Functional brain connectomes reflect acute and chronic cannabis use.

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.

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 ß-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.

Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution.

RATIONALE: Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. OBJECTIVES: The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca. RESULTS: Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca. CONCLUSION: It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.