Drug addicting pain pills, cocaine, heroin and antidepressants

Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized high-throughput microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects.

Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39 000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted.

Cocaine, heroin, and antidepressants (NMDA receptor antagonists)  are reported to have significant and distinctive changes in the profile of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse.

There are 52 transcripts (e.g. Dusp1, Per1 and Fkbp5) with altered expression (FDR < 1 %) in response to treatment with NMDA receptor antagonists and 25 for cocaine/heroin.

The percentage of people who took painkillers stronger than morphine, which include such drugs as fentanyl, hydromorphone, methadone and oxycodone, grew from 17% in 1999 to 37% in 2012, the study found.

Use of narcotic painkillers, such as Vicodin and OxyContin, has also grown. In 1999, 5% of adults 20 and older reported using a narcotic painkiller. Four years later, that number grew to 7%, where it has remained, Sales of the drugs quadrupled between 1999 and 2010, the report said.

  • As of 2012, overdose deaths involving prescription opioid analgesics, which are medications used to treat pain, have increased to almost 17,000 deaths a year in the United States.[3]
  • In 2013, only 16 percent of Americans believed that the United States is making progress in its efforts to reduce prescription drug abuse. Significantly more Americans, 37 percent, say the country is losing ground on the problem of prescription drug abuse. That figure is among the most pessimistic measures for any of the seven public health issues included in the survey. [4]
  • Experts say the increase in heroin use is linked to prescription opioid abuse. Young people often become addicted to pain pills and progress to heroin — which provides the same euphoric high — when pills are hard to come by. [5]
  • Heroin use rose by 75 percent between 2007 and 2011,with an 80 percent increase in first-time use among 12 to 17-year-olds since 2002, according to the Substance Abuse and Mental Health Services Administration (SAMSHA). [6]
  • In 2009, there were nearly 4.6 million drug-related emergency department (ED) visits of which about one half (49.8 percent, or 2.3 million) were attributed to adverse reactions to pharmaceuticals and almost one half (45.1 percent, or 2.1 million) were attributed to drug misuse or abuse.[7]
  • Nearly 9 out of 10 poisoning deaths are caused by drugs—both illicit and prescribed.[8] Between 2001 and 2010, drug poisoning deaths in the U.S. almost doubled to now measure nearly 17,000 deaths in 2010.[9] Moreover, opioid analgesic pain relievers were involved in more drug poisoning deaths than any other drug, including heroin and cocaine.[10]
  • The number of women who lost their lives opioid pain reliever overdoses rose 415 percent between 1999 and 2010 (compared to 250 percent for men), according the Centers for Disease Control and Prevention (CDC). In 2010, a total of 6,631 deaths among women involved opioid pain reliever overdose, compared with the 1999 total of 1,287 deaths among women due to opioid pain reliever overdose.[11]
  • In 2010, pharmaceutical drug overdoses were established as one of the leading causes of death in the United States. Below, some of the leading causes of death for 2010 are assembled in a table. Total drug overdoses killed more Americans than firearms or motor vehicle accidents in 2010.

  • In 2012, an estimated 493,000 persons aged 12 or older used a prescription pain reliever nonmedically for the first time within the past 12 months.[15] This averages to about 1,350 initiates per day.[16]
  • Of those who started abusing drugs in the last year, more than a quarter began by abusing a prescription medication (26.0 percent, including 17.0 percent with pain relievers, 4.1 percent with tranquilizers, 3.6 percent with stimulants, and 1.3 percent with sedatives).[17]
  • Over 1.2 million emergency room visits involved nonmedical use of prescription medication in 2011.[18] In 29 percent of these medical emergencies, opioids were involved.[19]
  • Medical emergencies resulting from prescription drug abuse increased 132 percent over the last seven years, with opioid involvement rising 183 percent

Competitive antagonists

  • AP5 (APV, R-2-amino-5-phosphonopentanoate)[30]
  • AP7 (2-amino-7-phosphonoheptanoic acid)[31]
  • CPPene (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid)[32]
  • Selfotel: an anxiolytic, anticonvulsant but with possible neurotoxic effects.

Uncompetitive channel blockers

Non-competitive antagonists[edit]

  • Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor.
  • HU-211: an enantiomer of the potent cannabinoid HU-210 which lacks cannabinoid effects and instead acts as a potent non-competitive NMDA antagonist.[46]
  • Remacemide: principle metabolite is an uncompetitive antagonist with a low affinity for the binding site.[47]
  • Rhynchophylline an alkaloid, found in Kratom and Rubiaceae.
  • Ketamine: a dissociative psychedelic with antidepressant properties used as an anesthesia in humans and animals, a possible treatment in bipolar disorder patients with Treatment-resistant depression, and used recreationally for its effects on the CNS[48]

Glycine antagonists

These drugs act at the glycine binding site:

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