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Recurrent Seizures from Chronic Kratom Use, an Atypical Herbal Opioid

April 2018
Epilepsy & Behavior Case Reports 10

DOI:10.1016/j.ebcr.2018.04.002

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CC BY-NC-ND 4.0

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Kratom is an herbal compound that has been used as a recreational drug though is not regulated by the Food and Drug Administration. We report a 19-year-old male with recurrent seizures that developed during daily Kratom abuse as a self-treatment for anxiety. Following recurrent focal impaired awareness seizures in addition to generalized tonic–clonic seizures, he was begun on anti-seizure drugs. Seizures subsided after completing rehabilitation. Brain MRI at 29 months revealed bilaterally symmetric T1-hyperintensity in globus pallidus, subthalamic nuclei, and cerebral peduncles. Our case suggests Kratom abuse may be associated with structural brain lesions on MRI and symptomatic focal epilepsy.

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Case Report

Recurrent seizures from chronic kratom use, an atypical herbal opioid☆

William O. Tatum

⁎, Tasneem F. Hasan

,ErinE.Coonan

, Christopher P. Smelick

Department of Neurology, United States

Department of Neurologic Surgery, Mayo Clinic, Jacksonville, Florida, United States

abstractarticle info

Article history:

Received 15 March 2018

Received in revised form 28 March 2018

Accepted 4 April 2018

Available online 17 April 2018

Kratom is an herbal compound that has been used as a recreational drug though is not regulated by the Food and

Drug Administration. We report a 19-year-old male with recurrent seizures that developed duringdaily Kratom

abuse as a self-treatment for anxiety. Following recurrent focal impaired awareness seizures in addition to

generalized tonic–clonic seizures, he was begun on anti-seizure drugs. Seizures subsided after completing

rehabilitation. Brain MRI at 29 months revealed bilaterally symmetric T1-hyperintensity in globus pallidus,

subthalamic nuclei, and cerebral peduncles. Our case suggests Kratom abuse may be associated with structural

brain lesions on MRI and symptomatic focal epilepsy.

(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords:

Kratom

Abuse

Epilepsy

MRI

Dependency

Opioid

1. Introduction

Kratom is an herbal supplement (leaves of extracts(s) of the Mitragyna

speciosa tree in the coffee family) that originated in Southeast Asia

where it is chewed or ingested as a tea to either give energy or curb

anxiety. In small doses, Kratom works as a stimulant, but in higher-

doses it has sedative and anti-nociceptive effects [1]. Oftentimes, supple-

ments are taken to fortify or maintain health and are believed to be

innocuous [2]. There is evidence that most supplements do not prevent

disease or death, and their use is not justiﬁed when they have no clear

beneﬁtbecausetheycouldbeharmful[3]. Since the 1990s, Kratom has

become a popular recreational drug in the West. This is largely due to

migration of people from Asia to the U.S. and from the dissemination of

information through internet marketing [4]. Its true prevalence of

usage has remained unclear due to limited reports. In 2016, several

million consumers were reported purchasing Kratom from greater than

10,000 retail locations in the U.S. with an estimated annual market of

207 million dollars [5]. Anecdotal reports have included side effects

such as seizure, hypothyroidism, hepatotoxicity, and coma [1,6–8].In

a case report, Kratom has shown to produce reversible injury to the

posterior white matter of the brain [9]. We report a patient with chronic

monotherapy Kratom use who developed focal epilepsy.

2. Case report

A 19-year-old right-handed Caucasian male with anxiety was

without risks factors for epilepsy. He was evaluated after experiencing

aﬁrst seizure. He was initially found down at school, in the bathroom

with post-event confusion and was suspected to have experienced an

unwitnessed generalized tonic–clonic (GTC) seizure. He was concur-

rently being treated with intermittent lisdexamfetamine dimesylate

usage for attention deﬁcit hyperactivity disorder. A brain MRI

performed shortly after the ﬁrst seizure was reported to reveal no

focal abnormalities. A complete metabolic proﬁle, blood count, urine

drug screen, and electroencephalogram were within normal limits. He

was not treated with anti-seizure drugs (ASDs).

One year later, the patent experienced a second seizure character-

ized by awakening from sleep in a transient “dream-like reverie state,”

with generalized muscle soreness and tongue laceration. At this time,

the patient admitted to excessive use of Kratom (several pills per day)

for several months to self-treat anxiety. Typically, Kratom dosage

can vary between 2 to 8 g, producing stimulant to sedative effects,

respectively. Further, ASDs were not administered for a suspected

provoked seizure.

After a third focal seizure, he was prescribed levetiracetam (LEV),

500 mg twice daily. Despite treatment, a witnessed focal to bilateral

GTC seizure occurred 21 months after the ﬁrst event, despite taking

LEV. The event was initially described as “blacking out”with disorienta-

tion and lip smacking prior to the GTC seizure. At this time, the patient

admitted to continued use of Kratom. A urine drug screen returned neg-

ative. Lisdexamfetamine dimesylate and intermittent use of alprazolam

had been discontinued, but he continued taking Kratom as an affordable

Epilepsy & Behavior Case Reports 10 (2018) 18–20

Abbreviations: ASD, anti-seizure drugs; DEA, Drug and Enforcement Administration;

FDA, Food and Drug Administration; GTC, generalized tonic–clonic.

☆Declaration of interest: None.

⁎Corresponding author at: FACNS, Department of Neurology, Mayo Clinic, Cannaday, 2

East. 4500 San Pablo Road, Jacksonville, Florida, 32224, United States.

E-mail address: tatum.william@mayo.edu.(W.O.Tatum).

Contents lists available at ScienceDirect

Epilepsy & Behavior Case Reports

journal homepage: www.elsevier.com/locate/ebcr

https://doi.org/10.1016/j.ebcr.2018.04.002

and available means of alleviating anxiety and providing him with en-

ergy. After his ﬁfth GTC seizure, he admitted to being non-compliant

with LEV due to changes in mood and was switched to lamotrigine for

its mood stabilizing effects.

The sixth GTC seizure resulted in a motor vehicle accident. In addi-

tion to Kratom use, he then admitted to intermittent use of marijuana

(once weekly), lisdexamfetamine dimesylate use (3 times weekly),

rare alprazolam use (monthly), and intermittent alcohol consumption

(4 drinks weekly). He followed up with Psychiatry and due to chronic

Kratom abuse was recommended to drug rehabilitation.

After switching to lamotrigine and discontinuing Kratom the patient

was seizure-free. Nonetheless, breakthrough seizures were noted when

a relapse of Kratom abuse occurred. A brain MRI performed 29 months

after the initial seizure revealed bilateral symmetric T1 hyperintensity

in the diencephalon including the globus pallidus, subthalamic nuclei,

and portions of the cerebral peduncles (Fig. 1). Repeat metabolic

proﬁles were within normal limits. After successful completion of a sub-

stance abuse rehabilitation program, no further seizures were reported

on lamotrigine. A follow-up brain MRI was sought to visualize if struc-

tural brain abnormalities had subsided since discontinuation of Kratom,

but the patient was lost to follow-up when insurance changed.

3. Discussion

Herbal supplements are used for their perceived beneﬁts without

much consideration given to harmful properties. They are used globally

and the prevalence of usage continues to rise. Like patients abusing

illicit drugs, our patient abusing Kratom beneﬁted from detoxiﬁcation

at a supervised facility with trained medical professionals to monitor

and provide medical support during the process. Kratom use in the

U.S. has received limited attention yet theactive ingredients are alkaloid

substances called mitragynine and 7-hydroxymitragynine, and are me-

diated via the monoaminergic and opioid (mu- and kappa-) receptors

[10]. These mechanisms of action are similar to opioids partly due to

its molecular structure referred to as biased agonist [4]. Given the

current worldwide opioid analgesic crisis and potential for misuse,

abuse, and dependence, Kratom may be subject to recreational abuse.

There are a number of herbal supplements that are associated with

seizures including Black cohosh [11], Bearberry [12], Ma Huang [13],

kava-kava [12],Yohimbe[14], and Monkshood [12]. On the other

hand, herbal supplements have had putative anti-seizure effects,

though thelack of evidence precludes this conclusion [15]. For example,

exogenous cannabinoids can mimic the endogenous system and may

have a role in reducing seizure frequency or protect against neurode-

generation [16]. Devinsky et al. performed an open-label trial in pa-

tients between ages 1–30 with severe, drug-resistant childhood-onset

seizures [17]. Oral cannabidiol 2–5 mg/kg/day and titrated to a maxi-

mum tolerated dose of 25 mg/kg or 50 mg/kg/day (depending on the

center) reduced seizure frequency and was safe in children and young

adults, though randomized controlledtrials like the trial of cannabindiol

in Dravet's syndrome [18] are necessary to validate these ﬁndings in

adults with focal seizures.

Between 1983 and 1989, National Poisons Unit in London reported

5131 inquiries. Of these, 968 were related to herbal supplements, and of

which, 245 (25%) were symptomatic [12]. Side effects arising from herbal

supplements may be due to various reasons, such as, misidentifying

the plant species, overlooking the toxicity of the plant, variability in the

chemical constituents of the herb, adulteration, incorrect dosing, and

differing potency depending on the conditions in which the plant was

grown [19].

Currently, no standard methods exist to detect Kratom or its metab-

olites on drug screening after ingestion and this is a contributing factor

to its abuse potential. Like our patient, this also complicates the clinical

scenario for the treating physician and delays management [10].

Evidence also suggests high rates of dependency, development of

withdrawal symptoms, and craving among chronic users [20]. In one

study, more than half of regular Kratom users (N6 months) developed

severe withdrawal symptoms while 45% demonstrated moderate de-

pendency [20]. Consequently, withdrawal symptoms tend to worsen

with chronic use. In a retrospective review in Thailand, 52 Kratom

cases were identiﬁed of which 76.9% resulted in Kratom poisoning and

23.1% were due to withdrawal [21]. Symptoms commonly reported

were palpitations in 22.5% and seizures in 17.5%. An infant born to a

chronic Kratom-abusing mother within this cohort experienced

withdrawal symptoms and emphasized the role of transplacental trans-

mission [21].Currently,nospeciﬁc treatment regimens for Kratom

withdrawal or addiction exist.

Increasing Kratom abuse in the U.S. has created disputes regarding

public safety. In parallel to the opioid crisis, the U.S. Drug and Enforce-

ment Administration (DEA) listed Kratom as a “Drug of Concern”in

2008 [22]. Several states have banned the sale of Kratom [5]. In 2016,

the DEA announced temporary placement of Kratom into a Schedule I

Fig. 1. A. BrainMRI, transverse T1-weighted demonstrating normal imaging afterﬁrst seizure event;B. Brain MRI, 3-T high-resolution,29 months after initial seizureevent demonstrating

increased signal in the globus pallidus bilaterally during chronic Kratom use.

19W.O. Tatum et al. / Epilepsy & Behavior Case Reports 10 (2018) 18–20

category governed by the Controlled Substances Act [22]. However,

public rebuttals, a bipartisan response from the U.S. congress, and

arguments made by the American Kratom Association resulted in the

DEA to withdraw its proposition [4]. Consequently, the DEA, with

input from the Food and Drug Administration (FDA) and National

Institute on Drug Abuse undertook a full abuse potential assessment

of Kratom use to develop regulatory recommendations [5]. The conclu-

sion was Kratom did not appear to be of a public health threat and

emergency scheduling of this supplement or any of its speciﬁc alkaloids

was considered insigniﬁcant [4]. Additionally, it was suggested

that those individuals who consume Kratom for reasons other than

recreational use may resort to illicit unregulated Kratom venders, thus

exposing them to additional risk [4]. Since the banning of its importation

by the FDA, its availability has ﬂown under the radar and has increased. It

is now being sold in powder and tablet form at tobacco stores, and

marketed in shops, purchased online, or mixed into drinks.

4. Conclusion

We associate structural brain abnormality on MRI and symptomatic

focal epilepsy with chronic Kratom abuse during initial use and again

during relapse. Thus far, complications from Kratom abuse have

received limited attention and untoward behavioral dependence and

complications have been largely anecdotal. Kratom abuse is likely to in-

crease due tomarket globalization and readily available internet-driven

supply chains, in addition to the relative safety of Kratom being en-

dorsed as a “natural”herbal supplement. The accessibility and unknown

safety proﬁle of Kratom calls for urgent safety assessment to help guide

appropriate regulatory control.

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Article

Jun 2023

Background: Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand. Methods: Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies. Results: Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users. Conclusion: Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.

Novel Methods for the Remote Investigation of Emerging Substances: Application to Kratom

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Full-text available

May 2023

The botanical product commonly called “kratom” is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods.

The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research

Article

Full-text available

Feb 2018
PSYCHOPHARMACOLOGY

RationaleConsideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health. Objective The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA. ResultsKratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems. Conclusions Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist. Furthermore, appropriate regulation by FDA is vital to ensure appropriate and safe use.

Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion

Article

Full-text available

Jul 2017

Posterior reversible encephalopathy syndrome has been associated with hypertension, preeclampsia, cancer chemotherapy, and drugs of abuse, such as amphetamine and methamphetamine. We report a young man who suddenly developed severe headache, disorientation, and aphasia following ingestion of kratom and Adderall. Computed tomography and magnetic resonance imaging of his head revealed foci of vasogenic edema in the posterior occipital lobes, frontal lobes, and brainstem. In addition, he had a small area of hemorrhage in the left posterior occipital lobe. Lumbar puncture revealed an increased number of red blood cells but no other abnormalities. His initial blood pressure was elevated but returned to normal during hospitalization. This case suggests that kratom can cause posterior reversible encephalopathy syndrome and needs to be considered when patients present to emergency centers with headaches, confusion, and visual disturbances.

The pharmacology and toxicology of kratom: From traditional herb to drug of abuse

Article

Full-text available

Jan 2016
INT J LEGAL MED

Mitragyna speciosa (Rubiaceae), commonly known as kratom, is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. In recent years, kratom has gained popularity for use as a recreational drug across the globe. Relatively new to the illicit market and used in a manner different from its traditional applications, preparations of kratom are touted by many as a safe and legal psychoactive product that improves mood, relieves pain, and may provide benefits in opiate addiction. Available literature was reviewed for M. speciosa via PubMed, Google Scholar, CINAHL, and EBSCO to summarize its traditional uses, phytochemical composition, pharmacology and toxicology of proposed active constituents, and potential for misuse and abuse. Research has demonstrated that both stimulant and sedative dose-dependent effects do exist, but a growing concern for the drug's effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are said to have been caused by extracts of the plant. The main active alkaloid substances in kratom, mitragynine and 7-hydroxymitragynine, present with a range of CNS stimulant and depressant effects mediated primarily through monoaminergic and opioid receptors. Recently, Palm Beach County, located in the southeastern corridor of Florida, has considered regulating kratom due to public safety concerns following the death of a young adult. At the local, state, and even federal levels, governments are now being confronted with the task of determining the safety and the possible regulation of kratom extracts. There are currently no standard analytical screening techniques for mitragynine and its metabolites following ingestion limiting its detection to more sophisticated techniques like liquid chromatography-mass spectrometry to determine kratom use. The growing concern of the abuse potential of kratom requires careful evaluation of its benefits and potential toxicities.

Why US Adults Use Dietary Supplements

Article

Full-text available

Feb 2013

Background: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements. Methods: Data from adults (≥20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey. Results: The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health. Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%). Older adults (≥60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ω-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers. Conclusions: Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

Article

May 2017

Background The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. Methods In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. Results The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. Conclusions Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)

Medical Marijuana for Epilepsy?

Article

Apr 2016

Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring.

Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial

Article

Dec 2015

Background: Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy. Methods: In this open-label trial, patients (aged 1-30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2-5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test. Results: Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n=18 [11%]). Five (3%) patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 (30%) patients, including one death-a sudden unexpected death in epilepsy regarded as unrelated to study drug. 20 (12%) patients had severe adverse events possibly related to cannabidiol use, the most common of which was status epilepticus (n=9 [6%]). The median monthly frequency of motor seizures was 30·0 (IQR 11·0-96·0) at baseline and 15·8 (5·6-57·6) over the 12 week treatment period. The median reduction in monthly motor seizures was 36·5% (IQR 0-64·7). Interpretation: Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profile and true efficacy of this compound. Funding: GW Pharmaceuticals, Epilepsy Therapy Project of the Epilepsy Foundation, Finding A Cure for Epilepsy and Seizures.

Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users

Article

Jun 2014

Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience

Article

Nov 2013

Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratom's effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.

Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements

Article