Does it reduce pain?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01PT-141PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 4 completed trials, 2,355 people given it.9 reported

   1,267 people given it1 trial

   • It raised sexual desire in women by a small but real amount, and made a lot of them feel sick. 1,267 premenopausal women with low sexual desire used bremelanotide as needed, or a dummy injection, over about six months across two matching trials. Desire scores rose and distress about low desire fell, more than on the dummy. The gain was modest, about a third of a point on the desire scale. Nausea, flushing and headache each hit at least one woman in ten.

     The numbers 1,267 premenopausal women across two identical 24-week trials: bremelanotide 1.75 mg as needed significantly increased FSFI desire scores (+0.35 integrated) and reduced desire-related distress versus placebo; nausea, flushing and headache in 10% or more.

     Obstetrics & Gynecology, 2019· 1,267 people

   What people using it report

   • Flushing and headache come up regularly alongside nausea, and the overall picture people describe is a compound that works but is difficult to tolerate at conventional doses.
2. 02Melanotan IIPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,310 people given it.9 reported

   1,267 people given it1 trial

   • The owned descendant of this chemistry was tested properly, and it worked a little. Two large trials gave bremelanotide or a dummy injection to 1,267 women before menopause who had lost interest in sex. Desire rose and distress fell on the drug, by a real but small margin. Nausea, flushing and headache were all commoner on the drug. This is what melanotan II's own effects look like once somebody funds the trial, and it is not melanotan II.

     The numbers Context for where the melanocortin money went: 1,267 premenopausal women randomized across two Phase 3 trials of bremelanotide, the owned descendant of this chemistry, with significant but small gains in desire and reductions in distress, and more nausea, flushing and headache than placebo.

     Obstetrics and Gynecology, 2019· 1,267 people

3. 03Relaxin-2PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 7,706 people given it.5 reported

   1,161 people given it1 trial1 found nothing

   • found nothingSerelaxin eased breathlessness a little in people admitted with sudden heart failure, and changed nothing that matters more. 1,161 people got either a two day drip of the drug or a dummy drip soon after reaching hospital. Breathlessness scored better on one scale and no better on the other. Deaths from heart causes and readmissions at two months were unchanged. A death count at six months leaned the drug's way, but that was a side question, not what the trial was built to prove. Funded by a Novartis company.

     The numbers 1,161 patients hospitalised with acute heart failure randomised 1:1 to a 48 hour infusion of serelaxin at 30 micrograms per kilogram per day or placebo within 16 hours of presentation. Serelaxin improved the visual analogue scale dyspnoea endpoint by 448 mm times hours (95 percent CI 120 to 775, p = 0.007) but had no effect on the co-primary Likert endpoint (27 percent against 26 percent, p = 0.70). There was no effect on cardiovascular death or readmission at 60 days (hazard ratio 1.02, 0.74 to 1.41) or on days alive out of hospital. Among prespecified additional endpoints, 42 deaths occurred by day 180 on serelaxin against 65 on placebo, hazard ratio 0.63 (0.42 to 0.93, p = 0.019). Funded by Corthera, a Novartis affiliate company. Registered as NCT00520806.

     The Lancet, 2013· 1,161 people

4. 04CGRPPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 968 people given it.

   968 people given it2 trials

   • The money in this peptide is in blocking it, and blocking it clearly works. 955 people with migraine got a monthly shot of one of two erenumab doses, or a dummy shot, for six months. They started with roughly eight migraine days a month. On the drug they lost between three and four of those days. On the dummy they lost under two. Half the people on the higher dose cut their migraine days by at least half. Side effects matched the dummy. Several authors work for the maker.

     The numbers The scale of evidence behind blocking this peptide, not administering it. 955 patients randomised to subcutaneous erenumab 70 mg (n=317), 140 mg (n=319) or placebo (n=319) monthly for six months. From a baseline of 8.3 monthly migraine days, days fell by 3.2 and 3.7 respectively against 1.8 on placebo (P<0.001 for each dose). A 50% or greater reduction was reached by 43.3% and 50.0% against 26.6% on placebo. Adverse event rates were similar to placebo. Several authors are Amgen employees.

     The New England Journal of Medicine, 2017· 955 people

   • Give a person this peptide and it gives them a migraine. Thirteen migraine patients each got CGRP on one day and a dummy infusion on another, without being told which was which. Ten of the thirteen developed a migraine-like attack on CGRP. Nobody did on the dummy. The headaches were worse and they lasted longer. That is why this peptide is something drug companies try to block, not something to take. The senior author advises several of those companies, which he declares.

     The numbers What happens when you give CGRP to a human. Thirteen migraine patients previously enrolled in erenumab trials received CGRP in a double-blind, placebo-controlled, randomised crossover design. CGRP induced migraine-like attacks in 10 of 13 patients (77%) compared with none after placebo, P = 0.002. Area under the curve for headache intensity was greater after CGRP at 0 to 90 minutes (P = 0.009) and 2 to 12 hours (P = 0.014), and median peak headache intensity was 5 against 2 on placebo (P = 0.004). Registered NCT03481400. The senior author discloses consultancy or advisory relationships with Allergan, Amgen, Alder, Eli Lilly, Novartis and Teva.

     The Journal of Headache and Pain, 2018· 13 people

5. 05Carbetocin (intranasal)PeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 343 people given it.

   175 people given it1 trial

   • This was the trial that settled the question, and carbetocin failed it. 175 people with Prader-Willi syndrome used either a carbetocin nasal spray or a dummy spray, three times a day for 12 weeks. The relentless hunger that defines the condition eased by the same amount in both groups, with the dummy group very slightly ahead. Nothing else the researchers looked at came apart either. Headache and fever were the commonest complaints. Four of the ten authors work for the company that paid for it.

     The numbers The decisive trial. 175 participants randomised 1:1 to carbetocin 3.2 mg three times daily (n=85) or placebo (n=90) over 12 weeks. Least squares mean change from baseline at week 12 on HQ-CT was -4.8 (SE 0.8) on carbetocin and -5.1 (SE 0.8) on placebo; treatment difference 0.3, 95% CI -1.8 to 2.4, P = 0.79. The authors state there was no separation between carbetocin and placebo for any secondary or exploratory endpoint. Most frequent treatment-emergent events on carbetocin were headache (6 participants, 7.2%) and pyrexia (5, 6.0%). The authors' own conclusion is that carbetocin nasal spray did not demonstrate efficacy compared with placebo. Four of the ten authors are employees and stakeholders of ACADIA Pharmaceuticals, the sponsor.

     Clinical Therapeutics, 2026· 175 people

6. 06ZiconotidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 111 people given it.2 reported

   111 people given it2 trials

   • Ziconotide clearly relieved severe pain that nothing else was touching. 111 people with cancer or AIDS, aged 24 to 85, got either the drug or a dummy into the fluid around the spinal cord, and nobody involved knew which. Pain scores dropped by about half on the drug and by under a fifth on the dummy. Just over half the treated group got moderate to complete relief, against about one in six. The trial hit the target it was built to hit.

     The numbers Double-blind, placebo-controlled, 32 centres in the United States, Australia and the Netherlands, 111 patients aged 24 to 85 randomised 2 to 1. Mean percentage improvement in the visual analogue scale of pain intensity was 53.1 percent (95 percent CI 44.0 to 62.2) with ziconotide versus 18.1 percent (95 percent CI 4.8 to 31.4) with placebo, P below 0.001. Moderate to complete pain relief in 52.9 percent versus 17.5 percent. Primary endpoint met.

     JAMA, 2004· 111 people

   • The drug worked for long term pain not caused by cancer, and the dose had to be cut mid trial to make it bearable. 255 hospital inpatients got ziconotide or a dummy into the spinal fluid over six days. Pain fell by about a third on the drug and by a twentieth on the dummy. Partway through, side effects forced the team to drop the starting dose fourfold and the ceiling by two thirds. It hit the target it was built to hit, but not at its original doses.

     The numbers 255 inpatients, 169 on ziconotide and 86 on placebo, treated over six days. Mean percent reduction in the visual analogue scale of pain intensity was 31.2 percent versus 6.0 percent. The protocol was amended during the trial, cutting the starting dose from 0.4 to 0.1 micrograms per hour and the maximum from 7.0 to 2.4 micrograms per hour, because of adverse events. The primary endpoint was met but at the original dosing the tolerability was not acceptable.

     Neuromodulation, 2006· number of people not given

7. 07MelittinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 658 people given it.4 reported

   54 people given it1 trial

   • A small study found less back pain after bee venom acupuncture. Fifty four people with long standing low back pain had six sessions over three weeks, either the real thing or a fake version, on top of a painkiller everyone took. Pain, bother and function all improved more in the venom group at three weeks. Fifty four people over three weeks tells you nothing about lasting benefit. Side effects were minor. Korean academic funding paid for it.

     The numbers 54 patients with non-specific chronic low back pain, six sessions of real or sham bee venom acupuncture over 3 weeks on top of loxoprofen. Bothersomeness, pain intensity and function improved more in the venom group at 3 weeks; minimal adverse events in both groups. Korean academic funding.

     Toxins, 2017· 54 people

8. 08BPC-157PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 31 people given it.10 reported

   17 people given it1 trial

   • This is not a trial, and it cannot show the peptide helped anyone. Doctors at one Florida clinic looked back through the records of 17 patients who had been injected in the knee. They phoned 16 of them six to twelve months later and asked how the knee felt. Of the 12 given BPC-157 on its own, 11 said the pain was meaningfully better. Nobody got a dummy injection, nobody was scored on a proper pain scale, and no scans were taken.

     The numbers Retrospective chart review of 17 patients given 2 to 4 mg intra-articularly at one Florida clinic; of the 16 reached by phone months later, 11 of 12 who received BPC-157 alone reported meaningful pain relief. No control group, no validated outcome measure, no imaging.

     Alternative Therapies in Health and Medicine, 2021· 17 people

9. 09DSIPPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 6 completed trials, 7 people given it.8 reported

   7 people given it1 trial

   • Pain fell in six of seven people, and there was nobody to compare them with. Seven patients with migraine, headache, long standing tinnitus or unexplained pain attacks got DSIP into a vein, daily for five days and then every few days. Their pain scores fell against their own earlier readings, and their low mood lifted at the same time. No control group. No sorting by chance. This is a first look and not an answer.

     The numbers 7 patients with migraine, vasomotor headache, chronic tinnitus or psychogenic pain given intravenous DSIP on five consecutive days then five injections every 48 to 72 hours. Pain fell significantly in 6 of 7 against their own baseline period, with depressive symptoms also falling. No control group.

     European Neurology, 1984· 7 people

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01CoQ10SupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 162 people given it.4 reported

   42 people given it1 trial

   • CoQ10 cut migraine attacks in a small trial that is not about ageing. 42 people took 100 mg three times a day, or a dummy. By the third month, 47.6 percent on CoQ10 had half as many attacks, against 14.4 percent on the dummy. That is a migraine result in 42 people.

     The numbers 42 adults with migraine randomised to CoQ10 100 mg three times daily or placebo. In month 3, CoQ10 was superior for attack frequency, headache-days and days with nausea. 50% responder rate 47.6% against 14.4% (number needed to treat 3).

     Neurology, 2005· 42 people

2. 02Collagen peptidesSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 69 people given it.4 reported

   0 people given it1 trial1 found nothing

   • found nothingCollagen did not beat a dummy for knee pain in a study nobody selling collagen paid for. Both groups got better, by roughly 1.6 to 1.9 points on the pain scale. That is a bigger improvement than the gap industry funded trials credit to collagen itself. Read that carefully. People improved, and collagen was not the reason they improved.

     The numbers Independent, academic, and null. Both arms improved by roughly 1.6 to 1.9 points on the pain scale, which is larger than the between-group differences industry-funded trials attribute to collagen.

     Applied Physiology, Nutrition, and Metabolism, 2020· number of people not given

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01Botulinum toxin type ABiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,681 people given it.5 reported

   1,384 people given it1 trial

   • Botulinum toxin cut chronic migraine days, and the dummy injections cut them almost as much. 1,384 adults were injected with either the toxin or a dummy every twelve weeks across two trials. After six months, headache days had fallen by about eight a month on the toxin and about seven on the dummy. The gap between them is under two headache days a month. That gap is real and it held at every check. It is also far smaller than the raw drop people quote.

     The numbers The therapeutic evidence that is usually left out of cosmetic coverage. Two multicentre phase 3 trials pooled, 1384 adults randomised 1 to 1 to onabotulinumtoxinA 155 to 195 units or placebo every 12 weeks. Mean change in headache days at week 24 was minus 8.4 versus minus 6.6 in favour of the toxin, P below 0.001, with significant differences at all other timepoints. Note that placebo also produced a large decrease, so the between-group difference is under two headache days per month.

     Headache, 2010· 1,384 people

2. 02CebranopadolSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 300 people given it.

   258 people given it2 trials1 found nothing

   • found nothingOne tablet beat both a dummy and morphine for pain after foot surgery. Two hundred and fifty eight patients got cebranopadol at one of three strengths, a slow release morphine tablet, or a dummy. The two higher strengths relieved pain over the first ten hours better than either comparison. Morphine worked, but later. The lowest strength was no better than the dummy. Side effects rose with the dose and were worst on morphine. The maker paid.

     The numbers 258 patients after bunionectomy randomised to a single oral dose of cebranopadol 200, 400 or 600 mcg, morphine controlled release 60 mg, or placebo. On the primary endpoint (summed pain intensity 2 to 10 hours), 400 and 600 mcg beat placebo and beat morphine, whose effect emerged later; 200 mcg did not differ from placebo. Adverse events rose with dose and were highest on morphine. Developer funded.

     Pain Physician, 2018· 258 people

   • This trial never got the people it needed and it did not show what it set out to show. It was built for more than five hundred patients with cancer pain and recruited a quarter of that before stopping. Those who took part got cebranopadol or slow release morphine for up to seven weeks. People on cebranopadol reached for less emergency morphine. On pain relief itself, cebranopadol was not shown to match morphine. Side effects were about equally common on both. The maker paid.

     The numbers Planned for 524, enrolled 126 because of low accrual; up to 7 weeks of cebranopadol (200 to 1,000 mcg) versus prolonged release morphine. On the primary endpoint, daily rescue morphine use, cebranopadol was non-inferior and superior (difference -7.48 mg, 95% CI -12.05 to -2.92). Non-inferiority on pain reduction itself was not shown. Adverse events in 83 versus 82 percent. Developer funded; corresponds to the terminated CORAL trial NCT01964378.

     European Journal of Pain, 2019· number of people not given

3. 03Alpha-2-MacroglobulinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 75 people given it.6 reported

   75 people given it1 trial1 found nothing

   • found nothingA2M injections helped knees, but no better than the cheaper options they were tested against. 75 people with moderate knee osteoarthritis were split by chance between an A2M-rich concentrate, ordinary platelet-rich plasma, and a steroid injection. Nobody involved knew which. 68 finished. At 12 weeks the A2M group had improved on every pain and function score, the platelet group on none, and the steroid group on one. But the groups did not differ from each other. The authors concluded A2M is not worth its higher cost.

     The numbers Double-blinded randomised controlled trial at a single centre, enrolling June 2018 to May 2019. 75 people with symptomatic Kellgren-Lawrence grade 2 or 3 knee osteoarthritis randomised to intra-articular A2M-rich concentrate, conventional platelet-rich plasma, or methylprednisolone, followed 12 weeks; 68 (90.7 percent) completed, 73 percent female, mean age 59. At 12 weeks the A2M group improved significantly on visual analogue scale, WOMAC, KOOS and Tegner; the platelet-rich plasma group improved on nothing; the steroid group improved on Lysholm only. Between-group changes did not differ significantly. The authors concluded A2M is not superior and, given higher preparation cost, may not be justifiable for routine treatment.

     Bulletin of the Hospital for Joint Diseases, 2024· 75 people

4. 04MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported

   50 people given it1 trial

   • In Cushing's syndrome, where cortisol is the problem, blocking its receptor with mifepristone improved blood sugar, blood pressure and weight over six months. 50 adults took part, and there was no dummy pill group. Tiredness, nausea, headache and low potassium were common. This is the approved use, not a study of ageing.

     The numbers 50 adults with endogenous Cushing's syndrome, after failed treatment, were given mifepristone 300 to 1,200 mg daily for 24 weeks, open-label, at 17 US centres. In the diabetes or impaired glucose tolerance group 60% had a glucose AUC response; HbA1c fell from 7.43% to 6.29% and fasting glucose from 149 to 105 mg/dL. In the hypertension group 38% had a diastolic pressure response. Mean weight change -5.7%; 87% judged clinically improved. Fatigue, nausea, headache, low potassium, arthralgia, vomiting, oedema and endometrial thickening were common.

     The Journal of Clinical Endocrinology and Metabolism, 2012· 50 people

Peptides and blends

1. 01SS-20PeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, 1 lab study, no human study.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Mice on a weekly cancer drug got nerve pain and lost tiny nerve fibres in their paws. A steady supply of SS-20 prevented the pain and kept the nerve fibres normal. It was given to prevent the damage, not to treat it. The authors declare a money interest, and nobody has followed this up in people.

     The numbers Mice given weekly oxaliplatin developed neuropathic pain and lost intraepidermal nerve fibres in the hind paw. Continuous SS-20 prevented the pain and returned nerve fibre density to normal levels. The authors note that SS-31 was the inventor's compound and declare that competing interest. Mice, prevention rather than treatment, and no human follow-up has been located.

     ACS Chemical Neuroscience, 2018· animal study