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South African Medical Journal =... Apr 2022In South Africa (SA), adolescent girls and young women (AGYW) aged 15 - 24 years account for nearly 25% of all new HIV infections in the country. The intersection of...
BACKGROUND
In South Africa (SA), adolescent girls and young women (AGYW) aged 15 - 24 years account for nearly 25% of all new HIV infections in the country. The intersection of substance use and sexual risk continues to drive the HIV epidemic among AGYW. For example, methaqualone, also known as Mandrax, has sedative effects that may affect women's ability to negotiate condom use during sex, refuse sex without a condom, or consent to sex, thereby increasing their risk for HIV. Consequently, it is critical to understand how Mandrax use affects HIV risk among AGYW and to assess awareness of and willingness to use biomedical HIV prevention methods, such as pre-exposure prophylaxis (PrEP), among AGYW who use Mandrax.
OBJECTIVES
To examine the role of Mandrax use in sexual behaviours and investigate the extent to which AGYW who use Mandrax are aware of and willing to initiate PrEP.
METHODS
Data for this report were derived from baseline and 6-month follow-up data provided by 500 AGYW participating in a cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. AGYW who self-identified as black African or coloured, reported using substances, reported condomless sex in the past 3 months, and had discontinued school early were recruited from 24 community clusters across Cape Town, SA. Following consent/assent, participants provided biological specimens to test for recent drug use (including Mandrax) and completed the self-report questionnaire.
RESULTS
Logistic regression analysis revealed that the AGYW who had a positive test result for Mandrax use were less likely to use a condom with their main partner (p=0.01), and almost three times more likely to use alcohol and/or other drugs before or during their last act of sexual intercourse (p<0.001), compared with the AGYW who had a negative Mandrax test result. Mandrax use was not significantly related to PrEP awareness (p>0.10) or willingness to use PrEP (p>0.10), but 70% of AGYW who used Mandrax were willing to initiate PrEP.
CONCLUSION
The study findings highlight how Mandrax use may contribute to HIV risk among SA AGYW. Key decision-makers should consider incorporating substance use prevention efforts into existing HIV reduction programmes and equip youth-friendly clinics with the resources to identify AGYW who use Mandrax and offer them PrEP.
Topics: Adolescent; Anti-HIV Agents; Diphenhydramine; Drug Combinations; Female; HIV Infections; Humans; Methaqualone; Pre-Exposure Prophylaxis; Sexual Behavior; South Africa; Substance-Related Disorders
PubMed: 35587247
DOI: No ID Found -
Food Additives & Contaminants. Part A,... Apr 2022In this study, we developed and validated a liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) method used to simultaneously determine levels of...
In this study, we developed and validated a liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) method used to simultaneously determine levels of four fluoroquinolones (ofloxacin, norfloxacin, lomefloxacin, and pefloxacin) and two antipsychotics (diazepam and methaqualone) in fish and shrimp. The samples were extracted with a mixture of anhydrous sodium sulfate and acetonitrile, and purified by C cartridge solid-phase extraction with an optimized eluent. The MS method was applied to recognize the molecular structure of these compounds according to a main fragmentation scheme. The key ions of identification and quantification were deduced from chemical structures. Multiple reaction monitoring was used to quantitatively analyse the compounds of interest. Satisfactory linearities were obtained ( ≥0.99) with the limits of quantitation (LOQs) ranging between 0.03 and 1.96 μg kg. The recoveries were 74-122%, with a relative standard deviation (RSD) below 4.9% for these compounds at the spiking level of three, five, and ten times the LODs, respectively. The LC-MS/MS method allows precise and sensitive determination of residues of six important banned veterinary drugs in fish and shrimp tissue. This methodological approach solved the problem imposed by the need for two or more analysis methods to analyse the compounds of interest described in this study.
Topics: Animals; Antipsychotic Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Crustacea; Fishes; Fluoroquinolones; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 35302928
DOI: 10.1080/19440049.2022.2032381 -
PloS One 2022People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess...
People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.
Topics: Adolescent; Adult; Contact Tracing; Cross-Sectional Studies; DNA, Bacterial; Diphenhydramine; Drug Combinations; Drug Users; Female; Humans; Male; Methamphetamine; Methaqualone; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Registries; South Africa; Sputum; Surveys and Questionnaires; Tuberculosis; Young Adult
PubMed: 35167586
DOI: 10.1371/journal.pone.0262440 -
Journal of Analytical Toxicology Sep 2021Methaqualone, known previously under the brand name Quaalude, is a Schedule I sedative hypnotic drug that may cause neurotoxicity in overdose, characterized by...
Methaqualone, known previously under the brand name Quaalude, is a Schedule I sedative hypnotic drug that may cause neurotoxicity in overdose, characterized by somnolence, hyperreflexia and muscular hyperactivity. We present a case of a 21-year-old male who reportedly ingested methaqualone in addition to insufflation of street cocaine. He subsequently developed hypoxia, hyperreflexia, myoclonus, and altered mental status. His laboratory results were notable for the presence of methemoglobinemia, which was most likely due to a cocaine contaminant. Laboratory analysis of the alleged methaqualone pills identified the substance as SL-164, a dichlorinated methaqualone analog. Urine toxicology results were positive for SL-164 (and presumed metabolites) as well as for cocaine and tetrahydrocannabinol metabolites. The patient was treated with supplemental oxygen and a benzodiazepine (lorazepam) and observed in the Emergency Department (ED) until his symptoms resolved. This case highlights current community access to methaqualone analogs. The case also focuses on laboratory techniques used to identify the methaqualone analog.
PubMed: 34545408
DOI: 10.1093/jat/bkab103 -
Journal of Clinical Pharmacology Aug 2021There are many nonopioid central nervous system depressant substances that share a gamma-aminobutyric acid (GABA) receptor-related mechanism of action. These...
There are many nonopioid central nervous system depressant substances that share a gamma-aminobutyric acid (GABA) receptor-related mechanism of action. These sedatives-hypnotics can be indicated to treat anxiety, seizures, depression, and insomnia but are also used as substances of abuse and used to facilitate sexual assault. Barbiturates, methaqualone, and glutethimide were among the first type A GABA receptor-mediated sedative-hypnotics. Their clinical use was limited for most indications by serious adverse events and strong abuse potential but continue to be used illicitly around the world. The benzodiazepines supplanted barbiturates for most indications because they were less likely to cause severe adverse events in monotherapy. Flunitrazepam is a newer benzodiazepine that is preferentially used recreationally and to facilitate sexual assault. Flunitrazepam has greater potency and higher affinity for the type A GABA receptor than most benzodiazepines. Gamma-hydroxybutyric acid is sought illicitly for its hypnotic, euphoric and anabolic effects as well as to facilitate sexual assault. When any of these GABAergic drugs are used in high doses or with other sedative hypnotic agents, respiratory depression, coma, and death have occurred. Chronic use of these GABAergic drugs can lead to significant withdrawal syndromes. Phenibut and selank are poorly studied Russian drugs with GABAergic mechanisms that are inexplicably sold to US consumers as dietary supplements. Poison control center calls regarding phenibut have increased substantially over the past 5 years. Desired euphoriant effects account for the recreational and illicit use of many GABA-modulating agents. However, illicit use can lead to significant toxicities related to abuse, dependence, and subsequent withdrawal syndromes. Significant evaluation of developing agents with GABA properties should be conducted to determine abuse potential before public access ensues.
Topics: Drug Overdose; Flunitrazepam; Humans; Hypnotics and Sedatives; Oligopeptides; Receptors, GABA; Receptors, Metabotropic Glutamate; Substance Withdrawal Syndrome; Substance-Related Disorders; gamma-Aminobutyric Acid
PubMed: 34396551
DOI: 10.1002/jcph.1922 -
Chemosphere Dec 2021This study evaluated the occurrence and fate of fourteen contaminants of emerging concern (CECs) at two South African wastewater treatment works (WWTW). Daily loads of...
This study evaluated the occurrence and fate of fourteen contaminants of emerging concern (CECs) at two South African wastewater treatment works (WWTW). Daily loads of the drug targets were calculated in the aqueous phase of influent- and effluent wastewater to evaluate their fate at the treatment works, along with population-normalised daily loads in raw influent wastewater to identify community-wide substance use patterns in the two study areas. Environmental risk characterisation of the CECs at WWTW effluent discharge was done using conventional risk quotient (RQ) estimations. A significant reduction of most CECs was observed at both WWTW locations, except for some that have been previously recorded to persist through various WWTW processes globally, including the illicit drug methaqualone that was reported here for the first time to evaluate its fate during wastewater treatment, substance use trends, and potential toxicological risk. Moderate-to high-RQs were estimated for several target CECs during the sampling period for both treatment facilities. The results presented here suggest the need for a multi-disciplinary approach to WWTW monitoring of CECs and highlight the need for further refinement of risk assessment approaches to mitigate recalcitrant- or pseudo-persistent CECs in wastewater discharge. Such refinement should include: (1) identifying the potential ecological risk on a wider range of sentinel indicators, (2) interaction of CECs with various biochemical pathways (including sub-lethal toxicity responses), (3) identifying the persistence and toxicological risks of breakdown products and (4) partitioning of CECs in the aqueous environment and/or bioaccumulation in freshwater biota.
Topics: Environmental Monitoring; Environmental Pollutants; Illicit Drugs; South Africa; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 34265704
DOI: 10.1016/j.chemosphere.2021.131460 -
Substance Abuse 2021: A 22-year-old male with a known history of drug abuse presented to our department with prolonged agitated delirium, myocloni, tachycardia and subfebrile temperature...
: A 22-year-old male with a known history of drug abuse presented to our department with prolonged agitated delirium, myocloni, tachycardia and subfebrile temperature after the deliberate ingestion of opium poppy tea ( L.) together with the methaqualone analog SL-164 (5-chloro-3-(4-chloro-2-methylphenyl)-2-methyl-4()-quinazolinone) which is sold online as a designer drug. : SL-164 and its hydroxy metabolites were detected in serum and urine via liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). : The pronounced delirium was treated with benzodiazepines and neuroleptics; temporary medical restraint had to be applied. Symptoms completely resolved over the next 72 h and the patient was discharged on day three able to give consent. : Although methaqualone was a popular and widespread sedative in the 1950s and 60 s before its discontinuation in the USA in 1985, derivatives of the methaqualone class have not previously played a large role as drugs of abuse in the rapidly growing market of new psychoactive substances. To our knowledge, this is the first case of agitated delirium with detection of SL-164 and hydroxylated metabolites in a patient's serum and urine.
Topics: Adult; Chromatography, Liquid; Delirium; Eating; Humans; Hypnotics and Sedatives; Male; Methaqualone; Substance Abuse Detection; Young Adult
PubMed: 33760714
DOI: 10.1080/08897077.2021.1903648 -
South African Medical Journal =... Dec 2020There is a high prevalence of substance use among youth in South Africa (SA), and adolescent girls and young women (AGYW) experience high rates of depression and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There is a high prevalence of substance use among youth in South Africa (SA), and adolescent girls and young women (AGYW) experience high rates of depression and anxiety. Substance use behaviours and mental health are associated with other public health problems among AGYW such as HIV and unintended pregnancy. Therefore, understanding the relationship between substance use and mental health is imperative to improve AGYW's health.
OBJECTIVES
To examine the association between heavy drinking, marijuana, methamphetamine and methaqualone (Mandrax) use and depressive and anxiety symptoms among AGYW aged 16 - 19 years who have dropped out of school in Cape Town, SA.
METHODS
Data for this report come from the baseline data of 500 participants of an ongoing cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. After AGYW consented/assented to participate, they completed a urine drug screen and a baseline questionnaire.
RESULTS
Logistic and negative binomial regressions, controlling for clustering at the neighbourhood level, revealed that frequency of depressive symptoms was significantly and positively related to a positive drug screen for Mandrax (β=0.07; p=0.03). All other associations between the frequency of depressive symptoms and substance use were not statistically significant (ps>0.05). The associations between frequency of anxiety symptoms and substance use were not statistically significant (ps>0.05).
CONCLUSIONS
Our findings highlight the need to address substance use, especially Mandrax use and its associated risk, and depression in an integrated, youth-friendly setting.
Topics: Adolescent; Alcohol Drinking; Anxiety; Depression; Female; HIV Infections; Humans; Mental Health; Prevalence; South Africa; Substance Abuse Detection; Substance-Related Disorders; Surveys and Questionnaires; Young Adult
PubMed: 33404004
DOI: 10.7196/SAMJ.2020.v111i1.14520 -
ACS Chemical Neuroscience Dec 2020Methaqualone (2-methyl-3-(-tolyl)-quinazolin-4(3)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABA receptors (GABARs). In a previous...
From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3)-ones as Positive Allosteric Modulators of GABA Receptors.
Methaqualone (2-methyl-3-(-tolyl)-quinazolin-4(3)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABA receptors (GABARs). In a previous structure-activity relationship (SAR) study probing the importance of 2- and 3-substituents in the quinazolin-4(3)-one scaffold, several potent GABAR PAMs were identified, including 2,3-diphenylquinazolin-4(3)-one (PPQ) and 3-(2-chlorophenyl)-2-phenylquinazolin-4(3)-one (Cl-PPQ). Here, PPQ was applied as lead in a SAR study of 6-, 7-, and 8-substituents in the quinazolin-4(3)-one by synthesis and functional characterization of 36 PPQ analogs at various GABAR subtypes. While none of the new analogs were significantly more potent than PPQ or displayed pronounced subtype selectivity across the GABARs tested, several interesting SAR observations were extracted from the study. In an study, the putative binding modes of MTQ, PPQ, and Cl-PPQ in the transmembrane β/α interface of the αβγ GABAR were predicted. Several plausible binding modes were identified for the three PAMs, and rationalization of the molecular basis for their different modulatory potencies was attempted.
Topics: Allosteric Regulation; Biphenyl Compounds; Computer Simulation; Methaqualone; Receptors, GABA-A; Structure-Activity Relationship; gamma-Aminobutyric Acid
PubMed: 33170625
DOI: 10.1021/acschemneuro.0c00600 -
The South African Journal of Psychiatry... 2020Substance use disorders (SUDs) occur frequently in patients with psychotic disorders and have been associated with various demographic and clinical correlates. There is...
BACKGROUND
Substance use disorders (SUDs) occur frequently in patients with psychotic disorders and have been associated with various demographic and clinical correlates. There is an absence of research on the prevalence and clinical correlates of SUDs in psychotic disorders in low-and-middle-income countries (LMICs).
AIM
We aimed to determine the prevalence and correlates of SUDs in psychotic disorders.
SETTING
Patients attending a large secondary-level psychiatric hospital in Cape Town South Africa.
METHODS
We used the Structured Clinical Interview for DSM-IV (SCID-I) to determine psychiatric and substance use diagnoses, depressive, anxiety, obsessive-compulsive and post-traumatic symptoms. We used logistic regression models to determine significant predictors of SUDs.
RESULTS
In total sample ( = 248), 55.6% of participants had any SUD, 34.3% had cannabis use disorders, 30.6% alcohol use disorders, 27.4% methamphetamine use disorders, 10.4% methaqualone use disorders and 4.8% had other SUDs. There were significant associations with male sex for most SUDs, with younger age and Coloured ethnicity for methamphetamine use disorders, and with lower educational attainment for cannabis use disorders. Anxiety symptoms and suicide attempts were significantly associated with alcohol use disorders; a diagnosis of a substance induced psychosis with cannabis and methamphetamine use disorders. Across most SUDs legal problems and criminal involvement were significantly increased.
CONCLUSION
This study found a high prevalence and wide distribution of SUDs in patients with psychotic disorders, consistent with previous work from high income countries. Given clinical correlates, in individuals with psychotic disorders and SUDs it is important to assess anxiety symptoms, suicidality and criminal involvement.
PubMed: 32832129
DOI: 10.4102/sajpsychiatry.v26i0.1473