cbd cognition

Cbd cognition

The regression allows us to assess how memory accuracy was affected by differences in the strength of neurophysiological exposure to each cannabinoid alone and in combination. Second, the effect of strain group on memory accuracy (d’) was analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor and strain group (THC and THC + CBD) as a between-subject factor. Because the THC content was lower in the product consumed by the THC + CBD group, we ran a second ANOVA with log (THC + metabolites) as a covariate in this ANOVA.

Multiple comparisons were assessed with Bonferroni post-hoc tests (with corresponding p-values reported as pbf) for all analyses.

Cannabinoid plasma biomarker levels taken immediately post-use were our primary assessment of the strength of the effects of each cannabinoid, but cannabinoid content weight is also reported to facilitate comparison with other studies. The total weight of the product that each participant used was measured as the difference between pre- and post-use weight (mg Total, Table 2). The amount of each cannabinoid consumed by each participant was estimated by multiplying the total weight used by the percentage of THC and CBD in that subject’s strain (mg THC and mg CBD, Table 2). To examine differences in cannabinoid content across groups, analyses were performed in a mixed-design ANOVA with cannabinoid type (CBD, THC) as a within-subject factor and strain group (THC, THC + CBD) as a between-subject factor.

Recognition memory task

Second, accuracy (d′, Fig. 3) was analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor, and strain group (THC, THC + CBD) as a between-subject factor. d′ significantly decreased between pre- and post-test, F(1, 29) = 5.84, p < .05, ( _p^2 ) = 0.17, and d ′ was significantly higher for the THC + CBD group compared to the THC group, F(1, 29) = 6.05, p < .05, ( _p^2 ) = 0.17. The significant session × strain group interaction, F(1,29) = 7.90, p < .01, ( _p^2 ) = 0.21, showed that accuracy was lower at posttest than pretest for the THC group (pbf < .01), but not for the THC + CBD group. We also observed that the accuracy at posttest was lower for the THC group than for the THC + CBD group (pbf < 0.01). Additionally, sum THC + metabolite blood plasma levels were included as a covariate since it significantly predicted memory accuracy in the regression analysis and because the THC content of the product consumed by the THC + CBD group was lower in THC. As performed in previous analyses, we used the log transform of metabolite data. The covariate log (THC) was significant, F(1,28) = 7.79, p < .01, ( _p^2 ) = 0.22. The significant session × strain group interaction, F(1,28) = 6.18, p < .05, ( _p^2 ) = 0.18, showed similar results as before, with lower accuracy at posttest compared to pretest for the THC group (pbf < .01), but not for the THC + CBD group. Also, the accuracy at posttest for the THC group was lower than for the THC + CBD group (pbf < 0.01).

Because the recognition task was added onto another ongoing protocol, it was always run after the primary outcome measures for the main study which included assessments of other memory tasks, attention, inhibitory control, balance, and subjective drug effects. These tasks are unlikely to interfere with recognition memory results. The only other verbal memory test included was the International Shopping List Task (ISLT), which used different words than the recognition task. Our larger study found that THC administration was negatively associated with ISLT performance, but CBD results await ongoing data collection and analysis (Bidwell et al. 2020).

Cannabinoid content

We do not have the specific time point for the memory assessment for each participant, so the time given here is an estimate based on the general flow of the protocol. The timing of the protocol should not differ between participants.

Compared to other recent studies examining the acute effects of THC on episodic memory, the present study included more naturalistic methods of cannabis use and higher dosage. Recognition accuracy was better before than after THC consumption and decreased as THC blood levels increased. Our participants self-administered their assigned products ad libitum using their normally preferred methods at home. The mean estimated THC dosage across both the THC and THC + CBD strain groups was 58.61 mg (range = 1.92–235.8 mg). In a broad review of studies of cannabis use on human cognition from 2004 to 2015, Broyd et al. (2016) identified 11 studies investigating acute effects on verbal episodic memory. Of those demonstrating acute memory deficits, five administered intravenous (IV) THC (D’Souza et al. 2004; D’Souza et al. 2008; Englund et al. 2013; Morrison et al. 2009; Ranganathan et al. 2012), two administered vaporized cannabis (Liem-Moolenaar et al. 2010; Theunissen et al. 2015), and one administered oral THC (nabilone) (Wesnes et al. 2009). Dosage in these studies ranged from 2 to 12 mg of THC. More recent studies have documented episodic memory impairments after acute use of 8 mg of THC with a vaporizer (Morgan et al. 2018) and 10.73 mg of THC with experimenter-regimented joint smoking (Hindocha et al. 2015). Thus, we have replicated prior work under more naturalistic conditions and higher doses, as well as replicating our previous free recall results in a separate sample of participants with a recognition memory task (Bidwell et al. 2018).

CBD may also create positive cognitive effects through its effects on neurogenesis and synaptic transmission. CBD is able to increase hippocampal mRNA expression of brain-derived neurotrophic factor, effectively promoting neurogenesis, which is critical for learning and memory. CBD can inhibit reuptake of adenosine at synaptic terminals and modulate brain-derived neurotrophic factor-mediated effects that improves neural transmission and therefore also cognition, according to study authors.

The review first dove into the potential mechanisms of CBD that could be impacting cognition. CBD is unique to many other phytocannabinoids as it displays poor affinity to the endocannabinoid system/cannabinoid receptors and instead utilizes alternative pathways. Study authors discussed how CBD reduces the reuptake of cannabinoids already present in the body, including anandamide and 2-arachidonoylglycerol. Data from previous research has shown that CBD’s neuroprotective and anti-inflammatory effects could create positive effects on cognition. These effects have been studied in Alzheimer disease, but could also demonstrate the same in epilepsy, authors wrote, as CBD has been shown to reduce neuroinflammation and prevent oxidative stress, both of which negatively impact patients with epilepsy.

Investigators aimed to determine the positive or negative effects CBD may have on cognition in patients with epilepsy, characterize acute and chronic effects, and examine whether the pure cannabinoid can lead to changes in brain structure or function in relation to cognitive function.

Some pre-clinical and animal models analyzing CBD as a treatment for various types of epilepsy have reported behavioral and cognitive results. In one animal study, a group of rats with epilepsy received chronic oral CBD treatment and demonstrated reduced occurrence of reference memory errors. “Those with epilepsy treated with CBD (p<0.05) error rates were significantly lower than the untreated rats with epilepsy,” the study authors explained.

The review identified 2 studies that assessed the effects of highly purified CBD on brain structure in patients with TRE. The first employed voxel-based morphometry to gauge structural changes resulting from 12 weeks of CBD use. Investigators examined gray matter volume and changes in cortical thickness, both of which did not significantly change by the end of the study period. The second study assessed participants with diffusion tensor imaging, where “some significant findings were observed with DSI Studio including increases and decreases in various DTI measures,” the study authors reported.

CBD also has the potential to address mood disorders that are common in patients with epilepsy that may lead to negative cognitive effects if not controlled. CBD acts on serotonin receptors to increase synaptic levels of noradrenaline. “Modulating both of these neurotransmitters has been implicated in the management of depression,” the study authors wrote.

However, a critical aspect of anti-seizure medication that remains understudied is its effect on cognition. “This is because of the high incidence of comorbid cognitive deficits in people with epilepsy,” authors noted. At least half of individuals with epilepsy experience cognitive deficits, in many cases caused by anti-seizure medications.