Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study.

Background: Cannabis is increasingly used in Parkinson disease (PD), despite little information regarding benefits and risks. Objectives: To investigate the safety and tolerability of a range of doses of cannabidiol (CBD), a nonintoxicating component of cannabis, and it's effect on common parkinsonian symptoms. Methods: In this open-label study Coloradans with PD, substantial rest tremor, not using cannabis received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL). CBD was titrated from 5 to 20-25 mg/kg/day and maintained for 10-15 days. Results: Fifteen participants enrolled, two were screen failures. All 13 participants (10 male), mean (SD) age 68.15 (6.05), with 6.1 (4.0) years of PD, reported adverse events, including diarrhea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (each 5%). Adverse events were mostly mild; none serious. Elevated liver enzymes, mostly a cholestatic pattern, occurred in five (38.5%) participants on 20-25 mg/kg/day, only one symptomatic. Three (23%) dropped out due to intolerance. Ten (eight male) that completed the study had improvement in total and motor Movement Disorder Society Unified Parkinson Disease Rating Scale scores of 7.70 (9.39, mean decrease 17.8%, p=0.012) and 6.10 (6.64, mean decrease 24.7%, p=0.004), respectively. Nighttime sleep and emotional/behavioral dyscontrol scores also improved significantly. Conclusions: CBD, in the form of Epidiolex, may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations. Randomized controlled trials are needed to investigate various forms of cannabis in PD.

Epilepsy during pregnancy: focus on management strategies.

In the US, more than one million women with epilepsy are of childbearing age and have over 20,000 babies each year. Patients with epilepsy who become pregnant are at risk of complications, including changes in seizure frequency, maternal morbidity and mortality, and congenital anomalies due to antiepileptic drug exposure. Appropriate management of epilepsy during pregnancy may involve frequent monitoring of antiepileptic drug serum concentrations, potential preconception switching of antiepileptic medications, making dose adjustments, minimizing peak drug concentration with more frequent dosing, and avoiding potentially teratogenic medications. Ideally, preconception planning will be done to minimize risks to both the mother and fetus during pregnancy. It is important to recognize benefits and risks of current and emerging therapies, especially with revised pregnancy labeling in prescription drug product information. This review will outline risks for epilepsy during pregnancy, review various recommendations from leading organizations, and provide an evidence-based approach for managing patients with epilepsy before, during, and after pregnancy.

The Impact of Psychoactive Drugs on Seizures and Antiepileptic Drugs.

Psychiatric comorbidities are very common in patients with epilepsy, and in fact, a bidirectional relationship between epilepsy and some psychiatric disorders have been identified. However, despite their high prevalence, these comorbidities are not routinely recognized or adequately treated causing a significant burden for these patients. Atypical presentations of some of these psychiatric comorbidities in epilepsy, the concern that some psychotropic drugs may lower seizure threshold worsening frequency of seizures, possibility of many drug-drug interactions, and the negative impact of some antiepileptic drugs on psychiatric conditions are some of the challenges faced by clinicians. Although the main focus in epilepsy has remained on treatment of seizures, acknowledgment of these comorbidities and their timely diagnosis and appropriate treatment not only can impact patients' quality of life but also may improve their response to antiepileptic therapies.

Current and emerging treatment of multiple sclerosis.

The treatment of multiple sclerosis (MS) falls into 3 categories: treatment of exacerbations, slowing disease progression with disease-modifying therapies (DMTs), and symptomatic therapies. The management of MS is becoming increasingly complex with the development of additional DMTs that, like the older DMTs, reduce the frequency and severity of relapses, and the accumulation of lesions detected by magnetic resonance imaging. Initiating treatment to slow or reverse inflammatory lesion formation early in the course of the disease is advocated as a way to prevent accumulation of disability. Nevertheless, there is a lack of comparative efficacy data and few clinical guidelines to aid healthcare providers in the optimal selection of DMTs. Given that some of the newer agents are associated with potentially serious, but rare, adverse events, careful consideration of the risk-benefit profile is necessary to minimize the risk to patients. This article provides an overview of the existing treatments for MS with an emphasis on DMTs and emerging therapies.