The Neurobiological Mechanisms Underlying The Interaction Between Music And Psychedelics

Music and psychedelics share overlapping brain mechanisms that underpin their effects and yield a beneficial synergy with therapeutic implications.

The neurobiological mechanisms underlying the interaction between music and psychedelics

Music has long played a central role in psychedelic therapy sessions (1,2). It has been suggested that brain regions recruited during music listening overlap at least partially with brain regions altered by the administration of psychedelics, particularly parts of the brain that govern processing of emotions (3-5). Psychedelics are serotonin 2A receptor agonists, this being an important mechanism underlying their effect which in turn influences music perception, with the serotonergic system responding specifically to sound.


Key Takeaways:
  • Classic psychedelics are serotonin 2A receptor agonists, an important mechanism underlying their effect which in turn influences music perception.

  • The structural correlates associated with the interaction between music and psychedelics are deeply tied to regions involved in emotional processing.

  • Music under psychedelics can lead to enhanced connectivity from the parahippocampus towards the visual cortex, which is correlated with enhanced mental imagery and the recollection of autobiographical memories.

  • Psychedelics can recruit brain regions involved in the attribution of personal meaning, considered to be conducive to their therapeutic effect.

  • Music-evoked emotions of wonder and transcendence are intensified under LSD, influenced by a musical quality known as timbre. These emotions are core facets of the transformative mystical-type experiences that can be occasioned by psychedelics.


Music, psychedelics and the brain: an overview of brain neurobiology and the role of the serotonin system

Under LSD, listening to music can lead to enhanced information flow from the parahippocampus towards the visual cortex. The parahippocampus is located at a junction between brain regions that play a key role in memory formation and visual processing. The increased connectivity between these brain regions under LSD in combination with a musical stimulus is associated with enhanced mental imagery and recollection of autobiographical memories (14).  

Anti-anxiety effect

Applied in a therapeutic context, music can be powerfully soothing, reducing stress and anxiety (17), and fostering feelings of calm, safety and support. It has been utilised beneficially in post-operative settings, and can lessen requirements for opioid pain medication and improve patient outcomes (18). This soothing capacity of music is important for psychedelic therapy during the onset, ascent, and return phases of the psychedelic experience (19). 

Meaning making

LSD can enhance the meaningfulness of music, corresponding to increased blood flow and activity in cortical midline brain regions linked with sound processing, emotion and autobiographical memory. This suggests a synergistic relationship between music and LSD, with attribution of personal meaning during a psychedelic experience considered to be conducive to some of the therapeutic effects (20).

Facilitating insight, mystical experiences and openness

Music can also have an important effect on the entropic brain state LSD yields - it acts to drive entropic brain dynamics further under the LSD, which in turn predicts subsequent increases in the personality trait openness to experience - this change was only observed when music was a part of the session and was not predicted by the intensity of the drug effect alone. This indicates that music can drive brain dynamics in important ways during a psychedelic experience, with important implications for long-term outcomes (21). In addition, music has also been demonstrated to help foster the occurrence of mystical-type experiences and insightfulness in psilocybin therapy, this being associated with reductions in clinical symptoms following the session, unlike overall drug intensity, which was not (19).

Timbre

The musical quality of timbre appears to play an important role in eliciting these heightened emotional states under psychedelics. Timbre is a sound’s tone, or color—essentially it is the sound quality of a note (26). Timbre differs from pitch, in that two instruments may play a sound at an identical note, or pitch, but result in very different timbres. A study investigating the acute effects of LSD on music-evoked brain activity under naturalistic music listening conditions reported that the most pronounced changes were observed for the “timbral complexity” component in comparison to other aspects of sound quality examined (12, 28). Timbral complexity refers to the shape and spread of music’s texture, or its spectral distribution (28).. Researchers found significant positive correlations between changes in music-evoked feelings of wonder and music-evoked brain activity to timbral complexity within brain regions associated with a wide spectrum of highly integrated tasks and higher-level executive functions. Timbre has a unique ability to convey important emotions, and understanding exactly how timbral properties convey emotions has important implications for musical choice in psychedelic therapy.

Conclusion

Psychedelics alter the brain’s processing of music through their action on the serotonin system, which in turn has important implications on the subjective experience of music under their effect, and thus its therapeutic potential. Through its dynamic and multifaceted power, music can both anchor and propel. It can soothe, enhance emotional states, foster meaningfulness and link up brain regions under the psychedelic which can in turn elicit mental imagery or recall of autobiographical memories, all of which may have therapeutic implications. Music under psychedelics plays a role in catalysing mystical-type experiences, facilitating psychological insight and eliciting subsequent increases in personality trait openness, which highlight its importance for fostering long-term therapeutic benefits.

The emerging research into the different effects of music, as well as the elements of the music that appear to be associated with therapeutic outcomes such as timbral complexity will help inform a personalised and flexible use of music for/as psychedelic therapy. Music has enraptured and entranced humankind for millenia. Through cutting edge neuroscience, we are starting to reveal the mechanisms by which music can move us and alter the substrate of a conscious experience. This in turn shed light on the potential clinical applications of music in different contexts.

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References
  1. Eisner BG, Cohen S (1958) Psychotherapy with lysergic acid diethylamide. Journal of Nervous & Mental Disease 127(6): 528-539.

  2. Leary T, Metzner R, Alpert R (1964) The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead, New York: University Books.

3. Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, et al. . 2016. b. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc Natl Acad Sci USA. 113(17):4853–4858.

4. Preller KH, Vollenweider FX. 2016. Phenomenology, structure, and dynamic of psychedelic states. Curr Top Behav Neurosci. doi: 10.1007/7854_2016_459.

5. Hoffer, A. (1965). D-Lysergic acid diethylamide (LSD): A review of its present status. Clinical Pharmacology & Therapeutics, 6(2), 183–255. doi:10.1002/cpt196562183

6. Silverman, J. (1971). Research with psychedelics. Some biopsychological concepts and possible clinical applications. Archives of General Psychiatry, 25(6), 498–510.

7. Timmermann, C., Spriggs, M. J., Kaelen, M., Leech, R., Nutt, D. J., Moran, R. J., … Muthukumaraswamy, S. D. (2017). LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm. Neuropharmacology. Advance online publication. doi:10.1016/j.neuropharm.2017.10.039

8. Umbricht, D., Vollenweider, F. X., Schmid, L., Grubel, C., € Skrabo, A., Huber, T., & Koller, R. (2003). Effects of the 5- HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: Implications for the neuropharmacology of cognitive deficits in schizophrenia. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 28(1), 170–181. doi:10.1038/sj.npp.1300005

9. Weber, K. (1967). Alteration of music perception in experimental psychosis (psilocybin.). Confinia Psychiatrica. Borderland of Psychiatry. Grenzgebiete Der Psychiatrie. Les Confins De La Psychiatrie, 10(3), 139–176.

10. Barrett FS, Preller KH, Kaelen M. Psychedelics and music: neuroscience and therapeutic implications. Int Rev Psychiatry. 2018 Aug;30(4):350-362. doi: 10.1080/09540261.2018.1484342

11. Hall I. C., Rebec G. V., Hurley L. M. (2010). Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli. J. Exp. Biol. 213, 1009–1017 10.1242/jeb.035956

12. Hurley, L. M. and Pollak, G. D. (1999). Serotonin differentially modulates responses to tones and frequency-modulated sweeps in the inferior colliculus. J. Neurosci. 19, 8071-8082.

13. Kaelen M, Lorenz R, Barrett F, Roseman L, Orban C, Santos-Ribeiro A, et al. Effects of LSD on music-evoked brain activity. bioRxiv. 2017. Available from: https://doi.org/10.1101/153031

14. Kraehenmann R, Preller KH, Scheidegger M, Pokorny T, Bosch OG, Seifritz E, Vollenweider FX. Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biol Psychiatry. 2015 Oct 15;78(8):572-81. doi: 10.1016/j.biopsych.2014.04.010

15. Vollenweider F., Kometer M. (2010) The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat Rev Neurosci 11: 642–651.

16. Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, et al. LSD modulates music-induced imagery via changes in parahippocampal connectivity. Eur Neuropsychopharmacol [Internet]. 2016;26(7):1099–109. Available from: http://dx.doi.org/10.1016/j.euroneuro.2016.03.018

17. Chanda, M. L., Levitin, D. J. (2013) The neurochemistry of music. Trends in Cognitive Sciences, 17, 179–19.

18. Fu VX, Oomens P, Klimek M, Verhofstad MHJ, Jeekel J. The Effect of Perioperative Music on Medication Requirement and Hospital Length of Stay: A Meta-analysis. Ann Surg. 2020 Dec;272(6):961-972. doi: 10.1097/SLA.0000000000003506.

19. Kaelen M, Giribaldi B, Raine J, Evans L, Timmerman C, Rodriguez N, et al. The hidden therapist: evidence for a central role of music in psychedelic therapy. Psychopharmacology (Berl) [Internet]. 2018;235(2):505–19. Available from: http://dx.doi.org/10.1007/s00213-017-4820-5

20. Haijen, ECHM, Kaelen, M, Roseman, L, et al. (2018) Predicting responses to psychedelics: A prospective study. Frontiers in Pharmacology 9: 897.

21. Studerus, E, Gamma, A, Kometer, M, et al. (2012) Prediction of psilocybin response in healthy volunteers. PLoS ONE 7(2): e30800.

22. Griffiths RR. et al. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008;22(6):621–632. Available from: https://doi.org/10.1177/0269881108094300

23. Lebedev, AV, Kaelen, M, Lövdén, M, et al. (2016) LSD-induced entropic brain activity predicts subsequent personality change. Human Brain Mapping 37(9): 3203–3213.

24. Strickland, J.C., Garcia-Romeu, A. & Johnson, M.W. Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy. ACS Pharmacol. Transl. Sci. 2021, 4, 2, 472–478.

25. Maslow AH (1993) The Farther Reaches of Human Nature. Arkana.

26. Kaelen M, Barrett FS, Roseman L, Lorenz R, Family N, Bolstridge M, Curran HV, Feilding A, Nutt DJ, Carhart-Harris RL. (2015) LSD enhances the emotional response to music. Psychopharmacology (Berl). 232(19):3607-14. doi: 10.1007/s00213-015-4014-y

27. Kaelen M. The psychological and human brain effects of music in combination with psychedelic drugs. Imperial College London. 2017;251. Available from: https://spiral.imperial.ac.uk/handle/10044/1/55900

28. J.C.R. Licklider., JCR (1951) Handbook of experimental psychology, chapter Basic Correlates of the Auditory Stimulus. A Wiley publication in psychology. New York, NY: Wiley.

29. Hailstone JC, Omar R, Henley SMD, Frost C, Kenward MG, Warren JD. It’s not what you play, it’s how you play it: Timbre affects perception of emotion in music. Q J Exp Psychol. 2009;62(11):2141–55. Available from:  https://doi.org/10.1080/17470210902765957

30. Eerola T, Ferrer R, Alluri V. Timbre and affect dimensions: Evidence from affect and similarity ratings and acoustic correlates of isolated instrument sounds. Music Percept. 2012;30(1):49–70. Available from: https://doi.org/10.1525/mp.2012.30.1.49