heroin and etonitazene

Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory depressant effects. We describe three patients in whom. This is a case series of patients with acute opioid overdose enrolled in an ongoing multicenter prospective cohort study. Data collected included reported substance use, clinical course, naloxone dose and response, outcome, and analytes detected in biological samples.. Between October 6, 2020 and October 31, 2021, 1006 patients were screened and 412 met inclusion criteria. Of these, three patients (age 33-55) tested positive for. These cases represent a local outbreak of a novel "nitazene" opioid. Public health toxicosurveillance should incorporate routine testing of this emerging class of synthetic compounds in the illicit drug supply.

Topics: Adult; Alprazolam; Analgesics, Opioid; Benzimidazoles; Cocaine; Codeine; Drug Overdose; Fentanyl; Heroin; Humans; Illicit Drugs; Levamisole; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Overdose; Phenacetin; Prospective Studies; Tramadol

In humans, micro opioid-cocaine combinations (speedballs) have been reported to heighten pleasurable effects and result in greater abuse potential compared to either drug individually. Emerging evidence in animals suggests that the ability of mu opioids to enhance the reinforcing effects of cocaine might be independent of their mu intrinsic efficacy even though mu agonist efficacy appears to be a determinant in the reinforcing effects of micro opioids themselves.. This study examined the relationship between agonist efficacy, self-administration, and the enhancement of cocaine self-administration using the high-efficacy mu agonist etonitazene.. Rhesus monkeys self-administered cocaine, heroin, etonitazene, and opioid-cocaine combinations under a progressive-ratio schedule of intravenous drug injection.. Unlike cocaine and heroin, etonitazene did not maintain consistent self-administration at any dose tested (0.001-1.0 microg/kg/injection). However, combining etonitazene (0.1-1.0 microg/kg/injection) with cocaine (0.01 and 0.03 mg/kg/injection) enhanced cocaine self-administration, and this enhancement was attenuated by naltrexone. These effects are similar to those obtained by combining non-reinforcing doses of heroin and cocaine. Antagonism of etonitazene-cocaine and heroin-cocaine self-administration by naloxonazine was short lasting and was not maintained after 24 h (when naloxonazine's purported micro(1) subtype antagonist effects are thought to predominate).. The results suggest that high micro agonist efficacy does not guarantee consistent drug self-administration and that the ability of mu agonists to enhance cocaine self-administration does not depend exclusively on reinforcing efficacy. Moreover, the results do not support a major role for micro(1) receptor mechanisms in either etonitazene- or heroin-induced enhancement of cocaine self-administration.

Topics: Animals; Benzimidazoles; Cocaine; Cocaine-Related Disorders; Conditioning, Operant; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drug Interactions; Female; Heroin; Injections, Intravenous; Macaca mulatta; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Receptors, Opioid, mu; Reinforcement, Psychology; Self Administration; Substance Abuse, Intravenous

The effect of CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclo-hesanol], heroin and etonitazene on intracerebroventricular (i.c.v.) self-administration in a free-choice procedure was evaluated in rats. Animals were trained in 1-h daily sessions with a continuous reinforcement schedule to press two active levers to obtain the vehicle of each drug. Then, when a stable baseline was reached, each drug could be self-administered by pressing the lever found to be less preferred during training, while the vehicle came from the other. The number of bar pressings associated with the delivery of increasing unit doses of CP 55,940 (0.1, 0.2, 0.4, 0.8, 1.6 microg/2 microl/infusion), heroin (0.125, 0.25, 0.5, 1, 2 microg/2 microl/infusion) or etonitazene (0.1--0.2--0.5--1 microg/ 2 microl/infusion) and with the delivery of the corresponding vehicle was fitted by symmetrical parabolas. The mean drug intake was linearly related to the log of self-administered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxone HCl (2 mg/kg/i.p.) 15 min before each daily session reduced the self-administration of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or etonitazene reduced the number of drug-associated lever pressings compared to that obtained with the maximal reinforcing unit dose of each drug alone. These findings suggest there may be a strong interaction between opioids and the cannabinoid system.

Topics: Analgesics; Analgesics, Opioid; Animals; Benzimidazoles; Conditioning, Operant; Cyclohexanols; Heroin; Male; Naloxone; Narcotic Antagonists; Narcotics; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptors, Cannabinoid; Receptors, Drug; Reinforcement Schedule; Rimonabant; Self Administration

There is evidence that blockade of Ca(2+) channels can modify the analgesia and respiratory depression produced by opioid drugs. The interaction between Ca(2+) channel blockade and drug-induced analgesia and respiratory depression was examined by administration of the L-type Ca(2+) channel blocker diltiazem together with various analgesic drugs. The antinociceptive effects of the drugs were evaluated using a warm-water (50 degrees C) tail-withdrawal assay in rhesus monkeys, and the respiratory depressant effects were evaluated using a pressure-displacement plethysmograph. Pretreatment with diltiazem (10-40 mg/kg, i.m.) 30 min before administration of morphine (0.3 to 10 mg/kg) or heroin (0.03 to 1.0 mg/kg) produced a dose-dependent potentiation of the opioid-induced analgesia. The analgesic potency of morphine and heroin was increased by approximately 0.5 log unit in the presence of 40 mg/kg diltiazem. However, diltiazem failed to alter the analgesic potencies of the mu-opioid receptor agonists, fentanyl, etonitazene, nalbuphine, the kappa-opioid receptor agonist, U-50,488 [(trans)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide ], or the non-opioid, clonidine. Respiratory frequency, minute volume, and tidal volume were suppressed by morphine, heroin, and fentanyl, but these effects were not modified by pretreatment with diltiazem (40 mg/kg). These results suggest that diltiazem selectively potentiates morphine- and heroin-induced analgesia without modifying the effects of these opioids on respiration.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Benzimidazoles; Calcium Channel Blockers; Clonidine; Diltiazem; Dose-Response Relationship, Drug; Drug Synergism; Female; Fentanyl; Heroin; Macaca mulatta; Male; Morphine; Nalbuphine; Pain Measurement; Receptors, Opioid; Respiration; Time Factors