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Published: 23 June 2022

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The importance of non-targeted testing to keep pace with a rapidly evolving synthetic opioid market.

The synthetic opioid market…is constantly evolving. Once a new substance is identified, it may only be prevalent for three to six months before it’s replaced by something new and yet to be identified by forensic laboratories.

For example, over one weekend in July 2018, Philadelphia-area hospitals experienced a surge of more than 100 patients with suspected opioid overdoses. Following the administration of naloxone, patients would become combative – an unusual reaction for an opioid overdose.

To help local public health and public safety agencies identify what was causing this troubling trend, the NPS Discovery drug early warning system at the Center for Forensic Science Research and Education (CFSRE) acquired a sample of “Santa Muerte,” the drug linked to the large number of overdoses. Advanced mass spectrometry analysis found within the sample a combination of fentanyl, heroin, and a synthetic cannabinoid – a combination not often seen in the region. Given the unique side effects that overdose patients were experiencing, it was thought this may be a synthetic drug combination worth tracking closely.

However, substances containing fentanyl and synthetic cannabinoids did not last long and were only a fraction of the whole drug supply in the region. After about six to nine months following the July overdoses involving “Santa Muerte,” these substances were largely replaced by new synthetic drug products, primarily fentanyl cut with xylazine.

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Published: 22 April 2022

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 (This is where the term ‘overdose’ is legitimate. Any drug not legally prescribed cannot be ‘overdosed’ on. Taking these drugs is an act of self-poisoning.)

In general, barbiturates can be thought of as so-called brain relaxers. Alcohol is also a brain relaxer. The effects of barbiturates and alcohol are very similar, and when combined can be lethal. Pain medicines, sleeping pills, and antihistamines also cause symptoms similar to those of barbiturates.

People who abuse barbiturates use them to obtain a “high,” which is described as being similar to alcohol intoxication, or to counteract the effects of stimulant drugs.

• In small doses, the person who abuses barbiturates feels drowsy, disinhibited, and intoxicated.
• In higher doses, the user staggers as if drunk, develops slurred speech, and is confused.
• At even higher doses, the person is unable to be aroused (coma) and may stop breathing. Death is possible.

It is important to note that the difference between the dose causing drowsiness and one causing death may be small. In the medical profession, this difference is called a narrow therapeutic index, which is the ratio of a drug's toxic dose to its therapeutically desirable dose. This is the reason why barbiturates are dangerous. It is also why barbiturates are not often prescribed today.

Symptoms of withdrawal

Symptoms of withdrawal or abstinence include tremors, difficulty sleeping, and agitation. These symptoms can become worse, resulting in life-threatening symptoms, including hallucinations, high temperature, and seizures.

Barbiturate Names

Generic Name	Street Name
Amobarbital	Downers, blue heavens, blue velvet, blue devils
Pentobarbital	Nembies, yellow jackets, abbots, Mexican yellows
Phenobarbital	Purple hearts, goof balls
Secobarbital	Reds, red birds, red devils, lilly, F-40s, pinks, pink ladies, seggy
Tuinal	Rainbows, reds and blues, tooies, double trouble, gorilla pills, F-66s

 

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Published: 20 April 2022

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Everything you need to know about psychedelics and mental illness

The science of psychedelics is everywhere – but we should treat it with serious scepticism

Research is me-search

It’s the same for psychedelics. This is just an anecdotal account, but there’s an interview with the psychedelics researcher Manoj Doss, who says that he “only know[s] one psychedelic researcher who’s never done psychedelics”, and notes (in an encouragingly self-critical way) that this is a conflict of interest. He’s right! Just as you’d feel extra-sceptical if all the research showing that pork is unhealthy was written by Muslims who’d already decided for religious reasons not to eat pork, you should be worried about the sheer number of studies by psychedelic researchers who are themselves aficionados of the drugs.

(You might wonder if they’re into psychedelics precisely because the research shows such impressive benefits, switching around cause and effect. But as we’ll see below, that evidence doesn’t exist yet. That particular horse is coming way after the cart).

This isn’t just the view of one researcher. Reading the literature on psychedelics, you continually encounter concerns about the “over-exuberance” of some scientific advocates of the drugs. There are also discussions of conflicts of the financial kind: we know that there are a lot of psychedelic-drug companies springing up all over the place, and we know they pay consultation fees to psychedelics researchers because these are disclosed in research papers (see e.g. the section near the end of this paper, which we’ll discuss in more detail below).

There are all kinds of problems—from outright publication bias to more subtle “questionable research practices”—that can creep in when researchers have a conscious or unconscious bias in one particular direction. It doesn’t take much to push the statistical results in a field towards unreliability and false-positivedom. One 2020 paper suggests methods, many of them from Open Science, that psychedelics researchers should consider using to try and reduce these biases. I doubt many papers on psychedelics use them already.

Yikes. He even lists the papers he’s reviewed on his website, so we can have some idea of which ones we might wish to be extra-sceptical about (Sessa has also been criticised on social media for a graph he made that, without clearly informing the reader, combines the results of two studies as if they were one).

But even if the specific scientist running a psychedelics trial isn’t themselves a “psychonaut”, there’s still the more mundane kind of bias, a bias that almost all scientists have: towards finding positive, cool, encouraging, exciting results (as opposed to null, shrug-inducing, disappointing, boring ones).

Here’s an example – and it happens to concern one of the most important psychedelic trials yet performed. In April 2021 the psychedelics researcher Robin Carhart-Harris (now at UC San Francisco; back then at Imperial College London where he still has an affiliation) wrote an article in The Guardian entitled “Psychedelics are transforming the way we understand depression and its treatment”. It was part of the publicity for a new randomised controlled trial (RCT) he’d co-authored, which had just been published in the world’s top medical journal, the New England Journal of Medicine. 

The psychedelic in question was psilocybin, the main active ingredient from magic mushrooms. Before we get to the 2021 trial, it’s worth backtracking slightly to look at what evidence on psilocybin and depression existed beforehand. Here are the trials:

• A “pilot study” from 2011 of psilocybin in advanced-stage cancer, including 12 patients, which found no statistically significant results on depression measures;
• A “feasibility study” in 2016. This had 12 patients and no control group, so can only really be used to, as the authors put it, “motivate further trials”;
• A double-blind RCT from 2016 in 51 patients with life-threatening cancer which found that psilocybin had very positive effects on mood that lasted for up to 6 months;
• Another double-blind RCT, also from 2016, in 29 patients with life-threatening cancer that again found beneficial effects on depression symptoms over 6 months;
• A final RCT from 2020, in 27 patients with major depression (of whom 24 actually finished the study) that found “large, rapid, and sustained antidepressant effects” over 8 weeks.

So, pretty tiny studies; some of them in very specific populations. The 2021 NEJM study was the first—and remains the only—study to compare psilocybin to an established, commonly-prescribed antidepressant drug – in this case the SSRI drug escitalopram. As with all the above, it was very small (59 people), but the comparison it looked at was a big deal. That’s because it’s not enough to show the psychedelic drug is better than placebo – after all, we already have treatments for depression. We need to know how it compares to those pre-existing treatments. 

The harm

Anyone who’s interested in psychedelics and mental illness should listen to the New York Magazine podcast series “Cover Story: Power Trip”. Among several other stories, the podcast reports investigative work around clinical trials of MDMA (ecstasy) therapy for Post-Traumatic Stress Disorder, run by an organisation called the Multidisciplinary Association for Psychedelic Studies, or MAPS. 

The crucial thing here is that it’s not just MDMA: it’s MDMA plus therapy (by the way, MDMA is only sometimes classified as a “psychedelic drug”, depending on who you talk to; but MDMA therapy is almost always classed as “psychedelic therapy”, since some of the effects overlap with drugs that are definitely psychedelics). And as described in the podcast, that therapy can get very weird.

The danger is that psychedelics can make users pliant and suggestible, leading to obvious dangers if a patient is left in the hands of anyone with less-than-noble intentions (there’s a reason so many cults over the years have used psychedelics–including MDMA–to help keep their members compliant). The podcast relates the story of Meaghan Buisson, a PTSD sufferer who underwent intense MDMA therapy with two therapists in a MAPS trial. The therapy was filmed in its entirety – and it’s grim. If you can stomach it, you should watch the video, which was uncovered in the NY Magazine investigation. But if you can’t, here’s a description:

“The therapists, Richard Yensen and Donna Dryer, guide Buisson through three long sessions with follow-ups in between. They give her the drugs and, as she recalls, coax her to relive her sexual assaults. They ask her to spread her legs, and at several points, they lie on top of her and pin her down, sometimes holding her wrists. The two then comfort Buisson by stroking her face and climbing into bed with her. There are periods in the video when Yensen is in constant physical contact with her.”

At other points, Yensen and Dryer blindfold Buisson, gag her with a towel, and ignore her as she screams at them to get off her. Yensen also “admitted to having sex with Buisson after the experimental sessions ended but while she was still enrolled in the clinical trial”. This is a far cry from the friendly, comfortable, hand-holding sessions you see in photos from other MDMA (and psilocybin) therapy sessions. MAPS has said that Yensen and Dryer did not stick to their therapy protocol and that they won’t be working with them again. 

Rick Doblin, Executive Director of MAPS—who, incidentally, has argued that psychedelic therapy could have prevented the War in Iraq and will produce a “spiritualised humanity” by 2070, and who encourages his employees to smoke marijuana while doing certain tasks at work—was asked about the potential for sexual abuse by therapists in a recent Q&A session. He had this to say:

“We’re trying to make it so that the source of the healing is inside the patient… that will hopefully make them stronger when there is, um, y’know, pressure perhaps from therapists to, y’know, engage in a sexual relationship.”

Perhaps not ideal.

Hopefully this article has convinced you that there are a lot of red flags in the psychedelic scientific literature, and that you should perhaps set your standards higher than usual when reading about this area. To summarise everything I’ve said, we should bear the following in mind:

1. The reasons people are so excited about psychedelics for mental illness are not necessarily related to how much evidence there is for the treatment;
2. The conflicts of interest in the psychedelic research field go very deep. It’s completely plausible that these conflicts help bias the studies toward reporting more positive results than are actually true;
3. The discussion of psychedelic research in the media often bears only a passing resemblance to what’s actually in the trials – or at least it sounds a lot more certain and optimistic than is warranted;
4. Even the best-quality trials are flawed in important ways because—mainly due to problems of expectations and blinding—this is an incredibly difficult thing to study;
5. We shouldn’t allow our excitement for psychedelic drug trials to run roughshod over safety concerns, and we shouldn’t be so desperate for a breakthrough mental health treatment that we roll out these drugs before we’ve tested whether they work in high-quality, smartly-designed studies.

We’re nowhere near reaching peak interest in psychedelics. With all the scientific research programmes, and all the companies vying with each other to create the bestselling psychedelic product, maybe there’s a chance some of the above uncertainties will be ironed out in the coming years. 

On the other hand, researchers might just continue doing low-quality, hard-to-interpret studies that back up their pre-existing beliefs, giving false hope to sufferers of mental illness. You don’t exactly have to be tripping to imagine that.

By Stuart Ritchie 15^th April 2022

 For complete article

Further Reading

• The Ethical Implications of Psychedelics
• Blinding and expectancy confounds in psychedelic randomized controlled trials: Expert Review of Clinical Pharmacology: Vol 14, No 9
• The problem at the heart of modern psychedelic clinical research
• Taking the ‘Novel’ Out of New Psychoactive Substances

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Published: 04 April 2022

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Many Teens Overdose on Meds Prescribed for ADHD, Anxiety. (Not a Low Risk Option for the issue – What else is in Play?)

14/3/2022 (HealthDay News) -- Taken correctly, prescription drugs used to treat attention-deficit/hyperactivity disorder (ADHD) can help teens and young adults navigate their condition, but a new study finds many are dying from overdosing on these medications.

In 2019, benzodiazepines like Xanax and stimulants like Adderall accounted for more than 700 and 900 overdose deaths, respectively, in the United States, according to the U.S. Centers for Disease Control and Prevention.

"In recent years, there has been considerable attention devoted to risks of addiction associated with diverted or illicitly obtained benzodiazepines and stimulants," said senior researcher Dr. Mark Olfson. He is a professor of psychiatry, medicine and law at Columbia University Irving Medical Center in New York City.

"The new study serves as a reminder that prescription benzodiazepines and stimulants also pose overdose risks to the patients who are prescribed them… Sadly, many of the overdose deaths among teens and young adults who had prescriptions for these drugs are intentional suicides,” Olfson said.

The upshot of the finding? Doctors and parents need to be careful about prescribing and having their kids take these drugs.

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(also see The Politics of ADHD | Psychology Today)