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.

Cognitive Safety Data from a Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase IIb Study of the Effects of a Cannabidiol and Δ9-Tetrahydrocannabinol Drug on Parkinson's Disease-Related Motor Symptoms.

BACKGROUND: Cannabis is increasingly available worldwide but its impact on cognition in Parkinson's disease (PD) is unknown. OBJECTIVE: Present cognitive safety data from study of an oral high-dose cannabidiol (CBD; 100 mg) and low-dose Δ9-tetrahydocannabinol (THC; 3.3 mg) drug in PD. METHODS: Randomized, double-blind, parallel-group, placebo-controlled study of a CBD/THC drug administered for 16.3 (SD: 4.2) days, with dosage escalating to twice per day. Neuropsychological tests were administered at baseline and 1-1½ hours after final dose; scores were analyzed with longitudinal regression models (alpha = 0.05). Cognitive adverse events were collected. RESULTS: When adjusted for age and education, the CBD/THC group (n = 29) performed worse than the placebo group (n = 29) on Animal Verbal Fluency. Adverse cognitive events were reported at least twice as often by the CBD/THC than the placebo group. CONCLUSION: Data suggest this CBD/THC drug has a small detrimental effect on cognition following acute/short-term use in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Higher Risk, Higher Reward? Self-Reported Effects of Real-World Cannabis Use in Parkinson's Disease.

Background: Despite limited evidence, people with Parkinson's disease (PD) use cannabis for therapeutic purposes. Given barriers to performing randomized trials, exploring real-world experiences with cannabis in PD is valuable. Objective: Investigate the frequency and magnitude of symptomatic effects reported with cannabis use in PD. Methods: An anonymous, 15-question, web-based survey was deployed on Fox Insight. Cannabis product types were defined (by relative tetrahydrocannabinol [THC] and cannabidiol [CBD] content) and respondents were asked to reference product labels. Questions focused on use patterns and subjective effects on 36 predefined symptoms (rated -2-markedly worse to +2-markedly better). Results: 1,881 people with PD responded (58.5% men; mean age 66.5; 50.5% <3 years of PD). 73.0% of respondents reported medicinal use, though 30.8% did not inform their doctor. 86.7% knew their type of cannabis product: 54.6% took higher CBD, 30.2% higher THC, and 15.2% took similar amounts of THC and CBD products. Most common use was oral administration, once daily, for less than six months. Frequent improvements were reported for pain, anxiety, agitation, and sleep (>50% of respondents, mean magnitude 1.28-1.51). Dry mouth, dizziness, and cognitive changes were common adverse effects (20.9%-30.8%, mean -1.13 to -1.21). Higher THC users reported more frequent improvements in depression, anxiety, and tremor, and more frequent worsening in dry mouth and bradykinesia than other product types. Conclusions: Respondents with PD reported using more CBD products, via oral administration, with mild subjective benefits primarily for sleep, pain, and mood. Higher THC products may be higher risk/higher reward for PD-related symptoms.

The APPCN multisite didactic initiative: Development, benefits, and challenges.

Objective: The Covid-19 pandemic disrupted instructional activity in neuropsychology training programs. In response, the Association of Postdoctoral Programs in Clinical Neuropsychology (APPCN) launched a multisite didactic initiative (MDI). This manuscript describes the development and implementation of the MDI and presents findings from a recently conducted online survey concerning MDI participation.Methods: Faculty and trainees at APPCN member programs were recruited to complete the MDI survey, administered using the Qualtrics platform, through email announcements and via website link and on-screen quick response code shared at online didactic sessions. The MDI survey instrument was designed to capture basic demographics and professional role; information regarding level of site participation, benefits of participation, barriers to participation, online conference platform(s) used, and interest in continued participation; as well as anxiety and work engagement ratings.Results: The response rate was estimated to be 21-29%. Transition to videoconferencing for didactics was noted by 80% due to Covid-19, with 17% of respondents experiencing cancellation or reduction in didactic activities. About 79% endorsed that participation in MDI activities was always or nearly always beneficial. Barriers to participation included not having time, difficulty accessing didactic information, and not knowing about the MDI. Interestingly, trainees at nonparticipating sites reported greater anxiety than trainees at participating sites.Conclusion: It is hoped that these findings will inform future efforts to develop and implement online training activities. The benefits reported by respondents suggest that this work is warranted, while reported barriers to participation identify areas for improvement.

Comparing two models of performance validity assessment in patients with Parkinson's disease who are candidates for deep brain stimulation surgery.

Utility of standalone and embedded performance validity tests (PVTs) as well as the decision-making algorithms used to reach clinical conclusions about credible and noncredible performance can be population specific. To better understand PVT utility in Parkinson's disease candidates for deep brain stimulation (DBS) we present on two aims: 1) establishing the frequency data of below-criterion responding for the Medical Symptom Validity Test and three embedded PVTs in a sample of 47 patients with Parkinson's disease, and 2) comparing the efficacy of two models for clinical-decision making regarding noncredible performance. Consistent with expectations from previous studies and desired specificity values, our retrospective analysis indicated that in this sample of presumably well-motived patients, the rate of below-criterion responding was less than 10% for all PVTs administered. Regarding our model comparison, we compared a typical PVT battery that required administration of a standalone measure in all cases against a recently proposed low risk algorithm that attempts to lower testing burden by relying more heavily on embedded PVTs with administration of a standalone measure only in the event of below-criterion performance on an embedded indicator. Results suggest that for patients with Parkinson's disease judged to be at limited risk for noncredible performance, a low risk PVT model may prove both more efficient and less prone to error than a more typical model. Implications for clinical decision-making are discussed, as are limitations of the study and its generalizability.

Are Established Embedded Performance Validity Test Cut-Offs Generalizable to Patients With Multiple Sclerosis?

OBJECTIVE: Data for the use of embedded performance validity tests (ePVTs) with multiple sclerosis (MS) patients are limited. The purpose of the current study was to determine whether ePVTs previously validated in other neurological samples perform similarly in an MS sample. METHODS: In this retrospective study, the prevalence of below-criterion responding at different cut-off scores was calculated for each ePVT of interest among patients with MS who passed a stand-alone PVT. RESULTS: Previously established PVT cut-offs generally demonstrated acceptable specificity when applied to our sample. However, the overall cognitive burden of the sample was limited relative to that observed in prior large-scale MS studies. CONCLUSION: The current study provides initial data regarding the performance of select ePVTs among an MS sample. Results indicate most previously validated cut-offs avoid excessive false positive errors in a predominantly relapsing remitting MS sample. Further validation among MS patients with more advanced disease is warranted.

The impact of cannabis use on intracarotid amobarbital testing.

Chronic cannabis use impacts memory functioning, even while users are not acutely intoxicated. The impact of cannabis use on Wada or intracarotid amobarbital testing (IAT) has not previously been described. We reviewed cannabis consumption in epilepsy patients undergoing IAT during pre-surgical work-up. Of 58 patients reviewed, 16 patients (28%) indicated regular use. During IAT, five regular cannabis users with suspected temporal lobe epilepsy exhibited poor memory while testing their presumptively healthy temporal lobe (i.e., the side opposite that targeted for epilepsy surgery), indicating the potential for an amnestic syndrome post-operatively. It was suspected that the pattern of IAT results for these patients was attributable to the deleterious impact of cannabis use on cognition. Thus, three of the five underwent repeat IAT after a period of enforced abstinence. On repeat IAT, each of the three patients exhibited improved memory performance while testing their healthy temporal lobe, suggesting that the healthy temporal lobe of each mediated sufficient memory ability to allow for epilepsy surgery. These findings raised concerns that frequent cannabis use may alter IAT results, leading to incorrect assessments regarding potential post-operative cognitive deficits, and led to a mandate at our institution that patients must stop cannabis use before IAT.

Exploring cannabis use by patients with multiple sclerosis in a state where cannabis is legal.

BACKGROUND: Studies suggest cannabis may improve symptoms like pain and muscle spasticity in patients with multiple sclerosis (PwMS). Despite cannabis' new-found legality and availability, few studies have explored the profile of PwMS cannabis users and characteristics of their use, particularly in a state where cannabis is legal both for recreational and medicinal use. The purpose of the current study was to evaluate cannabis use among PwMS at a large academic multiple sclerosis (MS) clinic, specifically: (1) prevalence, (2) products used (e.g., cannabidiol vs Δ9-tetrahydocannabinol), (3) symptom treatment, and (4) patient characteristics. METHODS: PwMS completed questions assessing personal opinions about cannabis use, characteristics of cannabis use, MS history, and sociodemographic details, as well as the self-reported disability-Patient Determined Disease Steps (PDDS), overall quality of life-the Patient Reported Outcome Measure Information System (PROMIS-10), and cognition-the Neuro-QoL ACGC v1.0 measures. RESULTS: Thirty-eight percent (n = 96) of PwMS were current Cannabis users (CUs). Although there were no sociodemographic or clinical differences (p ≤ 0.05) between CUs and Non-Cannabis users (NUs), CUs had significantly higher median disability compared to NUs (PDDS = 2 vs. 1; p = 0.02). Among CUs, 57% categorized their use as strictly medicinal. CUs reported using cannabis most often for pain and insomnia/poor sleep and experienced greater than 60% benefit/relief from cannabis use. Over 90% of respondents desire more research on cannabis for MS, and 74% indicated they would consider using cannabis for their MS. CONCLUSION: As cannabis legalization has impacted the variety of cannabis products available, there appears to be growing numbers of PwMS using cannabis, with this study's CUs reporting use of highly efficacious products with minimal side-effects.