(−)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties

Nencini, Paolo; Fraioli, Sabina; Pascucci, Tiziana; Nucerito, C Vania

doi:10.1016/s0166-4328(97)00123-x

Cited by 13 publications

(10 citation statements)

References 43 publications

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“…Similar to other psychostimulants, it is possible that chronic use of khat impacts several central functions related to dopaminergic, adrenergic, opioid, and HPA axis activity . Chronic exposure to khat and its constituents, such as cathinone and cathine, may lead to receptor and synaptic related changes in multiple regions of the brain, including the paraventricular nucleus and the locus coeruleus . To this end, it is possible that regular khat use is associated with an ongoing activation that would be associated with enhanced basal HPA activity but reduced responses to challenges, such as the adrenocortical increase after awakening that has been used as a marker of adrenocortical functional status …”

Section: Discussionmentioning

confidence: 99%

Effects of Chronic Khat Use on Cardiovascular, Adrenocortical, and Psychological Responses to Stress in Men and Women

et al. 2013

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Background: Khat is a psychostimulant plant widely used in Africa and its use has been growing rapidly in Europe and North America. Objectives: We investigated effects of chronic khat (Catha edulis) use on cardiovascular, adrenocortical, and psychological responses to acute stress. Methods: Chronic khat users and nonusers were compared on physiological measures and mood reports in a cross-sectional, mixed design. Measurements were conducted during 24-hour ambulatory monitoring and during a laboratory session. A total of 152 participants (58 women) were recruited by flyers posted around Sana’a University campus and the surrounding community in Sana’a, Yemen. Salivary cortisol and self-report measures were collected during a 24-hour ambulatory period prior to a lab testing session. In addition, blood pressures (BP), salivary cortisol, and mood measures were assessed during rest and in response to acute mental stress. Results: Khat users exhibited enhanced evening and attenuated morning cortisol levels, reflecting a blunted diurnal pattern of adrenocortical activity compared to nonusers. Khat users reported greater negative affect during the ambulatory period and during the laboratory session. In addition, they exhibited attenuated BP responses to stress. Conclusions and Scientific Significance: These novel results demonstrate altered adrenocortical activity and increased dysphoric mood among khat users. The extent to which these associations are due to effects of chronic khat use per se or instead reflect predisposing risk factors for khat use is yet to be determined.

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Section: Discussionmentioning

confidence: 99%

Effects of Chronic Khat Use on Cardiovascular, Adrenocortical, and Psychological Responses to Stress in Men and Women

et al. 2013

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“…Similar to psychostimulants, khat ingestion produces several central nervous system effects, including increased motor stimulation, euphoria, and a sense of excitement and energy (Widler et al, 1994; Kalix, 1996; Nencini et al, 1998). It also results in decreased appetite and increased blood pressure and heart rate.…”

Section: Pharmacology Of Khatmentioning

confidence: 99%

Khat use and neurobehavioral functions: Suggestions for future studies

Hoffman

Al’Absi

2010

Journal of Ethnopharmacology

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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.

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“…The two metabolites concentrations remain constant for no less than 9 hours from ingestion, when cathinone is no more found in plasma: in fact, its mean plasma concentration progressively declines to 0 in nearly 7 hours after reaching the peak (Widler et al, 1994). Since both norephedrine (Wellman, 1990) and (−)-norpseudoephedrine (Nencini, Fraioli, Pascucci, and Nucerito, 1998;Rothman et al, 2003) are pharmacologically active compounds, they may contribute to the general effects of khat chewing.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Khat Chewing from the Pharmacological Point of View: An Update

Graziani¹,

Milella²,

Nencini³

2008

Substance Use & Misuse

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Khat chewing is deeply rooted in the every day life of people living in the Horn of Africa and in South Arabia, where Catha edulis is endemic. Considered little more than an exotic habit producing just mild pharmacological effects, systematic investigations on its active principles have instead lead to the isolation and chemical characterization of cathinone, a compound structurally related to amphetamine. Three decades of intense experimental and clinical research on khat have depicted a consistently clear picture of its pharmacological and toxicological effects.

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(−)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties

Cited by 13 publications

References 43 publications

Effects of Chronic Khat Use on Cardiovascular, Adrenocortical, and Psychological Responses to Stress in Men and Women

Effects of Chronic Khat Use on Cardiovascular, Adrenocortical, and Psychological Responses to Stress in Men and Women

Khat use and neurobehavioral functions: Suggestions for future studies

Khat Chewing from the Pharmacological Point of View: An Update

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