Khat, a Natural Source of Amphetamine-like Substances

by Grow Up Conference | Jul 18, 2023 | Extraction Magazine, Media Partners

In the countries of the African Horn and the Arabian peninsula there is a long tradition in chewing Khat leaves and young inflorescences that goes back in centuries. [1]
The Catha edulis or Khat is a flowering plant commonly grown and used for its stimulant action. It appears as an evergreen shrub with an aromatic odor. The plant can be grown in dry soil and at different altitudes and climatic conditions. Chewing Khat is part of some social traditions in Saudi Arabia, Yemen and Somalia among other countries.

It is usually preserved in banana leaves and the taste is somewhat sweet and astringent. [2]

Khat is categorized by the World Health Organization as a possible addictive drug. For this, it is prohibited and some active compounds are included in the list of controlled substances.

Phytochemical Composition

Many different compounds are contained in this plant including terpenoids, flavonoids, sterols, tannins, glycosides, amino acids, vitamins, minerals and alkaloids. [2] The latter are responsible for the amphetamine-like effects of the plant, stimulating the central nervous system (CNS) leading to higher blood pressure, euphoria, excitement among other effects. The alkaloids contained in higher concentration are cathinone and cathine, two related compounds structurally similar to amphetamine and noradrenaline.
Young leaves and shoots mainly contain cathinone, which is subsequently metabolized to cathine and norephedrine during plant maturation. Among other relevant alkaloids contained in Khat and contributing in minor extent to the stimulant effects there are pseudomerucathine, merucathione and merucathine. Another important class of alkaloids contained in Khat are the cathedulins, which are polyesters of euonyminol containing a polyhydroxylated sesquiterpene skeleton.

Cathinone is a monoamine alkaloid responsible for psychoactive effects. It undergoes decomposition during the harvesting and drying of the plant material. [2] Because cathinone is both a primary amine and a ketone, it easily splits in two monomers. For this reason fresh leaves are preferred than dried ones and young buds are preserved in banana leaves in order to preserve the freshness and avoid cathinone dimerization. [2]

Pharmacological Effects 

Khat is chewed into a ball and it is kept for a while in the cheek causing a characteristic bump. [2] The plant active compounds are released into the saliva and they are rapidly absorbed in the digestive tube. The cathinone is metabolized in a stereoselective manner into cathine and norephedrine. [3]
Cathinone and its derivative has a CNS stimulant and sympathomimetic effects, similarly to other stimulant compounds such as cocaine and amphetamines.
Cathinone is capable of inducing dopamine release in the brain and inhibiting dopamine reuptake.

The effects start around 1.5-3 hours from the start of the plant chewing. The average plasma concentration of the main active constituents of Khat can reach 100 ng/ml starting from 1 hour of 60 g of fresh plant mastication. After a state of euphoria and feelings of improved alertness and happiness, it is usual to feel depressed, irritated, to have difficulties in sleeping or eating disorders such as anorexia. [4]

The concentration in blood of cathinone will decrease over the course of 8 hours. The first pass effect allows the liver metabolization of cathinone into norephedrine and only the 2% of cathinone is expelled through the urine. [5]

The use of Khat can induce addictive effects, but under normal conditions the psychotropic activity is just temporary: confusion and disorientation occur as transient phenomena. [1] Even if effects are similar to those of amphetamines such as Methamphetamine, there are some interesting differences in terms of toxicity, tolerance and addictive properties. To make an example, Khat does not cause physical dependence and the drug withdrawal symptoms are usually a mild depression or hypotension.

Nevertheless chronic use induces many adverse effects such as gastro-intestinal issues, urinary infections and cardio-vascular diseases.

Further work has to be done in order to reveal the entire composition of this plant and the variations of phytoconstituents depending on the geographical position. A part the main studied active ingredients cathinone and cathine, the pharmacology of other Catha edulis constituents is still poorly understood and researched. [6]

Short-term Effects on Human Health [7]

• Reduced sleepiness;
• Hypertension;
• Blurred vision;
• Hyperthermia;
• Dry mouth;
• Loquacity;
• Euphoria;
• Excitement;
• Depressive reactions at the end of Khat session;
• Psychotic reactions at high doses;
• Constipation;
• Lethargy (the next morning);
• Migraine;
• Impaired sexual potency in men.

Toxicity and Khat-induced Psychosis

The Khat-induced effects on the CNS looks like the ones of amphetamine, with differences being quantitative rather than qualitative. [2] From a biochemical point of view, some studies have been done showing that Catha edulis consumption in rabbits induces decreased levels of plasma cholesterol, glucose and triglycerides. Kidney lesions and acute liver damage were observed, even if the behavior and the activity of the animals looked normal.

If chewed in large amounts, can induce two kinds of psychosis: the first is a manic illness with delusions of omnipotence, and the second is a paranoid psychosis with auditory hallucination, persecutory delusions and fear. [2] Symptoms stop rapidly if the substance is withdrawn. Nevertheless in some severe cases, anti-psychotic drugs have been administered in order to alleviate the adverse Khat effects.

Khat psychosis can be accompanied by aggressiveness and violent reactions. It has been argued that these reactions to large Khat doses are linked to an exacerbation of pre-existing psychiatric disorders.
In any case chewing more than two bundles of Khat per day is associated with risks of psychiatric consequences. [2]

Socioeconomic Problems Associated with Khat

The estimated number of people using Catha edulis is around 5 to 10 million, mainly distributed in Yemen, Ethiopia and Somalia. Predominantly consumed by males, Khat is also chewed daily by children under the age of 12 years old. This intense abuse of the amphetamine-like plant is a serious problem impairing people’s life, the family balance and the overall society.

The intensification of the Khat cultivation made this drug globally widespread. Unlike coca leaves, it is still out of the control of the government in many countries. It is reported that in the years 1999-2000 the exportation of Khat in different countries worthed 55 millions of dollars.

Due to the ban of Khat in many countries it is difficult to answer all the questions linked to the addictive qualities of the plant and the effects on an economic and social point of view.
In Ethiopia 90% of Khat is cultivated in order to be exported. The Ethiopian government benefited from the Khat business, but also the people involved in the cultivation, preparation, selling and smuggling of the plant. Nevertheless due to the long term health problems linked to Khat daily consumption and abuse, the health care costs could increase in countries already problematic in terms of budget and administration.

More studies related to Catha edulis and the public health and economic problems in poor countries are essential in order to face the issue. The potential harmful effects of this amphetamine-like plant should be explained. Even if leaves chewing is a long-standing tradition, all the consumers should be aware about the health problems they could experience.

References:

[1] Al-Juhaishi T, Al-Kindi S, Gehani A. Khat: A widely used drug of abuse in the Horn of Africa and the Arabian Peninsula: Review of literature. Qatar Med J. 2013 Nov 1;2012(2):1-6. doi: 10.5339/qmj.2012.2.5. PMID: 25003033; PMCID: PMC3991038.
[2] Wabe NT. Chemistry, pharmacology, and toxicology of khat (catha edulis forsk): a review. Addict Health. 2011 Summer-Autumn;3(3-4):137-49. PMID: 24494129; PMCID: PMC3905534.
[3] Silva, B.; Soares, J.; Rocha-Pereira, C.; Mladěnka, P.; Remião, F.; on behalf of The OEMONOM Researchers. Khat, a Cultural Chewing Drug: A Toxicokinetic and Toxicodynamic Summary. Toxins 2022, 14, 71.
[4] Khat drug profile
[5] KHAT
[6] Getasetegn, Million (2016). Chemical composition of Catha edulis(khat): a review. Phytochemistry Reviews, 15(5), 907–920.
[7] World Health Organization (WHO) Expert Committee on Drug Dependence. Assessment of Khat (Catha edulis Forsk).