The pharmacology of psychoactive alkaloids from ephedra and catha

Ever since the introduction of the alkaloid ephedrine as an anti-asthmatic, the CNS stimulatory effects of this sympathomimetic have been a problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effects, but also by the occurrence of insomnia, restlessness and anxiety. Exceptionally, ephedrine may even induce toxic psychosis, and the possibility of this side effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis or khat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of khat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in khat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of khat; the results of various in vitro and in vivo studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that cathinone has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of khat as a stimulant and social drug.