Ibogaine (iboga tabernanthe) as a potential anti-addictive treatment in the pipeline : a short communication

Opioid addiction is still an emerging problem worlwide. In this South East Asia region, particularly Malaysia, opioid is identified as the main substance of dependency. Due to its nestled relationship between Intravascular opiod usage and the seroprevalence of Human Immunodeficiency Virus (HIV) in the population, the Malaysian government has adopted methadone maintenance therapy (MMT) as one of the harm reduction approaches in curbing the problem. Despite evidents of succes, methadone therapy has shown variabilities in terms of results and clinical outcomes which is very much dose and adherence dependence. This has no doubt suggesting for further research and development of anti-addiction treatment. Ibogaine on the other hand is far left behind from the streamline treatment of substance addiction though studies keep on showing auspicious results on the clinical use. Ibogaine or the name Iboga tabernanthe is one of the African shrubs which is used in ritual of African Bwiti Community. Due to its pharmacological properties, it is classified as psychedelic and has been used in various countries (Canada, New Zealand, Australia and Africa) to treat drug addiction. Pharmacologically, Ibogaine was found to exert its effects at various neurological systems including dopaminergic, glutamatergic, serotonergic, nicotinic and colinergic pathway as well as receptors including opioid, sigma and neurotransmitters such as gamma amino butyric acid (GABA). The mechanism of action is through its active metabolites of noribogaine which may act as addiction interrupter. With long half life, it will sustain in the blood concentration and prolong the pharmacological effects. In the case of opioid addiction, ibogaine exhibits the ability to reduce extracellular level of dopamine in the nucleus accumbens and further, its effects on dopaminergic function are largely regulated by its interaction with serotonin receptors. Physical side effects include QT prolongation, ataxia, dystonia, nausea, vomiting and light sensitivity. Various clinical and animal studies have been conducted worlwide with promising results. This paper will review the feasible evidence of clinical application. Keywords : Ibogaine, anti addictive, addiction interrupter

Therapeutic drug monitoring in methadone maintenance therapy (MMT) : an evaluation of genetic factors influencing clinical outcomes and serum concentrations of methadone

Terapi Gantian Methadone (TGM) telah digunakan secara meluas dan berfungsi untuk mengelakkan berlakunya gejala penarikan dalam kalangan penyalahguna dadah jenis opiat. Ia merupakan salah satu daripada kaedah pendekatan “pengurangan kemudaratan” (harm reduction) bagi menurunkan kadar penularan jangkitan melalui darah dalam komuniti terutamanya HIV AIDS yang boleh membawa maut. Walau bagaimanapun, proses penentuan dos yang optimum bagi setiap pesakit adalah sukar dan mencabar kerana ia menunjukkan kepelbagaian aktiviti farmakologi yang tinggi dalam individu yang berbeza. Kajian ini menghuraikan hubungkait di antara kepekatan methadone darah (Ctrough) dengan dos harian pesakit dan keberkesanan yang dikehendaki iaitu keterukkan gejala penarikan dan ujian pengesahan air kencing bagi pengambilan dadah terlarang. Hubungan antara pelbagai haplotaip gen CYP2B6 dengan kepekatan methadone darah dan variasi polimorfisme nukleotida tunggal OPRM1 (A118G) dengan tahap keberkesanan klinikal yang diukur juga dikaji. Methadone maintenance therapy (MMT) has been widely used to prevent withdrawal symptoms among opiate use disorder patients. It is one of the harm reduction approaches in order to reduce the spread of fatally blood borne diseases in the community especially HIV AIDS. However, determining the optimal dose in patients is somehow difficult and challenging as it shows wide inter-individual variability of pharmacological activity. This study correlates the trough serum methadone concentrations (Ctrough) at steady state with the methadone dose and the clinical outcomes namely severity of withdrawal symptoms and urinalysis for other illicit drugs. The relationship between various CYP2B6 haplotypes with the Ctrough and OPRM1 (A118G) single nucleotide polymorphisms (SNPs) with the clinical outcomes measures were also studied

Paperwork on legality and enforcement for experts meeting: Legalisation of cannabidiol products for medicinal use in Malaysia.

The term medical cannabis is not just a recent phenomenon but has long been introduced and used in the community. Many countries have legislatively amended cannabis from controlled to lesser regulated or unregulated substance groups – depending on the approved usage for either one, two, or all purposes of medical, recreational, and industrial purposes. It is not a surprise that cannabis was ranked as the most widely used substance worldwide. The prominent urge for legalisation in several countries is mainly due to industrial and economic pressure and, to a certain extent, for medical reasons. However, there are many issues reported from the legalizing countries, hence, the current legislation needs to be carefully scrutinized before any amendment is made so that in the long run, the later implementation will not produce any harm to the Malaysian population and the nation as a whole, especially to the young generations

Prescription-level of tramadol utilisation at a tertiary hospital setting in Malaysia: changing trends over a 7-year follow-up period

INTRODUCTION It was reported in a previous study that tramadol was the most frequently prescribed analgesic in Malaysia’s hospital outpatient setting. However, little is known of its trends of prescribing. OBJECTIVES This study evaluated the trends of tramadol prescribing in Malaysia. METHOD This retrospective cross-sectional study was conducted using the prescription database of a tertiary hospital in Malaysia. All tramadol prescriptions in outpatient setting issued for adult patients aged ≥18 years old from 2010 to 2016 were included. The annual number of prescriptions and patients measured in repeat cross-sectional estimates for each year were evaluated. Descriptive statistics and linear trend analysis were applied using Stata version 15.1. RESULTS A total of 64594 tramadol prescriptions were prescribed for 40965 patients from 2010 to 2016. Prescriptions for tramadol increased by 52.7% from 7643 in 2010 to 11763 in 2016, with an average annual increment of 7.1%. The number of new patients prescribed with tramadol increased gradually throughout the study period (a 7.2% increase annually) with the majority (75.6%, n=30974) of them receiving one tramadol prescription. CONCLUSION: Tramadol prescribing increased gradually over a 7-year study period, with the majority of patients receiving only one prescription of tramadol - most likely indicating the use of tramadol for acute pain conditions. Further investigation on the indication and its clinical outcomes are required to ensure safe and rational use of tramadol

Daily clinical dose (D) poorly predicts trough serum methadone concentration (ctrough) in patients undergo methadone maintenance therapy (MMT) with good adherence

Methadone maintenance therapy (MMT) has been used for opioid dependence as one of the harm-reduction approaches. It is also effectiveindirectlyto prevent the wide spread of HIV-related risks such as needle sharing behaviour and illicit drug use. With low costs calculated per patient, MMT has been put as top priorities on reducing opioid dependencies in Malaysia. However, the effective dose strategy of the therapy is still open to debate. The study aimed to investigate the potential of methadone trough concentration (Ctrough)tobe a surrogate marker for such purpose. We conducted a 9-months prospective study to assess the relationship between Ctrough and Dose (D) of methadone. A total of 115 subjects fulfilled the inclusion criteria and had given their consents to participate. Two (2) ml of the trough blood samples (Ctrough) were taken and centrifuged within 4 hours from the time taken at 5,000 Gfor 5 minutes. The resulting serum samples were kept at -20°C until further analysis. The methadone concentration was determined by using a validated method for Methadone ELISA kit. The patients were subjected to another 2 follow ups at 3 months interval each and the same method of serum sampling was applied. Initial correlation reveals significant positive correlation between the two variables in every follow up, ranging between r=0.403-0.419 (p<0.005). Further regression analysis reveals that the coefficient of determination, r2 was poor with only 15-17% of variation in the Ctrough can be explained by the changes in clinical doses (p<0.005). Based on the results, we conclude that daily clinical dose poorly predicts methadone Ctrough for the purpose of dosing adjustment and monitoring of therapy

Trends in the cost of medicines, consultation fees and clinic visits in Malaysia's private primary healthcare system : employer health insurance coverage

Abstract Objective: To examine trends in the cost of medicines, consultation fees and clinic visits among the employees covered by the employer health insurance in Malaysia’s private primary healthcare system in Malaysia Designs: Retrospective cross-sectional study Setting: PMCare claims database from January 2016 to August 2019 Participants: 83,556 outpatient clinic visits involving 10,150 IIUM employees of the International Islamic University Malaysia (IIUM) to private general practitioners (GPs). During the study period, IIUM adopts the incentive structure of capping coverage at Ringgit Malaysia (RM) 45/outpatient visit (USD 10.58) to cover for consultation fees and medicine costs. Main outcome measures: The monthly percentage change in the number of clinic visits, medicine costs, consultation fees and total costs between January 2016 and August 2019. A simple linear regression using Stata v15.1 was also performed to measure the association between the characteristics of the prescribed medicines and medicine charges. Results: The number of clinic visits per patient increased by 17% from January 2016 to August 2019, with consultation fees increasing by 113.9% and total costs by 7.9% per clinic visit per patient. Conversely, the cost of medicines and the number of medicines prescribed per clinic visit per patient decreased by 39.7% and 6.3% respectively. Conclusions: Within the incentive structure of capping the total amount of coverage per clinic visit, medicine costs were reduced by decreasing the number of medicines prescribed, to offset the increased consultation fees. This may create perverse incentives that affect medicine use with negative consequences for the health system and health insurers

Trends and patterns of analgesic utilization in Malaysia from 2010 to 2016: preference for tramadol

Background: Inappropriate or irrational use of analgesics not only leads to increased morbidity and mortality rates and deterioration in quality of life, but can also give rise to misuse of health care resources and increase health care costs. Objectives: To evaluate the trends of analgesics prescribing at outpa- tient tertiary hospital settings and examine the patterns of their utili- zation in NSAIDs, tramadol, and opioid users. Methods: This cross‐sectional study was conducted from 2010‐2016 using the prescription databases of two tertiary hospitals in Malaysia. Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib, ibuprofen, indomethacin, meloxicam, mefenamic acid, and naproxen), tramadol and five other opioids (morphine, fentanyl, oxyco- done, dihydrocodeine, and buprenorphine) were included in this study

Trends and patterns of analgesic prescribing in Malaysian public hospitals from 2010 to 2016 : Tramadol predominately used

Purpose: To examine the trends of analgesic prescribing at public tertiary hospital outpatient settings and explore the patterns of their utilization in NSAIDs, tramadol and opioid patients. Patients and methods: This cross sectional study was conducted from 2010 to 2016 using the prescription databases of two tertiary hospitals in Malaysia. Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib, ibuprofen, indomethacin, meloxicam, mefenamic acid and naproxen), tramadol and five other opioids (morphine, fentanyl, oxycodone, dihydrocodeine, and buprenorphine) were included in this study. Annual number of patients and prescriptions were measured in repeat cross sectional estimates. Descriptive statistics and linear trend analysis were performed using Stata v13. Results: A total of 192747 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 97227 patients (51.8% NSAIDs patients, 46.6% tramadol patients, and 1.7% opioid patients) from 2010 to 2016. Tramadol (37.9%, n = 72999) was the most frequently prescribed analgesic followed by ketoprofen (17.5%, n=33793), diclofenac (16.2%, n = 31180), celecoxib (12.2%, n =23487), and other NSAIDs (<4.5%). All the analgesics were increased over time except for meloxicam, indomethacin, and mefenamic acid. Opioids, primarily morphine (2.2%, n = 4021) and oxycodone (0.5%, n = 1049), were prescribed the least but the rate of increase was the highest. Conclusion: Tramadol was the most frequently prescribed analgesic at hospital outpatient settings in Malaysia. Opioids were prescribed the least but noted the highest increase in utilization