Khat - Chemistry and Pharmacology

Chemistry and Pharmacology

The stimulant effect of the plant was originally attributed to "katin", cathine, a phenethylamine-type substance isolated from the plant. However, the attribution was disputed by reports showing the plant extracts from fresh leaves contained another substance more behaviorally active than cathine. In 1975, the related alkaloid cathinone was isolated, and its absolute configuration was established in 1978. Cathinone is not very stable and breaks down to produce cathine and norephedrine. These chemicals belong to the PPA (phenylpropanolamine) family, a subset of the phenethylamines related to amphetamines and the catecholamines epinephrine and norepinephrine. In fact, cathinone and cathine have a very similar molecular structure to amphetamine. Khat is sometimes confused with methcathinone (also known as cat), a Schedule I substance that possess a similar chemical structure to the khat plant's cathinone active component. However, both the side effects and the addictive properties of methcathinone are much stronger than those associated with khat use.

When khat leaves dry, the more potent chemical, cathinone, decomposes within 48 hours leaving behind the milder chemical, cathine. Thus, harvesters transport khat by packaging the leaves and stems in plastic bags or wrapping them in banana leaves to preserve their moisture and keep the cathinone potent. It is also common for them to sprinkle the plant with water frequently or use refrigeration during transportation.

When the khat leaves are chewed, cathine and cathinone are released and absorbed through the mucous membranes of the mouth and the lining of the stomach. The action of cathine and cathinone on the reuptake of epinephrine and norepinephrine has been demonstrated in lab animals, showing that one or both of these chemicals cause the body to recycle these neurotransmitters more slowly, resulting in the wakefulness and insomnia associated with khat use.

Receptors for serotonin show a high affinity for cathinone suggesting that this chemical is responsible for feelings of euphoria associated with chewing khat. In mice, cathinone produces the same types of nervous pacing or repetitive scratching behaviors associated with amphetamines. The effects of cathinone peak after 15 to 30 minutes with nearly 98% of the substance metabolized into norephedrine by the liver.

Cathine is somewhat less understood, being believed to act upon the adrenergic receptors causing the release of epinephrine and norepinephrine. It has a half-life of about 3 hours in humans. Because the receptor effect are similar to those of cocaine medication, treatment of the occasional addiction is similar to that of cocaine. The medication bromocriptine can reduce cravings and withdrawal symptoms within 24 hours.