Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

<p>Abstract</p> <p>Background</p> <p>Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.</p> <p>Methods</p> <p>We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.</p> <p>Results</p> <p>Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.</p> <p>Conclusion</p> <p>We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.</p

Testing a dynamic field account of interactions between spatial attention and spatial working memory

Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: if attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal is reexamined in light of a neural process model of SWM. On the basis of the model’s functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color-discrimination task during the delay interval of a spatial recall task. In the critical shifting attention condition, the color stimulus could appear either toward or away from the memorized location relative to a midline reference axis. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors but no change in directional error, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations—as predicted by the model—there should be systematic changes in the pattern of spatial recall errors depending on the direction of the shift. Results were consistent with the latter possibility—recall errors were biased toward the location of discrimination targets appearing during the delay

Connectivity of the Primate Superior Colliculus Mapped by Concurrent Microstimulation and Event-Related fMRI

Background: Neuroanatomical studies investigating the connectivity of brain areas have heretofore employed procedures in which chemical or viral tracers are injected into an area of interest, and connected areas are subsequently identified using histological techniques. Such experiments require the sacrifice of the animals and do not allow for subsequent electrophysiological studies in the same subjects, rendering a direct investigation of the functional properties of anatomically identified areas impossible. Methodology/Principal Findings: Here, we used a combination of microstimulation and fMRI in an anesthetized monkey preparation to study the connectivity of the superior colliculus (SC). Microstimulation of the SC resulted in changes in the blood oxygenation level-dependent (BOLD) signals in the SC and in several cortical and subcortical areas consistent with the known connectivity of the SC in primates. Conclusions/Significance: These findings demonstrates that the concurrent use of microstimulation and fMRI can be used to identify brain networks for further electrophysiological or fMRI investigation