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Neurobiology of Kratom and its main alkaloid mitragynine

Suhaimi FW, Yusoff NH, Hassan R, Mansor SM, Navaratnam V, Müller CP, et al.

Brain Res Bull, 2016 09;126(Pt 1):29-40.
PMID: 27018165 DOI: 10.1016/j.brainresbull.2016.03.015

Kratom or its main alkaloid, mitragynine is derived from the plant Mitragyna speciosa Korth which is indigenous to Southeast Asian countries. This substance has become widely available in other countries like Europe and United States due to its opium- and coca-like effects. In this article, we have reviewed available reports on mitragynine and other M. speciosa extracts. M. speciosa has been proven to have a rewarding effect and is effective in alleviating the morphine and ethanol withdrawal effects. However, studies in human revealed that prolonged consumption of this plant led to dependence and tolerance while cessation caused a series of aversive withdrawal symptoms. Findings also showed that M. speciosa extracts possess antinociceptive, anti-inflammatory, anti-depressant, and muscle relaxant properties. Available evidence further supports the adverse effects of M. speciosa preparations, mitragynine on cognition. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca2+ channels, expression of cAMP and CREB protein and via descending monoaminergic system. Physicochemical properties of mitragynine have been documented which may further explain the variation in pharmacological responses. In summary, current researchs on its main indole alkaloid, mitragynine suggest both therapeutic and addictive potential but further research on its molecular effects is needed.

Matched MeSH terms: Psychotropic Drugs/adverse effects*
Fulltext Mitragyna speciosa use in the northern states of Malaysia: a cross-sectional study

Ahmad K, Aziz Z

J Ethnopharmacol, 2012 May 7;141(1):446-50.
PMID: 22440259 DOI: 10.1016/j.jep.2012.03.009

ETHNOPHARMACOLOGICAL RELEVANCE:
The consumption of Mitragyna speciosa (MS) for its psychoactive effects is widely reported amongst people in the villages in Thailand and Malaysia even though its use is illegal.
AIM OF THE STUDY: This study examined the pattern of MS use, its reported effects and explored its potential to cause dependence.
MATERIALS AND METHODS: We used both convenience and snowball-sampling methods to recruit participants in a border town between two northern states in Malaysia. Face-to-face interviews were conducted with the use of a structured questionnaire on 562 respondents who gave oral consent to participate in the study.
RESULTS: The response rate was 91%. The majority of the respondents (88%) reported daily use of MS. The main mode of using MS was by drinking the MS extract as tea (90%). The mean age of starting MS use was 28.3 (SD=8.1) years. A variety of reasons were given for using MS including for social and recreational needs, stamina and physical endurance, pain relief and improved sexual performance. Despite its reported usefulness in weaning off opiate addiction, 460 (87%) admitted they were not able to stop using MS. Only education level had a statistically significant association with the ability to stop or not stop the use of MS (χ(2)=31.0, df=1, p<0.001). Significantly higher proportions of those with a lower education level (38%) were able to stop using MS compared to respondents with a higher education level.
CONCLUSIONS: Our study provides important information on the pattern of MS use, its effects and its potential to cause addiction, as there has been growing interest in MS as evidenced by the number of advertisements for its sale on the Internet. Future study is required to explore its psychological and social impact on users.

Matched MeSH terms: Psychotropic Drugs/adverse effects
The consumption of two or more fall risk-increasing drugs rather than polypharmacy is associated with falls

Zia A, Kamaruzzaman SB, Tan MP

Geriatr Gerontol Int, 2017 Mar;17(3):463-470.
PMID: 26822931 DOI: 10.1111/ggi.12741

AIM: The presemt study aimed to determine the association between the risk of recurrent and injurious falls with polypharmacy, fall risk-increasing drugs (FRID) and FRID count among community-dwelling older adults.
METHODS: Participants (n = 202) were aged ≥65 years with two or more falls or one injurious fall in the past year, whereas controls (n = 156) included volunteers aged ≥65 years with no falls in the past year. A detailed medication history was obtained alongside demographic data. Polypharmacy was defined as "regular use of five or more prescription drugs." FRID were identified as cardiovascular agents, central nervous system drugs, analgesics and endocrine drugs; multiple FRID were defined as two or more FRID. Multiple logistic regression analyses were used to adjust for confounders.
RESULTS: The use of non-steroidal anti-inflammatory drugs was independently associated with an increased risk of falls. Univariate analyses showed both polypharmacy (OR 2.23, 95% CI 1.39-3.56; P = 0.001) and the use of two or more FRID (OR 2.9, 95% CI 1.9-4.5; P = 0.0001) were significantly more likely amongst fallers. After adjustment for age, sex and comorbidities, blood pressure, and physical performance scores, polypharmacy was no longer associated with falls (OR 1.6, 95% CI 0.9-2.9; P = 0.102), whereas the consumption of two or more FRID remained a significant predictor for falls (OR 2.8, 95% CI 1.4-5.3; P = 0.001).
CONCLUSIONS: Among high risk fallers, the use of two or more FRID was an independent risk factor for falls instead of polypharmacy. Our findings will inform clinical practice in terms of medication reviews among older adults at higher risk of falls. Future intervention studies will seek to confirm whether avoidance or withdrawal of multiple FRID reduces the risk of future falls. Geriatr Gerontol Int 2017; 17: 463-470.

Matched MeSH terms: Psychotropic Drugs/adverse effects*

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