Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition

Purpose of ReviewThe lack of clarity about the effect of cannabis use on cognition may be attributable to the considerable heterogeneity among studies in terms of cannabis composition. This article selectively reviews studies examining the distinctive effects of cannabinoids on human cognition, particularly those of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD).Recent FindingsResearch indicates that ∆9-THC administration acutely impairs cognition, particularly memory and emotional processing. Limited evidence suggests that CBD administration might improve cognition in cannabis users but not in individuals with neuropsychiatric disorders. Moreover, studies indicate that some acute Δ9-THC-induced cognitive impairments may be prevented if Δ9-THC is administered in combination or following CBD treatment. Δ9-THC and CBD have also shown opposite effects on cognition-related brain activation, possibly reflecting their antagonistic behavioral effects.SummaryResearch suggests greater cognitive impairments in individuals when exposed to high ∆9-THC or low CBD cannabis. It is unclear whether at specific concentrations CBD might outweigh any harmful effects of Δ9-THC on cognition

Cannabis: neuropsychiatry and its effects on brain and behavior

Editorial. [No abstract available

Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years:A systematic review and meta-analysis

BackgroundCannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years.Methods and findingsA systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those ConclusionsThis pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age

Unraveling the Intoxicating and Therapeutic Effects of Cannabis Ingredients on Psychosis and Cognition

Research evidence suggests a dose-response relationship for the association between cannabis use and risk of psychosis. Such relationship seems to reflect an increased risk of psychosis not only as a function of frequent cannabis use, but also of high-potency cannabis use in terms of concentration of \u394-9-tetrahydrocannabinol (\u3949-THC), its main psychoactive component. This finding would be in line with the evidence that \u3949-THC administration induces transient psychosis-like symptoms in otherwise healthy individuals. Conversely, low-potency varieties would be less harmful because of their lower amount of \u3949-THC and potential compresence of another cannabinoid, cannabidiol (CBD), which seems to mitigate \u3949-THC detrimental effects. A growing body of studies begins to suggest that CBD may have not only protective effects against the psychotomimetic effects of \u3949-THC but even therapeutic properties on its own, opening new prospects for the treatment of psychosis. Despite being more limited, evidence of the effects of cannabis on cognition seems to come to similar conclusions, with increasing \u3949-THC exposure being responsible for the cognitive impairments attributed to recreational cannabis use while CBD preventing such effects and, when administered alone, enhancing cognition. Molecular evidence indicates that \u3949-THC and CBD may interact with cannabinoid receptors with almost opposite mechanisms, with \u3949-THC being a partial agonist and CBD an inverse agonist/antagonist. With the help of imaging techniques, pharmacological studies in vivo have been able to show opposite effects of \u3949-THC and CBD also on brain function. Altogether, they may account for the intoxicating and therapeutic effects of cannabis on psychosis and cognition

Is it time to test the antiseizure potential of Palmitoylethanolamide in human studies? A systematic review of preclinical evidence

Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA's role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy

Does Anti-dumping Enforcement Generate Threat?

The last two decades have witnessed that countries across the world are guided by the rules and regulations of multilateral trading institutions (for example, World Trade organization [WTO], International Monetary Fund [IMF]) in order to promote free and fair trade through gradual reduction in trade barriers. The World economy has noticed significant reduction in tariffs, yet we find a rise in non-tariff barriers (NTBs). However, we still find dumping and few other trade strategies of the exporting countries as a major hindrance to free and fair trade. Such behaviour has led to “contingent protection” as a tool of new-protectionism. Among the contingent protection measures, anti-dumping (AD) has evolved as the most popular choice of strategy for the trading nations. The AD policy invokes a threat to the exporter and thereby can change its strategic behaviour. We describe the phenomenon of dumping through a price-leadership model and thereby compute the optimal level of anti-dumping duty that can offset dumping. Using a sequential game, we conclude that the credible threat of an AD duty restricts dumping and thereby leads to a win-win situation for both the foreign and domestic firms

Does Anti-dumping Enforcement Generate Threat?

The last two decades have witnessed that countries across the world are guided by the rules and regulations of multilateral trading institutions (for example, World Trade organization [WTO], International Monetary Fund [IMF]) in order to promote free and fair trade through gradual reduction in trade barriers. The World economy has noticed significant reduction in tariffs, yet we find a rise in non-tariff barriers (NTBs). However, we still find dumping and few other trade strategies of the exporting countries as a major hindrance to free and fair trade. Such behaviour has led to “contingent protection” as a tool of new-protectionism. Among the contingent protection measures, anti-dumping (AD) has evolved as the most popular choice of strategy for the trading nations. The AD policy invokes a threat to the exporter and thereby can change its strategic behaviour. We describe the phenomenon of dumping through a price-leadership model and thereby compute the optimal level of anti-dumping duty that can offset dumping. Using a sequential game, we conclude that the credible threat of an AD duty restricts dumping and thereby leads to a win-win situation for both the foreign and domestic firms