Pusat Penyelidikan Dadah dan Ubat-Ubatan - Tesis

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Evaluation Of Mitragyna Speciosa Korth. (Ketum) Extracts Prepared By Accelerated Solvent Extraction Technique, On Antinociceptive And Cytotoxicity Effects
(2021-12)
Goh, Yong Sean
Mitragyna speciosa Korth. (Ketum) leaves are well known for their psychoactive and analgesic properties. Mitragynine, is the principal alkaloid of ketum leaf, is a well-known factor that contributes to ketum’s pharmacological activities. The present study underlined the use of green solvent and green extraction technique for the yield of a better and safe ketum extract. At first, ketum was extracted with pure water using conventional extractions, Soxhlet, and maceration, as well as modern extraction techniques, ultrasound-assisted extraction (UAE), and accelerated solvent extraction (ASE) techniques. Subsequently, two green extraction techniques which are ASE, and UAE were selected. Solvents such as water, methanol, ethanol, and ethyl acetate were used in the optimisation of ASE and UAE. Comparing both extractions, ASE demonstrated a better dry yield (0.53 – 2.91 g) with consistent mitragynine content (6.53 – 7.19 %), shorter time (5 minutes), and reduced solvent usage (< 100 mL).
A Study On Treatment Barriers Among Amphetamine-Type Stimulant (Ats) Drug Users In Malaysia
(2022-03)
Shanmugam, Thorairaj
People who use amphetamine-type stimulant (PWUA) often hesitate to participate in treatment program, and may encounter various barriers while seeking treatment. This study sought to identify treatment barriers and gender differences in barriers (if any) that precluded PWUA from participating in drug treatment programs in Malaysia. Three hundred and eighty-six treatment inmates who were mandated to undergo rehabilitation for their ATS use history were recruited through convenience sampling from five drug rehabilitation centres (CCRCs) for this cross-sectional study. The study data was collected through face-to-face interviews by a trained student using the Treatment Barriers Questionnaire (TBQ) scale. The majority (83%, n=321/386) were males, only 17% (n=65) consisted of females. Most were ethnic Malays (95%, n=365/386), single (61%), and were employed (85%) prior to their confinement.
Prevalence And Risk Factors Of Intimate Partner Violence (Ipv), Sexual Reproductive Health Issues And Treatment Barriers Among Females Who Use Drugs (Fwuds) In Malaysia
(2022-07)
Anandan, Asnina Nair
Females who use drugs (FWUDs) are vulnerable to intimate partner violence (IPV) and other issues stemming from violence and drug use. This study aims to identify prevalence and risk factors associated with IPV, the extent of illicit substance use during pregnancy and breastfeeding, reproductive health knowledge and practice, and treatment barriers among FWUDs in Malaysia. Two hundred FWUDs who were confined in a mandatory drug rehabilitation centre (CCRC) for their drug use offenses were recruited through convenience sampling for this cross-sectional study. All the study data were collected using a semi-structured questionnaire. The majority of respondents were Malay (86%, n=171/200), with a mean age of 32.3 years (SD=8.61). The lifetime IPV prevalence rate in this study was 53% (n=105/200), far exceeding the reported rate for non-drug dependent married women in Malaysia. The prevalence rates for physical, psychological and sexual violence in this study were 41%, 29% and 24%, respectively. Lifetime IPV incidence among FWUDs were associated with unstable living environments, having a regular intimate male partner who uses drugs, and have been a victim of underage rape. FWUDs victimised by IPV had higher odds of engaging in risky sexual practices compared to non-victims. The majority (60%) lacked knowledge on condom particularly for female use, and 67% disliked wearing a condom, as it is alleged to affect their sexual performance. Conversely, IPV victimised FWUDs had adequate knowledge on family planning than FWUDs who have never experienced IPV.
A Preliminary Study On Pain Tolerance And Withdrawal Symptoms Among Active Ketum (Mitragyna Speciosa) Users In Malaysia
(2022-09)
Abdul Rahim, Azlan
Kratom is known locally as ketum or biak (Mitragyna speciosa) in Thailand, Malaysia, and Indonesia. Southeast Asian countries are home to the ketum plant. Ketum leaves are extensively used as an herbal supplement (traditional medicine) for self-treatment of medical conditions in the West and Southeast Asia, including pain and opioid use disorder (OUD). However, ketum consumption over a prolonged period was associated with withdrawal effects. Therefore, to systematically investigate the effects of ketum based on claims from previous research (pain tolerance and withdrawal symptoms), a human laboratory study was conducted with 26 male participants in Pusat Sejahtera, Universiti Sains Malaysia (USM). The study aimed to investigate withdrawal symptoms using a validated clinical measurement, the Clinical Opiate Withdrawal Scale (COWS), after 12 hours of ketum cessation. Secondly, the study investigated ketum effects on pain tolerance using the cold pressor task. Study findings suggested no significant association between ketum consumption with withdrawal symptoms and pain tolerance. However, mild withdrawal symptoms were observed during the 12 hours of ketum cessation such as runny nose, yawning, restlessness and axiety.
The Evaluation Of The Potential Of Tetrahydro-Β-Carboline Derivatives For The Treatment Of Addiction Using In-Vivo Model With Zebrafish And Using Liquid Chromatography-Tandem Mass Spectrometry For The Neurotransmitter Analysis
(2022-10)
Mohamed, Siti Mazleena
Drug addiction treatment can include behavioural therapies, medications, or their combination. The available drug used in medication treatment is limited and has known side effects. The present study evaluates the addictive property of synthesized tetrahydro-β-carboline derivatives compounds since the previous study showed that the compounds positively impact analgesic activity. Forty-nine compounds have been screened for physicochemical properties before selecting further for in-vitro and in-vivo studies. Out of forty-nine compounds, fourteen compounds were chosen for in-vitro screening. Four compounds showed toxicity toward SK-N-SH cells, and two compounds were insoluble in the cell medium. Thus, only eight compounds proceeded for receptor functional activity through cAMP production. (6-methoxy-1,3,4,9-tetrahydro-2H-β-carbolin-2-yl)(phenyl)ethanone (OD1b) and 6-methoxy-2,3,4,9-tetrahydro-1H-β-carbolin-1-one (OD2a) showed the highest cAMP stimulation. Bioavailability radar for drug-likeness showed OD1b and OD2a located inside the optimal range suggesting good drug-like properties of the compounds. The rewarding effects of OD1b and OD2a were evaluated using the behavioural technique of conditioned place preference (CPP) using zebrafish as an animal model, and their neurotransmitters in the brain and body were measured.
Behavioural And Hippocampal Neuroplasticity Effects Of A Bioactive Fraction From Clitoria Ternatea Linn. Root Extract In A Rat Model Of Chronic Cerebral Hypoperfusion
(2022-11)
Ahad, Mohamad Anuar
Pharmacological therapy is highly recommended for reducing the severity of the behavioural and psychiatric syndromes of dementia, as well as for effectively reversing cognitive decline in symptomatic dementia patients. Scientific evidence on cognition-oriented approaches for treating cognitive impairment using natural-based products is well discovered. Therefore, the thesis investigates the effects of bioactive fraction from Clitoria ternatea (CT) root extract in the behavioural and hippocampal neuroplasticity in chronic cerebral hypoperfusion (CCH) rats model. The bioassay-guided fractionation approach was carried out to produce the CT root bioactive fraction. To begin with, CT root powder was extracted using sequential extraction of solvent varying polarity. Then, the extracts were screened for their bioactivity using in vitro and in vivo studies. The CT root chloroform extract was further subjected to fractionation and isolation compound(s) using column chromatography to produce the bioactive fraction and active compound(s). The amount of clitorienolactone A (CLA) in the CT root bioactive fraction (255 mg/g) and active extract (150 mg/g) was quantified using high-performance liquid chromatography and diode array detection analysis for quality control purposes.
A Study On Drug Use And Criminal Behaviours Of Criminal Offenders In The State Of Penang
(2023-01)
Hadep Singh, Balber Singh
People who use drugs (PWUDs) tend to commit crime under the influence of drugs compare with people without drug use history. Though researchers have argued that drug use can cause people to engage in crime, however, the relationship between drug use and crime seems insufficiently investigated. This study aims to investigate the criminal profile of Police detainees who were caught under the Penal Code (Act 574) for various crime offenses between June and December 2019 in the Northeast and Southwest Districts of Penang State. A total of 73 Police detainees were recruited through convenience sampling for this cross-sectional study. Majority were males (93%, n=68/73), most Malays (58%, n=42/73), and the sample’s mean age in this study was 32.8 years (SD=8.13). About 16% (n=12/73) of the detainees had previous drug rehabilitation history, while 55% (n=40/73) had been incarcerated before. Fifty-six percent (n=41/73) of the detainees were detained for non-violent offenses (e.g., property crime), and 44% for violent offenses (e.g., gang robbery, physical assault, etc.) under the Penal Code (Act 574). Of this, 81% (n=59/73) of the offenses were categorised as bailable offenses. As for their drug use status, 62% (n=45/73) of the detainees tested positive for illicit drug use, most (53%) for amphetamine-type stimulant (ATS) and opiate (18%), when they were brought into detention. Sixty-eight percent (n=50/73) of the detainees had illicit drug use history. Most (59%, n=43/73) reported committing crime individually, and 41% usually committed crime with their acquaintances. About 8% held dangerous weapons while committing crime, and 41% (n=30/73) claimed that they were ordered by their superiors to commit crime.
A Study On Drug Use And Criminal Behaviours Of Criminal Offenders In The State Of Penang
(2023-01)
Hadep Singh, Balber Singh
People who use drugs (PWUDs) tend to commit crime under the influence of drugs compare with people without drug use history. Though researchers have argued that drug use can cause people to engage in crime, however, the relationship between drug use and crime seems insufficiently investigated. This study aims to investigate the criminal profile of Police detainees who were caught under the Penal Code (Act 574) for various crime offenses between June and December 2019 in the Northeast and Southwest Districts of Penang State. A total of 73 Police detainees were recruited through convenience sampling for this cross-sectional study. Majority were males (93%, n=68/73), most Malays (58%, n=42/73), and the sample’s mean age in this study was 32.8 years (SD=8.13). About 16% (n=12/73) of the detainees had previous drug rehabilitation history, while 55% (n=40/73) had been incarcerated before. Fifty-six percent (n=41/73) of the detainees were detained for non-violent offenses (e.g., property crime), and 44% for violent offenses (e.g., gang robbery, physical assault, etc.) under the Penal Code (Act 574). Of this, 81% (n=59/73) of the offenses were categorised as bailable offenses. As for their drug use status, 62% (n=45/73) of the detainees tested positive for illicit drug use, most (53%) for amphetamine-type stimulant (ATS) and opiate (18%), when they were brought into detention. Sixty-eight percent (n=50/73) of the detainees had illicit drug use history. Most (59%, n=43/73) reported committing crime individually, and 41% usually committed crime with their acquaintances. About 8% held dangerous weapons while committing crime, and 41% (n=30/73) claimed that they were ordered by their superiors to commit crime.
Discovery Of New Potential Pyrido[2,3-D]Pyrimidin-7-One Based Cdk4 Inhibitors Using Molecular Modelling Approaches
(2023-02)
Al Attraqchi, Omar Husham Ahmed
Cyclin-dependent kinases (CDKs) are a class of regulatory enzymes that modulate various biochemical properties of the cell such as cell division. Different CDK enzymes have been shown to be promising biological targets for combating different types of cancer. In particular, the CDK4 enzyme has been observed to be overexpressed in several types of cancer including breast cancer. The usage of small-drug molecules that inhibits the activity of the CDK4 enzyme has proved to be clinically valid approach. However, currently available solutions suffer from various limitations such as insufficient activity. Among the most notable inhibitors of the CDK4 enzyme are the compounds based on the pyrido[2,3-d]pyrimidin-7-one scaffold. In this study, computer-aided drug design (CADD) methods including ligand-based and structure-based methods have been applied on the compounds derived from this scaffold. The applied CADD methods revealed the correlation of the physicochemical properties with the activity and gave insights into the binding process. The used ligand-based CADD methods included quantitative structure-activity relationship (QSAR) and pharmacophore modeling.
Poverty Reduction Community And Social Development Projects (Csdp) In Yobe State, Nigeria
(2023-04)
Suleiman, Kawuwa
Poverty is increasingly affecting development and wellbeing in Sub-Sahara Africa, Nigeria and Yobe State in particular. Many communities suffer from poverty due to inadequate access to basic infrastructure of health, education, water, and environmental projects. The Community and Social Development Project (CSDP) is a poverty reduction programme which provides micro infrastructure projects in Yobe state. Therefore, this study explores the effects of the CSDP infrastructure projects on wellbeing and poverty reduction. The study also finds out the community perception on CSDP poverty reduction strategies as well as stakeholders’ views on the challenges of poverty reduction programme in Yobe state. The study adopted a mixed-method approach to data collection. The method involved the use of techniques of both quantitative and qualitative methods of data collection. The study also adopted a multi-stage cluster sampling technique in which Yobe State was divided into the existing Senatorial Zones, States, LGAs and Communities. A total of 360 respondents were selected and served with questionnaires while Key Informant Interviews (KIIs) were conducted with three participants, one each from CSDP, Yobe State Ministry of Social Welfare, and CSOs. Moreover, twelve Focus Group Discussion (FGD) sessions were conducted with relevant stakeholders across the twelve communities selected for the study. The quantitative data was analysed using Statistical Package for Social Science (SPSS) and Smart Partial Least Square Structural Equation Modelling (SmartPLS) software and the qualitative data was analysed with thematic analysis of codes, categories and themes identification.
Kajian Pematuhan Program Pengawasan Komuniti Dalam Kalangan Klien Yang Disabitkan Di Bawah Kesalahan Seksyen 15(1) Akta Dadah Berbahaya (Adb) 1952
(2023-07)
Mohd Saref, Nadiah
Pengguna dadah (atau PWUDs) yang ditangkap atas kesalahan “kecil” menggunakan dadah seperti dikesan positif untuk penggunaan amphetamine-type stimulants (ATS) boleh dipenjarakan di Malaysia. Disebabkan peningkatan kadar tangkapan tahunan yang membimbangkan dibawah Seksyen 15(1)(a) Akta Dadah Berbahaya 1952, kajian jangka masa panjang ini bertujuan untuk mengenalpasti kadar pematuhan rawatan dan menilai fungsi sosial diantara responden yang telah menjalani hukuman penjara (ditahan dalam tempoh dua tahun) dan telah membayar denda mahkamah (tidak melebihi lima ribu ringgit) dibawah Seksyen 15(1)(a) dan kemudiannya diperintahkan menjalani pengawasan dalam komuniti dengan Agensi Anti-Dadah Kebangsaan (AADK) di Daerah Timur Laut, Pulau Pinang. Sejumlah 85 responden (59 klien penjara dan 26 klien mahkamah) telah direkrut dan diikuti untuk tempoh maksimum selama enam bulan. Kesemua klien dinilai menggunakan borang soal-selidik berstruktur dan separa berstruktur sepanjang kajian ini berlangsung. Majoriti responden adalah lelaki (91%, n=77/85), kebanyakan berbangsa Melayu (51%), dan 69% masih bujang. Lapan puluh peratus mempunyai sejarah penjara sebelum ini dibawah Seksyen 15(1)(a), manakala 50% (42/85) mempunyai sejarah lampau pengawasan dalam komuniti bersama AADK. Kesemua responden pernah mengguna ATS dan dadah lain menjadikan kebanyakan responden adalah polydrug user.
Ketum (Mitragyna Speciosa Korth.) Consumption, Lipid Profile And Electrocardiogram (Ecg) Abnormalities
(2023-07)
Korindasamy, Novline Yuvashnee
Ketum (Mitragyna speciosa Korth.) a native medicinal plant of Southeast Asia, has been used in Malaysia for decades for its unique curative properties. Given its broad therapeutic properties and increasing utility, ketum’s long-term safety profile, especially on its cardiotoxicity risk remains poorly investigated in regular ketum users. Given this research limitation, this study aims to evaluate the electrocardiogram (ECG) abnormalities and lipid profile between regular ketum users and healthy control subjects. A total of 200 respondents (n=100 regular ketum users and n=100 healthy control subjects) were recruited through convenience sampling from the northern peninsular state of Penang for this clinical, cross-sectional study. All were required to undergo an ECG evaluation, and blood samples were also drawn to characterize the respondent’s lipid profile. All males, a majority were Malays (97%, n=194/200), and the samples mean age in this study was 33 years (SD=6.7), while ketum users mean duration of ketum use was 6.4 years (SD=4.31). Ketum users mean systolic and diastolic blood pressure rates were 132.9 beats per minute (SD=17.3) and 77.1 beats per minute (SD=11.1), respectively.
Ketum (Mitragyna Speciosa Korth.) Consumption, Lipid Profile And Electrocardiogram (Ecg) Abnormalities
(2023-07)
Korindasamy, Novline Yuvashnee
Ketum (Mitragyna speciosa Korth.) a native medicinal plant of Southeast Asia, has been used in Malaysia for decades for its unique curative properties. Given its broad therapeutic properties and increasing utility, ketum’s long-term safety profile, especially on its cardiotoxicity risk remains poorly investigated in regular ketum users. Given this research limitation, this study aims to evaluate the electrocardiogram (ECG) abnormalities and lipid profile between regular ketum users and healthy control subjects. A total of 200 respondents (n=100 regular ketum users and n=100 healthy control subjects) were recruited through convenience sampling from the northern peninsular state of Penang for this clinical, cross-sectional study. All were required to undergo an ECG evaluation, and blood samples were also drawn to characterize the respondent’s lipid profile. All males, a majority were Malays (97%, n=194/200), and the samples mean age in this study was 33 years (SD=6.7), while ketum users mean duration of ketum use was 6.4 years (SD=4.31). Ketum users mean systolic and diastolic blood pressure rates were 132.9 beats per minute (SD=17.3) and 77.1 beats per minute (SD=11.1), respectively.
Modulation Of Dopaminergic System By Mitragynine And The Underlying Mechanisms Instigating Impairment Of Hippocampal Synaptic Plasticity
(2023-09)
Salim, Mohamad Azmeer Effendy Md
Mitragynine is the primary indole alkaloid of kratom (M. speciosa) Korth and is thought to be part of kratom’s main psychoactive components. Besides contributing to the addiction, it is known to induce rewarding effects by acting as an agonist to opioid receptors and block the dopamine D2 receptor. Moreover, mitragynine causes cognitive deficit and impairs the hippocampal synaptic plasticity, but the underlying mechanisms are still unknown. In the early part of the study, the modulation of dopaminergic system by mitragynine was investigated in rats treated with mitragynine (1 and 30 mg/kg) acutely (1-day treatment) and repeatedly (4-days treatment) through electroencephalography (EEG) recording. Level of dopamine release was quantified using electrochemical biosensor and ELISA kit analysis. The expression of dopamine transporter was measured using RT-qPCR. Results indicated that administration of mitragynine at both doses triggered changes in spectral frequencies demonstrating adaptations of dopaminergic system in freely moving rats. Repeated exposure of mitragynine (1 and 30 mg/kg) evoked increase of dopamine release after 4 days of administration, where at low dose (1 mg/kg) shows irregular increase of mitragynine released. High dose (30 mg/kg) shows a stable intensification of dopamine released, not after acute exposure in real time recording through an electrochemical biosensor. The adaptations of dopaminergic systems by mitragynine are coupled with increased expression of dopamine transporter in the prefrontal cortex.

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