Wednesday, December 7, 2016

Sasha Shulgin, godfather of MDMA

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Alexander "Sasha" Shulgin, the "godfather of MDMA," in his basement laboratory

Shulgin Research

"Alexander T. Shulgin (June 17, 1925–June 2, 2014), known to friends and admirers as “Sasha”, was a biochemist and pharmacologist best known for his synthesis, creation, and personal bioassay of hundreds of novel psychoactive compounds.
Sasha was born in Berkeley, California. He first began his study of organic chemistry at Harvard University. In 1943 at the age of 18, Sasha left Harvard to join the U.S. Navy. After serving in World War II, Sasha returned to Berkeley to earn his PhD in biochemistry from the University of California, Berkeley, and complete post-doctoral work in the fields of psychiatry and pharmacology at University of California, San Francisco. After a short period working at Bio-Rad Laboratories as a research director, he joined Dow Chemical Company as a senior research chemist.
While at Dow, Sasha’s interest in psychopharmacology was inspired by a profound experience with mescaline:
“I first explored mescaline in the late ’50s… Three-hundred-fifty to 400 milligrams. I learned there was a great deal inside me.”
— Alexander Shulgin, Los Angeles Times (1995)
After developing the first biodegradable pesticide, Zectran, for Dow, resulting in a highly profitable patent, Sasha was given freedom to pursue research of his own design. He began to research new drugs and their activity; over the years, he published his findings in the Journal of Analytic Toxicology, the Journal of Medicinal Chemistry, the Journal of Organic Chemistry, the Journal of Pharmacy and Pharmacology,  the Journal of Psychedelic DrugsNature, Psychopharmacology Communications, as well as other journals and numerous books.
Sasha first tested his new creations on himself, starting with minuscule doses and cautiously ramping them up until some manner of effect was noticed. Beginning in 1960, following Sasha’s initial bioassays, a small group of friends began to join in regular group testing sessions, meticulously recording their results. The Shulgin Rating Scale was developed to quantify the experiences and effects of the substances. Working primarily with phenethylamines and tryptamines, a body of objective and subjective reports was created for hundreds of psychoactive chemical compounds.
After a rash of bad press about street drug abuse in the 1960s, Dow became concerned with the possibility of an adverse public reaction to the nature of Sasha’s work, and requested that he cease to publish as an employee of the company. Sasha subsequently ended his career with Dow in the mid-1960s to pursue independent research and employment as a consultant. He began teaching classes in local universities and at the San Francisco General Hospital.
In 1976, Sasha was alerted to the potential for MDMA by a bioassay report from a graduate student at San Francisco State University in a medicinal chemistry group he advised. MDMA had been previously synthesized and patented in 1912 by Merck, but was never fully explored within humans. Sasha went on to develop a new synthesis method, and later that year he introduced the chemical to Leo Zeff, a psychologist from Oakland, California. Zeff used small doses of the substance in his practice as an aid to talk therapy, and he personally introduced it to hundreds of psychologists across the nation."

Alexander Shulgin at Dow Chemical

Tuesday, December 6, 2016

The Agony and the Ecstasy: MDMA-augmented psychotherapy for PTSD

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Say what you will about the New York Times -- their reporters know how to write a lede.

"CHARLESTON, S.C. — After three tours in Iraq and Afghanistan, C. J. Hardin wound up hiding from the world in a backwoods cabin in North Carolina. Divorced, alcoholic and at times suicidal, he had tried almost all the accepted treatments for post-traumatic stress disorder: psychotherapy, group therapy and nearly a dozen different medications.
“Nothing worked for me, so I put aside the idea that I could get better,” said Mr. Hardin, 37. “I just pretty much became a hermit in my cabin and never went out.”
Then, in 2013, he joined a small drug trial testing whether PTSD could be treated with MDMA, the illegal party drug better known as Ecstasy.
“It changed my life,” he said in a recent interview in the bright, airy living room of the suburban ranch house here, where he now lives while going to college and working as an airplane mechanic. “It allowed me to see my trauma without fear or hesitation and finally process things and move forward.” 
Based on promising results like Mr. Hardin’s, the Food and Drug Administration gave permission Tuesday for large-scale, Phase 3 clinical trials of the drug — a final step before the possible approval of Ecstasy as a prescription drug.
If successful, the trials could turn an illicit street substance into a potent treatment for PTSD."


Monday, December 5, 2016

Psilocybin reduces death anxiety in cancer patients?

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What are you hippies up to now? There are some problems with this study: 1) It calls itself a randomized, double-blind clinical trial, but the control arm of the study was administered a homeopathic dose of psilocybin (i.e., an inactive placebo). If you want to show that your intervention does something worthwhile, please put it up against a real intervention. 2) As for the "double-blind," when asked to guess the dose (10 = max), the "monitors" rated the high-dose patients as 7.0 (mean) versus 1.7 for the low-dose -- meaning they could clearly tell. 3) Also, something really funky happened with the LAP-R Death Acceptance scores (measuring death anxiety). There was significant improvement in the high-dose group 5-weeks after the session, but then at 10-weeks the low-dose/placebo group caught up to them for some reason -- 10 weeks after the session there were no significant differences between the high-dose and placebo groups on any measure (see Table 4 in the original study). So, the headlines should read: "Psilocybin treatment accelerates the natural reduction of death anxiety in cancer patients by 5 weeks."

If you want to reduce your death anxiety, may I humbly suggest Plato's Phaedo, Marcus Aurelius, Spinoza, and/or the New Testament.

NY Times
"On a summer morning in 2013, Octavian Mihai entered a softly lit room furnished with a small statue of Buddha, a box of tissues and a single red rose. From an earthenware chalice, he swallowed a capsule of psilocybin, an ingredient found in hallucinogenic mushrooms.
Then he put on an eye mask and headphones and lay down on a couch. Soon, images flew by like shooting stars: a spinning world that looked like a blue-green chessboard; himself on a stretcher in front of a hospital; his parents, gazing at him with aching sadness as he reached out to them, suffused with childlike love.
Psilocybin has been illegal in the United States for more than 40 years. But Mr. Mihai, who had just finished treatment for Stage 3 Hodgkin’s lymphoma, was participating in a study looking at whether the drug can reduce anxiety and depression in cancer patients. Throughout that eight-hour session, a psychiatrist and a social worker from NYU Langone Medical Center stayed by his side.
Published Thursday, the results from that study, and a similar small, controlled trial, were striking. About 80 percent of cancer patients showed clinically significant reductions in both psychological disorders, a response sustained some seven months after the single dose. Side effects were minimal.
In both trials, the intensity of the mystical experience described by patients correlated with the degree to which their depression and anxiety decreased."

Here are their data. See those significant differences between the active and control groups at Post 1 (5-weeks after session)? They are marked with an asterisk, indicating their statistical significance. Note how the significance disappears by 10-weeks. Again, very curiously, the placebo group improved between weeks 5 and 10; the treatment group didn't return to baseline. So, something's going on, and it's good -- but it ain't the psilocybin that's doing it.

Sunday, December 4, 2016

Gretel in Darkness -- Louise Glück (b. 1943)

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This might be my new favorite poem.

This is the world we wanted.
All who would have seen us dead
are dead. I hear the witch's cry
break in the moonlight through a sheet
of sugar: God rewards.
Her tongue shrivels into gas . . .

Now, far from women's arms
and memory of women, in our father's hut
we sleep, are never hungry.
Why do I not forget?
My father bars the door, bars harm
from this house, and it is years.

No one remembers. Even you, my brother,
summer afternoons you look at me as though
you meant to leave,
as though it never happened.
But I killed for you. I see armed firs,
the spires of that gleaming kiln--

Nights I turn to you to hold me
but you are not there.
Am I alone? Spies
hiss in the stillness, Hansel,
we are there still and it is real, real,
that black forest and the fire in earnest.                         

Saturday, December 3, 2016

Baby Please Don't Go -- Them, ft. Van Morrison (1965)

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Baby, please don't go
Baby, please don't go
Baby, please don't go, down to New Orleans
You know I love you so

Before I be your dog
Before I be your dog
Before I be your dog
I get you way'd out here, and let you walk alone

Turn your lamp down low
Turn your lamp down low
Turn your lamp down low
I beg you all night long, baby, please don't go

You brought me way down here
You brought me way down here
You brought me way down here
'bout to Rolling Forks, you treat me like a dog

Baby, please don't go
Baby, please don't go
Baby, please don't go, back the New Orleans
I beg you all night long

Before I be your dog
Before I be your dog
Before I be your dog
I get you way'd out here, and let you walk alone

You know your man down gone
You know your man down gone
You know your man down gone
To the country farm, with all the shackles on

Friday, December 2, 2016

Alternatives to Suicide in the Netherlands: Euthanasia

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Independent (UK)
"More than 5,500 people ended their life using Holland’s euthanasia laws last year. One of those who died was a sex abuse victim who suffered severe anorexia, chronic depression and hallucinations.
Fiona Bruce, a Conservative MP, told the Daily Mail news of Mr Landedijk's death was "deeply concerning and yet another reason why assisted suicide and euthanasia must never be introduced into the UK".
“What someone suffering from alcoholism needs is support and treatment to get better from their addiction – which can be provided – not to be euthanised," she added.
“It is once again a troubling sign of how legalised euthanasia undermines in other countries the treatment and help the most vulnerable should receive.”
Responding to Mrs Bruce, Marcel Langedijk told the Independent: "You can close your eyes to it and keep telling yourself everyone is curable but the fact remains, not everyone is.
"My brother suffered from depression and anxiety and tried to 'cure' it with alcohol. He's from a normal family, he did not want this to happen. He did not take an easy way out. Just a humane one.
"If that's troubling for Mrs Bruce that's a pity. I am just glad my brother did not have to jump in front of a train or live a few more years in agony before dying of his abuse.
"Alcoholism and depression are illnesses, just like cancer. People who suffer from it need a humane way out.
"It's not like we go around killing people in Holland. It took my brother a year and a half and many struggles to get it done.""

Thursday, December 1, 2016

"We shall never surrender" -- Winston Churchill

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Spitfires, 1940

We Shall Fight on the Beaches

"I have, myself, full confidence that if all do their duty, if nothing is neglected, and if the best arrangements are made, as they are being made, we shall prove ourselves once again able to defend our Island home, to ride out the storm of war, and to outlive the menace of tyranny, if necessary for years, if necessary alone. At any rate, that is what we are going to try to do. That is the resolve of His Majesty's Government-every man of them. That is the will of Parliament and the nation. The British Empire and the French Republic, linked together in their cause and in their need, will defend to the death their native soil, aiding each other like good comrades to the utmost of their strength. Even though large tracts of Europe and many old and famous States have fallen or may fall into the grip of the Gestapo and all the odious apparatus of Nazi rule, we shall not flag or fail. We shall go on to the end, we shall fight in France, we shall fight on the seas and oceans, we shall fight with growing confidence and growing strength in the air, we shall defend our Island, whatever the cost may be, we shall fight on the beaches, we shall fight on the landing grounds, we shall fight in the fields and in the streets, we shall fight in the hills; we shall never surrender, and even if, which I do not for a moment believe, this Island or a large part of it were subjugated and starving, then our Empire beyond the seas, armed and guarded by the British Fleet, would carry on the struggle, until, in God's good time, the New World, with all its power and might, steps forth to the rescue and the liberation of the old."