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Pediatrics Oct 2018The Food and Drug Administration categorizes marijuana (cannabis) as a Schedule I drug, meaning that it has no currently accepted medical use, a high potential for...
The Food and Drug Administration categorizes marijuana (cannabis) as a Schedule I drug, meaning that it has no currently accepted medical use, a high potential for abuse, and no good data on safety. Other Schedule I drugs are heroin, lysergic acid diethylamide, peyote, methaqualone, and 3,4-methylenedioxymethamphetamine ("ecstasy"). The authors of some studies have shown that marijuana can reduce nausea and vomiting from chemotherapy, can improve food intake in patients with HIV, can reduce neuropathic pain, and may slow the growth of cancer cells. In many states, marijuana use is illegal. No state has approved its use for children. What, then, should doctors do if they become aware that parents are using marijuana to treat medical conditions in their children? What if the children have adverse reactions to the marijuana? In this Ethics Rounds, we present such a case and ask experts in child protection and child abuse to discuss the appropriate response.
Topics: Antineoplastic Agents; Child Abuse; Child Protective Services; Child, Preschool; Humans; Lymphoma; Male; Medical Marijuana; Nausea; Vomiting
PubMed: 30213842
DOI: 10.1542/peds.2017-4310 -
Forensic Science International Jul 2018Drug-facilitated sexual assault (DFSA) is a well-recognised public health concern. In South Africa however, epidemiological and toxicological data associated with...
BACKGROUND
Drug-facilitated sexual assault (DFSA) is a well-recognised public health concern. In South Africa however, epidemiological and toxicological data associated with suspected DFSA are not available. Toxicological screening is currently not routinely available in clinical forensic practice in the Western Cape, or elsewhere in South Africa.
OBJECTIVES
To preliminary investigate and characterize DFSA in a specific metropolitan setting in South Africa and to identify the drugs/xenobiotics associated with these reported DFSAs.
METHODS
In total, 107 survivors of suspected DFSA who reported to Victoria Hospital Clinical Forensic Unit in Cape Town, between 1 October 2013 and 30 June 2016, were included. Blood, urine, and/or hair specimens from survivors were screened for drugs of abuse using a targeted LC-MS/MS method. Breath alcohol measurements were conducted using the Dräger Alcotest 6820 after July 2015. Patient, incident and examination history were recorded on standardized data sheets.
RESULTS
Of the 107 cases investigated, most of the patients were female (n=104, 97%), between the ages of 18-25years (n=54, 50%), and had reported to the Clinical Forensic Unit within 24h (n=78, 73%). Altogether, 30 patients (28%) reported a history of mental health issues, drugs and/or alcohol use, or prior sexual abuse. Most incidents took place in the late evening/early morning at the home of the assailant(s), a friend or of the patient (n=62, 58%), and most assailants were known to the victim (n=66, 62%). Specimens were positive for drugs and/or ethanol in 72 patients (67%), with drugs other than ethanol being detected in 60 patients (56%). Breath alcohol measurements were conducted in 58 cases during the prospective leg of the study with an average reading of 0.1mg/L (range not detected-0.98mg/L).
CONCLUSION
DFSA in this setting is mostly opportunistic, with ethanol suggested to be the most commonly involved drug, despite limitations in detection due to delays in reporting. Other common drugs observed were methamphetamine, methaqualone and diphenhydramine either alone or in combinations. The complexity and current inadequacy surrounding investigation of these cases is highlighted in this study as well as the necessity for greater investment into the development of infrastructure to support systematic toxicological analyses and services to assist in the investigation and understanding of these intricate cases. Training and empowerment of role players dealing with the investigation and management of DFSA is required, and subsequent public health education and policy development is essential.
Topics: Adolescent; Adult; Breath Tests; Central Nervous System Depressants; Chromatography, Liquid; Crime Victims; Cross-Sectional Studies; Ethanol; Female; Forensic Medicine; Genitalia; Hair; Humans; Male; Mental Disorders; Middle Aged; Narcotics; Pharmaceutical Preparations; Physical Abuse; Prospective Studies; Retrospective Studies; Sex Offenses; South Africa; Substance Abuse Detection; Tandem Mass Spectrometry; Urban Health Services; Young Adult
PubMed: 29738993
DOI: 10.1016/j.forsciint.2018.04.028 -
Biochemical Pharmacology Jan 2018The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABA receptors...
The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABA receptors (GABARs) (Hammer et al., 2015). In the present study, we have identified a novel methaqualone analog, 2-phenyl-3-(p-tolyl)quinazolin-4(3H)-one (PPTQ), in a screening of 67 analogs at five αβγ GABAR subtypes and delineated its functional properties and mechanism of action at wild-type and mutant GABARs expressed in Xenopus laevis oocytes by two-electrode voltage clamp electrophysiology. PPTQ was found to be an allosteric agonist and a PAM (ago-PAM) at human αβγ and αβδ GABARs, exhibiting intrinsic activity at micromolar concentrations and potentiating the GABA-evoked signaling through the receptors at concentrations down to the low-nanomolar range. Whereas PPTQ exclusively increased the potency of GABA at the αβγ receptor, it increased both GABA potency and efficacy at αβδ and displayed modest potency-based preference for αβδ over αβγ. In elaborate mutagenesis and competition experiments PPTQ was found to act through the same or an overlapping site as etomidate in the transmembrane β/α subunit interfaces, whereas it did not seem to target the other three transmembrane interfaces in the GABAR. Finally, the PPTQ site was shown to be allosterically linked with sites targeted by neurosteroids and barbiturates but not with the high-affinity benzodiazepine site in the αβγ receptor. In conclusion, the development of a highly potent, bioavailable GABAR ago-PAM by subtle modifications to the methaqualone scaffold demonstrates that derivatization of this infamous drug from the past can lead to modulators with distinct functional characteristics at the receptors.
Topics: Allosteric Regulation; Animals; GABA Agonists; HEK293 Cells; Humans; Male; Methaqualone; Mice; Mice, Inbred C57BL; Receptors, GABA-A; Xenopus laevis
PubMed: 29155148
DOI: 10.1016/j.bcp.2017.11.006 -
Climacteric : the Journal of the... Aug 2017The Pan-Asian REVIVE survey aimed to examine women's experiences with genitourinary syndrome of menopause (GSM) and their interactions with health-care professionals...
OBJECTIVES
The Pan-Asian REVIVE survey aimed to examine women's experiences with genitourinary syndrome of menopause (GSM) and their interactions with health-care professionals (HCPs).
METHODS
Self-completed surveys were administered face-to-face to 5992 women (aged 45-75 years) in Indonesia, Malaysia, Singapore, Taiwan, and Thailand.
RESULTS
Of 638 postmenopausal women with GSM symptoms, only 35% were aware of the GSM condition, most of whom first heard of GSM through their physician (32%). The most common symptoms were vaginal dryness (57%) and irritation (43%). GSM had the greatest impact on sexual enjoyment (65%) and intimacy (61%). Only 25% had discussed their GSM symptoms with a HCP, and such discussions were mostly patient-initiated (64%) rather than HCP-initiated (24%). Only 21% had been clinically diagnosed with GSM and only 24% had ever used treatment for their symptoms. Three-quarters of those who had used treatment for GSM had discussed their symptoms with a HCP compared to only 9% of those who were treatment-naïve.
CONCLUSION
GSM is underdiagnosed and undertreated in Asia. As discussion of GSM with HCPs appears to be a factor influencing women's awareness and treatment status, a more active role by HCPs to facilitate early discussions on GSM and its treatment options is needed.
Topics: Aged; Atrophy; Dyspareunia; Female; Female Urogenital Diseases; Health Knowledge, Attitudes, Practice; Health Surveys; Humans; Indonesia; Malaysia; Methaqualone; Middle Aged; Postmenopause; Sexual Behavior; Singapore; Surveys and Questionnaires; Syndrome; Taiwan; Thailand; Vagina; Vulva; Women's Health
PubMed: 28453308
DOI: 10.1080/13697137.2017.1315091 -
The South African Journal of Psychiatry... 2016Substance use and psychiatric disorders cause significant burden of disease in low- and middle-income countries. Co-morbid psychopathology and longer duration of...
BACKGROUND
Substance use and psychiatric disorders cause significant burden of disease in low- and middle-income countries. Co-morbid psychopathology and longer duration of untreated psychosis (DUP) can negatively affect treatment outcomes.
OBJECTIVES
The study assessed substance use amongst adults with severe mental illness receiving services at a regional psychiatric hospital in KwaZulu-Natal (South Africa). We describe the prevalence and correlates of lifetime substance use and examine the association between substance use and DUP.
METHODS
A cross-sectional survey recruited adults diagnosed with severe mental illness and assessed lifetime and past 3-month substance use using the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test. Regression analyses were conducted to determine associations between lifetime substance use (other than alcohol and tobacco) and DUP as measured by the World Health Organization Encounter Form.
RESULTS
Amongst 87 participants, alcohol (81.6%), tobacco (75.6%) and cannabis (49.4%) were the most common substances reported for lifetime use. Risk of health-related problems (health, social, financial, legal and relationship) of cannabis use was associated with younger age, single marital status and lower education. Adjusted regression analyses indicated that use of amphetamines and methaqualone is associated with longer DUP.
CONCLUSIONS
Substance use is prevalent amongst psychiatric patients in KwaZulu-Natal and may contribute to longer DUP. Mental health services in this region should address co-morbid substance use and psychiatric disorders.
PubMed: 27307782
DOI: 10.4102/sajpsychiatry.v22i1.852 -
Archiv Der Pharmazie Jul 2016A series of new N-(substituted)-1-methyl-2,4-dioxo-1,2-dihydroquinazoline-3(4H)-carboxamides were designed, synthesized, and evaluated for their anticonvulsant activity....
A series of new N-(substituted)-1-methyl-2,4-dioxo-1,2-dihydroquinazoline-3(4H)-carboxamides were designed, synthesized, and evaluated for their anticonvulsant activity. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock (MES) and pentylenetetrazol (PTZ) test. The most promising compound 4c showed significant anticonvulsant activity with a protective index value of 3.58. The compounds 4a-c were also found to have encouraging anticonvulsant activity in the MES and PTZ screen when compared with the standard drugs, valproate and methaqualone. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drugs.
Topics: Animals; Anticonvulsants; Dose-Response Relationship, Drug; Electroshock; Methaqualone; Mice; Pentylenetetrazole; Picrotoxin; Quinazolines; Seizures; Structure-Activity Relationship; Valproic Acid
PubMed: 27231098
DOI: 10.1002/ardp.201600024 -
International Health Mar 2016This study was designed to identify the extent to which self-reported Mandrax use impacts condom-use beliefs amongst South African prison inmates.
BACKGROUND
This study was designed to identify the extent to which self-reported Mandrax use impacts condom-use beliefs amongst South African prison inmates.
METHODS
Participants were inmates from four prisons in the provinces of KwaZulu-Natal and Mpumalanga. In total, 357 inmates participated in the parent study of which 121 are included in this analysis based on their self-reported use of Mandrax. The questionnaire was developed in English, translated into Zulu, and back translated into English. Age significantly predicted the use of Mandrax: younger prison inmates reported higher use. Linear regression analysis was conducted to determine whether the use of Mandrax was associated with length of incarceration and other demographic variables, as well as participants' self-reported condom use beliefs behavior.
RESULTS
Regression results indicated that two factors operationalizing condom-use beliefs were impacted by Mandrax use: 1) it is important to use condoms every time you have sex (p<0.01); 2) condoms work well to prevent the spread of HIV (p<0.02). Both factors were also inversely related to Mandrax use.
CONCLUSION
STI prevention programs among prison inmates that seek to promote safer sex behaviors among men must address attitudes to condom use, specifically consistent and correct use of latex condoms and reducing substance misuse.
Topics: Adolescent; Adult; Condoms; Diphenhydramine; Drug Combinations; Health Knowledge, Attitudes, Practice; Humans; Male; Methaqualone; Prisoners; Prisons; Sexually Transmitted Diseases; Socioeconomic Factors; South Africa; Substance-Related Disorders; Surveys and Questionnaires; Young Adult
PubMed: 26316220
DOI: 10.1093/inthealth/ihv048 -
Molecular Pharmacology Aug 2015In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an...
In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2,3,5β2,3γ2S GABAA receptors (GABAARs) expressed in Xenopus oocytes, whereas it displayed highly diverse functionalities at the α4,6β1,2,3δ GABAAR subtypes, ranging from inactivity (α4β1δ), through negative (α6β1δ) or positive allosteric modulation (α4β2δ, α6β2,3δ), to superagonism (α4β3δ). Methaqualone did not interact with the benzodiazepine, barbiturate, or neurosteroid binding sites in the GABAAR. Instead, the compound is proposed to act through the transmembrane β((+))/α((-)) subunit interface of the receptor, possibly targeting a site overlapping with that of the general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of methaqualone was further investigated in multichannel recordings from primary frontal cortex networks, where the overall activity changes induced by the compound at 1-100 μM concentrations were quite similar to those mediated by other CNS depressants. Finally, the free methaqualone concentrations in the mouse brain arising from doses producing significant in vivo effects in assays for locomotion and anticonvulsant activity correlated fairly well with its potencies as a modulator at the recombinant GABAARs. Hence, we propose that the multifaceted functional properties exhibited by methaqualone at GABAARs give rise to its effects as a therapeutic and recreational drug.
Topics: Animals; Binding Sites; Brain; Humans; Hypnotics and Sedatives; Illicit Drugs; Locomotion; Male; Methaqualone; Mice; Mutation; Receptors, GABA-A; Xenopus
PubMed: 26056160
DOI: 10.1124/mol.115.099291 -
Drug Testing and Analysis Jul 2015Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are...
Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.
Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively.
Topics: Amines; Anticonvulsants; Carbamazepine; Chromatography, High Pressure Liquid; Cyclohexanecarboxylic Acids; Forensic Toxicology; Gabapentin; Humans; Levetiracetam; Oxcarbazepine; Piracetam; Tandem Mass Spectrometry; gamma-Aminobutyric Acid
PubMed: 25331692
DOI: 10.1002/dta.1733 -
Journal of Pharmaceutical and... Sep 20147-O-Succinyl macrolactin A (SMA) and its major metabolite macrolactin A (MA) are generated from Bacillus polyfermenticus KJS-2. Both substances show inhibitory effects...
7-O-Succinyl macrolactin A (SMA) and its major metabolite macrolactin A (MA) are generated from Bacillus polyfermenticus KJS-2. Both substances show inhibitory effects on angiogenesis and cancer cell invasion. SMA in rat plasma is known to be relatively stable at room temperature, but MA was not detected due to its instability. Therefore, a stabilizer is required to accurately measure the substance in biological rat samples. In this study, NaF and eserine were examined to determine whether they could stabilize MA to allow for accurate measurement in rat plasma. We also developed a rapid and simple chromatographic method using tandem mass spectrometry (MS/MS) for the simultaneous determination of these compounds in rat plasma. After simple protein precipitation with acetonitrile including methaqualone (internal standard), the analytes were chromatographed on a Hilic column with a mobile phase of 10mM formic acid aqueous solution, methanol, and acetonitrile (15:15:70, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This analytical method was successfully applied to monitor plasma concentrations of both compounds over time following intravenous administration of a salt form of SMA in rats.
Topics: Animals; Chromatography, Liquid; Drug Stability; Macrolides; Plasma; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 24887484
DOI: 10.1016/j.jpba.2014.05.009