Kratom

Background: Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as a potential substance of abuse, with limited data on its use and effects. This study characterized kratom user demographics, use patterns, and perceived drug effects. Methods: A cross-sectional, anonymous online survey was conducted between January and December 2017. Results: 2,798 kratom users-mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %)-completed the survey. Kratom was primarily taken orally in doses of 1−3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting > 1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100. Conclusion: Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic.

Background: Kratom ( Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. Aims: This study details the characteristics of such fatalities and provides a ‘state-of-the-art’ review. Methods: UK cases were identified from mortality registers by searching with the terms ‘kratom’, ‘mitragynine’, etc. Databases and online media were searched using these terms and ‘death’, ‘fatal*’, ‘overdose’, ‘poisoning’, etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. Results: Typical case characteristics ( n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine a...

Background and Purpose
Mitragyna speciosa, more commonly known as kratom, is a plant that contains opioidergic alkaloids but is unregulated in most countries. Kratom is used in the self‐medication of chronic pain and to reduce illicit and prescription opioid dependence. Kratom may be less dangerous than typical opioids because of the stronger preference of kratom alkaloids to induce receptor interaction with G proteins over β‐arrestin proteins. We hypothesized that kratom (alkaloids) can also reduce alcohol intake.

Experimental Approach
We pharmacologically characterized kratom extracts, kratom alkaloids (mitragynine, 7‐hydroxymitragynine, paynantheine, and speciogynine) and synthetic carfentanil‐amide opioids for their ability to interact with G proteins and β‐arrestin at μ, δ, and κ opioid receptors in vitro. We used C57BL/6 mice to assess to which degree these opioids could reduce alcohol intake and whether they had rewarding properties.

Key Results
Kratom alkaloids were strongly G protein‐biased at all three opioid receptors and reduced alcohol intake, but kratom and 7‐hydroxymitragynine were rewarding. Several results indicated a key role for δ opioid receptors, including that the synthetic carfentanil‐amide opioid MP102—a G protein‐biased agonist with modest selectivity for δ opioid receptors—reduced alcohol intake, whereas the G protein‐biased μ opioid agonist TRV130 did not.

Conclusion and Implications
Our results suggest that kratom extracts can decrease alcohol intake but still carry significant risk upon prolonged use. Development of more δ opioid‐selective synthetic opioids may provide a safer option than kratom to treat alcohol use disorder with fewer side effects.

Introduction: Among ex-opioid users on methadone maintenance therapy (MMT), the prevalence of chronic severe pain (CSP) was reported as 37-48.2%. The CSP causes distress, adversely affects quality of life, addiction treatment outcome and exacerbates patients ambivalence towards MMT. Neuroticism personality trait is associated with CSP, but the similar association has yet to be explored in ex-opioid users on MMT. Objectives: This study aims to determine the prevalence of CSP among ex-opioid users on MMT, and to examine whether neuroticism is significantly associated with CSP. Methods: In this cross-sectional study, validated Malay version of big five inventory (BFI), brief pain inventory (BPI), Beck's depression inventory (BDI), and Beck's anxiety inventory (BAI) were utilized for measurement of neuroticism, pain, depression and anxiety symptoms, respectively. Subjects were recruited from two MMT centres in Alor Star, Malaysia. Results: A total of 151 subjects were recruited, consisting of 104 from Klinik Kesihatan Bandar Alor Setar, and 47 from Hospital Sultanah Bahiyah. The prevalence of CSP, regular use of over-the-counter (OTC) analgesics and kratom product were 22.5%, 28.5%, and 40.4%, respectively. Using multiple logistic regression analyses, neuroticism score (p < 0.001), BAI score (p = 0.012) and regular OTC analgesic use (p = 0.016) were found to be statistically significant in association with CSP, with adjusted odds ratio of 1.60 (95% CI 1.27, 2.12), 1.44 (95% CI 1.08, 1.93), and 3.56 (95% CI 1.27, 10.01), respectively. Conclusion: Neuroticism, anxiety and regular use of OTC analgesics were independently associated with CSP among ex-opi-oid users on MMT. Otherwise, no significant association was observed for depression, HIV status, regular use of kratom, and other socio-demographic or clinical characteristics.

The anti-depression capability of Kratom is one of its many benefits that is gaining a fraction of users. Recently, a report from researchers shows that one out of three Americans suffer from depression being the reason why Kratom is very popular in the United States. Contrary to people beliefs, depression is not a physiological disorder. However, regardless of depression not being classified as an ailment, it is very dangerous if left uncontrolled or untreated.

Conclusion and Implications: Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window.