Mapping ‘psychedelic trips’ in the brain to better direct their therapeutic effects

Image cred­it: Shutterstock

For the past sev­er­al decades, psy­che­delics have been wide­ly stig­ma­tized as dan­ger­ous ille­gal drugs. But a recent surge of aca­d­e­m­ic research into their use to treat psy­chi­atric con­di­tions is spurring a recent shift in pub­lic opinion.

Psy­che­delics are psy­chotrop­ic drugs: sub­stances that affect your men­tal state. Oth­er types of psy­chotrop­ics include anti­de­pres­sants and anti-anx­i­ety med­ica­tions. Psy­che­delics and oth­er types of hal­lu­cino­gens, how­ev­er, are unique in their abil­i­ty to tem­porar­i­ly induce intense hal­lu­ci­na­tions, emo­tions and dis­rup­tions of self-awareness.

Researchers look­ing into the ther­a­peu­tic poten­tial of these effects have found that psy­che­delics can dra­mat­i­cal­ly reduce symp­toms of depres­sion and anx­i­ety, PTSD, sub­stance abuse and oth­er psy­chi­atric con­di­tions. The intense expe­ri­ences, or “trips,” that psy­che­delics induce are thought to cre­ate a tem­po­rary win­dow of cog­ni­tive flex­i­bil­i­ty that allows patients to gain access to elu­sive parts of their psy­ches and forge bet­ter cop­ing skills and thought patterns.

Pre­cise­ly how psy­che­delics cre­ate these effects, how­ev­er, is still unclear. So as researchers in psy­chi­a­try and machine learn­ing, we were inter­est­ed in fig­ur­ing out how these drugs affect the brain. With arti­fi­cial intel­li­gence, we were able to map people’s sub­jec­tive expe­ri­ences while using psy­che­delics to spe­cif­ic regions of the brain, down to the mol­e­c­u­lar level.

Psilo­cy­bin, a psy­choac­tive com­pound found in some mush­rooms, has been the focus of many stud­ies for its poten­tial ther­a­peu­tic qual­i­ties. 24K-Pro­duc­tion/i­S­tock via Get­ty Images

 

Mapping ‘trips’ in the brain

Every psy­che­del­ic func­tions dif­fer­ent­ly in the body, and each of the sub­jec­tive expe­ri­ences these drugs cre­ate have dif­fer­ent ther­a­peu­tic effects. Mys­ti­cal type expe­ri­ences, or feel­ings of uni­ty and one­ness with the world, for exam­ple, are asso­ci­at­ed with decreas­es in depres­sion and anx­i­ety. Know­ing how each psy­che­del­ic cre­ates these spe­cif­ic effects in the body can help clin­i­cians opti­mize their ther­a­peu­tic use.

To bet­ter under­stand how these sub­jec­tive effects man­i­fest in the brain, we ana­lyzed over 6,000 writ­ten tes­ti­mo­ni­als of hal­lu­cino­genic expe­ri­ences from Erowid Cen­ter, an orga­ni­za­tion that col­lects and pro­vides infor­ma­tion about psy­choac­tive sub­stances. We trans­formed these tes­ti­mo­ni­als into what’s called a bag-of-words mod­el, which breaks down a giv­en text into indi­vid­ual words and counts how many times each word appears. We then paired the most com­mon­ly used words linked to each psy­che­del­ic with recep­tors in the brain that are known to bind to each drug. After using an algo­rithm to extract the most com­mon sub­jec­tive expe­ri­ences asso­ci­at­ed with these word-recep­tor pairs, we mapped these expe­ri­ences onto dif­fer­ent brain regions by match­ing them to the types of recep­tors present in each area.

We found both new links and pat­terns that con­firm what’s known in the research lit­er­a­ture. For exam­ple, changes in sen­so­ry per­cep­tion were asso­ci­at­ed with a sero­tonin recep­tor in the visu­al cor­tex of the brain, which binds to a mol­e­cule that helps reg­u­late mood and mem­o­ry. Feel­ings of tran­scen­dence were con­nect­ed to dopamine and opi­oid recep­tors in the salience net­work, a col­lec­tion of brain regions involved in man­ag­ing sen­so­ry and emo­tion­al input. Audi­to­ry hal­lu­ci­na­tions were linked to a num­ber of recep­tors spread through­out the audi­to­ry cortex.

Our find­ings also align with the lead­ing hypoth­e­sis that psy­che­delics tem­porar­i­ly reduce top-down exec­u­tive func­tion, or cog­ni­tive process­es involved in inhi­bi­tion, atten­tion and mem­o­ry, among oth­ers, while ampli­fy­ing brain regions involved in sen­so­ry experience.

Why it matters

The U.S. is going through a pro­found men­tal health cri­sis that has been exac­er­bat­ed by the COVID-19 pan­dem­ic. Yet there have been no tru­ly new psy­chi­atric drug treat­ments since Prozac and oth­er selec­tive sero­tonin reup­take inhibitors, the most com­mon type of anti­de­pres­sants, of the 1980s.

Our study shows that it’s pos­si­ble to map the diverse and wild­ly sub­jec­tive psy­che­del­ic expe­ri­ences to spe­cif­ic regions in the brain. These insights may lead to new ways to com­bine exist­ing or yet to be dis­cov­ered com­pounds to pro­duce desired treat­ment effects for a range of psy­chi­atric conditions.

Pychi­a­trist Stanislav Grof famous­ly pro­posed, “[P]sychedelics, used respon­si­bly and with prop­er cau­tion, would be for psy­chi­a­try what the micro­scope is to the study of biol­o­gy and med­i­cine or the tele­scope for astron­o­my.” As psy­che­delics and oth­er hal­lu­cino­gens become more com­mon­ly used clin­i­cal­ly and cul­tur­al­ly, we believe more research will fur­ther illu­mi­nate the bio­log­i­cal basis of the expe­ri­ences they invoke and help real­ize their potential.

Galen Bal­len­tine is a Res­i­dent in Psy­chi­a­try at SUNY Down­state Health Sci­ences Uni­ver­si­ty and Sam Fried­man is a Machine Learn­ing Sci­en­tist at the Broad Insti­tute of MIT & Har­vard Uni­ver­si­ty. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

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About SharpBrains

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SHARPBRAINS es un think-tank y consultoría independiente proporcionando servicios para la neurociencia aplicada, salud, liderazgo e innovación.

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