of the opioid antagonist naltrexone with each dose of codeine was found in both cases to obviate the expected opioid withdrawal syndrome, resulting in asymptomatic and uneventful transitions from physical opioid dependency states to exogenous opioid-free metabolism. These experiments are analyzed in the context of a conjectured, rapid, iterative reduction and complete elimination of opioid tolerance, once acquired. It was found that coadministration of naltrexone with codeine phosphate obviated the development of both tolerance and physical dependency over several months of four daily oral doses of 200 mg, allowing abrupt ("cold turkey"), asymptomatic and uneventful withdrawal. This points the way to the biochemical substrate of opioid tolerance itself, and shows that this can easily and inexpensively be blocked, even over months of iterative oral administration of substantial doses of opioid analgesics. Finally, it suggests the opioid withdrawal syndrome is directly related to the physiology of opioid tolerance, and can be prevented by blocking tolerance itself. Even when tolerance has been acquired, this can be reduced stepwise over a matter of days, with no symptoms of opioid withdrawal syndrome.
Parallel to the "poppy-seed defense" strategy commonly reported in the United States, donors of urine samples tested positive for opiates in Taiwan often claimed the consumption of Brown Mixture (BM) as the source of the observed morphine and codeine. Because BM contains opium powder (10.0-10.5% morphine), opium tincture (0.9-1.1% morphine), or camphorated opium tincture (0.045-0.055% morphine) and is a popular remedy, and heroin use is considered a serious criminal act, the claim of BM use has to be adequately addressed. In this study, BM from seven different manufacturers (5 tablets and 2 solutions) and urine samples from alleged heroin users and volunteers with various ingestion patterns and were analyzed for their morphine and codeine contents. The analytical procedure included hydrolysis, trimethylsilylation, and gas chromatography-mass spectrometry analysis. The contents of morphine and codeine in the tablets were found to be very consistent, but with significant differences in the two BM solutions. Morphine concentrations found in urine specimens collected from volunteers ingesting BM tablets (or solutions) were always < 4000 ng/mL. The following morphine-to-codeine ([M]/[C]) ratios were observed for urine specimens with morphine concentration > or = 300 ng/mL: (A) < 3.0 for volunteers ingesting BM solution and (B) > 3.0 (mostly > 5.0) for volunteers ingesting BM tablets and alleged heroin users. It appeared that (A) BM ingestion (tablet or solution) was unlikely to result in a morphine concentration > 4000 ng/mL; and (B) [M]/[C] ratio might not be an effective parameter to differentiate heroin use from BM tablet ingestion.
Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshalled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.