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Past articles: 2015 • 2016

What's up, Soylenteers? I've got to write another one of these? #420TooMainstream.

Legalization Status

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Timeline of cannabis laws in the United States
Timeline of cannabis law

Since this time last year, Ohio, Florida, North Dakota, and Arkansas legalized medical cannabis, Illinois decriminalized it, and California, Nevada, Maine and Massachusetts legalized recreational cannabis. An attempt to legalize recreational cannabis in Arizona narrowly failed.

29 U.S. states and the District of Columbia have legalized cannabis for medical use, although restrictions vary widely from state to state.

Germany's medical cannabis law was approved in January and came into effect in March. Poland has also legalized medical cannabis, and Georgia's Supreme Court has ruled that imprisonment for possession of small amounts of cannabis is unconstitutional.

Recently: West Virginia on Course for Medical Marijuana

🍁 Cannada: Not So Fast 🍁

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Last week, Canadian Prime Minister Justin Trudeau unveiled (archive) legislation (archive) that would make Canada the first major Western country to legalize recreational cannabis (the only country to legalize it to date is Uruguay, although implementation has taken years), dealing a serious blow to the crumbling United Nations Single Convention on Narcotic Drugs. However, the Liberal Party of Canada intends to wait more than a year to act on its campaign promise, during which time Canadians can still face prosecution for possession of the drug:

True to form, this government has written down a series of talking points, in this case, trying to make it sound like it's cracking down on pot rather than legalizing it. And Justin Trudeau's ministers are sticking to the messaging from party central like a child reciting Dr. Seuss.

Not once in that As It Happens interview did [Justice Minister Jody] Wilson-Raybould explain why the government intends to keep on criminalizing Canadians so unfairly (see the Liberal party's website statement) for another year. Instead, literally every second time she opened her mouth, she re-spouted the line about "strictly regulating and restricting access." Off asked eight questions. Four times, Wilson-Raybould robotically reverted to the same phrase.

Meanwhile, Public Safety Minister Ralph Goodale, a parliamentary lifer who mastered the art of repetitive dronetalk sometime back in the last millennium, was out peddling more or less the same line, but with an added warning: Not only will the government continue to criminalize Canadians for what it considers a trifling offence, enforcement will be vigorous. "Existing laws prohibiting possession and use of cannabis remain in place, and they need to be respected," Goodale declared. "This must be an orderly transition. It is not a free-for-all." Why the government cannot simply decide to invoke prosecutorial and police discretion, and cease enforcing the cannabis laws it considers unjust, was not explained. Why that would necessarily be a "free for all" also went unexplained.

The Liberal Party of Canada has taken pains to remind everyone that the Conservative Party will "do everything they can to stop real change and protect a failed status quo". Unfortunately, they did not get the memo that "marijuana" is a term with racist origins.

Make like a tree and legalize it, Cannadia... Cannibinoidia.

President Trump and Attorney General Jeff Sessions

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Backtrack to April 20th, 2016. Bernie Sanders still seemingly had a shot at becoming the President of the United States. Sanders, as well as Hillary Clinton (though begrudgingly), supported decriminalization of cannabis, medical use, and the continuation of states making decisions about recreational use. The #2 Republican candidate Ted Cruz also had a "let the states sort it out" stance.

One contender stood out, and he went on to become the @POTUS to #MAGA. The widely predicted "third term" was prevented, and that outcome may greatly affect a burgeoning semi-legal cannabis industry. One recent casualty are Amsterdam-style "cannabis clubs" (think: brewpubs). Colorado's legislature has backed off on a bill that would have allowed on-site consumption of cannabis at dispensaries due to the uncertain future of federal enforcement of cannabis prohibition.

Trump's position on cannabis has been ill-defined, although he supports medical use and has indicated that states should handle the issue. But the same can't be said of his Attorney General, former Senator Jeff Sessions. Here are some quotes about the drug from Mr. Sessions:

I thought those guys were OK until I learned they smoked pot. [Source. Context: Sessions later testified that the comment was a joke.]

We need grown-ups in charge in Washington to say marijuana is not the kind of thing that ought to be legalized, it ought not to be minimized, that it's in fact a very real danger.

I think one of [President Obama's] great failures, it's obvious to me, is his lax treatment in comments on marijuana... It reverses 20 years almost of hostility to drugs that began really when Nancy Reagan started 'Just Say No.

You can't have the President of the United States of America talking about marijuana like it is no different than taking a drink... It is different... It is already causing a disturbance in the states that have made it legal.

Good people don't smoke marijuana.

Cannabis advocates are becoming increasingly paranoid about the federal government's stance towards the states (and a certain District) that have legalized cannabis. And this is following an Obama administration that was criticized for conducting raids in states with legalization. It is too early to tell how the Trump administration will choose to deal with cannabis, but there are signs that harsher policies and greater enforcement could be coming:

On Wednesday, [April 5th,] Jeff Sessions directed Justice Department lawyers to evaluate marijuana enforcement policy and send him recommendations. And some state officials are worried. This week the governors of Alaska, Colorado, Oregon and Washington wrote the attorney general. They asked Sessions and the new Treasury secretary to consult with them before making any changes to regulations or enforcement.

At the White House, press secretary Sean Spicer said recently that the president is sympathetic to people who use marijuana for medical reasons. He pointed out that Congress has acted to bar the Justice Department from using federal money to interfere in state medical cannabis programs. But Spicer took a harsh view of recreational marijuana. "When you see something like the opioid addiction crisis blossoming in so many states around this country, the last thing we need to be doing is encouraging people. There is still a federal law we need to abide by," Spicer said.

Really, Spicer? Recreational cannabis use shouldn't be encouraged during an opioid addiction crisis? Read on.

Politics nexus unavailable for comment.

The Opioid Crisis Drags On _{(it's relevant)}

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Heroin use has become more dangerous as dealers have increasingly added other substances that massively increase potency without affecting the size of a dose significantly. Carfentanil, which is used as an elephant tranquilizer, has led to hundreds of deaths over very short timespans. It is impossible for the average user to predict the potency and potential danger of street heroin. While there have been international responses to these compounds, new chemical analogues are being created all the time:

Chinese labs producing the synthetic opiates play hide-and-seek with authorities. On their websites, they list fake addresses in derelict shopping centers or shuttered factories, and use third-party sales agents to conduct transactions that are hard to trace. The drugs themselves are easy to find with a Google search and to buy with a few mouse clicks. A recent check found more than a dozen Chinese sites advertising fentanyl, carfentanil, and other derivatives, often labeled as "research chemicals," for sale through direct mail shipments to the United States. On one website, carfentanil goes for $361 for 50 grams: tens of thousands of lethal doses.

The cat-and-mouse game extends to chemistry, as the makers tinker with fentanyl itself. Minor modifications like adding an oxygen atom or shifting a methyl group can be enough to create whole new entities that are no longer on the list of sanctioned compounds. Carfentanil itself was, until recently, unregulated in China.

2016 saw the addition of kratom to Schedule I of the Controlled Substances Act in the U.S. Advocates for the tree leaf drug, which was formerly classified as a supplement, believe that its painkiller effects and low risk factors make it a useful replacement for the oft-deadly opioids that millions of Americans are addicted to. Kratom users have treated their pain and opioid withdrawal symptoms using the formerly "legal high". The DEA has refused to acknowledge this application and points out the "skyrocketing" number of calls to the Poison Control Center regarding kratom in recent years. One skeptic of kratom, Dr. Josh Bloom of the American Council on Science and Health, has looked at the same evidence and concluded that the trail of bodies left by substances like fentanyl and the scarce number of deaths (perhaps wrongly) attributed to kratom make it clear that the substance is the better "poison". He also notes that:

The number of calls to poison control centers is not reliable for determining how many poisonings actually occurred. It is a crude approximation at best.

Much like kratom, medical cannabis has been touted as a solution to the opioid crisis. States with legalized medical cannabis have seen a reduction in reported instances of opioid dependence [DOI: 10.1016/j.drugalcdep.2017.01.006] [DX] So it is puzzling that White House Press Secretary Sean Spicer would use opioids as a bludgeon against cannabis legalization while AG Sessions expresses astonishment over the suggestion of using cannabis as a "cure" for the opioid crisis.

Bonus: Here's a video (2m14s) of a woman getting administered Narcan/naloxone. Here's an alternate video (2m39s) in which a man who overdosed on heroin is able to sit up in about a minute after being administered naloxone.

⚚ The Slow March for Science ⚕

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While the Drug Enforcement Agency has refused to reclassify cannabis from its current Schedule I status, citing the supposedly rigorous conclusions reached by the Food and Drug Administration, it will allow more than one institution to grow cannabis for research purposes, ending the monopoly held by the University of Mississippi. However, the Schedule I status of cannabis remains an impediment to further research:

[...] DEA's decision not to reschedule marijuana presents a Catch-22. By ruling that there is not enough evidence of "currently accepted medical use"—a key distinction between the highly restrictive Schedule I classification and the less restrictive Schedule II—the administration essentially makes it harder to gather such evidence.

"They're setting a standard that can't be met," says David Bradford, a health economist at the University of Georgia, Athens. "That level of proof is never going to be forthcoming in the current environment because it requires doing a really extensive clinical trial series, and given that a pharmaceutical company can't patent whole plant marijuana, it's in no company's interest to do that."

Schedule I status presents obstacles for clinical researchers because of restrictions on how the drugs must be stored and handled, Bradford says. Perhaps more significant, that listing may evoke skittishness at funding agencies and on the institutional review boards that must sign off on research involving human subjects.

Researchers have disparaged the quality and potency as well as the appearance and odor of the University of Mississippi's cannabis products:

"It doesn't resemble cannabis. It doesn't smell like cannabis," Sisley told PBS NewsHour last week.

Jake Browne, a cannabis critic for the Denver Post's Cannabist marijuana news site, agrees. "That is, flat out, not a usable form of cannabis," he said. Browne should know: He's reviewed dozens of strains professionally and is running a sophisticated marijuana growing competition called the Grow-Off.

"In two decades of smoking weed, I've never seen anything that looks like that," Browne said. "People typically smoke the flower of the plant, but here you can clearly see stems and leaves in there as well, parts that should be discarded. Inhaling that would be like eating an apple, including the seeds inside it and the branch it grew on."

Research on cannabinoids and psychedelics is proceeding, slowly. One study published yesterday (74 years after the first LSD trip) came to an astounding conclusion: Psychedelics can induce a "heightened state of consciousness":

Healthy volunteers who received LSD, ketamine or psilocybin, a compound found in magic mushrooms, were found to have more random brain activity than normal while under the influence, according to a study into the effects of the drugs. The shift in brain activity accompanied a host of peculiar sensations that the participants said ranged from floating and finding inner peace, to distortions in time and a conviction that the self was disintegrating.

[...] What we find is that under each of these psychedelic compounds, this specific measure of global conscious level goes up, so it moves in the other direction. The neural activity becomes more unpredictable," said Anil Seth, a professor of neuroscience at the University of Sussex. "Until now, we've only ever seen decreases compared to the baseline of the normal waking state."

Inconceivable!

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin (open, DOI: 10.1038/srep46421) (DX)

♯ Ending on High Notes ♯

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And now to scrape the bottom of the barrel:

• Americans Don't Care If Their Parents Know They Smoke Weed, Survey Says
• California Today: At Newspapers, Covering Pot Like Wine (archive)
• Nation's first public needle vending machine for drug users debuts in Las Vegas
• GRiZ Won the Celebrity Weed Game Without Selling Out
• Secret A.T.F. Account Paid for $21,000 Nascar Suite and Las Vegas Trip (archive)
• Legal Marijuana Ends at Airport Security, Even if It's Rarely Stopped (archive)
• Anti-Heroin Video From a Florida Sheriff Appalls Critics but Impresses Constituents (archive)

Vape Naysh, y'all! VΛ

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:

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

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:

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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