thebaine and Opioid-Related-Disorders

Oxycodone, a semisynthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for more than 100 years. Although thebaine cannot be used therapeutically due to the occurrence of convulsions at higher doses, it has been converted to a number of other widely used compounds that include naloxone, naltrexone, buprenorphine, and oxycodone. Despite the early identification of oxycodone, it was not until the 1990s that clinical studies began to explore its analgesic efficacy. These studies were followed by the pursuit of several preclinical studies to examine the analgesic effects and abuse liability of oxycodone in laboratory animals and the subjective effects in human volunteers. For a number of years oxycodone was at the forefront of the opioid crisis, playing a significant role in contributing to opioid misuse and abuse, with suggestions that it led to transitioning to other opioids. Several concerns were expressed as early as the 1940s that oxycodone had significant abuse potential similar to heroin and morphine. Both animal and human abuse liability studies have confirmed, and in some cases amplified, these early warnings. Despite sharing a similar structure with morphine and pharmacological actions also mediated by the

Topics: Analgesics, Opioid; Animals; Humans; Morphine; Opioid-Related Disorders; Oxycodone; Receptors, Opioid; Thebaine

Opioids are commonly prescribed across the United States (US) for pain relief, despite their highly addictive nature that often leads to abuse and overdose deaths. Abuse deterrent formulations (ADFs) for prescription opioids make the non-therapeutic use of these drugs more difficult and less satisfying. Although approximately one-third of surveyed abusers in the US reported smoking opioids, to our knowledge, no commercialized ADF effectively prevents opioid smoking. Here, we report a novel approach to deter smoking of a model prescription opioid drug, thebaine (THB), by using polymer blend microspheres (MS) comprising polylactic acid (PLA) and polycaprolactone (PCL). We utilized high-performance liquid chromatography (HPLC) and thermogravimetric analysis (TGA) to test the ability of PLA-PCL MS to limit the escape of vaporized THB. Additionally, we compared the abuse-deterrent potential of PLA-PCL MS to that of activated carbon (AC) and mesoporous silica (MPS), two materials with excellent drug-adsorbing properties. Our MS formulation was effective in reducing the amount of both active drug and thermal degradation products in the vapor generated upon heating of THB. These results support that PLA-PCL microspheres can be co-formulated in a tablet with common prescription opioids to deter their abuse via the smoking route.

Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Charcoal; Humans; Microspheres; Opioid-Related Disorders; Polyesters; Prescriptions; Silicon Dioxide; Smoking; Thebaine; United States

Opium poppy products are often illegally used for both recreational and medicinal purposes. In order to demonstrate the ingestion of opium poppy substances, morphine, codeine and their metabolites have been identified. However, morphine and codeine also originate from the ingestion of therapeutic drugs. Therefore, thebaine, one of the main opium alkaloids, in hair was suggested as a marker for chronic use of illegal opium poppy substances in the present study. First, thebaine was included in the analyte list of our routine analytical method for the simultaneous quantification of codeine, morphine, norcodeine, normorphine and 6-acetylmorphine (6-AM) in hair, which was fully validated previously. Then, the incorporation of thebaine and other opiates into hair and the effect of hair pigmentation were examined using lean Zucker rats with both dark grey and white hair on the same body. Thebaine was also measured in hair samples from actual cases of opium poppy substance use. Consequently, thebaine in hair was demonstrated as a marker of chronic use of illegal opium poppy substances using an animal study and actual cases. Thebaine and other opiates were successfully measured in pigmented hair from rats that ingested raw opium suspension. Moreover, thebaine identified in hair excluded possibility of ingestion of pharmaceutical opiates in actual cases.

Topics: Adult; Animals; Biomarkers; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Hair; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Opium; Papaver; Rats; Rats, Zucker; Substance Abuse Detection; Thebaine

Topics: Animals; Behavior, Animal; Dogs; Guinea Pigs; Haplorhini; Humans; Mice; Opioid-Related Disorders; Rats; Reinforcement, Psychology; Thebaine