Hug the Monkey

More Info on Ecstasy and PTSD

A small, phase 2 pilot study found that MDMA, also known as Ecstasy, might help treating people with post-traumatic stress disorder.

Michael Mithoefer, MD, a psychiatrist in private practice in Mount Pleasant, South Carolina, was the lead author on the study, 20 people received MDMA or placebo along with two days  of "experimental" therapy. The idea was to use the drug to reduce subjects' fear and reactivity to traumatic events.

Mithoefer told Medscape, 

"We didn't want to just test the drug," explained Dr. Mithoefer. "We wanted to test the drug's ability to catalyze psychotherapy. It's important that people realize that MDMA should be used in the right way, and that it's not a stand-alone solution for PTSD."

He found that subjects didn't need to take the drug every time they had therapy, nor for a long period of time. It was able to get them over the therapeutic hump enough to make progress; they could then continue to progress on their own.

Keith Young, MD, vice chair of research in the Department of Psychiatry at Texas A&M Health Science Center College of Medicine, who was interviewed for the article, noted that the effects shown might be due to the release of oxytocin that MDMA causes, and that it might be better to simply dose PTSD patients with oxytocin.

The study was paid for by Multidisciplinary Association for Psychedelic Studies (MAPS).

See two earlier posts on the use of Ecstasy to treat PTSD:

Ecstasy Helps PTSD Treatment

Ecstasy Could Be PTSD Breakthrough

Viagra and Oxytocin A Hot Topic at Edguider Forum

Here’s a post from Paul, a moderator for the Edguider.com forum. He monitors the forum and has been seeing an increasing interest for oxytocin among men with erectile dysfunction:

A discussion in the Edguider Forum on how oxytocin helps men decrease their sexual performance anxiety and erectile dysfunction has become one of the most popular topics.

Meyer Jackson of the University of Wisconsin's Madison School of Medicine and Public Health found that sildenafil, AKA Viagra, increased the amount of oxytocin released by the pituitary glands of rats. It's very likely that it does the same thing for men.

Sildenafil is the active ingredient in Viagra. It was always thought to be a physical reactive drug by helping increase the blood flow in and around the penis arteries allowing the penis to become hard for sexual intercourse.

Enzymes in the body can act like a braking system for hormones like oxytocin, controlling the release and also dampening the excitation of cells. One enzyme, PDE5 (phosphodiesterase type 5), can also contract blood vessels limiting the amount of blood flow.

According to the Daily Mail,

Viagra overcomes impotence by blocking phosphodiesterase type 5, a chemical that limits blood flow. Scientists have now discovered that this chemical also regulates the release of 'love hormones' in the brain.

Edguider.com is an online forum for men to discuss all related news and information regarding erectile dysfunction, Viagra and other therapies. Here is an example of what the members of the forum are saying about oxytocin:

 “The drug was wonderful: oxytocin has anti anxiety effects, and stimulates various types of positive social interaction. I've never felt so calm, confident and relaxed. This may be a God's send if you suffer from sexual performance anxiety, like me. The effect lasted the whole evening.”

Read more: I tried oxytocin and Levitra yesterday

Oxytocin Inhalant Helps Chronic Headache

Trigemina announced the results of a small clinical trial of intranasal oxytocin for headache. Twenty-five patients  with chronic daily headache who didn't get relief from any available remedies received either oxytocin or a placebo.

While 47 percent of people treated with oxytocin reported at least a 50 percent reduction in pain, only 11 percent of those getting the placebo got relief.

According to the press release, Trigemina researchers don't think it's as simple as oxytocin opening up blood vessels in the head.  Instead, inhalants seem to be able to deliver medication to the trigeminal nerve and other parts of the central nervous system.

According to the company, "Trigemina, Inc. exploits a newly discovered pathway that allows for targeting of the trigeminal nerves and central nervous system, allowing direct access to pain mediating sites and minimizing off-target side effects. Trigemina’s drug development pipeline includes intranasal oxytocin (TI-001) and TI-002, which may offer an alternative for the massive opiate market."

Massage Helps the Bereaved

Weekly massages for eight weeks after the loss of a loved one consoled the bereaved and helped them recover from their grief.

As reported in The Medical News, 18 people of varying ages who had lost a relative to cancer were offered massage. All but one reported that they received considerable benefits.

The Karolinska Institute is the Swedish research facility where Kerstin Uvnas Moberg did her pioneering research on oxytocin.

This study adds to the small bit of research validating the idea that massage causes the release of oxytocin in the recipient. However, we should note that the study does not seem to have actually measured levels of oxytocin in the participants' blood.  But the researchers have the very informed opinion that this is the case:

"Soft tissue massage is gentle, but firm" explains Dr [Berit S.] Cronfalk [from the Stockholms Sjukhem Foundation], who carried out the research with colleagues from the Karolinska Institutet. "This activates touch receptors which then release oxytocin, a hormone known for its positive effects on well-being and relaxation.

Although you'll see it all over the internet, I've only seen one scientific study measuring the oxytocin levels of massage recipients. Still, it makes intuitive sense; and the emotion study participants felt is certainly that oxytocin feeling.

"All the people we spoke to used the word consolation" says Dr Cronfalk.

Oxytocin for Chronic Headache?

with Jasvir Singh

Oxytocin therapy may help  patients with chronic headaches, which is 3 percent of the U.S. population. There is no current effective treatment, so this would be a real breakthrough.

Trigemina Inc.  is a start-up company that is examining new opportunities for treating pain. One of these new opportunities is intranasal oxytocin. They are conducting a study  comparing intranasal oxytocin with placebo for treating debilitating, recurrent headaches.

There's just a bit more information in their press release. 

With studies underway looking at oxytocin to treat social anxiety disorder, autism, schizophrenia and autism, it certainly seems that oxytocin could be a wonder drug.

French Confirm Nasal Oxytocin Helps ASD

A new French study of 13 high-functioning adults with autism spectrum disorder found that inhaling oxytocin made the subjects more social and open to relating to others.

According to the London Times, Elissar Andari, of the Institut des Sciences Cognitives, a French government centre for neuroscience research presented the findings at a conference.

The article doesn't say how long improvements lasted; in the first study of oxytocin for autism, Eric Hollander and Jennifer Bartz of the Seaver Centers for Autism found they lasted up to two weeks.

Good Interview with Eric Hollander on Oxytocin and ASD

-- with Jasvir Singh

Writer James Ottar Grundvig, who has an autistic child, spoke with Hollander about his past research, in which he showed that oxytocin could improve some of the symptoms of autism spectrum disorder, as well as what he plans for the future.

Hollander recently moved from the Seaver and New York Autism Center of Excellence at Mt. Sinai School of Medicine to the Child Psychiatry Annex at the Montefiore Medical Center University Hospital for Albert Einstein College of Medicine.

 The interview recaps Hollander's ground-breaking studies showing that intravenous or intranasal oxytocin  improved emotions, strengthened trust bonds, and reduced or eliminated repetitive behavior in healthy adults with ASD -- with improvement lasting two weeks after a single dose.

 Hollander also comments on other studies showing that oxytocin may help with schizophrenia and social anxiety disorder.

 Dr. Hollander is a clinical psychiatrist who spearheaded autism research at Mount Sinai School of Medicine and chairs the Advisory Board of icare4autism. He believes that doing oxytocin studies on ASD (Autism Spectrum Disorder) children is over two years away. More evidence and safety needs to be obtained before the FDA approves that phase of research. Until then, studies will focus on young adults, according to the interview.

 You can read the entire interview here in the Epoch Times.

The Peptide That Binds: Overview of Human Research

UC Berkeley researchers just published a review of human oxytocin studies in the Harvard Review of Psychiatry. Behavioral Health Central has a brief report. In a nutshell:

The researchers concluded: "Key conclusions are (1) human research with intranasal oxytocin has uniquely enhanced our understanding of the microstructure and function of the human social brain, and (2) the oxytocin system is a promising target for therapeutic interventions in a variety of conditions, especially those characterized by anxiety and aberrations in social function."

The paper is called The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans.

New Oxytocin Trials Recruiting

Most of us should be able to increase our oxytocin by practicing comfortable behaviors, which may be as simple as calling a good friend or going to the dog park and scratching some ears. But I know that there's strong interest in some kind of drug we could take to either amplify our natural oxytocin or to experience the kind of oxytocin release that doesn't come naturally to us.

At this point in time, most researchers are focusing on using oxytocin to treat diagnosable disorders including social anxiety, autism and schizophrenia. While these studies test oxytocin's use in diagnosed disorders, if they result in marketable drugs, it's very likely that psychiatrists will begin to prescribe them off-label, that is, for other permissible treatments besides those for which the drug is sold.

UC San Diego is recruiting subjects for two studies of the effects of oxytocin on psychiatric disorders. One study will test whether an oxytocin inhalant can improve residual symptoms of schizophrenia. Another will look at oxytocin's effects on anxiety. If you have a diagnosis of SAD, GAD or PTSD and want to enroll, contact Angel Nguyen at 619-543-8296 or by email.

Meanwhile, if you're curious and live in the Boston area, Harvard is recruiting for a study of the connection between social support and oxytocin.  For more information or to enroll in the study, contact Laura D Kubzansky at 617-432-3589 or by email.

When I began researching my book four years ago, there were very few clinical studies of oxytocin. Now, there are lots, more than I want to mention in this newsletter. To find out about these -- or trials for other kinds of drugs -- search ClinicalTrials.gov.

WAY-267464: The Love and Connection Drug?

Jett asked me about WAY-267,464, after finding this Wikipedia entry on it. After looking through my archives, I found that I had discussed this potential drug that Wyeth is working on with Dr. Robert Ring, Head of Molecular Neurobiology, Depression & Anxiety Disorders, Discovery Neuroscience, Wyeth Research.

The original draft of my book, The Chemistry of Connection, contained a whole chapter about potential oxytocin therapies. Unfortunately, my publisher didn't want much of this in the book. But there's immense interest in oxytocin drugs, and I believe that oxytocin is going to be the wonder drug of this decade -- or maybe next decade.

In February 2007, I interviewed Wyeth's Robert Ring about the potential for oxytocin therapies. Below is the section of the chapter discussing WAY 267,464, with some additional comments.

The delivery method -- how to get a drug inside someone -- is a huge issue for oxytocin. The nasal spray stings and doesn't last very long; injections hurt; IVs are cumbersome and unpleasant; pills break down in the digestive system before they have a chance to work.

That's why pharmaceutical companies will likely produce drugs containing proprietary oxytocin-like molecules, instead of bio-identical oxytocin. These designer molecules will bind with oxytocin receptors, but they'll have other characteristics that make them more effective or limit what they do.

Robert Ring, head of molecular neurobiology, depression and anxiety disorders, discovery neuroscience for drug giant Wyeth Pharmaceuticals, is unusual among drug company executives for being willing to discuss oxytocin drug development.

"We're blown away at the various diverse range of functions oxytocin seems to be acting on," he says. "Working at a drug company, you can't ignore the fact that oxytocin seems to be a multifunctional anti-stress peptide -- and it seems to be a potent analgesic as well."

One hot prospect is Wyeth's WAY 267,464. It's not a peptide like oxytocin is, which means that it won't degrade into other neurologically active substances. Instead, it's an oxytocin agonist, that is, it increases the effects of oxytocin. The advantage of treating with an agonist instead of simply trying to supplement the brain's natural supply is that often, when docs dose someone with a hormone, it further inhibits the body from producing it. WAY 267,464 also is less likely to cross over and bind to vasopressin receptors. This is important because, while scientists haven't nailed down vasopressin's role in human bonding and social interaction, it definitely seems to be important. So, the less you get in there and muck with unknown systems, the better.

In animal studies, the substance, known as 464, behaves much like oxytocin in reducing anxiety, and it also has some promise as an anti-psychotic.

Eric Hollander of the The Seaver Center for Autism Research and Treatment, Mount Sinai Medical Center, would seem to have a patent lock on teating symptoms of autism spectrum disorder, or ASD, and other disorders using oxytocin. Wyeth isn't concerned about Hollander's patents; it hopes to develop a unique molecule that binds to oxytocin receptors but has better properties for a drug. Neither is it working on an autism drug -- at least, Ring wouldn't say it is.

He pointed out that, although there's intense interest in using oxytocin to treat ASD symptoms. Because oxytocin and oxytocin-like drugs are a novel category, the path to FDA approval isn't clear. It might not be easy to demonstrate positive outcomes using standard methodologies.

Oxytocin's broad reach, relieving pain, reducing stress and soothing anxiety, could be an extra benefit for conditions with complex pathologies. Depression, for example, may go along with anxiety, chronic pain or physical illness. Oxytocin could potentially relieve these "co-morbid" conditions, Ring says. Easing any one of them would be important. Anxiety itself, he adds, is "a huge market."

Another promising area for the industry might be an antidepressant without the sexual side effects of selective serotonin-reuptake inhibitors like Prozac and Paxil. Over time, as these drugs increase the level of serotonin in the brain, prolactin also rises. Among its many roles in the body, prolactin induces the feeling of sexual satiety after orgasm. Chronically high levels of prolactin therefore can make you feel you've had enough sex, even if you aren't having any at all. An apathetic sex life is a common complaint among people on SSRIs.

Although oxytocin release is often promoted by serotonin, oxytocin also helps regulate sexuality, and it seems to be involved in erections of the penis and, presumably, the clitoris. So, it's possible that an oxytocin-based antidepressant could actually improve someone's sex life, as well as his frame of mind. Dr. Ring told me, "It's one thing to treat male erectile dysfunction, but there's a much bigger market for therapeutics for female dysfunction." While lubrication or engorgement problems may be neurological, oxytocin might be important for the motivational side of things. For example, if some aspect of sexual dysfunction had to do with anxiety about interacting with your partner, anything that would lower that anxiety might help.

(My editorial comment: For most women, anxiety about potential sexual partners is protective and a good thing. Ideally, any of these potential drugs would only be given to women with anxiety disorders. We hope.)

But don't expect 464 to turn into a pharmacological silver bullet. While its action in the body is remarkably like oxytocin's, Ring cautioned that this molecule may lack some of the properties of a good medicine. A successful oxytocin mimic should be able to be taken orally, and ideally, just once a day.

Wyeth Research is, of course, focusing on developing drugs to treat psychiatric disorders. But if a drug like this comes out, it may, like SSRIs or Provigil, also be taken up by people who haven't been diagnosed with a disorder but are just hoping to warm up their lives a bit.

This July 2009 paper in Neuropharmacology details tests of WAY-267464 on mice.

Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin agonist. 

And here is the Wyeth patent application for using oxytocin receptor agonists to treat schizophrenia and anxiety disorders.