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Nature Communications Jun 2024Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a...
Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a notorious recreational drug in the 1960s-80s. Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance. Methaqualone principally targets GABA receptors, which are the major inhibitory neurotransmitter-gated ion channels in the brain. The restricted status and limited accessibility of methaqualone have contributed to its pharmacology being understudied. Here, we use cryo-EM to localize the GABA receptor binding sites of methaqualone and its more potent derivative, PPTQ, to the same intersubunit transmembrane sites targeted by the general anesthetics propofol and etomidate. Both methaqualone and PPTQ insert more deeply into subunit interfaces than the previously-characterized modulators. Binding of quinazolinones to this site results in widening of the extracellular half of the ion-conducting pore, following a trend among positive allosteric modulators in destabilizing the hydrophobic activation gate in the pore as a mechanism for receptor potentiation. These insights shed light on the underexplored pharmacology of quinazolinones and further elucidate the molecular mechanisms of allosteric GABA receptor modulation through transmembrane binding sites.
Topics: Receptors, GABA-A; Binding Sites; Cryoelectron Microscopy; Humans; Animals; Etomidate; Propofol; Quinazolinones; Allosteric Regulation; HEK293 Cells; Hypnotics and Sedatives
PubMed: 38898000
DOI: 10.1038/s41467-024-49471-y -
The South African Journal of Psychiatry... 2024Epidemiological studies suggest that nyaope, a heroin-based drug, is widely used in South Africa. Yet few reliable research tools are available to assess treatment...
BACKGROUND
Epidemiological studies suggest that nyaope, a heroin-based drug, is widely used in South Africa. Yet few reliable research tools are available to assess treatment outcomes of users. The Opiate Treatment Index (OTI), a tool developed in Australia, could potentially facilitate research on context-specific South African treatment outcomes. However, we know little of its test-retest reliability.
AIM
This study aimed to assess the test-retest reliability of the OTI among a sample of nyaope users in Johannesburg.
SETTING
This study was conducted across three substance use treatment facilities in Johannesburg.
METHODS
The OTI was administered to 53 nyaope users at baseline and one week later. To determine the test-retest reliability of the OTI, the intra-class correlation coefficients (ICC) and the Brennan-Prediger coefficients of the two interviews were calculated.
RESULTS
The ICC of the Q-scores from the data sets along with the Brennan-Prediger coefficient for the substance use domain were calculated. The ICC for nyaope was 0.38. Brennan-Prediger coefficients were as follows: alcohol - 0.96, crack-cocaine - 0.89, cannabis - 0.92, methaqualone - 0.85 and crystal methamphetamine - 0.89.
CONCLUSION
A significant positive finding was the excellent test-retest reliability of the injecting and sexual behaviour domains and moderate reliability of the criminality, general health and social functioning domains.
CONTRIBUTION
The results of this study provide insight into the reliability of this tool and for its use in future studies in the South African context.
PubMed: 38444406
DOI: 10.4102/sajpsychiatry.v30i0.2087 -
Burns : Journal of the International... May 2024In South Africa, fire-related deaths are common, particularly within dense informal housing settlements. Published data on deaths from fire incidents in Cape Town is...
BACKGROUND
In South Africa, fire-related deaths are common, particularly within dense informal housing settlements. Published data on deaths from fire incidents in Cape Town is sparse. Additionally, little emphasis has been placed on the role of toxicological investigations in these deaths, despite the known risk of alcohol and drug impairment to burn injury.
METHODS
A retrospective, descriptive analysis of post-mortem case reports from Salt River Mortuary was conducted to investigate all deaths in which fires were involved in the west metropole of Cape Town, between 2006 to 2018. Demographic, circumstantial, and toxicological data were analyzed using R software.
RESULTS
In total 1370 fire deaths occurred over 13 years, with a mean of 106 (SD ± 18) cases per annum (≈3% of the annual caseload and a mortality rate of 5.5 per 100,000). Males (70.4%), adults (mean=30.7 years), and toddlers (1-4 years old) were notably at risk. Deaths typically occurred in the early morning (00h00 - 06h00) (45.7%), during winter (32.1%), and in lower socioeconomic areas with highly dense informal settlements (65.6%), with 29% of deaths occurring in multi-fatality incidents. Ethanol was detected (≥0.01 g/100 mL) in 55.1% of cases submitted for analysis (71.5%), with a mean of 0.18 g/100 mL, and with 93.8% of positive cases > 0.05 g/100 mL. Carboxyhaemoglobin (COHb) analysis was requested in 76.4% of cases, with 57% of cases having a %COHb of ≥ 20%. Toxicology results (for drugs other than ethanol) from the national laboratory were outstanding in 34.4% of the cases at the conclusion of the study. BAC and %COHb were significantly higher in deaths from burns and smoke inhalation (usually accidents) than deaths from combined trauma and burns (typically homicides). Fire deaths with high COHb levels were more likely to display cherry-red discoloration (OR=3.1) and soot in the airways (OR=2.7) at autopsy.
CONCLUSION
This article provides an updated description of fire deaths in the west metropole of Cape Town. The importance of BAC and COHb testing in these cases was noted, and the authors call for an investigation of the role of drug impairment (specifically frequently misused drugs methamphetamine and methaqualone) as a risk factor in these deaths. Areas of high-density informal settlements, where open flames are used to heat, light, and cook, were noted as high risk.
Topics: Humans; South Africa; Retrospective Studies; Male; Adult; Female; Burns; Fires; Infant; Child, Preschool; Child; Middle Aged; Adolescent; Young Adult; Carboxyhemoglobin; Aged; Blood Alcohol Content; Methamphetamine; Age Distribution; Ethanol; Sex Distribution; Smoke Inhalation Injury; Carbon Monoxide Poisoning; Seasons; Aged, 80 and over; Substance-Related Disorders; Central Nervous System Depressants
PubMed: 38290966
DOI: 10.1016/j.burns.2024.01.001 -
The International Journal of... Jun 2023Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association...
Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy. Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation. People who smoked drugs (PWSD) comprised 54.8% ( = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10-1.97; 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22-4.34; = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62-1.87; = 0.799) was not associated with increased cavitation. PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.
Topics: Humans; Tuberculosis, Pulmonary; Smoke; Mycobacterium; Smoking; Tobacco Use; Sputum; HIV Infections
PubMed: 37231597
DOI: 10.5588/ijtld.22.0650 -
Forensic Toxicology Jul 2023
Topics: Humans; Methaqualone; Substance-Related Disorders
PubMed: 37169943
DOI: 10.1007/s11419-023-00665-x -
Forensic Toxicology Jan 2023The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study,...
The next addiction-causing drug class 4-quinazolinone derivatives: analyses of methaqualone analogs including recently discovered 2-methoxyqualone by different modes of mass spectrometry.
PURPOSE
The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study, product ion spectra of gas chromatography-tandem mass spectrometry (GC-MS/MS) with different collision energies were presented for these drugs. Because 2-methoxyqualone is a new recreational drug discovered in dubious tablets very recently, much more detailed data obtained by different types of mass spectrometry instruments, and quantification data of 2-methoxyqualone in the tablet together with its validation were demonstrated.
METHODS
The methods for analyses were GC-MS/MS, high-resolution ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry.
RESULTS
The GC-MS/MS product ion spectra of the three compounds with different collision energies have not been reported before. They were very useful to tentatively identify unknown compounds. If a reference standard is available, the final identification and quantification can be achieved by measurements of product ion spectra and in selected reaction monitoring mode very easily by GC-MS/MS. The final identification and quantification for the new 2-methoxyqualone were performed in this way. The content of the compound was 69.8 ± 0.5% (w/w) in the tablet. Acetaminophen and caffeine coexisted in the tablet with approximate concentrations at 10 and 5%, respectively.
CONCLUSIONS
In this article, we have presented product ion spectra of methaqualone, etaqualone and 2-methoxyqualone at different collision energies by GC-MS/MS for the first time. In addition, this is the first paper to describe the details of quantification of 2-methoxyqualone in the authentic seized product.
Topics: Tandem Mass Spectrometry; Gas Chromatography-Mass Spectrometry; Methaqualone; Tablets
PubMed: 36652055
DOI: 10.1007/s11419-022-00631-z -
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 -
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 -
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 -
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