thebaine and Substance-Related-Disorders

The dependence potential of thebaine is at least partially attributed to oripavine which is one of the principal metabolites of thebaine. The analgesic potency of oripavine in mice is found to be much higher than that of thebaine and comparable to morphine. The reinforcing effect of this substance also appears to be more potent than thebaine. In rats the physical dependence potential of oripavine at a dose of 4 mg/kg is almost comparable to that of morphine at 0.5 mg/kg. Studies carried out on monkeys show that oripavine possesses weak morphine-antagonist properties. Further pharmacological studies of the metabolites of thebaine are recommended.

Topics: Animals; Humans; Macaca mulatta; Mice; Rats; Reinforcement, Psychology; Self Administration; Substance-Related Disorders; Thebaine

Topics: Animals; Benzomorphans; Chemical Phenomena; Chemistry; Cyclazocine; Humans; In Vitro Techniques; Models, Biological; Morphinans; Morphine Derivatives; Nalbuphine; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Pentazocine; Receptors, Opioid; Structure-Activity Relationship; Substance-Related Disorders; Thebaine

This report presents the recommendations of a WHO Expert Committee responsible for reviewing information on dependence-producing drugs to assess the need for their international control. The first part of the report contains a summary of the Committee's evaluations of seven substances (dronabinol, oripavine, buprenorphine, butorphanol, ketamine, khat and zopiclone). The report also discusses the substances that were pre-reviewed (gamma-hydroxybutyric acid and tramadol) and recommended gamma-hydroxybutyric acid for critical review at a future meeting. Two substances (gamma-butyrolactone and 1,4-butanediol) were identified for future pre-review). The second part of the report discusses the guidelines for the WHO review of dependence-producing psychoactive substances for international control. It includes sections on amending the current guidelines, interpretation of specific aspects of the guidelines and access to information necessary for the evaluation of substances. The final section considers other matters including activities of the EMCCDA, the use of pharmacovigilance data, promotion of education and information on the appropriate use of psychoactive drugs and the impact of international control on medical availability of substances.

Topics: 4-Butyrolactone; Advisory Committees; Azabicyclo Compounds; Buprenorphine; Butorphanol; Catha; Dronabinol; Drug and Narcotic Control; Drug Evaluation; Health Services Accessibility; Humans; Hydroxybutyrates; Ketamine; Piperazines; Psychotropic Drugs; Substance-Related Disorders; Thebaine; Tramadol; World Health Organization

7 alpha-bis (beta-chloroethyl) aminomethyl-6, 14-endoetheno-tetrahydro oripavine (alpha-CAM) is a new irreversible opioid receptor agonist. Its effect on isolated tissues (guinea pig ileum, mouse vas deferens, rat vas deferens and rabbit vas deferens) were studied. It was shown to be bound irreversibly to rat brain P2 membrane preparations. The ED50 of its analgesic effect in mice (icv) was found to be 0.12 nmol/mouse, and the effect may last as long as 2-3 days. It is a compound which produces the longest analgesia known up to date. A single dose (icv) of alpha-CAM was sufficient to produce dependence in mice. Thus, the compound may serve as an agent for studying the mechanism of physical dependence.

Topics: Analgesics; Animals; Brain; Guinea Pigs; Ileum; In Vitro Techniques; Male; Mice; Muscle Contraction; Muscle, Smooth; Rabbits; Rats; Receptors, Opioid; Substance-Related Disorders; Thebaine; Vas Deferens

Molecular mechanism of opioid effect was studied in mouse brain using alpha-CAO (7 alpha-N, N-Bis (beta-chloroethyl)amino-6, 14-endo-ethenotetrahydrooripavine), an irreversible opioid receptor agonist. There was a biphasic response in cerebral cAMP content, including an initial sharp decline and a subsequent increase 3 days later, the response being in line with analgesic effect initiated by administration of alpha-CAO and development of habituation due to sustained drug administration. Further laboratory study indicated that in the acute stage, adenylate cyclase activity in the mouse brain was inhibited by 48% and the inhibitory effect was reversible by naloxone. The delayed effect of alpha-CAO in development of habituation was accompanied by increase of AC activity and cAMP content of the brain, calmodulin content in the brain. The later being also causative factor in development of habituation.

Topics: Adenylyl Cyclases; Animals; Brain; Calmodulin; Cyclic AMP; Injections, Intraventricular; Male; Mice; Receptors, Opioid; Substance-Related Disorders; Thebaine

The effects of thebaine were studied in nondependent and morphine-dependent chronic spinal dogs as well as in chronic spinal dogs receiving thebaine chronically. Thebaine did not produce any morphine-like effects in nondependent dogs nor did it precipitate an abstinence syndrome in morphine-dependent dogs. Large doses of naltrexone precipitated a mild abstinence syndrome in dogs receiving thebaine chronically; however, no withdrawal abstinence syndrome was observed after abrupt withdrawal. Thebaine is not a morphine-like drug, nor does it produce appreciable physical dependence in the dog.

Topics: Animals; Dogs; Humans; Naloxone; Naltrexone; Spinal Cord; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors

Topics: Codeine; Heroin; Humans; Mexico; Morphine; Opium; Papaver; Plants, Medicinal; Politics; Substance-Related Disorders; Thebaine; Turkey; United States

Topics: Costs and Cost Analysis; Heroin; Humans; Legislation, Drug; Narcotics; Substance-Related Disorders; Thebaine; United States

Topics: Analgesics; Animals; Cyclazocine; Female; Haplorhini; Humans; Male; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pentazocine; Stereotyped Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors

Topics: Albumins; Animals; Blood Proteins; Brain; Half-Life; Humans; Kinetics; Male; Protein Binding; Rats; Substance-Related Disorders; Thebaine; Tritium

Topics: Animals; Behavior, Animal; Brain Chemistry; Caudate Nucleus; Cerebellum; Cerebral Cortex; Dopamine; Haplorhini; Humans; Hypothalamus; Iproniazid; Macaca; Medulla Oblongata; Mesencephalon; Methyldopa; Morphine; Norepinephrine; Pons; Reserpine; Serotonin; Spinal Cord; Substance Withdrawal Syndrome; Substance-Related Disorders; Thalamus; Thebaine

Topics: Adrenal Glands; Animals; Body Weight; Brain; Drug Tolerance; Epinephrine; Female; Growth; Humans; Levorphanol; Methadone; Monoamine Oxidase Inhibitors; Morphine; Morphine Dependence; Norepinephrine; Organ Size; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors