Social Pain Institute

A third use for opioid medications

2026-09-29T00:00:00+00:00

Following its September 9 public meeting on Addressing the Public Health Effects of Opioid Medications</strong>, the Reagan-Udall Foundation for the FDA took written comments through September 23. Its questions covered opioids for pain and for addiction. We submitted a comment about a third use: low-dose buprenorphine for social pain. This is what we said, with links to the evidence.</p>

The use that was left out</h2>
Social pain, the distress of rejection and lost connection, runs on the same mu-opioid system that opioid medications act on. The conditions defined by it, including borderline personality disorder (BPD), complex PTSD, and some presentations of autism, have few effective medications. BPD has none approved, and one of the highest suicide attempt rates in psychiatry.</p>
People whose main problem is social pain fit neither route on offer. Addiction treatment requires an opioid use disorder diagnosis, and pain treatment requires a pain condition.</p>
Social pain may connect pain and addiction</h2>
65% of BPD outpatients in one sample met criteria for a pain disorder, and about 30% of chronic pain patients meet BPD criteria (Nance et al., 2024</a>). 18.2% of people with opioid use disorder have BPD (Santo et al., 2022</a>), about three times the general population rate (Grant et al., 2008</a>).</p>
Nance et al. cite the opioid-deficiency hypothesis for BPD, then recommend only extra monitoring and psychosocial support. They don’t consider buprenorphine, which treats pain, treats opioid use disorder, has been proposed for BPD, and is safer than full agonists alongside other substances.</p>
Adding an option, not replacing one</h2>
At the September 9 meeting, patients described losing function and quality of life after opioid treatment they said had worked was taken away. Nothing in our comment should be used to move people off full agonists that work for them. Some patients do poorly on buprenorphine, and they should be believed.</p>
The evidence</h2>
Social pain runs on the opioid system.</strong> Social exclusion activates regions involved in physical pain (Eisenberger et al., 2003</a>). PET imaging shows rejection triggers mu-opioid release in humans (Hsu et al., 2013</a>). Naltrexone, which blocks opioid receptors, reduces everyday feelings of social connection (Inagaki et al., 2016</a>).</p>
Low-dose buprenorphine acts on social stress below the dose that produces a high.</strong> In healthy adults, 0.2 mg blocked the cortisol response to a social stress test with no rise in feeling high (Bershad et al., 2015</a>), and reduced attention to fearful faces, most in people with more depression and anxiety (Bershad et al., 2018</a>).</p>
It helps the population most at risk.</strong> In a randomized controlled trial of severely suicidal patients without substance use disorders, 0.1 to 0.8 mg a day reduced suicidal ideation more than placebo, and a BPD diagnosis did not affect response (Yovell et al., 2016</a>). After ketamine infusion, 0.2 to 0.8 mg a day kept 78% of patients responding at one month, against 48% on placebo (Tucciarone et al., 2026</a>).</p>
The mechanism fits BPD and autism.</strong> PET shows dysregulated opioid function in BPD (Prossin et al., 2010</a>), and Stanley and Siever proposed buprenorphine for it (2010</a>). PET shows altered mu-opioid receptors in autism (Noppari et al., 2025</a>), and an autistic adult had confirmed long-term social improvement on low-dose buprenorphine that reversed when it stopped (Skoglund et al., 2022</a>).</p>
Benefit and risk.</strong> These doses are a small fraction of the 8 to 24 mg used for opioid use disorder, and buprenorphine has a ceiling on respiratory depression. An assessment that counts misuse and overdose but not untreated suicidality is incomplete. Blocking the system isn’t neutral either: in autism, naltrexone hasn’t improved core social symptoms (Roy et al., 2015</a>).</p>
Research on these uses largely stopped as the overdose epidemic grew. The gap is missing investigation, not negative results.</p>
Where regulation gets in the way</h2>

Labeling decides who gets treated.</strong> Buprenorphine is labeled for pain or opioid use disorder, so clinicians outside those specialties treat any other use as out of bounds. Psychiatrists, who see the patients in question, often won’t prescribe a pain-labeled product.</li>
There is no dose form for this use.</strong> The lowest sublingual buprenorphine tablet is 2 mg. Patients at 0.2 mg dissolve a 2 mg tablet in water and measure out a tenth, or rely on a pain-labeled patch they can’t get prescribed.</li>
“Nonaddictive” should not mean “no mu activity.”</strong> Development priorities that route around the mu-opioid receptor entirely will not produce anything for social pain. A partial agonist with a ceiling effect should be evaluated on its benefit-risk, not excluded by category.</li> </ul>
We asked FDA to stop describing every non-pain, non-addiction use as misuse, to acknowledge that opioid medications act on affective and social systems and not only on pain and reward, and to encourage low-dose formulations and the studies that would support a psychiatric indication.</p>
What we asked for</h2>

Bring this population into scope.</strong> Include psychiatric and social pain uses in future FDA and Reagan-Udall work, and invite psychiatry alongside pain and addiction medicine.</li>
Fund the next trials.</strong> Low-dose buprenorphine for suicidal ideation has two positive trials; the 2026 one was funded by AFSP, the Pritzker Foundation, NIDA, and NCATS. The same support should go to trials in BPD, complex PTSD, and autism with social functioning as a primary outcome, and in people with both BPD and chronic pain.</li>
Study buprenorphine alongside full agonists, and study the switch.</strong> In a post hoc analysis of a Purdue-sponsored trial, patients using immediate-release opioids for breakthrough pain on the buprenorphine patch reached pain scores similar to patch-only patients, without more adverse events (Silverman et al., 2017</a>). Combination treatment deserves independent, controlled study so it can become a standard option. Low-dose initiation, which keeps the full agonist until buprenorphine takes over, has never been compared head to head with standard initiation (Zimmerman et al., 2023</a>). Some bad experiences with buprenorphine may come from how patients were switched.</li>
Measure what restrictions cost.</strong> Track psychiatric outcomes and suicide, not only overdose. In our screen of the HHS 7-OH docket</a>, 20.7% of 19,344 distinct comments mentioned a psychiatric or neurodevelopmental condition, and 5.6% raised one with no pain condition. These people are self-treating with no supervised route.</li>
Give clinicians guidance.</strong> None exists for a psychiatrist whose patient benefits from low-dose buprenorphine and doesn’t meet criteria for opioid use disorder. Developing it would move this care from the unregulated market to the clinic.</li> </ol> References</h2>

Bershad AK, Jaffe JH, Childs E, de Wit H (2015). Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans. Psychoneuroendocrinology</em> 52:281-288. doi:10.1016/j.psyneuen.2014.12.004</a></li>
Bershad AK, Ruiz NA, de Wit H (2018). Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology. International Journal of Neuropsychopharmacology</em> 21(2):120-127. doi:10.1093/ijnp/pyx077</a></li>
Eisenberger NI, Lieberman MD, Williams KD (2003). Does rejection hurt? An fMRI study of social exclusion. Science</em>. doi:10.1126/science.1089134</a></li>
Grant BF et al. (2008). Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survery on alcohol and related conditions. Journal of Clinical Psychiatry</em> 69(4):533-545. doi:10.4088/JCP.v69n0404</a></li>
Hsu DT et al. (2013). Response of the μ-opioid system to social rejection and acceptance. Molecular Psychiatry</em>. doi:10.1038/mp.2013.96</a></li>
Inagaki TK et al. (2016). Opioids and social bonding: naltrexone reduces feelings of social connection. Social Cognitive and Affective Neuroscience</em>. doi:10.1093/scan/nsw006</a></li>
Nance M, Stetsiv K, McNamara IA, Carpenter RW, Hepp J (2024). Acute, chronic, and everyday physical pain in borderline personality disorder. Current Psychiatry Reports</em>. doi:10.1007/s11920-024-01498-0</a></li>
Noppari T et al. (2025). Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder. European Journal of Nuclear Medicine and Molecular Imaging</em>. doi:10.1007/s00259-025-07620-5</a></li>
Prossin AR et al. (2010). Dysregulation of regional endogenous opioid function in borderline personality disorder. American Journal of Psychiatry</em> 167(8):925-933. doi:10.1176/appi.ajp.2010.09091348</a></li>
Roy A et al. (2015). Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. Journal of Intellectual Disability Research</em>. doi:10.1111/jir.12122</a></li>
Santo T Jr et al. (2022). Prevalence of mental disorders among people with opioid use disorder: a systematic review and meta-analysis. Drug and Alcohol Dependence</em> 238:109551. doi:10.1016/j.drugalcdep.2022.109551</a></li>
Silverman S, Raffa RB, Cataldo MJ, Kwarcinski M, Ripa SR (2017). Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system. Journal of Pain Research</em> 10:1255-1263. doi:10.2147/JPR.S132595</a></li>
Skoglund C, Leknes S, Heilig M (2022). The partial µ-opioid agonist buprenorphine in autism spectrum disorder: a case report. Journal of Medical Case Reports</em>. doi:10.1186/s13256-022-03384-w</a></li>
Stanley B, Siever LJ (2010). The interpersonal dimension of borderline personality disorder: toward a neuropeptide model. American Journal of Psychiatry</em> 167(1):24-39. doi:10.1176/appi.ajp.2009.09050744</a></li>
Tucciarone J et al. (2026). Low-dose buprenorphine following ketamine treatment for suicidal ideation in major depressive disorder: a randomized, double-blind, placebo-controlled trial. American Journal of Psychiatry</em>. doi:10.1176/appi.ajp.20250840</a></li>
Yovell Y et al. (2016). Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. American Journal of Psychiatry</em> 173(5):491-498. doi:10.1176/appi.ajp.2015.15040535</a></li>
Zimmerman C, Clark S, Guerra ME, Bratberg J, Adams KK (2023). Low dose buprenorphine initiation: a guide for the inpatient clinician. Substance Abuse & Addiction</em>. doi:10.1177/08897077231196417</a></li> </ul>

Questions for the FDA nominee on 7-OH

2026-09-23T00:00:00+00:00

The Senate Committee on Health, Education, Labor and Pensions holds the confirmation hearing for Dr. Heidi Overton, nominee for Commissioner of Food and Drugs, on Thursday, September 24, at 10:30 AM Eastern</strong>. Today we called committee offices to ask that senators raise the proposed federal scheduling of 7-OH with her. This is what we asked, and why.</p>
Senate HELP Committee</span>Hearing September 24, 2026, 10:30 AM ET</span>Questions for the record due September 25, 5 PM ET</span>Re: HHS-OASH-2026-0232-0001</span></p>
Update, September 24:</strong> The hearing has taken place. At its close, senators were told to submit written questions for the record by 5 PM Eastern on Friday, September 25</strong>. If you want an office to submit one of the questions below, contact them before then. In her opening statement, Dr. Overton listed “continuing to tackle the opioid crisis, and the new dangers of synthetic 7-OH” among FDA’s public health priorities.</p>
Why the FDA nominee</h2> FDA recommended scheduling 7-hydroxymitragynine in July 2025 and published the scientific assessment</a> behind that recommendation. That assessment also states that “surveillance systems do not provide estimates for the prevalence of 7-OH use.” The comment period on HHS’s proposed threshold closed September 10, and DEA may now issue a temporary Schedule I order at any time.</p>
The next commissioner will shape what FDA does after that, including whether the research that could answer the open questions stays possible.</p>
Who uses 7-OH, according to the record</h2>
We analyzed the public comments</a> on the HHS docket. About 60% of commenters mention pain. One in five mention mental health, and more than a thousand mention it without mentioning pain at all.</p>
The care pathway problem</h2>
This week we attended a continuing-education training for clinicians on kratom and 7-OH. It described people using these products for severe pain, anxiety and depression, and then recommended treating all of it as opioid use disorder, with buprenorphine as the recommended first-line treatment.</p>
Buprenorphine is already FDA-approved for pain, at lower doses usually taken two or more times a day, while addiction treatment is typically a single daily dose. Research protocols for suicidal ideation use 5 to 10% of addiction doses. So people who do get buprenorphine may still get the wrong dose for their actual condition. And most people with opioid use disorder don’t get medication at all: of the 4.0 million people with opioid use disorder in 2025, 15.7% received medications for it (SAMHSA, 2025 NSDUH</a>). Most pain patients already can’t get good pain management, and there is no care pathway for people using 7-OH for their mental health.</p>
We are not suggesting that anyone using 7-OH switch to buprenorphine. The point is that the only prescribed route on offer is built for a different condition, and most people can’t reach it.</p>
The threshold has no human data behind it</h2>
The medical organizations commenting on this docket, including those that support scheduling, told HHS there is no human dose-response study or established lethal level to support the proposed 1 mg threshold, or any other threshold:</p>

American Society of Addiction Medicine:</strong> “Current evidence is insufficient to validate 0.050%, 1mg, or any alternative human harm threshold at present.”</li>
American Psychiatric Association</strong>, which said it was “encouraged” that DEA is taking steps to schedule 7-OH: “There are no controlled human dose-response studies that would allow identification of a precise human toxicity threshold for 7-OH.”</li>
FED UP! Coalition</strong>, which supports scheduling: “There is no established human therapeutic range, toxic range, or lethal blood concentration that would allow a scientifically confident determination that a particular consumer dose […] is below the level associated with imminent hazard.”</li> </ul>
In the docket’s own comments, the median dose people report taking is 30 mg. About 3% report taking 1 mg or less.</p>
What we asked senators to raise</h2>
We asked offices to raise these with Dr. Overton at the hearing, or to submit them as written questions for the record:</p>

FDA’s own assessment says surveillance can’t estimate how many people use 7-OH or why. Before FDA supports a Schedule I threshold, what evidence would it need to see that the threshold is set at the right level?</li>
If 7-OH is scheduled, what care pathway will FDA make sure is available for people using it for pain, anxiety, or depression without an opioid use disorder diagnosis?</li>
Some people are using 7-OH as over-the-counter self-treatment for opioid addiction, and only 15.7% of people with opioid use disorder received medications for it in 2025. If 7-OH is scheduled, how does FDA plan to address access to self-treatment?</li> </ol>
If you want to do the same</h2>
Video of the hearing will be posted on the committee’s website</a>. Committee members can submit written questions for the record until 5 PM Eastern on Friday, September 25, so contact their offices before then. If you call, it helps to mention the hearing and the document ID above.</p>
Our full comment on the proposed threshold, with the method behind the figures here, is on this site</a>.</p>

Our comment on the proposed 7-OH threshold

2026-09-08T00:00:00+00:00

The Social Pain Institute has filed a public comment in HHS-OASH-2026-0232</strong>, the docket on temporarily placing 7-hydroxymitragynine above a specified threshold in Schedule I. The comment and its technical appendix are below, together with the text we submitted alongside them.</p>
Docket HHS-OASH-2026-0232</span>Comment period closes September 10, 2026</span>17 pages, comment and appendix</span></p>
Why we filed</h2>
SPI translates neuroscience concerning social pain and the endogenous opioid system into clinical research and policy. That is a narrow remit, and most scheduling dockets fall outside it. This one does not.</p>
We are small, we are new, and we have no dose-response data of our own to add. What we can add is a reading of the record OASH already holds, so we screened it. We retrieved the posted comments from the regulations.gov API on August 19, 2026, while the docket was closed after its original July 31 deadline, and collapsed near-duplicate campaign submissions, leaving 19,344 distinct comments. The period has since reopened and runs to September 10, so the corpus is the original comment window as posted, and nothing filed since.</p>
Pain is the most common reason in that record, and it is the reason a person can state plainly and be understood. 60.5% of comments mention pain in some form. Alongside it, 20.7% mention a psychiatric or neurodevelopmental term, and 5.6% raise one with no pain or physical condition anywhere in the comment. Those are floors rather than rates, and a comment record will understate them.</p>
That population sits inside the exposure estimate FDA says it cannot supply, and it is the population our work is about. A record that does not describe it now will be considerably harder to describe afterward.</p>
What we are and are not saying</h2>
We take no position on whether any scheduling action should occur. The comment addresses only the two questions OASH posed, and its argument is about measurement and attribution: what the record can support, what it cannot, and what it does not describe. The five points and the recommendations are in the submitted text below, and set out in full in the comment itself.</p>
SPI has no financial interest in kratom or 7-OH products and receives no industry funding. The comment recommends no compound and takes no position on the relative merits of any μ-opioid agent. It does not claim that restriction has caused or will cause an increase in overdose deaths, because, as far as we’re aware, that data does not exist. Where we say the competing hazard is unmeasured, we mean unmeasured, not absent.</p>
The population the record does not describe</h2>
At least two filers address what happens to people who lose access. Between them the record offers two routes: opioid use disorder treatment, and pain management. Both are gated on a diagnosis that a measurable part of this cohort does not have.</p>
Someone using 7-OH for panic, for depression, or for the aftermath of trauma is not on that basis a person with opioid use disorder, and is not a person in pain management. Under the pathway the record describes, reaching any alternative would mean accepting a label whether or not it fits. Needing something that acts on the opioid system in order to function is not currently a legible reason to need it.</p>
That is the part of this SPI expects to still be working on after the docket closes. Our long-term interest is the endogenous opioid system as a therapeutic target for social pain, chronic suicidality, and trauma-spectrum conditions. Whether 7-OH has any place in that is an empirical question, and one that this action makes harder to answer. We did not ask OASH to answer it. We asked that the action not foreclose it, and that the people in question be counted while they are still reachable.</p>
Read the comment</h2>
</iframe></div>
Open the comment in your PDF reader</a> (17 pages, 260 KB)</p>
Download the comment (PDF, 260 KB)</a></div></div>
The appendix begins after the comment and carries the method behind every figure reported, along with the filed passages the comment summarizes. The deduplication and screening code, the random seed, and the list of retained comment IDs are available on request.</p>
The text we submitted with it</h2>
The Social Pain Institute is a Colorado nonprofit that translates neuroscience concerning social pain and the endogenous opioid system into clinical research and policy. SPI has no financial interest in kratom or 7-OH products and receives no industry funding. We take no position on whether any scheduling action should occur, and address only the two questions OASH has posed.</p>
The full comment and a technical appendix are attached. The appendix carries the method behind every figure reported and the filed passages the comment summarizes.</p>
Our comment makes five points:</p>
On Question 1, the record does not identify a concentration or quantity of 7-OH that constitutes an imminent hazard, and this is not contested. Filers on both sides of the scheduling question, including ASAM, the APA, the AAP, FED UP!, Shatterproof, R Street, and the Consumer Choice Center, say so in their own words.</li>
On Question 2, the threshold is disjunctive, and the operative prong is the 1.00 milligram per “article” limit rather than the 0.050 percent concentration limit. “Article” is undefined, so no measurement expression here has a determinate meaning.</li>
The harm data cannot currently be attributed to the product class the threshold defines. 7-OH in a toxicology result may come from a concentrated product, from kratom leaf, or from metabolism of mitragynine. The discriminator is not reported in DEA’s 85-case series, and the pro-scheduling filer closest to that data is asking DEA to release it.</li>
The exposure characterization is incomplete in a nameable way. FDA states that surveillance cannot supply a prevalence estimate for 7-OH use. Within the uncounted population is a cohort using 7-OH for anxiety, depression, and trauma-related distress, large enough to appear at scale in this docket’s own record and characterized by no organizational filer.</li>
The care pathway the record proposes is narrower than the population it is meant to catch. The two filers who address displacement name two routes, opioid use disorder treatment and pain management. Both are gated on a diagnosis a measurable part of this cohort does not have.</li></ol>
SPI’s recommendations, set out in full in the attached comment, ask OASH to define “article,” to characterize any adopted threshold as a policy judgment rather than a validated no-effect level, to specify what evidence would revise it, to treat the exposure characterization as incomplete, to report the data that would attribute the harm cases, and not to treat substance-attributed surveillance as evidence on displacement.</p>
Jesse Haigh, Executive Director
Social Pain Institute
Denver, Colorado</p></div>

Social Pain Institute

A third use for opioid medications

Questions for the FDA nominee on 7-OH

Who uses 7-OH, according to the record</h2> We analyzed the public comments</a> on the HHS docket. About 60% of commenters mention pain. One in five mention mental health, and more than a thousand mention it without mentioning pain at all.</p>

What we asked senators to raise</h2> We asked offices to raise these with Dr. Overton at the hearing, or to submit them as written questions for the record:</p>

Our comment on the proposed 7-OH threshold

Who uses 7-OH, according to the record</h2>
We analyzed the public comments</a> on the HHS docket. About 60% of commenters mention pain. One in five mention mental health, and more than a thousand mention it without mentioning pain at all.</p>