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mendax writes:

I may start growing 'shrooms in my dark and dank pantry and get off Celexa after reading this New York Times article about what may be the medicinal qualities of magic mushrooms:

A study published last month in the Journal of the Royal Society Interface compared M.R.I.s of the brains of subjects injected with psilocybin [the psychoactive agent in magic mushrooms] with scans of their normal brain activity. The brains on psilocybin showed radically different connectivity patterns between cortical regions (the parts thought to play an important role in consciousness). The researchers mapped out these connections, revealing the activity of new neural networks between otherwise disconnected brain regions.

The researchers suspect that these unusual connections may be responsible for the synaesthetic experience trippers describe, of hearing colors, for example, and seeing sounds. The part of the brain that processes sound may be connecting to the part of the brain that processes sight. The study’s leader [said that] his team doubted that this psilocybin-induced connectivity lasted. They think they are seeing a temporary modification of the subject’s brain function.

The fact that under the influence of psilocybin the brain temporarily behaves in a new way may be medically significant in treating psychological disorders like depression. “When suffering depression, people get stuck in a spiral of negative thoughts and cannot get out of it,” [the study's leader] said. “One can imagine that breaking any pattern that prevents a ‘proper’ functioning of the brain can be helpful.” Think of it as tripping a breaker or rebooting your computer.

tt0120889 writes:

Beginning in the nineteen-fifties, psychedelics had been used to treat a wide variety of conditions, including alcoholism and end-of-life anxiety. The American Psychiatric Association held meetings centered on LSD. Some of the best minds in psychiatry had seriously studied these compounds in therapeutic models, with government funding.

Between 1953 and 1973, the federal government spent four million dollars to fund a hundred and sixteen studies of LSD, involving more than seventeen hundred subjects. Through the mid-nineteen-sixties, psilocybin and LSD were legal and remarkably easy to obtain. Sandoz, the Swiss chemical company, gave away large quantities of Delysid—LSD—to any researcher who requested it, in the hope that someone would discover a marketable application.

Now, forty years after the Nixon Administration effectively shut down most psychedelic research, the government is gingerly allowing a small number of scientists to resume working with these powerful and still somewhat mysterious molecules.

cafebabe writes:

The British Medical Journal provides an editorial from Professor David Healy, Head of Psychiatry at the Hergest psychiatry unit in Bangor in which it is stated:

When concerns emerged about tranquilliser dependence in the early 1980s, an attempt was made to supplant benzodiazepines with a serotonergic drug, buspirone, marketed as a non-dependence producing anxiolytic. This flopped. The lessons seemed to be that patients expected tranquillisers to have an immediate effect and doctors expected them to produce dependence. It was not possible to detoxify the tranquilliser brand.

Instead, drug companies marketed SSRIs for depression, even though they were weaker than older tricyclic antidepressants, and sold the idea that depression was the deeper illness behind the superficial manifestations of anxiety. The approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied a chemical imbalance. The tricyclics did not have a comparable narrative.

Serotonin myth

In the 1990s, no academic could sell a message about lowered serotonin. There was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew if SSRIs raised or lowered serotonin levels; they still don’t know. There was no evidence that treatment corrected anything.

[More...]

takyon writes:

The BBC reports on a small trial (12 patients) that used psilocybin to treat "moderate-to-severe, unipolar, treatment-resistant" depression:

A hallucinogenic chemical in magic mushrooms shows promise for people with untreatable depression, a short study on just 12 people hints. Eight patients were no longer depressed after the "mystical and spiritual" experience induced by the drug. The findings, in the Lancet Psychiatry [open, DOI: 10.1016/S2215-0366(16)30065-7], showed five of the patients were still depression-free after three months.

Experts cautiously welcomed the findings as "promising, but not completely compelling". There have now been calls for the drug to be tested in larger trials.

From the study:

Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Original Submission

Phoenix666 writes:

The clinical trials at N.Y.U.—a second one, using psilocybin to treat alcohol addiction, is now getting under way—are part of a renaissance of psychedelic research taking place at several universities in the United States, including Johns Hopkins, the Harbor-U.C.L.A. Medical Center, and the University of New Mexico, as well as at Imperial College, in London, and the University of Zurich. As the drug war subsides, scientists are eager to reconsider the therapeutic potential of these drugs, beginning with psilocybin. (Last month The Lancet, the United Kingdom's most prominent medical journal, published a guest editorial in support of such research.) The effects of psilocybin resemble those of LSD, but, as one researcher explained, "it carries none of the political and cultural baggage of those three letters." LSD is also stronger and longer-lasting in its effects, and is considered more likely to produce adverse reactions. Researchers are using or planning to use psilocybin not only to treat anxiety, addiction (to smoking and alcohol), and depression but also to study the neurobiology of mystical experience, which the drug, at high doses, can reliably occasion. Forty years after the Nixon Administration effectively shut down most psychedelic research, the government is gingerly allowing a small number of scientists to resume working with these powerful and still somewhat mysterious molecules.

As I chatted with Tony Bossis and Stephen Ross in the treatment room at N.Y.U., their excitement about the results was evident. According to Ross, cancer patients receiving just a single dose of psilocybin experienced immediate and dramatic reductions in anxiety and depression, improvements that were sustained for at least six months. The data are still being analyzed and have not yet been submitted to a journal for peer review, but the researchers expect to publish later this year.

The results taste orange.

takyon: Michael Pollan's article was published in 2015 (covered by us here) and is now featured in The Best American Nonrequired Reading 2016. Here is some fresher material:

Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use (DOI: 10.1016/j.cobeha.2016.10.009) (DX)

Psychedelics not linked to mental health problems or suicidal behavior: A population study (open, DOI: 10.1177/0269881114568039) (DX)

MDMA could be on the market legally by 2021:

In small studies around the country, a handful of researchers have been investigating how MDMA-assisted psychotherapy can help heal the psychological and emotional damage caused by sexual assault, war, violent crime, and other traumas. Now, federal regulators have approved the drug for use in large-scale clinical trials too—a move that could set the stage for making "ecstasy" legally available as a new medicine. The Phase III trials will involve at least 230 patients, and will be sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization that advocates for the medical use of various psychedelics, including MDMA (otherwise known as ecstasy or Molly or millennial aspirin). The organization funded early safety and efficacy trials of the drug in the past. And in one pilot study involving 19 PTSD patients, more than half experienced decreased symptoms for up to six years after receiving three doses of MDMA.

Original Submission

hubie writes:

President Trump will likely nominate Dr. Scott Gottlieb as head of the FDA. Though he is presently a resident fellow at the conservative American Enterprise Institute and a partner at a large venture capital fund, he used to be an FDA deputy commissioner known for advocating dramatic reforms in the process to approve new medical products.

According to his statements as well as comments to people familiar with his thinking on the FDA, Gottlieb intends to shoot for the rapid approval of complex generics, ushering in a wave of less expensive rivals to some of the biggest blockbusters on the market. He's also likely to spur the FDA to follow the course laid out by agency cancer czar Richard Pazdur in speeding new approvals, possibly setting up a special unit aimed at orphan drugs to hasten OKs with smaller, better designed clinical trials. Other potential reforms include the possible quick adoption of new devices that could be used to improve the kind of medtech Apple, Verily and others have been working on.

Gottlieb is viewed very favorably within the pharmaceutical industry as a regulatory reformer but not destroyer. If nominated, he will have been chosen over another high-profile name on the short list: Jim O'Neill.

The close associate of Peter Thiel, O'Neill famously suggested that drugs should be approved based on safety alone, letting consumers sort out what works. That left many fearing that Trump intended to toss out the regulatory framework for new drug approvals, raising fears that his idea of competition would allow de facto placebos to compete for market share.

Original Submission

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

takyon writes:

Ketamine could become an approved treatment for depression in the UK soon:

Ketamine has 'fast-acting benefits' for depression

Ketamine has "shown promise" in the rapid treatment of major depression and suicidal thoughts, a US study says. Ketamine has a reputation as a party drug but is licensed as an anaesthetic. The study found use of the drug via a nasal spray led to "significant" improvements in depressive symptoms in the first 24 hours. The Royal College of Psychiatrists said it was a "significant" study that brought the drug "a step closer to being prescribed on the NHS".

The report by researchers from Janssen Research and Development, a Johnson and Johnson company, and Yale School of Medicine, is the first study into ketamine as a treatment for depression that has been done by a drug company.

[...] The study found those using esketamine had a much greater improvement in depression symptoms at all points over the first four weeks of treatment. However, at 25 days the effects had levelled out. The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.

Also at Medical Daily.

Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study (DOI: 10.1176/appi.ajp.2018.17060720) (DX)

Can a Framework Be Established for the Safe Use of Ketamine? (DOI: 10.1176/appi.ajp.2018.18030290) (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
Studies Identify How Ketamine Can Reverse Symptoms of Depression
Over Years, Depression Changes the Brain, new Study Shows

Original Submission

MrPlow writes:

Submitted via IRC for AndyTheAbsurd

"Leon" is a young Brazilian man who has long struggled with depression. He keeps an anonymous blog, in Portuguese, where he describes the challenge of living with a mental illness that affects some 300 million people worldwide, according to the World Health Organization.

Leon is among the roughly 30 percent of those patients with treatment-resistant depression. Available antidepressant drugs like selective serotonin reuptake inhibitors do not alleviate his depressed mood, fatigue, anxiety, low self-esteem and suicidal thoughts.

A new study may offer hope for Leon and others like him.

Our team of Brazilian scientists has conducted the first randomized, placebo-controlled clinical trial of ayahuasca – a psychedelic drink made of Amazonian plants. The results, recently published in the journal Psychological Medicine, suggest that ayahuasca can work for hard-to-treat depression.

Source: Amazonian psychedelic may ease severe depression, new study shows

Original Submission

takyon writes:

Study shows how LSD interferes with brain's signalling

A group of volunteers who took a trip in the name of science have helped researchers uncover how LSD messes with activity in the brain to induce an altered state of consciousness.

Brain scans of individuals high on the drug revealed that the chemical allows parts of the cortex to become flooded with signals that are normally filtered out to prevent information overload.

The drug allowed more information to flow from the thalamus, a kind of neural gatekeeper, to a region called the posterior cingulate cortex, and it stemmed the flow of information to another part known as the temporal cortex. [...] The scientists wanted to test a hypothesis first put forward more than a decade ago. It states LSD causes the thalamus to stop filtering information it relays to other parts of the brain. It is the breakdown of this filter that gives rise to the weird effects the drug induces, or so the thinking goes.

Effective connectivity changes in LSD-induced altered states of consciousness in humans (open, DOI: 10.1073/pnas.1815129116) (DX)

Related: Research into Psychedelics, Shut Down for Decades, is Now Yielding Exciting Results
Research Into Psychedelics Continues
Lucy in the Sky With Protein: Key to LSD's Psychoactive Potency Possibly Found
From 'problem Child' to 'prodigy'? LSD Turns 75

Original Submission