Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment.

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research. Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis. Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes. Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary. Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance. Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) µg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) µg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed. Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial.

OBJECTIVES: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. METHODS: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. RESULTS: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen's d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. CONCLUSIONS: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

UNLABELLED: Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PERSPECTIVE: A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain.

Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment.

BACKGROUND: Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear. OBJECTIVE: We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI). DESIGN: In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure. RESULTS: MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects. CONCLUSIONS: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244.

Effects of a Supplement Containing Apoaequorin on Verbal Learning in Older Adults in the Community.

CONTEXT: The changes in verbal learning and working memory that often occur with aging may result in reduced social and intellectual interactions. These changes significantly affect an individual's quality of life. As humans age, the body's ability to regulate and maintain calcium levels is diminished. Pharmacological manipulation of the entry of free calcium (Ca2+) has been shown to be effective in increasing some aspects of cognitive function in the aged brain. Apoaequorin has been shown in laboratory studies to regulate levels of intracellular calcium in neuronal cells and to provide protection against ischemic cell death. OBJECTIVE: The study was designed to assess the effects of a supplement of apoaequorin on verbal learning and working memory. DESIGN: The current study, the Madison Memory Study, was a randomized, double-blind, placebo-controlled trial. SETTING: The study occurred in Madison, WI, USA. PARTICIPANTS: Participants were 218 community-dwelling adults, aged 40-91 y, with self-reported memory concerns. INTERVENTION: Participants were randomly assigned to receive either apoaequorin (apoaequorin group) or a matched placebo (control group) for 90 d. OUTCOME MEASURES: The study used quantitative, computerized tools for cognitive assessment the CogState International Shopping List (ISL) and the CogState ISL-Delayed Recall (ISL-DR). Scores from computerized cognitive tasks were measured at baseline and at several points during the 90-d study. RESULTS: No significant differences existed between the intervention and control groups in any parameter at baseline. The intervention group (apoaequorin group) showed a statistically significant improvement in verbal learning and recall on the ISL and the ISL-DR, respectively, during the 90-d study. Apoaequorin was tolerated very well in the study. CONCLUSIONS: The results indicated a strong relationship between apoaequorin and improvements on a quantitative measure of cognitive function, specifically verbal learning. The study found that apoaequorin is a well-tolerated supplement that improved cognitive function in aging adults. The results suggest potential utility for apoaequorin in addressing the declines in cognitive function associated with aging.

Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People.

Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed.

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans.

RATIONALE: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information. OBJECTIVE: The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways. METHODS: Fifteen occasional cannabis users participated in a double-blind, placebo-controlled, six-way cross-over study. On separate test days, subjects received combinations of pretreatment (placebo, vardenafil 20 mg or rivastigmine 3 mg) and treatment (placebo or 1,376 mg cannabis/kg body weight). Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory (visual verbal learning task, prospective memory test, Sternberg memory test), perceptual-motor control (critical tracking task), attention (divided attention task) and motor impulsivity (stop signal task). RESULTS: The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks, in critical tracking, divided attention and the stop signal task. Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall. When cannabis was given in combination with vardenafil, there were no significant interaction effects in any of the tasks. CONCLUSIONS: The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment, whereas similar results for glutamate have not been demonstrated in this study.

Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention.

Little is known about the effects of combined micronutrient and sugar consumption on growth and cognition. In the present study, we investigated the effects of micronutrients and sugar, alone and in combination, in a beverage on growth and cognition in schoolchildren. In a 2 × 2 factorial design, children (n 414, 6-11 years) were randomly allocated to consume beverages containing (1) micronutrients with sugar, (2) micronutrients with a non-nutritive sweetener, (3) no micronutrients with sugar or (4) no micronutrients with a non-nutritive sweetener for 8.5 months. Growth was assessed and cognition was tested using the Kaufman Assessment Battery for Children version II (KABC-II) subtests and the Hopkins Verbal Learning Test (HVLT). Micronutrients decreased the OR for Fe deficiency at the endpoint (OR 0.19; 95% CI 0.07, 0.53). Micronutrients increased KABC Atlantis (intervention effect: 0.76; 95% CI 0.10, 1.42) and HVLT Discrimination Index (1.00; 95% CI 0.01, 2.00) scores. Sugar increased KABC Atlantis (0.71; 95% CI 0.05, 1.37) and Rover (0.72; 95% CI 0.08, 1.35) scores and HVLT Recall 3 (0.94; 95% CI 0.15, 1.72). Significant micronutrient × sugar interaction effects on the Atlantis, Number recall, Rover and Discrimination Index scores indicated that micronutrients and sugar in combination attenuated the beneficial effects of micronutrients or sugar alone. Micronutrients or sugar alone had a lowering effect on weight-for-age z-scores relative to controls (micronutrients - 0.08; 95% CI - 0.15, - 0.01; sugar - 0.07; 95% CI - 0.14, - 0.002), but in combination, this effect was attenuated. The beverages with micronutrients or added sugar alone had a beneficial effect on cognition, which was attenuated when provided in combination.

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning.

OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

Brahmi for the better? New findings challenging cognition and anti-anxiety effects of Brahmi (Bacopa monniera) in healthy adults.

RATIONALE: A number of studies have indicated positive effects of long-term administration (3 months) of Bacopa monniera (Brahmi) on various cognitive functions especially memory and anxiety. However, inconsistent results in literature may be linked to various methodological issues. OBJECTIVE: The present study aimed to test the chronic effects (12 weeks) of 450 mg of a B. monniera (Brahmi) extract on learning and memory, information processing and anxiety in healthy adult Indian population. METHODS: The study design was a randomised, double-blind, placebo-controlled parallel design. Participants comprised of 72 healthy urban adults, both men and women, in the age range of 35-60 years who were educated and English speaking with basic knowledge of computers from Bangalore. The outcome measures included verbal learning and memory, inspection time, attention and interference. State and trait anxiety were additional outcome variables. RESULTS: In the present study, there were no significant differences between the two groups on any of the cognitive measures. However, there was a trend for lower state anxiety in the B. monniera (Brahmi) group as compared to placebo group. CONCLUSIONS: The current study attempted to determine the chronic effects of single daily dose of 450 mg of Brahmi extract on cognitive performance and anxiety in healthy adults. The results of the current study are not in agreement with findings of some of the earlier studies which have found improvement both on cognitive parameters and a reduction of anxiety scores.

Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

A healthy dietary pattern at midlife is associated with subsequent cognitive performance.

Few studies have investigated the long-term impact of overall dietary patterns (DP) on cognition. We evaluated the association between empirically derived DP in midlife and cognitive performance 13 y later. Dietary data were based on 24-h dietary records obtained from a subsample of the Supplémentation en Vitamines et Minéraux Antioxydant Study. Cognitive performance was assessed via a battery of neuropsychological tests that included verbal fluency, the RI-48 cued recall test, the trail-making test, and forward and backward digit span. Three composite variables, for global cognitive function, verbal memory, and executive functioning, were built. The multivariate analyses were adjusted for baseline characteristics (age, gender, intervention group, education, alcohol and energy intake, number of dietary records, physical activity, BMI, tobacco use, self-reported memory troubles, diabetes, hypertension, and, for women, menopausal status and hormone therapy use), follow-up time, history of cardiovascular disease, and depressive symptoms. Adjusted means ± SEM of composite variables across quartiles (Q4 vs. Q1) of DP were estimated using ANCOVA. A healthy and a traditional DP were identified. In the multivariate model, the healthy pattern was associated with better global cognitive function (50.1 ± 0.7 vs. 48.9 ± 0.7; P-trend = 0.001) and verbal memory (49.7 ± 0.4 vs. 48.7 ± 0.4; P-trend = 0.01). These relationships were stronger in participants scoring below the gender-specific median values for energy intake (<2490 kcal for men and <1810 for women) than in those scoring at or above those values. Adherence to a healthy DP in middle life may help preserve global cognitive function, especially verbal memory, when total energy intake is regulated.

Effects of a diet integration with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan in elderly patients suffering from mild cognitive impairment.

Age-related changes in nutritional status can play an important role in brain functioning. Specific nutrient deficiencies in the elderly may exacerbate pathological processes in the brain. Consequently, the potential of nutritional intervention to prevent or delay cognitive impairment and the development of dementia is an important topic. A randomized, double-blind, placebo-controlled trial has been performed in 25 elderly subjects (86 ± 6 years, 20 females, 5 males) with mild cognitive impairment (MCI). These subjects were randomly assigned to supplement their diet with either an oily emulsion of docosahexaenoic acid (DHA)-phospholipids containing melatonin and tryptophan (11 subjects) or a placebo (14-matched subjects) for 12 weeks. The main aim of this study was to evaluate the efficacy of the dietary supplement on cognition, by the assessment at the start and after 12 weeks of: (1) Orientation and other cognitive functions: Mini-Mental State Examination (MMSE); (2) Short-term memory: digit, verbal, and spatial span (digit span; verbal span; Corsi's test); (3) Long-term memory: Rey's auditory-verbal learning test; 'short story' test; Rey-Osterrieth complex figure (recall); (4) Attentional abilities: attentive matrices; (5) Executive functions: Weigl's sorting test; phonological fluency 'FAS'; (6) Visuo-constructional and visuo-spatial abilities: copy of simple drawings; Rey-Osterrieth complex figure (copy); (7) Language: semantic fluency; (8) Mood: Geriatric Depression Scale (GDS). Moreover, Sniffin' Sticks olfaction test and Mini Nutritional Assessment (MNA) have been performed. After 12 weeks, a significant treatment effect for the MMSE (P < 0.001) and a positive trend for the semantic verbal fluency was found in the supplement group (P < 0.06). A significant treatment effect was found out for the olfactory sensitivity assessment (P < 0.009). As regards the nutrition evaluation, after 12 weeks of treatment the supplemented group showed an improvement in the MNA score with a significant difference relative to placebo (P < 0.005). Older adults with MCI had significant improvements in several measures of cognitive function when supplemented with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan for 12 weeks, compared with the placebo.

Can micronutrients improve neurocognitive functioning in adults with ADHD and severe mood dysregulation? A pilot study.

OBJECTIVES: Little research has investigated how micronutrients (minerals and vitamins) affect cognitive functioning, despite preliminary studies showing they may improve psychiatric functioning. INTERVENTION: This pilot study investigated the impact of a 36-ingredient micronutrient formula consisting mainly of vitamins and minerals on neurocognitive functioning in 14 adults with attention-deficit/hyperactivity disorder (ADHD) and severe mood dysregulation. DESIGN: The formula was consumed in an open-label trial over an 8-week period. OUTCOME MEASURES: The participants completed tests of memory (Wide Range Assessment of Memory and Learning) and executive functioning (Delis-Kaplan Executive Functioning System and Conners Continuous Performance Test) at baseline and at the end of the trial. A gender- and age-matched control group of 14 non-ADHD adults not taking the formula were assessed on the same tests 8 weeks apart in order to investigate the impact of practice on the results. RESULTS: There were no group differences in ethnicity, socio-economic status and estimated IQ. Significant improvement was observed in the ADHD group, but not the control group, across a range of verbal abilities including verbal learning, verbal cognitive flexibility and fluency, and verbal inhibition. These neurocognitive improvements were large and consistent with improved psychiatric functioning. No changes were noted above a practice effect in visual-spatial memory and there were no improvements noted in reaction time, working memory, or rapid naming for either groups. CONCLUSIONS: Although the pilot and open-label design of the study limits the generalizability of the results, it supports a growing body of literature recognizing the importance of nutrients for mental health and cognition. The results also provide evidence supporting the need for randomized clinical trials of micronutrients as well as other experimental studies in order to better assess whether improved neurocognitive functioning may contribute to improved psychiatric symptoms.

Improvement in immediate memory after 16 weeks of tualang honey (Agro Mas) supplement in healthy postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the verbal learning and memory performance of postmenopausal women who received tualang honey (Agro Mas) in comparison with women receiving estrogen plus progestin therapy and untreated controls. METHODS: A total of 102 postmenopausal women were recruited and randomly assigned to three groups: tualang honey (20 g/d)[corrected], estrogen plus progestin therapy (Femoston 1/5), and untreated control. Their verbal learning and memory performances were assessed using the Malay version of the Auditory Verbal Learning Test before and after 16 weeks of intervention. Data were analyzed using the repeated-measures analysis of variance, and a P value of less than 0.05 was considered significant. RESULTS: There were significant differences in the mean scores of total learning as well as the mean scores of trials A1, A5, A6, and A7 between the three groups. There were also significant differences in the overall mean scores of total learning and trials A1 and A5 between both estrogen plus progestin therapy and tualang honey groups when compared with the untreated control group. However, significant differences in the mean score for trials A6 and A7 were only observed between the estrogen plus progestin therapy and untreated control groups. CONCLUSIONS: Postmenopausal women who received tualang honey showed improvement in their immediate memory but not in immediate memory after the interference and delayed recall. This is comparable with the improvement seen in women receiving estrogen plus progestin therapy.

Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.

OBJECTIVE: The aim of this study was to characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. METHODS: In a phase II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89 from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. RESULTS: Neither of the botanical treatments had an impact on any cognitive measure. Compared with placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (P = 0.057) in unadjusted analyses but reached significance (P = 0.02) after adjusting for vasomotor symptoms. Neither of the botanical treatment groups showed a change in verbal memory that differed from the placebo group (Ps > 0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. CONCLUSIONS: Results indicate that a red clover (phytoestrogen) supplement or black cohosh has no effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory.

Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers.

BACKGROUND: Emotional processing measures are sensitive to acute administration of clinically useful antidepressant drugs. We wished to test the hypothesis that these models would also be able to detect agents likely to cause depression as an adverse effect. The anti-obesity drug and cannabinoid type 1 receptor antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use. MATERIALS AND METHODS: Thirty healthy adult volunteers were randomly assigned to receive a single dose of rimonabant (20 mg) or lactose placebo in a double-blind, between-groups design. Three hours after medication administration, subjects undertook an emotional processing test battery including facial emotion recognition, emotional word attentional dot probe, self-relevant word classification, emotional and declarative memory and the emotion-potentiated acoustic startle response. Subjective state was assessed via self-report measures. RESULTS: A single dose of rimonabant did not alter subjective mood. However, rimonabant selectively reduced incidental recall of positive self-relevant adjectives, an effect contrary to that seen following the administration of antidepressants. There were no effects of rimonabant on the other measures of emotional processing. CONCLUSIONS: These results suggest that a single dose of rimonabant decreases positive emotional memory in the absence of changes in subjective state. Further studies are required to examine whether rimonabant might produce a wider range of negative emotional biases with repeated treatment.

Sensorimotor gating and attentional set-shifting are improved by the mu-opioid receptor agonist morphine in healthy human volunteers.

Prepulse inhibition (PPI) of the acoustic startle response (ASR) has been established as an operational measure of sensorimotor gating. Animal and human studies have shown that PPI can be modulated by dopaminergic, serotonergic, and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems. Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating. Thus, the present study investigated the influence of the mu-opioid receptor agonist morphine on PPI in healthy human volunteers. Eighteen male, non-smoking healthy volunteers each received placebo or 10 mg morphine sulphate (p.o.) at a 2-wk interval in a double-blind, randomized, and counterbalanced order. PPI was measured 75 min after drug/placebo intake. The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side-effects were assessed by the List of Complaints. Additionally, we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test. Morphine significantly increased PPI without affecting startle reactivity or habituation. Furthermore, morphine selectively improved the error rate in an attentional set-shifting task but did not influence vigilance, memory, or executive functions. These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia.

Modulation of cognitive performance and mood by aromas of peppermint and ylang-ylang.

This study provides further evidence for the impact of the aromas of plant essential oils on aspects of cognition and mood in healthy participants. One hundred and forty-four volunteers were randomly assigned to conditions of ylang-ylang aroma, peppermint aroma, or no aroma control. Cognitive performance was assessed using the Cognitive Drug Research computerized assessment battery, with mood scales completed before and after cognitive testing. The analysis of the data revealed significant differences between conditions on a number of the factors underpinning the tests that constitute the battery. Peppermint was found to enhance memory whereas ylang-ylang impaired it, and lengthened processing speed. In terms of subjective mood peppermint increased alertness and ylang-ylang decreased it, but significantly increased calmness. These results provide support for the contention that the aromas of essential oils can produce significant and idiosyncratic effects on both subjective and objective assessments of aspects of human behavior. They are discussed with reference to possible pharmacological and psychological modes of influence.

Apomorphine effects on episodic memory in young healthy volunteers.

RATIONALE: Dopamine (DA) modulates working memory. However, the relation between DA systems and episodic (declarative) memory is less established. Frontal lobe DA function may be involved. We were interested in assessing whether apomorphine (Apo), a drug used extensively in clinical research as a probe of DA function, has an effect on episodic memory test performance in healthy volunteers. OBJECTIVE: To investigate the effect of a presynaptic dose of Apo on episodic memory tests and on other tests thought to be sensitive to frontal lobe functions. METHODS: Twenty healthy subjects were treated with Apo HCl (5 microg/kg sc) or placebo (10 subjects/group) in a randomized, double blind parallel group design and performance on a battery of cognitive tests was assessed. RESULTS: Apomorphine significantly impaired performance on tests of source recognition (d.f.=19, p=0.05) and item recognition memory (d.f.=19, p<0.05), and memory interference (d.f.=19, p<0.010). No significant change was found on other tests (Go/no-Go Test, Categorized Words, Stroop, Trail Making Test, and verbal fluency). CONCLUSION: Findings in this small sample of subjects suggest that dopaminergic transmission affects episodic memory functions.