Cathinone

The drug discrimination paradigm was employed to evaluate the effect of coadministration of both caffeine and nikethamide upon the discrimination of a low dose of cathinone. In rats trained to discriminate between 0.8 mg/kg l-cathinone and its vehicle in a two-lever food-motivated operant task, 0.2 mg/kg cathinone produced 29.2% of responses on the cathinone-appropriate lever. This lever was chosen in 0 and 50% of trials with 25 mg/kg nikethamide and 20 mg/kg caffeine, respectively. Coadministration of caffeine, nikethamide, or caffeine plus nikethamide with low-dose cathinone produced strong cathinone-like discriminative performance. This potentiattion of cathinone by caffeine and nikethamide is reflective of noncontrolled drugs of abuse containing similar combinations especially for that of antiadipositum X-112, a drug containing all three agents and widely abused in Europe.

The effect of (-)-cathinone, caffeine and their combinations was studied on the sexual behavior of male rats. Male sexual activities were assessed by recording the erectile responses (grooming of genitalis, yawning/stretching and homosexual mounting), in the absence of females. The copulatory behavior was observed by caging males with receptive females brought into oestrus with s.c. injection of estradiol benzoate and progesterone. The copulatory pattern of male rats (mounting, intromissions, ejaculations and refractory period) was recorded. The oral treatment of cathinone (5 mg/kg day), caffeine (50 mg/kg day) and their combinations for 15 days increased arousal (motivation) in male rats as evidenced by increased mounting performance and anogenital investigatory behavior. However, erectile and ejaculatory responses, measured in the present study, showed no stimulant effect. It is conceivable from the present results that cathinone, the psychostimulant constituent of khat modified masculine pattern behavior and caffeine also changed the effect of cathinone when administered concomitantly. However, our data provide no evidence that cathinone could be considered as an aphrodisiac.

/HUMAN EXPOSURE STUDIES/ The stimulant effects of cathinone were evaluated in 6 healthy male volunteers (mean age 32 yr) who were given a single oral dose of 0.5 mg/kg cathinone hydrochloride or placebo in a double blind randomized crossover study. Cathinone produced increases in blood pressure and heart rate, concomitant with the presence of the drug in blood. The physical and mental changes that subjects reported indicate that the drug has euphorigenic and psychostimulant effects. These observations support the assumption that cathinone is the constituent mainly responsible for the effects of khat (Catha edulis) and show that this alkaloid has amphetamine-like effects in humans. /Cathinone hydrochloride/

/HUMAN EXPOSURE STUDIES/ The main effect of khat is an increase of energy and alertness. This effect is thought to be attributable to the phenylalkylamine cathinone ... . Six drug-naive volunteers received a single dose of khat corresponding to 0.8 mg/kg body weight, as well as alkaloid-free khat as a placebo. Psychologic effects were evaluated by the Addiction Research Center Inventory (ARCI) and visual analog scales. Physiologic measures were systolic blood pressure, diastolic blood pressure, and heart rate. Plasma concentrations of cathinone and its metabolites norephedrine and R,R-(-)norpseudoephedrine were determined by HPLC. Maximal plasma concentrations of cathinone (127 +/- 53 (SD) ng/mL) were attained after 127 +/- 30 minutes. The area under the plasma concentration-time curve from 0 to 9 hours was 415 +/- 207 ng/mL hour, and the terminal elimination half-life was 260 +/- 102 minutes. An effect of khat was observed in the ARCI scales Abuse Potential (p < 0.01), Motor Stimulation (p < 0.02), Amphetamine-Like Effect (p < 0.005), and Stimulation-Euphoria (p < 0.005), as well as in the visual analog scales Excited-Calm (p < 0.001) and Energetic-Lethargic (p < 0.001). ... Results provide ... evidence for the amphetamine-like stimulatory effects of khat leaves. These effects were closely similar to those observed after cathinone, 0.5 mg/kg body weight, although peak plasma concentrations of cathinone after khat were delayed.

/HUMAN EXPOSURE STUDIES/ The leaves of the khat plant (Catha edulis) are chewed for their pleasurable effects. Chewing releases cathinone which may decrease appetite through an unknown mechanism. Levels of the peptide ghrelin increase with hunger and decrease immediately post-prandially, while peptide YY is released following a meal. /It was/ hypothesized that the anorexigenic effects of khat may be mediated through changes in these hormones. Six habitual khat chewers attended on two separate occasions. For a period of 3hr they chewed either khat leaves or lettuce. Blood pressure and pulse rate were monitored throughout, as were subjective assessments of hunger and fullness. Plasma samples were analyzed for cathinone, ghrelin and PYY levels. Chewing khat significantly decreased subjective feelings of hunger and increased fullness (p<0.05) but had no effect on ghrelin and PYY levels. Khat led to an increase in cathinone levels as well as an increase in blood pressure and pulse rate. Cathinone levels correlated positively with fullness and pulse rate and negatively with hunger. Chewing khat decreases subjective feelings of hunger and increases systemic sympathetic tone, but has no effect on ghrelin and PYY levels. The anorexigenic effect of khat may be secondary to central mechanisms mediated via cathinone.

/HUMAN EXPOSURE STUDIES/ ... Hagigat (capsules of 200 mg cathinone) have been marketed in Israel as a natural stimulant and aphrodisiac. A prospective observational study of calls to the Poison Center regarding exposure to Hagigat during the course of 10 months /is reviewed/. Demographic and clinical data were abstracted from patients' records and telephone follow up was performed. Data of 34 consecutive patients aged 16-54 years were analyzed. The amount consumed was 1/2-6 capsules (ingestion-32, sniffing-2). Main clinical manifestations were headache, vomiting, hypertension, nausea, tachycardia, dyspnea, chest pain, and myalgia. Main complications were myocardial ischemia (3), pulmonary edema (2), and intracerebral hemorrhage (1), all in young subjects. Treatment was supportive; one patient underwent neurosurgery.

For more Human Toxicity Excerpts (Complete) data for Cathinone (23 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Three groups of mice were treated with aqueous solution of khat extract in the dose of 50, 100, and 200 mg/kg body weight daily by oral intubation route for 6 weeks. The results indicated a dose-dependent decrease in body weight, an increase in the incidence of mortality and induction of site specific body and eye lesions. The histopathological examination of the lesions revealed reactive hyperplasia and necrosis in the lymphoid tissues. The necrotic areas in the subcutaneous tissues showed the presence of numerous polymorphs. /Khat/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.

/LABORATORY ANIMALS: Neurotoxicity/ ... Three experiments were, therefore, conducted to measure locomotor activity following central administration of cathinone in rats. The first experiment determined the dose-dependent effects of cathinone on activity following intracerebroventricular (ICV) administration. As psychostimulant effects are believed, at least in part, to be mediated by dopaminergic systems, in Experiment 2 cathinone was injected into the dopamine nerve terminals of the nucleus accumbens. Experiment 3 examined the effects of cathinone injection into the dopamine cell body region of the substantia nigra, and activity was measured. Results of the ICV injection of cathinone revealed a dose-dependent increase of activity. The highest dose tested (64 ug) yielded a 117% increase in activity when compared to baseline, whereas a 20 ug bilateral nucleus accumbens (NA) injection of cathinone increased activity fivefold. These findings evidence the hypothesis that the effects of cathinone are dopaminergically mediated. Substantia nigra (SN) injections of cathinone were without effect.

/LABORATORY ANIMALS: Neurotoxicity/ The effects of repeated oral administration of the psychostimulant plant, Catha edulis and its active principle, cathinone on rats were studied using isolation induced aggression paradigm. The behavioral responses were videotaped and scored later by offline data analyses. Rats were decapitated at the end of the behavioral experiment and in the relevant brain regions, monoamines were assessed. The results demonstrate that isolation of male rats produces a baseline aggression. Treatments with the psychostimulant plant, Catha edulis or commercial S-(--)-cathinone enhanced significantly: The locomotor activities and the baseline aggression behaviors compared with vehicle treated rats. Neurochemical correlates revealed a significant depletion of serotonin (5-HT) and its corresponding metabolites (5-HIAA) in both the anterior and posterior striatum. There was also a reduction in the level of homovanillic acid (HVA) in the hippocampus. Additionally, elevation of dopamine level was observed in the nucleus accumbens, especially, in those rats treated with Catha edulis extract. Cathinone, on the other hand, increased the level of HVA in the posterior striatum and decreased HVA in the nucleus accumbens. In conclusion, the present data demonstrate that repeated administration of Catha edulis or S-(--)-cathinone enhances aggression in rats, presumably by decreasing the level of serotonin and its corresponding metabolites. Besides, the data obtained do not rule out the involvement of dopamine in aggression behavior. /S-(-)cathinone/

Treatment of khat ingestion is largely symptomatic. Symptomatic patients should be placed on a monitor, have an ECG obtained, and have vital signs monitored frequently. Most symptoms resolve in 4 to 6 hours. Patients with persistent vital sign abnormalities, evidence of end-organ ischemia, or psychiatric symptoms should be admitted for observations. /Khat/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers, and salts of isomers. Cathinone (DEA Code Number: 1235) is included on this list.

SRP: This is a Schedule I controlled substance in the USA.

Khat is used as a traditional medicine by some indigenous people of East Africa, but neither khat nor its isolated active ingredients /including cathinone/ have been widely recognized for their therapeutic use.

Fresh khat (Catha Edulis) contains around 0.1 % cathinone and smaller amounts of cathine. Although khat comprises an inhomogeneous plant preparation, it is not normally adulterated with other material.

Designer drug