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

Memory and mood during MDMA intoxication, with and without memantine pretreatment

Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of a Special Issue entitled 'CNS Stimulants'

Brain reactivity to alcohol and cannabis marketing during sobriety and intoxication

Theoretical and Experimental Linguistic

A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience

A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience