Fronto-temporal cortical atrophy in ‘nyaope’ combination heroin and cannabis use disorder
Introduction
Global statistics on substance use disorders (SUDs) suggest that illicit drug use costs the globe tens of millions of disability adjusted life years with opioids causing the most harm (Peacock et al., 2018). Sub-Saharan Africa is one of the three regions in the world with the highest rates of opioid-related premature mortality. In South Africa, heroin is the most commonly abused opioid. Nyaope is the street name for a heroin-based powder that is predominantly smoked together with cannabis (Khine et al., 2015; Mokwena, 2015a, 2015b; Mokwena and Huma, 2014; Morgan et al., 2019a), notwithstanding recent reports of use by injection (Khine et al., 2015; Morgan et al., 2019a). Nyaope is commonly referred to as a drug cocktail and the heroin content is understated in the community, yet the composition, as recently measured across twelve different regions in South Africa, indicates that nyaope powder consists of minor quantities of other substances (e.g. caffeine, antiretrovirals, antidepressants), but all samples contain high levels of heroin (Khine et al., 2015; Mthembi et al., 2018).
Due to the heroin content of nyaope, it is highly addictive which results in the addicted individual re-orienting their lives towards the acquisition of the drug which has several social and health repercussions for the individual, family, and community (Fernandes and Mokwena, 2016; Masombuka, 2013). Despite this growing concern, treatment and management of nyaope use disorder remains a challenge. Currently patient retention and treatment outcomes are rather poor and reflect inadequate treatment services for those affected by opioid dependence (Morgan et al., 2019b). Due to the increasing burden of this drug in low-income communities we initiated the first ever cohort study in order to identify the neuroanatomical sequelae to guide treatment policy.
The neuroanatomical sequelae of nyaope use disorder are unknown. SUDs are often associated with severe brain morphological irregularities that correlate with cognitive dysfunction, psychiatric diagnoses, and history of substance abuse (Koob and Volkow, 2010; Li et al., 2014, 2017; Lorenzetti et al., 2019). Prefrontal regions are the most affected in SUDs and atrophy in these regions have been suggested to represent an initial vulnerability to developing SUD (Volkow et al., 2011) whereas other brain regions appear to be more specific to the substance of abuse itself and contribute differentially to the complex phenotype observed in the addicted individuals (Koob and Volkow, 2010; Li et al., 2014, 2017; Lorenzetti et al., 2019). Meta-analysis of structural magnetic resonance imaging (MRI) results show that opioid abuse (primarily heroin) is linked to frontal-temporal atrophy and grey matter deficits (Wollman et al., 2017). Furthermore, heavy use of cannabis is linked to significantly smaller volumes in the hippocampus and orbitofrontal cortex (Lorenzetti et al., 2019) or no significant brain changes as reported in a mega-analysis (Mackey et al., 2019). Nyaope consumption can be considered as polysubstance use as it is heroin smoked with cannabis. To our knowledge, despite the severe impact of nyope on health and social behavior (Fernandes and Mokwena, 2016; Masombuka, 2013), no human structural neuroimaging investigations have been conducted on combination heroin and cannabis use disorder. Previous polysubstance neuroanatomical investigations did not show unique alterations in the brain when substances are combined but showed that the areas altered were similar to areas altered by the individual constituents (Nurmedov et al., 2016). We are, therefore, interested to observe the specific neuroanatomical sequelea of nyaope use disorder and conducted the first MRI study to assess whether morphological irregularities would overlap with those found in heroin use, cannabis use or a combination of both.
Section snippets
Methods
This study was approved by the Human Research Ethics Committee (Medical) of the University of the Witwatersrand and was carried out in accordance with the Declaration of Helsinki. All participants signed a written informed consent prior to participation.
Results
Means and standard deviations for demographics of the two study groups as well as drug use history in NDI are presented in Table 1. The mean age of NDI was 26.75 SD ± 3.79 years and the mean age of the controls was 25.7 SD ± 4.25 years. There were no significant differences in age range, and also handedness was comparable between the two groups with both groups including 25 of the participants who were right-handed. Alcohol and nicotine use were similarly reported in both groups (NDI 26/28;
Discussion
Our results suggest that nyaope use is associated with patterns of cortical change in prefrontal, temporal, and parietal regions, with most pronounced effects in the right medial orbitofrontal (mOFC), right rostral middle frontal (a region of the dorsolateral prefrontal cortex; dlPFC), right superior frontal (dorsomedial prefrontal cortex; dmPFC), right superior temporal and right supramarginal (a region of the inferior parietal lobule) cortical regions. From previous literature, it is evident
Author disclosures
This project was funded by grants from the University of the Witwatersrand, the South African Medical Research Council and the National Research Foundation (118174 and 118508).
Role of funding source
Nothing declared.
CRediT authorship contribution statement
Nhanisi A. Ndlovu: Formal analysis, Writing - original draft. Nirvana Morgan: Investigation, Writing - review & editing. Stella Malapile: Visualization, Investigation. Ugasvaree Subramaney: Supervision, Writing - review & editing. William Daniels: Conceptualization, Supervision, Writing - review & editing. Jaishree Naidoo: Conceptualization, Methodology. Martijn P. van den Heuvel: Supervision, Methodology, Formal analysis, Software, Writing - review & editing. Tanya Calvey: Funding acquisition,
Declaration of Competing Interest
All authors reported no biomedical financial interests or potential conflicts of interest.
Acknowledgements
The authors would like to thank the Nelson Mandela Children’s Hospital for technical assistance on the project, particularly Mrs. Zanele Ngobese, Mr. Alfred Mazibuko and Mr. David Pooe. The authors would also like to thank Prof. Frans Verstraten, Dr. Joshua Davimes and Dr. Sahba Besharati for their support during the project and for interesting discussions.
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