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Study issues warning: Opioid inhibitor naltrexone (often used to treat addictions) can reduce feelings of social connection

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Sci­ence has long known that hav­ing pos­i­tive social con­nec­tion is impor­tant to a hap­py and healthy life. But less is under­stood about how our brains sup­port and encour­age con­nect­ing with oth­ers.

While pri­or research has sug­gest­ed oxy­tocin plays a role in nur­tur­ing and trust­ing oth­ers, there­by strength­en­ing social bonds, many researchers also sus­pect that brain opi­oids are impor­tant to social con­nec­tion. Opi­oids are nat­u­ral­ly occur­ring brain chemicals—perhaps the most well-known being endorphins—that cause plea­sur­able sen­sa­tions in the body and encour­age us to enjoy what­ev­er we are expe­ri­enc­ing. It’s pos­si­ble that opi­oids also cause the warm feel­ings we get in social encoun­ters, there­by encour­ag­ing us to be more engaged with oth­ers.

But, accord­ing to a recent study, the role of opi­oids may be a lit­tle more com­pli­cat­ed than that—and there are prac­ti­cal impli­ca­tions for how we treat drug addic­tion.

Opioids target social connection

– Nal­trex­one, a med­ica­tion that inhibits opi­oids’ impact

Par­tic­i­pants unaware of the study’s pur­pose took an opi­oid inhibitor called nal­trex­one for a four-day tri­al and a place­bo for anoth­er four-day tri­al in ran­dom­ized order, with a break in between to clean out their sys­tem.

Over the course of the exper­i­ment, the par­tic­i­pants kept dai­ly track of how social­ly con­nect­ed they felt and how pos­i­tive their moods were. On the fourth day of each tri­al, they com­plet­ed a task in the lab, read­ing six very kind mes­sages that loved ones had sent to the researchers in advance, unbe­knownst to the participants—messages like “I am so grate­ful to have you in my life” and “Thank you for lov­ing me at my worst.” Then par­tic­i­pants report­ed how con­nect­ed they felt toward the mes­sage writer, as well as how good it felt to read the mes­sages.

After­wards, the researchers com­pared how much social con­nec­tion par­tic­i­pants had in their every­day lives, as well as how much of a sense of con­nec­tion they felt dur­ing the lab task. Results showed that par­tic­i­pants felt more con­nec­tion in both every­day activ­i­ties and dur­ing the lab task when they were on place­bo than when on nal­trex­one, sug­gest­ing that nal­trex­one was block­ing endor­phins impor­tant to social close­ness.

We test­ed a long-stand­ing theory—based on ani­mal data—that sug­gests brain opi­oids con­tribute to feel­ings of con­nec­tion. But no one had shown that rela­tion­ship causal­ly in humans,” says the study’s lead author, Tris­ten Ina­ga­ki.

She and her col­leagues also found that tak­ing nal­trex­one did not decrease pos­i­tive emo­tion in every­day life, even though it affect­ed the par­tic­i­pants’ sense of con­nec­tion to oth­ers. This sug­gests that opi­oids play a tar­get­ed role in social con­nec­tion that is above and beyond just feel­ing good.

 

All of this work is try­ing to get at what makes us feel con­nect­ed to oth­ers and how we can help those who are feel­ing lone­ly or social­ly iso­lat­ed.”
Tris­ten Ina­ga­ki

 

Opi­oids seem to affect our response to the most reward­ing or most plea­sur­able stim­uli in the envi­ron­ment,” says Ina­ga­ki. “For humans, being social or being around your loved ones is like­ly to be the most salient reward­ing stim­uli.”

Ina­ga­ki points to oth­er research show­ing that opi­oids reduce the sense of con­nec­tion peo­ple get from sim­ply hold­ing a warm object, but don’t affect rat­ings of plea­sure. This lends fur­ther sup­port to her own find­ings.

The mech­a­nisms for opi­oids must be smarter than we think,” she says.

The addiction connection

While much of the research on opi­oids and social con­nec­tion is pre­lim­i­nary, Ina­ga­ki thinks her study war­rants atten­tion, giv­en that opi­oid inhibitors like nal­trex­one are often used with patients to treat addic­tions. Though nal­trex­one may indeed inhib­it the high peo­ple feel when tak­ing illic­it drugs—and there­by help them kick the habit—it may also shape their social rela­tion­ships.

Lots of research shows that peo­ple real­ly need their social net­works when they’re deal­ing with major stressors—addiction being a major stres­sor,” says Ina­ga­ki. “So, if the drug pre­scribed to help some­one over­come addic­tion is also reduc­ing how con­nect­ed they feel toward oth­ers or reduc­ing the time they spend with oth­er folks, that’s not a great out­come.”

At the very least, she says, clin­i­cians should be aware of the poten­tial down­side of using nal­trex­one, so they can warn patients about social side effects and make sure patients are remain­ing social­ly inte­grat­ed.

While Inagaki’s find­ings are intrigu­ing in their own right, they may also be rel­e­vant to under­stand­ing the cur­rent opi­oid addic­tion. Research has shown that genet­ic dif­fer­ences in opi­oid recep­tors lead to increased risk of addic­tion, just as her research sug­gests block­ing opi­oid recep­tors decreas­es social close­ness. Doesn’t that sug­gest feel­ings of dis­con­nec­tion and addic­tion could be relat­ed?

Ina­ga­ki thinks so.

One off­shoot of the opi­oid the­o­ry is that those with low opi­oid tone show exag­ger­at­ed respons­es to social stressors—like feel­ing lone­ly, feel­ing social­ly reject­ed,” she says. “So, the idea that neg­a­tive social encoun­ters could pro­duce a risk fac­tor for all kinds of men­tal health issues, includ­ing addic­tion, is being re-appre­ci­at­ed right now.”

While the jury is still out, Ina­ga­ki and her team will con­tin­ue to research the role that opi­oids play. She is cur­rent­ly run­ning a neu­roimag­ing study to see how nal­trex­one impacts neur­al activ­i­ty in response to social con­nec­tion. She hopes that her research will help inform how we humans bond, with impli­ca­tions beyond addic­tion.

“All of this work is try­ing to get at what makes us feel con­nect­ed to oth­ers and how we can help those who are feel­ing lone­ly or social­ly iso­lat­ed,” she says. “My hope is that peo­ple who are strug­gling don’t have to turn to drugs.”

Jill Sut­tie, Psy.D., is Greater Good’s book review edi­tor and a fre­quent con­trib­u­tor to the mag­a­zine.  Based at UC-Berke­ley, Greater Good high­lights ground break­ing sci­en­tific research into the roots of com­pas­sion and altru­ism. Copy­right Greater Good.

The Study

Opi­oids and social bond­ing: nal­trex­one reduces feel­ings of social con­nec­tion (Social Cog­ni­tive and Affec­tive Neu­ro­science):

  • Abstract: Close social bonds are crit­i­cal to a hap­py and ful­filled life and yet lit­tle is known, in humans, about the neu­ro­chem­i­cal mech­a­nisms that keep indi­vid­u­als feel­ing close and con­nect­ed to one anoth­er. Accord­ing to the brain opi­oid the­o­ry of social attach­ment, opi­oids may under­lie the con­tent­ed feel­ings asso­ci­at­ed with social con­nec­tion and may be crit­i­cal to con­tin­ued bond­ing. How­ev­er, the role of opi­oids in feel­ings of con­nec­tion toward close oth­ers has only begun to be exam­ined in humans. In a dou­ble-blind, place­bo-con­trolled, crossover study of nal­trex­one (an opi­oid antag­o­nist), 31 vol­un­teers took nal­trex­one for 4 days and place­bo for 4 days (sep­a­rat­ed by a 10-day washout peri­od). Par­tic­i­pants came to the lab­o­ra­to­ry once on the last day of tak­ing each drug to com­plete a task designed to elic­it feel­ings of social con­nec­tion. Par­tic­i­pants also com­plet­ed dai­ly reports of feel­ings of social con­nec­tion while on nal­trex­one and place­bo. In line with hypothe­ses, and for the first time in humans, results demon­strat­ed that nal­trex­one (vs place­bo) reduced feel­ings of con­nec­tion both in the lab­o­ra­to­ry and in dai­ly reports. These results high­light the impor­tance of opi­oids for social bond­ing with close oth­ers, lend­ing sup­port to the brain opi­oid the­o­ry of social attach­ment.

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