"Long before it's in the papers"
December 10, 2015


LSD found to act by reorganizing brain networks 

Dec. 10, 2015
Courtesy of the American College 
of Neuropsychopharmacology
and World Science staff

The drug LSD cre­ates its bi­zarre ef­fects on the brain in part by stop­ping some nerve cells from act­ing syn­chro­nous­ly, as they should—while mak­ing oth­ers act in con­cert where they should­n’t.

That’s the con­clu­sion of a group of re­search­ers pre­sent­ing new find­ings Dec. 10 at the an­nu­al meet­ing of the Amer­i­can Col­lege of Neu­ropsy­cho­phar­ma­col­ogy in Hol­ly­wood, Flor­i­da.

LSD, an il­le­gal drug that rose to pop­u­lar­ity along­side 1960s coun­ter­cul­ture, causes changes in con­scious­ness, in­clud­ing what psy­chol­o­gists call “ego-dissolution,” or a loss of the sense of self. But it’s not clear what causes the pro­found ef­fects on con­scious­ness, al­though there is a de­tailed knowl­edge of how the drug works on mo­lec­u­lar struc­tures in the brain called ser­o­to­nin re­cep­tors.

The new re­port pro­poses that the drug re­duces con­nec­ti­vity with­in brain net­works, or the ex­tent to which nerve cells in the brain, called neu­rons, with­in a net­work fire in syn­chrony. LSD al­so seems to re­duce the ex­tent to which sep­a­rate brain net­works re­main dis­tinct in their pat­terns or syn­chron­iz­a­tion of fir­ing, the au­thors said.

Over­all, LSD—which stands for ly­ser­gic ac­id di­ethy­lamide—in­ with the pat­terns of ac­tiva­t­ion in the dif­fer­ent brain net­works that un­der­lie hu­man thought and be­hav­ior.

Rob­in Carhart-Harris and col­leagues at Im­pe­ri­al Col­lege Lon­don car­ried out brain scans of 20 healthy vol­un­teers over six hours. The re­search­ers used func­tion­al mag­net­ic res­o­nance im­ag­ing, or fMRI, which maps brain ac­ti­vity by de­tect­ing changes in blood flow. They al­so used mag­ne­toen­ceph­al­o­graphy or MEG, a tech­nique that im­ages brain func­tion by re­cord­ing mag­net­ic fields pro­duced by elec­tri­cal cur­rents oc­cur­ring in the brain. 

Us­ing the first meth­od, the in­ves­ti­ga­tors found that LSD led to a more cha­ot­ic brain state not en­tirely un­like what is seen in the “pro­dro­mal” phase, or early warn­ing signs, of psy­cho­sis.

Spe­cif­ic­ally, neu­rons, or nerve cells in the brain, that were sup­posed to fire sig­nals to­geth­er with­in a net­work fell out of syn­chrony, the sci­en­tists found. Mean­while net­works that are nor­mally dis­tinct started to overlap in their con­nec­ti­vity pat­terns. 

Carhart-Harris al­so found in­creases in blood flow in the vis­u­al cor­tex at the back of the brain, which pro­cesses vis­u­al sig­nals. This might ex­plain the vis­u­al hal­lu­cina­t­ions and dis­tor­tions so com­mon in LSD in­toxica­t­ion, he added.

MEG al­so showed that nat­u­ral brain os­cilla­t­ions changed to be­come highly cor­re­lat­ed with vis­u­al hal­lu­cina­t­ion­s—sug­gest­ing that the LSD-influenced vis­u­al sys­tem is teth­ered more to the in­ter­nal than to the outer world.

“With bet­ter as­sess­ment tools avail­a­ble to­day than in the 1950’s and 1960’s, it may be pos­si­ble to eval­u­ate po­ten­tial uses of LSD as a treat­ment for ad­dic­tion and oth­er dis­or­ders, such as treat­ment-resistant de­pres­sion—which we are cur­rently in­ves­ti­gat­ing with a si­m­i­lar drug to LS­D,” Car­hart-Harris said. He added that LSD al­so may pro­vide a use­ful mod­el of psy­cho­sis.

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The drug LSD creates its bizarre effects on the brain in part by stopping some nerve cells from acting synchronously, as they should—while making others act in concert where they shouldn’t. That’s the conclusion of a group of researchers presenting new findings Dec. 10 at the annual meeting of the American College of Neuropsychopharmacology in Hollywood, Florida. LSD, an illegal drug that rose to popularity alongside 1960s counterculture, causes changes in consciousness, including what psychologists call “ego-dissolution,” or a loss of the sense of self. But it’s not clear what causes the profound effects on consciousness, although there is a detailed knowledge of how the drug works on molecular structures in the brain called serotonin receptors. The new report proposes that the drug reduces connectivity within brain networks, or the extent to which nerve cells in the brain, called neurons, within a network fire in synchrony. LSD also seems to reduce the extent to which separate brain networks remain distinct in their patterns or synchronization of firing, the authors said. Overall, LSD—which stands for Lysergic acid diethylamide—interferes with the patterns of activation in the different brain networks that underlie human thought and behavior. Robin Carhart-Harris and colleagues at Imperial College London carried out brain scans of 20 healthy volunteers over six hours. The researchers used functional magnetic resonance imaging, or fMRI, which maps brain activity by detecting changes in blood flow. They also used magnetoencephalography or MEG, a technique that images brain function by recording magnetic fields produced by electrical currents occurring in the brain. Using the first method, the investigators found that LSD led to a more chaotic brain state not entirely unlike what is seen in the “prodromal” phase, or early warning signs, of psychosis. Specifically, neurons, or nerve cells in the brain, that were supposed to fire signals together within a network fell out of synchrony, the scientists found. Meanwhile networks that are normally distinct started to overlap in their connectivity patterns. Carhart-Harris also found increases in blood flow in the visual cortex at the back of the brain, which processes visual signals. This might explain the visual hallucinations and distortions so common in LSD intoxication, he added. MEG also showed that natural brain oscillations changed to become highly correlated with visual hallucinations—suggesting that the LSD-influenced visual system is tethered more to the internal than to the external world. “With better assessment tools available today than in the 1950’s and 1960’s, it may be possible to evaluate potential uses of LSD as a treatment for addiction and other disorders, such as treatment-resistant depression—which we are currently investigating with a similar drug to LSD,” Carhart-Harris said. He added that LSD also may provide a useful model of psychosis.