Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cannabis and Pediatric Inflammatory Bowel Disease: Change Blossoms a Mile High.

The trend toward decriminalization of cannabis (marijuana) continues sweeping across the United States. Colorado has been a leader of legalization of medical and recreational cannabis use. The growing public interest in the medicinal properties of cannabis and its use by patients with a variety of illnesses including inflammatory bowel disease (IBD) makes it important for pediatric gastroenterologists to understand this movement and its potential effect on patients. This article describes the path to legalization and "medicalization" of cannabis in Colorado and the public perception of safety despite the known adverse health effects of use. We delineate the mammalian endocannabinoid system and our experience of caring for children and adolescents with IBD in an environment of increasing awareness and acceptance of its use. We then summarize the rationale for considering that cannabis may have beneficial and harmful effects for patients with IBD. Finally, we highlight the challenges federal laws impose on conducting research on cannabis in IBD. The intent of this article is to inform health care providers about the issues around cannabis use and research in adolescents and young adults with IBD.

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.

Effects of developmental exposure to lead, magnesium and zinc mixtures on spatial learning and expression of NMDA receptor subunit mRNA in Fischer 344 rats.

The N-methyl-D-aspartate receptor (NMDAR) is important for learning. Lead (Pb) exposure impairs learning ability and affects the NMDAR. This study tested whether developmental exposure to a combination of Pb, zinc (Zn), and magnesium (Mg) would result in effects different from those seen with individual metals. Fischer 344 (F344) rat pups of both genders were exposed from gestation day 5 to post-natal day (PND) 40, either to Pb, Mg, or Zn individually or to a (one-third or full concentration) mixture of the three metals. All Zn-treated pups died before PND7, but half of the litters given the full concentration mixture survived to PND40. Impaired learning in the Morris water maze was seen in the Mg and full concentration mixture groups. There were gender differences in NR2A subunit mRNA expression in the hippocampal CA3 region in the Mg and Pb groups, but combining the three metals in the full concentration showed no gender effect. Our results showed that exposure to all three metals affected mortality, learning ability and gender-dependent expression patterns of an NMDAR subunit in a different way from that seen with exposure to the individual metals.