Khat and the brain: the SSA talks to Ayan Ahmed
Ayan Ahmed is an SSA funded PhD student looking at the impact of khat use on neurobehavioural function. Ayan’s systematic review on this subject was recently published in PLOS One. The SSA caught up with Ayan to find out more:
SSA: Your systematic review focused on khat and neurobehavioural functions. Is there a relationship between the two?
Ayan: “Yes, I think so. Current findings indicate that use is associated with learning and memory deficits or problems in both animal and human studies. However, not many studies have looked at the neurobehavioural or even neurocognitive functions relating to Khat. So, we had a small pool of articles that we could explore to see whether there was a relationship..”
What kind of neurobehavioural and neurocognitive outcomes did you look at? Were there differences in what was being measured?
“We explored neurobehavioural functions implicated in other stimulant researches, mainly executive functions in terms of working memory, cognitive (mental) flexibility and inhibition. Despite the small pool of khat literature available, we found that long-term khat usage is associated with impairments in numerous cognitive areas, including learning, motor speed/coordination, set-shifting/response inhibition skills, cognitive flexibility, short term/working memory, and conflict resolution. Most of the studies we found focused on working memory and learning. However, acute effects show that Khat improves cognitive performance in selected domains, e.g. response conflict.
Having said that, the lack of normative data for many of the tasks used in the studies makes it hard to truly determine whether there is any clinical significance in these findings.
“Ethiopia is one of the countries where Khat is heavily cultivated because it’s financially more profitable for the farmers to grow than general agricultural produce. As a result, there’s just been a surge of people using it.”
Did any of the studies look at causal pathways and why Khat was associated with these neurobehavioural or cognitive functions changes?
“This is perhaps the biggest gap in khat research and the very few articles out there about neurobiological pathways in humans. The main psychostimulant component of Khat is cathinone, which is similar in both structure and pharmacological properties to amphetamines. This provides a model for us to explore whether khat use results in similar neurobiological alterations in dopaminergic pathways observed in long-term amphetamine users. More specifically, the pathways involved in higher-order functions, e.g. working memory, and inhibition involved in the maintenance of drug-taking behaviours. As far as I’m aware, there haven’t been any neurobiological or brain imaging studies to explore this further. For me, this review identified studies looking at neurobehavioural function and highlights the current gaps that remain with regards to understanding the biological processes that underline these functions.”
What first interested you in the association between Khat and neurocognitive or behavioural function?
“Many of the migrants from the region are fleeing conflict, poverty and have experienced trauma, loss, separation, and other migration-related issues. Several studies suggest individuals from this group have a higher incidence rate of psychiatric disorders and substance use or misuse.
Refugees and migrants are a very distinct population due to cultural practices such as linguistic differences, race, and ethnicity, which profoundly impact the screening, diagnosis, and treatment of psychiatric and substance use disorders. Often immigrants and refugees’ views or denial of substance use and the added social exclusion, racism and lack of or mistrust of the western healthcare system have contributed to the underutilization of health services (especially around substance abuse/mental health services). As a result, this drive towards compulsive and problematic use is reported to be a way to self-medication.
“Understanding the social and cultural context of use and the underlying biological consequences of khat use is essential. Does chronic use lead to changes in structure and function in the brain? If so, what does this mean in terms of treatments?”
There were a couple of reasons why I wanted to do this. Firstly, only a few studies have looked at the consequences of Khat on cognition or behaviour. Those conducted had small sample sizes or were related to specific settings outside of Ethiopia and the UK. Secondly, despite the ban of Khat in the UK, it is used and remains an ongoing problem among the East African diaspora, specifically its association with mental and physical health.
Although there is a lack of culturally suitable tools and normative data to determine if the cognitive differences observed are abnormal and associated with khat use. My initial studies looked at behavioural and cognitive function. This provides a stepping-stone to identifying areas of interest further to investigate the effects of long-term khat on the brain using brain imaging.
Understanding the social and cultural context of use and the underlying biological consequences of khat use is essential. Does chronic use lead to changes in structure and function in the brain? If so, what does this mean in terms of treatments? And other problematic substance use such as alcohol and nicotine. Which currently, no one is really thinking or talking about it. If we explore some of these questions, perhaps this information can develop a culturally suitable treatment for users both in Africa and the UK. Currently, there is only one rehabilitation centre in the whole of East Africa, and that’s in Ethiopia.
Ethiopia is one of the countries where Khat is heavily cultivated because it’s financially more profitable for the farmers to grow than general agricultural produce. As a result, there’s just been a surge of people using it. Traditionally it was used by the elders in the community during social settings once in a while. Now it’s consumed more frequently. Alarmingly, the age of onset and the consumption rate among children and young adults has increased over the years. In some regions, Khat is seen as a gateway drug to other substances, with young adults reporting to use Khat along with alcohol, cannabis and smoking cigarettes. So, it’s one of those problems that’s brewing in East Africa at the moment, and that has huge consequences on the development of the country.
In order to understand the cultural practices and traditions around khat use, I wanted to go to Ethiopia, where Khat is culturally accepted and legal. For many health professionals in understanding whether Khat is causing any harm, and if so, what harm and how can we prevent that or develop strategies for helping people to reduce the amount that they chew.”
Is this systematic review part of a wider set of studies that form your PhD?
“Yes, the systematic review allowed to examine current literature on the effects of khat use on neurobehavioural studies. Based on this, I identified key gaps and groups that have not yet been explored. With that in mind, I went to Ethiopia to carry out replicate studies on young adults and adolescents. In particular, we recruited university students as they were identified as being high risk for developing khat dependency. Most literature reports that the onset of khat use is between 15-18 years in Ethiopia. With regards to brain development, early khat use could lead to long-term cognitive deficits (e.g. inhibitory control) and substantially increase the likelihood of developing khat dependency and polysubstance use and/ or substance use disorder. In the UK, I am also looking to see whether cognitive performance improves with abstinence by comparing the neurobehavioural function of past users who have stopped chewing after the ban, display and current khat users.
You’re now working on a meta-analysis. Can you tell us a bit about that?
For the meta-analysis, we’re broadening out the inclusion criteria to look at other substances. The reason is that if you look at the literature, even the systematic review, a lot of the comparisons as to the potential harms of Khat with regards to neurobehavioural function comes from its pharmacological similarity with cathinones and amphetamines. So, we’re looking at what impairments or deficits are associated with amphetamines and other psychostimulants to give us a potential overview of what other cognitive domains to examine. At the moment, I’m just doing the results, with the goal to publish this new review along with all the studies I have carried out both in the UK and Ethiopia.
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