SoylentNews

takyon writes:

The U.S. Food and Drug Administration has given its approval for Phase 3 trials to treat participants with PTSD using MDMA ("ecstacy"):

The non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to MDMA for the treatment of posttraumatic stress disorder (PTSD). MAPS and the FDA have also reached agreement under the Special Protocol Assessment Process (SPA) for the design of two upcoming Phase 3 trials (MAPP1 and MAPP2) of MDMA-assisted psychotherapy for patients with severe PTSD.

MDMA-assisted psychotherapy is a novel treatment package that combines psychotherapeutic techniques with three administrations of MDMA as a pharmacological adjunct. By granting Breakthrough Therapy Designation, the FDA has agreed that this treatment may have a meaningful advantage and greater compliance over available medications for PTSD.

The first Phase 3 trial (MAPP1), "A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder," will begin enrolling subjects in Spring 2018, after the completion of an open-label lead-in training study at Phase 3 sites starting this fall.

[...] The Phase 3 trials will assess the efficacy and safety of MDMA-assisted psychotherapy in 200-300 participants with PTSD, aged 18 and older, at sites in the U.S., Canada, and Israel. Participants will be randomized to receive three day-long sessions of either MDMA or placebo in conjunction with psychotherapy over a 12-week treatment period, along with 12 associated 90-minute non-drug preparatory and integration sessions. The primary endpoint will be the Clinician Administered PTSD Scale (CAPS-5), as assessed by a blinded pool of independent raters.

In MAPS' completed Phase 2 trials with 107 participants, 61% no longer qualified for PTSD after three sessions of MDMA-assisted psychotherapy two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. All Phase 2 participants had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years.

Also at ScienceAlert, the Washington Post, and Science Magazine:

Since 2012, FDA has designated close to 200 drugs as breakthrough therapies, a status that indicates there's preliminary evidence that an intervention offers a substantial improvement over other options for a serious health condition. The agency aims to help develop and review these treatments faster than other candidate drugs.

Original Submission

takyon writes:

An fMRI study has found evidence of a reduction in depressive symptoms after treatment with psilocybin:

A hallucinogen found in magic mushrooms can "reset" the brains of people with untreatable depression, raising hopes of a future treatment, scans suggest.

The small study gave 19 patients a single dose of the psychedelic ingredient psilocybin. Half of patients ceased to be depressed and experienced changes in their brain activity that lasted about five weeks.

However, the team at Imperial College London says people should not self-medicate.

There has been a series of small studies suggesting psilocybin could have a role in depression by acting as a "lubricant for the mind" that allows people to escape a cycle of depressive symptoms. But the precise impact it might be having on brain activity was not known.

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms (open, DOI: 10.1038/s41598-017-13282-7) (DX)

Original Submission

takyon writes:

Study: Suicidal Thoughts Rapidly Reduced with Ketamine

Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's anti-suicidal effects occurred within hours after its administration.

The findings were published online last week in the American Journal of Psychiatry.

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial (DOI: 10.1176/appi.ajp.2017.17060647) (DX)

The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.

Wikipedia's entry on midazolam notes:

Midazolam, marketed under the trade name Versed, among others, is a medication used for anesthesia, procedural sedation, trouble sleeping, and severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ability to create new memories. It is also useful for the treatment of seizures

Related: 4/20: The Third Time's Not the Charm
Study Suggests Psilocybin "Resets" the Brains of Depressed People

Original Submission

takyon writes:

New studies zero in on roots of depression and why ketamine reverses it

[There's] been significant progress in unravelling the confusion over ketamine, with researchers identifying a ketamine derivative that tackles depression with far fewer side effects. And this week, a team of researchers at China's Zhejiang University announced that they've figured out where in the brain ketamine acts when it blocks depression, a finding that gives us significant insights into the biology of the disorder.

The new studies rely on the work of a number of other labs, which have identified a specific structure deep in the brain that's associated with depression. Called the lateral habenula, it's been associated with a variety of activities, the most relevant of which seems to be the processing of unpleasant outcomes and punishment. Electrodes implanted there have been used to relieve depression in at least one instance.

To test whether this might be the site of ketamine's activity, one team of researchers infused the drug directly into the lateral habenula of rats with depression-like symptoms; it blocked them. So did a separate chemical that inhibits the same proteins that ketamine acts on. Tracking the activity in the area, the researchers were able to show that there are bursts of activity in rats with symptoms of depression that are absent in healthy rats. The drugs that blocked depression suppressed these bursts.

Ketamine blocks bursting in the lateral habenula to rapidly relieve depression (DOI: 10.1038/nature25509) (DX)

Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression (DOI: 10.1038/nature25752) (DX)

Related: FDA Designates MDMA as a "Breakthrough Therapy" for PTSD; Approves Phase 3 Trials
Study Suggests Psilocybin "Resets" the Brains of Depressed People
Ketamine Reduces Suicidal Thoughts in Depressed Patients

Original Submission

martyb writes:

Research shows that longstanding depression alters the brain -- treatment may require different approaches depending on not just the severity of the depression but also on its longevity:

Is clinical depression always the same illness, or does it change over time?

New brain imaging research from the Centre for Addiction and Mental Health (CAMH) shows that the brain alters after years of persistent depression, suggesting the need to change how we think about depression as it progresses.

The study, led by senior author Dr. Jeff Meyer of CAMH's Campbell Family Mental Health Research Institute, is published in The Lancet Psychiatry.

The research shows that people with longer periods of untreated depression, lasting more than a decade, had significantly more brain inflammation compared to those who had less than 10 years of untreated depression. In an earlier study, Dr. Meyer's team discovered the first definitive evidence of inflammation in the brain in clinical depression.

This study provides the first biological evidence for large brain changes in long-lasting depression, suggesting that it is a different stage of illness that needs different therapeutics - the same perspective taken for early and later stages of Alzheimer's disease, he says.

"Greater inflammation in the brain is a common response with degenerative brain diseases as they progress, such as with Alzheimer's disease and Parkinson´s disease," says Dr. Meyer, who also holds Canada Research Chair in the Neurochemistry of Major Depression. While depression is not considered a degenerative brain disease, the change in inflammation shows that, for those in whom depression persists, it may be progressive and not a static condition.

Over years, depression changes the brain, new study shows
Depression Can Actually Leave Long-Term Changes in Your Brain, Study Shows

More information: Elaine Setiawan et al, Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study, The Lancet Psychiatry (2018). DOI: 10.1016/S2215-0366(18)30048-8

Original Submission

takyon writes:

Past articles: 2015 • 2016 • 2017 👀

U.S. Senate Minority Leader Chuck Schumer (D-NY) has come out in support of federal cannabis decriminalization, just in time for 4/20:

The Minority Leader of the Senate is making it official the day before 4/20: He's down with legal weed. In an exclusive interview with VICE News, Sen. Chuck Schumer (D-NY) confirmed he is putting his name on legislation that he said is aimed at "decriminalizing" marijuana at the federal level. For Schumer, this is a shift. While he has backed medical marijuana and the rights of states to experiment with legal sales of pot, what he is proposing is a seismic shift in federal drug policy.

"Ultimately, it's the right thing to do. Freedom. If smoking marijuana doesn't hurt anybody else, why shouldn't we allow people to do it and not make it criminal?" Schumer said.

The legislation should be available within a week or so, and would remove cannabis (still listed as "Marihuana") from the Drug Enforcement Administration's list of Schedule I substances. States would then be free to regulate or continue to prohibit the plant. Cannabis advertising would be regulated as are alcohol and tobacco advertising. (Also at NPR, CNN, The Washington Post, and CNBC, as well as Reason taking a shot at Schumer for not doing it sooner.)

A majority of Americans support the legalization of cannabis, including, for the first time, a majority (51%) of Republicans, according to Gallup. Nine states and the District of Columbia have legalized cannabis for recreational use. 29 states, D.C., Guam, and Puerto Rico have legalized medical use of cannabis, and another 17 states have legalized the use of cannabidiol (CBD). Cannabis became available for recreational purposes in California on January 1.

takyon writes:

Fast-Acting Depression Drug, Newly Approved, Could Help Millions

Of the 16 million American adults who live with depression, as many as one-quarter gain little or no benefit from available treatments, whether drugs or talk therapy. They represent perhaps the greatest unmet need in psychiatry. On Tuesday, the Food and Drug Administration approved a prescription treatment intended to help them, a fast-acting drug derived from an old and widely used anesthetic, ketamine.

The move heralds a shift from the Prozac era of antidepressant drugs. The newly approved treatment, called esketamine, is a nasal spray developed by Janssen Pharmaceuticals Inc., a branch of Johnson & Johnson, that will be marketed under the name Spravato. It contains an active portion of the ketamine molecule, whose antidepressant properties are not well understood yet. "Thank goodness we now have something with a different mechanism of action than previous antidepressants," said Dr. Erick Turner, a former F.D.A. reviewer and an associate professor of psychiatry at Oregon Health & Science University. "But I'm skeptical of the hype, because in this world it's like Lucy holding the football for Charlie Brown: Each time we get our hopes up, the football gets pulled away."

[...] Esketamine, like ketamine, has the potential for abuse, and both drugs can induce psychotic episodes in people who are at high risk for them. The safety monitoring will require doctors to find space for treated patients, which could present a logistical challenge, some psychiatrists said.

The wholesale cost for a course of treatment will be between $2,360 and $3,540, said Janssen, and experts said it will give the company a foothold in the $12 billion global antidepressant market, where most drugs now are generic.

[...] One question that will need to be answered is how well esketamine performs in comparison to intravenous ketamine.

Also at STAT News, Reuters, and NPR.

Previously: Ketamine Reduces Suicidal Thoughts in Depressed Patients
Studies Identify How Ketamine Can Reverse Symptoms of Depression
Ketamine Shows Promise as a Fast-Acting Treatment for Depression

Related:

*SPOILER* (click to show) *SPOILER* (click to hide)

Psychiatrists Investigate Using Mushrooms to Treat Depression
Research into Psychedelics, Shut Down for Decades, is Now Yielding Exciting Results
Depression Not Caused by Low Serotonin Levels - Most Drugs for Treatment Based on Myth
Psilocybin Successfully Treats Severe Depression in Small Clinical Trial
Research Into Psychedelics Continues
What a Gottlieb-Led FDA Might Mean for the Pharmaceutical Industry
Study Suggests Psilocybin "Resets" the Brains of Depressed People
FDA Designates MDMA as a "Breakthrough Therapy" for PTSD; Approves Phase 3 Trials
Amazonian Psychedelic May Ease Severe Depression, New Study Shows
Study Shows How LSD Alters Directed Connectivity Within Brain Pathways in Humans

Original Submission