Review article
A review of the neuropharmacological properties of khat

https://doi.org/10.1016/j.pnpbp.2007.12.033Get rights and content

Abstract

Background

The psychostimulant khat (Catha edulis Forsk), is a herbal drug cultivated and chewed as a recreational and socializing drug in East Africa and the Arabian Peninsula for centuries. Due to increasing air transportation and the loosening of customs restrictions, it is now readily available in the Western Countries mainly used by immigrants from khat growing areas causing a concern to policy-makers.

Objective

We conducted this review to further gain an insight to the neuropharmacological effects of khat.

Methodology

PubMed search engine with key terms ‘khat’ or ‘qat’ or ‘mirra’ or’qaad/jaad’ or ‘cathinone’ was used to obtain articles relevant to khat chewing. In total 284 English written articles published from 1959 to 2007 were screened.

Results

Most of the studies focused on cathinone, the postulated active psychostimulant alkaloid in khat. There were few studies which investigated the entire plant extract in either in vitro or animal studies. In the majority of the studies it was reported that both cathinone and cathine, another psychoactive constituent, have actions that are similar to those of amphetamine.

Conclusions

It seems that the well investigated khat alkaloids have many features similar to amphetamines; however there is a need for a more thorough examination of khat itself in well designed in vitro, animal and human studies with a range of comparator drugs before confirming the claim that khat is a “natural amphetamine”.

Introduction

Khat, Catha edulis Forsk, is an evergreen shrub or tree found growing wild or cultivated in the east of a region extending from Southern Africa to the Arabian Peninsula (Krikorian, 1984). The habit of khat chewing has prevailed for centuries in this part of the world, being cited in certain ancient texts, including the Old Testament (Cox and Rampes, 2003). The earliest scientific report on khat in the West was in the eighteenth century when the botanist Peter Forskal identified the plant in Yemen and called it C. edulis. There are several names for the plant, depending on its origin: tchat—Ethiopia, qat—Yemen (Alem et al., 1999), qaad/jaad—Somalia (Elmi, 1983), miraa—Kenya (Patel, 2000), mairungi—Uganda (Ihunwo et al., 2004), Muhulo—Tanzania, Hagigat—Hebrew (Bentur et al., 2007), cat, catha, gat, tohai, and muraa (Fasanmade et al., 2007). The dried leaves of khat are known as Abyssinian tea or Arabian tea (WHO, 2006). These many names attest to the widespread and presumably fairly old knowledge of C. edulis by native peoples of eastern and Southeastern Africa (Krikorian, 1984). However, the most common name is khat (Alem et al., 1999).

Recently published reviews on khat and cathinone focus on adverse health aspects and have only briefly addressed their pharmacology (Cox and Rampes, 2003, Al-Hebshi and Skaug, 2005, Al-Habori, 2005), or they investigate whether khat causes mental disorders in general (Warfa et al., 2007) or how it is specifically linked to psychosis (Odenwald, 2007). In particular, there is a lack of emphasis on the pharmacokinetics and behavioural pharmacology of khat. Thus the principal purposes of this review are to:

  • a)

    determine whether khat and its active principles are comparable to other stimulants such as amphetamines; and

  • b)

    to detect gaps in our knowledge of the neuropharmacology of khat.

To our knowledge, this review is the first in its kind in the area to critically analyze past literature and to propose suggestions for further investigation based on the limitations identified in this review.

Fresh leaves from khat trees are chewed daily by over 20 million people on the Arabian Peninsula and East Africa (Saha and Dollery, 2006, Al-Motarreb et al., 2002). The khat chewing habit is deeply rooted in the sociocultural traditions of these countries (Stevenson et al., 1996, Kennedy et al., 1983). Many of the users originate from countries between Sudan and Madagascar and in the southwestern part of the Arabian Peninsula. Khat use is particularly widespread in Ethiopia, Kenya, Djibouti as well as Yemen, where its use is socially sanctioned and even prestigious (Kalix, 1990, Belew et al., 2000). Khat is consumed at parties in combination with smoking cigarettes and drinking tea and soft drinks (Baron, 1999). The biggest population of chewers is in Yemen, where the plant is used as a social stimulant (Al-Motarreb et al., 2002). Recent reports suggest that 80–90% of the male adult and 10–60% of the female adult population in East Africa consume khat on a daily basis (Odenwald et al., 2005, Numan, 2004).

The use of khat has traditionally been confined to the regions where khat is grown (Yousef et al., 1995, Kalix and Khan, 1984, Al-Zubairi et al., 2003), because the shoots must be used fresh for the desired effects (Kite et al., 2003). In recent years, however, the economic importance and consumption of khat leaves have increased dramatically (Sawair et al., 2007, Odenwald, 2007). This change is due to improved road and air transport, which has allowed a much wider distribution (Mathys and Brenneisen, 1992, Cox and Rampes, 2003). Moreover, the use of the Internet has seen the emergence of several websites which advertise and sell fresh khat leaves (Toennes and Kauert, 2002, Beyer et al., 2007, Bentur et al., 2007). In addition, the influx of immigrants from East Africa and Arabian Peninsula, who continue to use khat, has resulted in the importation of khat to countries where these immigrants have settled, including Europe and the United States (Toennes and Kauert, 2004, Rousseau et al., 1998). In these immigrant communities, the khat party is an important social event and is a way for the participants to keep their ethnic identity (Stevenson et al., 1996, Nencini et al., 1989) and relieve the stress of living in a foreign country (Griffiths et al., 1997, Bhui et al., 2006, Bhui et al., 2003). In the UK, khat is used by (mainly male) members of the Somali and Yemeni community (Griffiths et al., 1997, Cunningham, 1998), and the prevalence has been shown to reach 80% in Somali immigrants in London (Griffiths et al., 1997), whilst in the USA khat use, which gained popularity during the first Persian Gulf crisis (Lurie et al., 1994, Giannini et al., 1992), is most prevalent amongst immigrants from Yemen, Somalia and Ethiopia (Browne, 1990). Khat use has also been reported in East African communities in Italy (Nencini et al., 1989), Israel (Granek et al., 1988), Australia (Stevenson et al., 1996), Norway, Holland, Belgium, German, Switzerland and Canada (Vanwalleghem et al., 2006, Nielen et al., 2004, Mathys and Brenneisen, 1992, Al-Motarreb et al., 2002).

Khat circulates freely in Yemen, Ethiopia (despite the Orthodox Tewahdo Church prohibiting its use), Somalia (though briefly banned during the six months rule of the United Islamic Courts in Mogadishu in 2006) and some other East African countries (Widler et al., 1994, Hattab and Angmar-Månsson, 2000, Alem et al., 1999). Almost every small kiosk in Addis Ababa, the Ethiopian capital, openly sells khat, and in small cities and towns all over the country it is brought to market as produce, where people publicly chew it and offer it to visitors as a mark of hospitality (Selassie and Gebre, 1996). In Yemen and Ethiopia there have been attempts to curtail the habit for social and economic reasons but these have met with little success (McKee, 1987, Kandela, 2000, Elmi et al., 1987, Elmi, 1983, Drake, 1988). One reason for this is that in Yemen (Al-Motarreb et al., 2002) and in some parts of Ethiopia it is consumed by government officials, making its regulation very difficult.

Although the active alkaloids of khat, namely cathinone and cathine have been labeled as Schedule I and Schedule III substances respectively by WHO since 1971 (WHO, 2003), its status in European countries is not uniform (Kalix, 1990). For example, khat is prohibited in Ireland, France, Switzerland, Sweden and Norway (Widler et al., 1994, Saha and Dollery, 2006) whilst it is legal in the U.K. and in the Netherlands (Nielen et al., 2004, Griffiths et al., 1997). Outside of Europe, it is illegal in the U.S.A. and Canada but permissible in Australia (Saha and Dollery, 2006, Patel, 2000, Fasanmade et al., 2007). Recently, the WHO Committee reviewed the data on khat and determined that the potential for abuse and dependence is low and the threat to public health is not significant enough to warrant international control, and did not recommend the scheduling of khat (WHO, 2006). Several authors have also suggested weighing the evidence dispassionately before sounding alarm on what is an important substance for sections of the immigrant population of many western countries (Weir and Thuriaux, 1988, Warfa et al., 2007).

Section snippets

Methodology

A literature research was conducted via PubMed search engine with the search terms ‘khat’ or ‘qat’ or ‘miraa’ or ‘qaad/jaad’ or ‘cathinone’. We also examined the reference sections of these articles to identify additional potentially relevant studies. A limited number of references that were not listed in the database were also used. The search was performed up to September 20, 2007. The research only included articles available in English that were published from 1959 to 2007. The full text of

Active constituents of khat leaf

The leaves and young shoots of C. edulis, a species of the plant family Celastraceae, are usually referred to as khat [Family: Celastraceae, genus: Catha, and Species C. edulis] (Nordal, 1980). Most taxonomists consider that the genus Catha consists of the single species Catha edulis (Nordal, 1980, Elmi, 1983). Khat is mainly grown in Ethiopia, Kenya, Yemen, Somalia, Uganda, South Africa and Madagascar (Odenwald et al., 2005, Ihunwo et al., 2004, Elmi, 1983, Al-Hebshi and Skaug, 2005). Many

Neuropharmacology of khat

The effects observed following khat consumption are generally of central stimulation and include euphoria, excitation, anorexia, increased respiration, hyperthermia, logorrhea, analgesia, and increased sensory stimulation (Patel, 2000, Nencini and Ahmed, 1989, Kebede et al., 2005). These effects, which have been observed in several clinical trials and animal studies with khat and or cathinone (Widler et al., 1994, Kalix et al., 1990, Brenneisen et al., 1990), are similar to those observed with

Algorithms of laboratory/preclinical studies on khat

After reviewing each article, which we obtained through one of the previously mentioned methods, we made an attempt to critically analyse the relevance and possibility of translation of the preclinical studies to human khat users (Fig. 6). For the analysis, original studies conducted on khat or its active principles in vitro and in vivo were used. Articles which emphasized the epidemiology, prevalence and socioeconomic aspects of khat were excluded from this assessment. Moreover, studies

Conclusions

The leaves of the tree C. edulis, known as khat, have for centuries been chewed for psychostimulant and socializing effects by people living in east African and Arabian Peninsula. Recently, this deep rooted socio-cultural tradition has also spread to East African and Middle Eastern communities in Europe and North America. The ingredients of khat leaves are numerous, but the major and most abundant active constituents include six major alkaloids, tannins (7–14%) and flavonoids. To date, urine

Recommendations

Although a number of investigations have been carried out using cathinone, the psychoactive component of khat, these may not wholly reflect the effect observed after administering khat in a dose similar to those used traditionally. Human addicts take the drug in its entirety; hence any translation from experimental studies could only be feasible when the entire extract is used. A case in point is cathedulins and the phenypentenylamine alkaloids, which have not been studied well, yet could

Acknowledgments

AM was supported in this research with a scholarship award from the NUI Galway International Scholarship Programme.

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