Once again researchers from the Psychedelic Research Programme jointly set up by the Beckley Foundation and Imperial College London have published trailblazing research on the effects of psychedelics on the brain. These trendsetting studies are the first to apply multimodal neuroimaging to subjects who were injected with LSD. Dr. Carhart-Harris and his fellow colleagues from Imperial College London have revealed the effects of lysergic acid diethylamide (LSD) on the brain’s network communication, blood flow and electrical activity using fMRI BOLD, arterial spin labelling and magnetoencephalography (Carhart-Harris et al., 2016).

From these neuroimaging studies, researchers have gained an important and novel insight into the basis of ego-dissolution, the way in which closed-eye visuals occur and effects of the combination of LSD and music in the brain. The studies were conducted with 20 subjects who were injected once with 75µg LSD and once with a placebo, at least two weeks apart. All participants had prior experience with psychedelics.

Functional magnetic resonance imaging (fMRI) based on the evaluation of blood oxygen level dependent (BOLD) contrast was applied to evaluate the activity of different brain regions and their interconnection while on LSD. The scans were performed in the resting state, i.e. in the absence of any external stimuli or specific cognitive tasks. Subsequently the levels of (dis)integration/(de)segregation were evaluated, with certain regions of interest (ROI) being picked up to analyse their interaction with the other brain regions.

LSD - Global FCD

Average functional connectivity density (FCD) in cortical and subcortical regions under the placebo and LSD conditions – Tagliazucchi et al., 2016.

One of the main findings of the study was that LSD facilitates an inflation of globalised communication between various brain regions. Using positron emission tomography (PET), the researchers found that the highest level of such communication occurred in the regions with the highest density of serotonin-2A (5-HT2A) receptors, LSD acting as an agonist to this type of receptors. One interesting aspect of this is that the higher interaction between brain regions corresponded with lower integration within certain networks. All in all, the study identified 12 resting state networks affected by LSD in this way, with the default mode network (DMN) being the most important for the case at study.

Ego dissolution

The DMN is the network of the brain that becomes activated when a person is experiencing resting states such as daydreaming, and becomes inactivated during goal-oriented tasks. According to the present study, the disintegration within the DMN is directly related to the onset of a state of consciousness commonly described as ego dissolution. Ego dissolution is the subjective experience of losing one’s sense of identity. It is sometimes described as unity with the outside world and oneness with the universe resulting from a blurring of the boundaries of the autonomous self. The altered state of consciousness questionnaire used at the end of each scanning day revealed that ego dissolution correlated with the experience of altered meaning, i.e. attaching importance to objects previously deemed unimportant and giving surroundings new, alien meaning. Also correlated with the state of ego dissolution was disintegration in other brain regions such as the salience network and the thalamus.

LSD - Ego dissolution

Brain regions where a significant correlation between FCD and subjective reports of ego dissolution (LSD minus placebo) was found are colored in red. Brain regions presenting the most selective correlations between FCD increases and ego dissolution scores are colored in green – Tagliazucchi et al., 2016

Disintegration in the DMN and other resting networks was also accompanied by decreased alpha power in regions such as the posterior cingulate cortex (PCC). Regular alpha oscillations are hypothesised to inhibit spontaneous neuronal activity, i.e. that which occurs without exposure to particular stimuli (Tagliazucchi et al., 2016). LSD was found to decrease alpha power and thus trigger spontaneous activity in neurons, an effect that could partially explain the closed-eye imagery associated with the LSD experience.

The mechanisms of closed-eye imagery

Striking results were obtained in the study of closed-eye imagery induced by LSD. The researchers investigated both simple images like geometrical patterns and complex ones including autobiographical scenes occurring under LSD. The study revealed that although there was no visual input, under LSD the visual cortex (VC) behaved as if there was (Carhart-Harris et al., 2016). This observation supports ongoing theories that the appearance of geometrical imagery may be caused by the rendered instability of the VC (Butler et al., 2011).

Apart from the increase in blood flow level, the visual cortex also displayed increased functional connectivity with other brain regions, mainly the parahippocampal cortex (PHC), typically involved in memory retrieval, music-evoked emotion and mental imagery. The researchers used a Dynamic Causal Modelling analysis to reveal increased effective connectivity between the VC and the PHC, where the PHC triggered the activity of the VC. The interconnection of these brain regions can be held responsible for the “colouring” of personal recollections experienced by the subjects under LSD. Apart from the PHC, other brain regions such as those in occipital and inferior frontal lobes also became activated during visuals, leading to the conclusion that a much larger portion of the brain is involved in producing imagery under LSD than in the normal waking state.

The influence of music

The study further revealed the highly important role of music during the psychedelic experience. Mendel Kaelen, a PhD candidate at Imperial College London and board member of the OPEN Foundation, explored the synergistic effects of music during the LSD experience (Kaelen et al., 2016). Three fMRI scans were performed, the first and the third of which were done without the use of music, the second being performed while the subjects listened to music (two excerpts from the album Yearning by the ambient artist Robert Rich and the Indian classical musician Lisa Moscow).

The study showed that the PHC becomes highly activated when subjects are exposed to music and LSD. Furthermore, the increase of interaction between the PHC and the visual cortex corresponded with the intensity of the closed-eye visuals, both simple (geometrical patterns) and complex ones (e.g. based on personal recollections). This certainly underscores the importance of incorporating music into LSD-assisted psychotherapy.

Expanding the knowledge

The findings of the present study with LSD provide firmer ground to the knowledge that has been gathered in experiments using other psychedelics. Psilocybin has been found to have similar effects on brain activity including the disintegration in certain regions such as the default mode network and the emergence of new connections between normally segregated networks. These conclusions emerged from two independent researches, one of which was performed by the authors of the present LSD study (Carhart-Harris et al., 2012, Kometer et al., 2015). Still another research group discovered analogous effects of the Amazonian psychedelic ayahuasca on the human brain (Riba et al., 2002).

The findings of this groundbreaking study have several important implications. First, they hint at a neurological understanding of the therapeutic potential of LSD. Due to its “entropic” effect on the brain – the increase of disintegration within and simultaneous increase of interaction between certain brain regions – LSD may hold the potential for breaking down pathological patterns associated with depression, for instance, and thus increasing the effectiveness of psychotherapy.

The study also demonstrated the potential of LSD in the study of the neurobiology of consciousness, as it seems to put subjects into the so-called primary state of consciousness characteristic of the earlier stages of consciousness development in children, of REM sleep and of early psychosis (Carhart-Harris et al., 2016). This also means that LSD could be applied in psychological research in the study of pathologies (Carhart-Harris et al., 2016).

Apart from the short-term effects of LSD on brain chemistry, more investigation is warranted on the potential of the LSD experience to provoke sustainable changes in personality.

Robin Carhart-Harris and Mendel Kaelen will speak at the OPEN Foundation’s ICPR conference next June.

References:

Butler T. C., Benayoun M., Wallace E., van Drongelen W., Goldenfeld N. and Cowan J. (2012) Evolutionary constraints on visual cortex architecture from the dynamics of hallucinations. Proceedings of the National Academy of Sciences of the United States of America, 606-609. https://dx.doi.org/10.1073/pnas.1118672109

Carhart-Harris R. L., Errizoe D., Williams T., Stone J. M., Reed L. J., Colasanti A., Tyacke R.J., Leech R., Malizia A.L., Murphy K., Hobden P., Evans J., Feilding A., Wise R.G. and Nutt D.J. (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl. Acad. Sci. USA 109, 2138–2143. https://dx.doi.org/10.1073/pnas.1119598109

Carhart-Harris R. L., Muthukumaraswarmy S., Roseman L., Kaelen M., Droog W., Murphy K., Taggliazzuchi E., Schenberg E.E., Nest T., Orban C., Leech R., Williams, L., Williams T., Bolstridge M., Sessa B., McGoniglea J., Sereno M., Nichols D., Hellyer P.J., Hobden P., Evans J., Singh K.D.,  Wise R.G., Curran V., Feilding A. and Nutt D.J. (2016) Neural Correlates of the LSD Experience Revealed by Multimodal Neuroimaging. Proceedings of the National Academy of Sciences of the United States of America, 1-6. https://dx.doi.org/10.1073/pnas.1518377113

Kaelen M., Roseman L., Kahan J., Santos-Ribeiro A., Orban C., Lorenz R., Barett F.S., Bolstridge M., Williams T., Williams L., Wall M.B., Feilding A., Muthukumuraswamy S., Nutt D.J and Carhart-Harris, R. (2016) LSD modulates music-induced imagery via changes in the parahippocampal connectivity. European Neuropsychopharmacology, 1-10. http://dx.doi.org/10.1016/j.euroneuro.2016.03.018

Kometer M., Pokorny T., Seifritz E. and Vollenweider F.X. (2015) Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations. Psychopharmacology (Berl) 232(19):3663–3676. https://dx.doi.org/10.1007/s00213-015-4026-7

Riba J., Anderer P., Morte A., Urbano G., Jané F., Saletu B. and Barbanoj M.J. (2002) Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol 53(6):613–628. https://dx.doi.org/10.1046/j.1365-2125.2002.01609

Tagliazucchi E., Roseman L., Kaelen M., Orban C., Muthukumaraswamy S. D., Murphy K., Laufs H., Leech R., McGonigle J., Crossley N., Bullmore E., Williams T., Bolstridge M., Feilding A., Nutt D.J. and Carhart-Harris R. (2016) Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology, 26, 1-8. http://dx.doi.org/10.1016/j.cub.2016.02.010