norpseudoephedrine and Substance-Related-Disorders

Khat, Catha edulis Forsk, is among the most widely used plant-based psychoactive substance in the world. Grown in Eastern Africa, Horn of Africa, and southwestern part of the Arabian Peninsula, its fresh young leaves and twigs are used daily by over 20 million people for the psychostimulatory effects it produces in the user, a practice deeply rooted in the history, tradition, and culture of the indigenous population. Once hardly known outside the regions where it is grown and used, khat use has now spread to other countries. This review will cover the, phytochemistry, pharmacokinetics of the active ingredients-cathinone, cathine, norephedrine, neurochemistry, effects on cognitive and executive functions as well as its ability to produce dependency in the user. Whether it is an innocuous cultural practice or a drug of abuse is debatable as the preclinical and clinical data needed to arrive at an authoritative conclusion is lacking.

Topics: Alkaloids; Brain; Catha; Child Development; Cognition; Humans; Infant; Phenylpropanolamine; Psychoses, Substance-Induced; Substance-Related Disorders

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures.

Topics: Alkaloids; Amphetamines; Catha; Central Nervous System Stimulants; Cognition; Humans; Phenylpropanolamine; Plant Leaves; Psychotropic Drugs; Substance Withdrawal Syndrome; Substance-Related Disorders

Drug abuse affects a significant number of individuals of all ages. Health care practitioners must be knowledgeable about both the physiological effects of such drugs and the impact of drug-seeking behavior on their patients.

Topics: 4-Butyrolactone; Catha; Designer Drugs; Dibenzothiazepines; Diterpenes; Diterpenes, Clerodane; DOM 2,5-Dimethoxy-4-Methylamphetamine; Drug and Narcotic Control; Flunitrazepam; Hallucinogens; Humans; Illicit Drugs; Ketamine; Lysergic Acid Diethylamide; Methamphetamine; Motivation; N-Methyl-3,4-methylenedioxyamphetamine; Phencyclidine; Phenylpropanolamine; Piperazines; Psilocybin; Quetiapine Fumarate; Sodium Oxybate; Substance-Related Disorders; United States

Several phenylethylamines are under consideration for international control. The effects of repeated administration of these compounds, including tolerance, physical dependence and central nervous system (CNS) toxicity, are reviewed here. The compounds can be divided into two major chemical groups: those with substituents on the ethylamine portion of the molecule and those with substituents on the phenyl ring. Although the effects of repeated administration have not been directly determined for most of the compounds, certain representative compounds of each chemical group have been examined in some detail. Prominent among the effects of repeated administration are CNS toxicity and tolerance development. Physical dependence has not been reported for any of these compounds. Future research with these compounds should emphasize the investigation of the CNS toxicity and the functional consequences of such effects for the organism.

Topics: 3,4-Methylenedioxyamphetamine; Alkaloids; Amphetamines; Animals; Central Nervous System; Central Nervous System Diseases; Chemical Phenomena; Chemistry; Corpus Striatum; Dogs; Dopamine; Drug Tolerance; Humans; In Vitro Techniques; Macaca mulatta; Norepinephrine; Phenethylamines; Phenylpropanolamine; Rabbits; Rats; Serotonin; Substance-Related Disorders; Synaptic Transmission; Synaptosomes

Topics: Alkaloids; Amphetamine; Animals; Behavior; Catha; Central Nervous System Stimulants; Dopamine; Humans; Norepinephrine; Phenylpropanolamine; Plant Extracts; Receptors, Dopamine; Serotonin; Substance-Related Disorders

Topics: Alkaloids; Animals; Catha; Dextroamphetamine; Female; Humans; Male; Mice; Motor Activity; Phenylpropanolamine; Plant Extracts; Social Behavior; Stereoisomerism; Stereotyped Behavior; Substance-Related Disorders

The consumption of Khat leaves represents an ancient kind of drug abuse mainly observed in Eastern Africa and the Arab Peninsula among adult men. For this purpose, the leaves are directly collected from the shrub "Catha edulis" prior to extensive chewing process. Seizures in Europe are rare, since the leaves have to undergo quick transportation: After a short period of time, the harvested leaves decompose and suffer in decrease of concentration of the active ingredient cathinone, which makes long term transportation difficult. As an alternative, plant material can be dried to increase life period. In the past years, an increasing number of seizures were made by Austrian police, however, the content of cathinone and cathine in dry material is widely unknown. In this work, a seizure of fresh Khat leaves was compared with two seizures of dried material in terms of concentration of cathinone and cathine using LC-MS/MS analysis. For fresh leaves, a purity grade was found to be 0.115-0.158% for cathinone and 0.172-0.192% for cathine, respectively. In contrast, subsequent storage of dried Khat leaves over months led to a dramatic loss of cathinone: Analysis of two seizures revealed that concentration of cathinone dropped to 0.021-0.023%. These findings are intended to serve as a guideline for Justice authorities to estimate the content of the controlled ingredients of Khat leaves in future.

Topics: Alkaloids; Catha; Chromatography, Liquid; Desiccation; Humans; Phenylpropanolamine; Plant Leaves; Substance-Related Disorders; Tandem Mass Spectrometry

Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g., locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed "synthetic cathinones", and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i.e., as substrates) or reuptake inhibitors (i.e., as transport blockers), it has now become possible to better examine their SAR and even their quantitative SAR (QSAR), in a more effective and systematic manner. An SAR picture is beginning to emerge, and key structural features, such as the nature of the terminal amine, the size of the α-substituent, stereochemistry, and the presence and position of aromatic substituents, are being found to impact action (i.e., as releasing agents or reuptake inhibitors) and transporter selectivity.

Topics: Adrenergic Uptake Inhibitors; Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Humans; Phenylpropanolamine; Propiophenones; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship; Substance-Related Disorders

Khat chewing amongst the UK communities originating from Yemen and the East African coast is suggested to create dependency through its main stimulant components (cathinone, norephedrine and norpseudoephedrine) on the central nervous system.. To validate self-reported khat chewing behaviours by measuring levels of cathinone, norephedrine and norpseudoephedrine in saliva and to explore their associations with self-reported khat chewing dependency.. Face-to-face interviews were conducted amongst 30 male UK-resident khat chewers. Saliva samples were collected from each participant and high-performance liquid chromatography (HPLC) employed to extract and quantify the levels of the biomarkers.. The mean (SD) for cathinone and the composite norephedrine and norpseudoephedrine levels were 33.93 (±39.20) and 29.28 (±26.32)μg/mL respectively. These biomarkers were significantly associated (p≤0.05) with khat chewing dependency.. Validation of self-reported khat chewing is possible. Khat chewing dependency correlates significantly with biomarker levels in saliva. Replication is required.

Topics: Adult; Africa; Alkaloids; Biomarkers; Catha; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Dangerous Behavior; Disclosure; Humans; Interviews as Topic; Male; Mastication; Middle Aged; Phenylpropanolamine; Plant Preparations; Reproducibility of Results; Saliva; Self Report; Substance-Related Disorders; United Kingdom; Yemen

Topics: Alkaloids; Humans; Phenylpropanolamine; Plants; Substance-Related Disorders; United Kingdom

Information is presented on legal manufacture, distribution, medical uses and in various countries of the stimulants and hallucinogens under consideration by the World Health Organization (WHO). Data are reported from the Substance Abuse Warning System (SAWS) in the F.R.G. and other surveillance systems regarding illicit manufacture, trafficking and abuse of these compounds internationally. In addition, it is pointed out that assessment of the liability of these compounds for abuse must consider not only the substance itself but also its potential metabolic products. These data, collectively, indicate that the substances currently of most concern with respect to abuse are fenetylline and norpseudoephedrine.

Topics: Amphetamines; Antipyrine; Central Nervous System Stimulants; Diethylpropion; Hallucinogens; Humans; Phenylpropanolamine; Propylamines; Substance-Related Disorders; Theophylline; World Health Organization

Three cases of psychological dependence upon the over-the-counter preparation of cinnamedryl, caffeine and aspirin (Midol) are reviewed. The relationship between cinnamedryl, amphetamine and other sympathomimetics is discussed. Similarities are noted in symptomatic response and chemical structure.

Topics: Adolescent; Amphetamine; Ephedrine; Female; Humans; Phenylpropanolamine; Propiophenones; Structure-Activity Relationship; Substance-Related Disorders

Topics: Alkaloids; Animals; Central Nervous System Stimulants; Conditioning, Operant; Dose-Response Relationship, Drug; Humans; Male; Phenylpropanolamine; Plants, Medicinal; Propiophenones; Rats; Substance-Related Disorders; Time Factors

Topics: Adult; Appetite Depressants; Humans; Male; Phenylpropanolamine; Substance-Related Disorders