Metamorphosis

Warning: rare self-indulgent post.

Blogging has been and will be light over the next few days while we are packing up things around here to move to our next, more permanent home.

In the meantime, you may have noticed here and on Twitter that part of my big news is that I will begin writing under my PharmMom-given name.

My dilemma has been that I have two Twitter accounts. @AbelPharmboy has been the one I use for all blog-related stuff as well as any other gems of my mind that can fit into 140 characters.  Thanks to you, I have 1,600 followers at that account. However, I also have a real name Twitter account that I used for my now-fledgling-and-almost-nonexistent music career and local banter with folks in the Durham-Chapel Hill area. That one only had 200 followers until I began announcing my metamorphosis.

With the pending blog move and melding of my IRL and online identities, one of my mentors, Twitter follower, writer, editor, and Johns Hopkins journalism professor, Mary Knudson, asked what I was going to do regarding the two avatars I use for each Twitter account.

One of my dear friends was enthusiastic about me coming up with a new avatar for the real name account but I’ve been worried about losing old followers who might not recognize the real name avatar.

But coming to the rescue from across the pond is my devoted reader and neuropharmacology enthusiast, Synchronium – world-famous for showing not one but both nipples in the British press.

Here is my metamorphosis:

Follow me now @davidkroll on Twitter.

More news on our move as it becomes available.

From Mind Hacks: Illegal drugs found in legal highs sold in the UK

I’ve been kind of tied up with work things this week so my apologies for lack of original content. But I just had to share this with you because it was so reminiscent of the herbal adulteration story I brought you just a few days ago.

Many times when I post something on drugs that affect the central nervous system, I’ll get a tweet from Dr Vaughan Bell at Mind Hacks pointing me to his coverage on the same topic a few weeks ago. This time, he shares with us a report where dietary supplements sold in England have been found to contain newly-illegal psychoactives and related compounds.

For example, before the ban, a legal pill sold as ‘Doves Original’ was advertised as containing a blend of amino acids and ketones but actually contained the psychedelic drugs mephedrone and butylone. Both were completely legal but were simply not mentioned by the manufacturers.

Interestingly, after the ban, it seems that several companies just changed their packaging without changing their ingredients.

Out of the six products tested, all advertised as being legal, five included recently banned substances – including mephedrone, 4-fluoromethcathinone and methylone – and the other contained dimethocaine, a legal but unmentioned local anaesthetic (presumably to emulate the nose-numbing effect of cocaine).

Drugmonkey, newly installed at Scientopia.org, has in his archives a nice series of posts on mephedrone for your further reading on these compounds.

Read Vaughan’s full post here.

JUNIORPROF returns to blogging with the #PainResearchMatters campaign

As I’ve noted elsewhere, practicing biomedical scientists often turn to blogging out of passion for their work and their desire to connect with the public to raise awareness about societal benefit of their research.

Exhibit A: Pain researcher, JuniorProf.  JP has come roaring back from a hiatus, joined Twitter, and has put forth a near-manifesto on his previous posts about pain research and why it is important:

1) The World Health Organization considers relief from pain to be a universal human right
2) Migraine headache is the most common neurological disorder in the world
3) More people seek medical attention for pain than for any other reason
4) Nearly 50% of people who seek medical treatment for pain report that they do not achieve pain relief with treatment
5) Chronic pain conditions disproportionately affect women

And like many of us, some critical personal and training experiences led him to this particular research area. You’ll learn about these if you go further in his post.

On a personal note, JuniorProf is a good online friend and has helped me out professionally as well. Our friendship began when he was a commenter at DrugMonkey and PhysioProf’s place. I told JP that his comments were so insightful and content-rich that he really needed to start his own blog.  So, he did (I wish I had that power of persuasion over others.).

Work issues pushed his nose to the grindstone at the university and on grant applications, but I knew he’d be back when he was ready.

He is now inspired.

Some of the most useful drugs in the management of pain come from natural products, such as morphine from Papaver somniferum. Unfortunately, some pain medications also have the potential to cause drug dependence. For this reason, chronic pain is largely undertreated. So, I’m really looking forward to learning more from JP about the advances in his field and his work that is designed to truly relieve human suffering.

I hope that you’ll follow his writing as well.

Update: Zuska now has a detailed post up on her migraines, allodynia, and the litany of drugs she has gone through to find some relief with botulinum toxin injections (Botox). That is why pain research matters.

And a hat-tip to DrugMonkey for making me aware of #PainResearchMatters

Sustained interest in K2 Spice, JWH-018, and related currently-legal cannabimimetic products

Just a quick post this morning as I am performing my professional responsibility to our nation’s health research agency.
In yesterday’s issue of USA Today (which I only read on the iPhone app or when staying at a hotel that gives it to us free), Donna Leinwand wrote about a currently legal substitute for marijuana called by various names such as K2, Spice, Black Mamba.

Nearly a dozen states and several cities are banning or debating bans on K2 — a packet of herbs coated with a synthetic chemical that mimics a marijuana high when it’s smoked — amid fears that its use is spreading among young people.

Each of these products is comprised of a generic plant material fortified with one of more marijuana mimics, or cannabimimetics, originally synthesized in the 1990s by Clemson University organic chemist John W. Huffman and his graduate students. These compounds generally go by JWH followed by the lab’s code number for the compound. The most popular of these is JWH-018.
These compounds are not considered cannabinoids since they are synthetic and do not bear obvious structural similarity to Δ9THC or other naturally-occurring cannabinoids. However, these compounds do bind cannabinoid receptors in the brain and appear to produce psychoactive effects similar to that of marijuana. Descriptions of various K2 Spice products, and now pure JWH compounds that have become available, are richly described by our commenters to the February post. In fact, a comment received this week, speaks of the risks of the variable levels of JWH compounds that might be sprayed on different products.
The primary driver of K2 use appear to be by cannabis enthusiasts who are either on probation or otherwise subject to urinary drug screening tests that detect THC but not (yet) the JWH compounds. Others simply wish to purchase a still-legal high rather than risk the variable ire of law enforcement officials around the US.
For much more on the pharmacology and risks of dependence on K2 or pure JWH-018, you can read two posts written under the ScienceBlogs masthead in February, one by me and one by my blog brother, DrugMonkey.
Brother Drug and I have been completely blown away by the sustained interest in each of our posts that has actually grown over the last 100 days. In both of our cases, approximately 50% of our readership lands on our February K2 posts. Perhaps this is no surprise given that each of our posts show up at the top, or at least the first page, of Google search results for “K2 Spice.” On top of this, I was the beneficiary yesterday of Reddit member Travesura who recommended his followers to us with the teaser:

“Heard of that “K2 Spice” that everyone has their shorts in a wad over? Here is the best explanation that I have seen about what it is, and how it works.”

Thanks to Travesura and the timeliness of Leinwand’s USA Today article, our February K2 Spice was the landing site of 2,853 of our last 4,000 visitors.
Holy moly.
But I learned possibly of another trend: we received a fair number of hits yesterday from various US military IP addresses, some coming via search terms involving detection of JWH-018.
For our military readers, has any directive come down the pike that soldiers will now be screened for JWH-018 use? Or is this just a coincidence?
But I still have no explanation as to why both DrugMonkey and I are getting such sustained interest in this topic, even more than for previous posts that had short-term high readership such as herbal products adulterated with erectile dysfunction drugs and the Evolv water/M.D. Anderson kerfuffle.
Update: The always-excellent Erowid site has information on the approach to K2 Spice by the US military. The US Army has banned the substance and this January 23, 2010 article by Hope Hodge at the Jacksonville (NC) Daily News on the possible discharge of two Marines at Camp Lejune:

Marine Corps officials did not immediately respond to queries about working policies surrounding spice or how Marines aboard Camp Lejeune are briefed about it. Base officials said that, in place of specific guidance, the use of spice is illegal under SecNav Instruction 5300.28d and OpNav Instruction 5350.4c, which broadly regard substance abuse prevention and control.

Hodge followed up on February 5 with a report that the US Marines has issued a ban of 10 substances that include Spice and Salvia divinorum, the source of the disturbing hallucinogen, salvinorin A.

Former date rape drug reincarnated as answer to unmet medical needs

Just a quick post on an article that caught my eye: Jazz Pharmaceuticals of Palo Alto, CA, has announced that the US FDA has accepted their new drug application (NDA) filing for JZP-6, or sodium oxybate, for the treatment of pain and fatigue associated with fibromyalgia.
The NDA was based on positive outcomes of two, Phase III clinical trials – those randomized, placebo-controlled double-blind trials that serve as the gold standard for drug efficacy. The company expects an approval decision from FDA by October 2010.
Jazz has already garnered approval for sodium oxybate under the brand name Xyrem® for the treatment of daytime sleepiness in patients with narcolepsy. The company stresses, however, that the drug has not yet been approved for symptoms associated with fibromyalgia.
200px-4-hydroxybutanoic-acid.pngThe item of note here is that sodium oxybate is another name for the sodium salt of gamma-hydroxybutyrate or GHB, a sedative that resembles the inhibitory neurotransmitter GABA but also has its own receptors in the central nervous system. GHB was implicated as far back as the early 1990s on college campuses where young men who lacked any other redeeming qualities to attract women used it to dope the drinks of their dates.
But here we see the study of a drug of abuse giving rise to a useful pharmaceutical, first in narcolepsy and, soon perhaps, for fibromyalgia.
It is a paradox of pharmacology that a sedative like GHB would prevent excessive sleepiness or fatigue. But a similar paradox exists with the use of the stimulant methyphenidate in hyperactivity conditions.
Now that I’ve seen the business reports, I’ll turn to some of my CNS pharmacology colleagues to help explain the neurobiology.
However, this compound demonstrates to me the unanticipated benefits of funding research that aims to investigate drugs of abuse.
Beneficial therapeutic agents come when and where you may least expect them.

Excellent neuroscience grad student blogger breaks my writer’s block with her flippant comment about a cytochrome P450

The always-outstanding neuroblogger, SciCurious, put up an excellent post overnight on a presentation she saw at the current Annual Meeting of the Society for Neuroscience (SfN) in Chicago. Therein, she wrote about a poster presentation she saw on the relationship between iron, cholesterol, and Alzheimer’s disease.
All was quite well until near the end of her post. That is where my writer’s block of the last week dissipated and manifest itself as a blogpost-length comment.

This is a lovely post otherwise but you’ve obviously been drinking if you think you could get away with “an enzyme known as CYP46A1 (yeah, I don’t know what that means either)” knowing that I am reading.
CYP46A1 is a member of the cytochrome P450 family of monooxygenases (look for “CYP” you young whippersnapper; there’s a whole international allele nomenclature org for this). In fact, neuroscientist god and 1970 Nobel laureate, Julius Axelrod in Bernard Brodie’s group first identified this xenobiotic oxidizing system in 1955 – oh, but I’m sorry – you kids don’t read papers before 1966 that aren’t on PubMed because you can’t find the building we used to call a library. Well, rest assured, Dear Weedhopper, that the journal Science has archived their papers online and you can find one of the original papers (Science 121:603-4, 1955 – PDF here) without leaving your computer. Axelrod’s original solo paper is in Journal of Pharmacology and Experimental Therapeutics 114:430-8, 1955.
But, I digress.
While we mostly think of P450s as hepatic, adrenal, renal, or pulmonary enzymes, we’ve known that many other tissues possess P450 activities. CYP46A1 can exist in glia and is otherwise known as cholesterol-24-hydroxylase. The product of this reaction creates a hydroxylated version (at carbon 24 if you can believe it) that cannot cross the blood-brain-barrier as you note.
And while alcohol dehydrogenase is primarily responsible for oxidizing the EtOH coursing through your veins, the higher concentrations you were likely to encounter after writing this post would be handled by CYP2E1. But that all involves things like differences in Km (yeah, I don’t know what that means either.)
Have fun and say hello to all of our friends!

Yes, I closed the comment on a happy note so that she knows I’m just giving her a hard time. However, Sci is fortunate that I am not on her dissertation examining committee.
By the way, this excellent biography of Julius Axelrod by Harry Smith details Axelrod’s relationship as a technician in Brodie’s lab and his pursuit of a PhD at age 42. Axelrod had a tremendous influence on a generation of scientists, including one of my own professors. Smith’s article quotes the philosophy of Axelrod:

  • Ask simple questions. (But look beyond the obvious.)
  • Do something new, but not too new. (Work just left or right of mainstream questions.)
  • Talk to people and read! (Then talk more, read more. You never know where the next idea will come from.)
  • Science is 99% discouragement. Stay focused!
  • Do one good experiment a day.
  • Find and exploit your own scientific style.
  • Skimming the cream is a good thing. (But do enough science to know that the cream is real.)
  • Don’t sweat the details. Focus on your hypothesis and don’t get swayed by complexity.
  • Publish to clarify your thinking and your hypothesis. Nothing more.

You can follow the twitterings of Sci and other SfN-certified neurobloggers by following the hashtags #sfn09 and #sfnthemeh.
That is all.

Destigmatizing depression among medical (and graduate) trainees

ResearchBlogging.orgThe Clinical and Translational Science Network (CTSciNet) section of Science Careers has just published a superb article by Karyn Hede on the issues of depression precipitated during the rigors of medical education. Hede is a freelance writer in Chapel Hill and has contributed before to Science Careers, particularly with this article on the challenges of women MD-PhDs and another on why so many of us have crappy interpersonal and lab management skills.
The current article focuses primarily on the medical profession given its placement in the clinical/translational section but these issues are true for PhD trainees as well:

Depression among medical trainees is well-documented. A recent large-scale survey of medical students and residents at six major medical schools revealed that one in five have mild to severe depression, a rate 15% to 30% higher than the general public. One out of every 17 even said they had thought about suicide. The study, reported in the journal Academic Medicine in February, brought to the fore the problem of depression among students immersed in the rigors of medical training.
“Certainly, medical school, residency, Ph.D. training, all those kinds of advanced degrees are set up with a lot of expectations, and by and large the people that are doing them are driven,” says Deborah Goebert, a psychiatrist at the University of Hawaii, Manoa, and lead investigator of the study. These stressors, along with lack of sleep, financial concerns, and family pressures, can push people into an episode of clinical depression, she says.

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Second confirmed poppy tea death in Boulder, Colorado

Papaver somniferum.jpgThe Boulder County coroner announced today that the July death of a Boulder teen was indeed due to opioid intoxication from preparation of a poppy pod tea.

Jeffrey Joseph Bohan, 19, of Boulder, was found dead in his friend’s Boulder home about 6 p.m. July 21 after drinking poppy-pod tea the night before with his brother, according to Boulder police.
Investigators suspected the Fairview High graduate, who was going to Colorado State University, died from the psychoactive tea, which is brewed from the plant that produces opium. But they couldn’t be sure until the Coroner’s Office confirmed Monday that Bohan’s cause of death was morphine overdose, and his manner of death was accident.

Here is also coverage from The Boulder Daily Camera.
This marks the second death in Boulder from young adults mixing up decoctions of seeds or pods from the poppy, Papaver somniferum. We reported in March on the death of CU-Boulder student, Alex McGuiggan, in March.
In a subsequent post, we expanded on a commenter’s story of his own efforts to raise awareness of the dangers of poppy seed tea following the death of his own son. Commenter Tom’s site can be viewed at Poppy Seed Tea Can Kill You (http://poppyseedtea.com).
Extracts from poppy pods can contain up to 10% morphine and 1-5% codeine together with several other benzomorphan compounds. Seeds themselves are intrinsically devoid of morphine but the drug can remain on the seeds in reasonable quantities simply from their processing. The Santa Clara County crime laboratory investigating the death of Tom’s son determined that a tea made with the same seeds he used contained 259 µg/mL of morphine.
Depending on the starting material, however, the extract may also contain thebaine, a natural intermediate used for semi-synthetic opioid synthesis that causes intense nausea, vomiting, and even convulsions.

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Sexy autism education PSA videos from Rethinking Autism: What would Prof Nisbet (and you) say about this framing?

RethinkingAutism.com is the brainchild of Dana Commandatore, a friend of one of my high school classmates. Dana is a former NYC advertising guru and the mother of Michaelangelo, a child with autism. His story inspired her to write the children’s book, Michaelangelo the Diver.
Dana has now taken her creativity and contacts in her new home of Los Angeles to produce a series of controversial public service announcements to combat misinformation about the causes and treatment of autism and the acceptance and celebration of neurodiversity. Here is the spirit in which they are presented:

All too often in the world of autism, celebrity and sex appeal are used to promote pseudo-science that exploits autistic people, their family members and the public. We decided to put those very same factors to work in service of the truth.
Just because a person with autism may not speak, it does not mean they have an inferior intellect.
Every reputable study has failed to find a link between vaccines and autism.
Aversives, seclusion and restraint are unacceptable ways to treat a person with autism.
No special diet has been proven to cure autism.
School districts need to support inclusive education.
Learn about the dangers of unnecessary chelation treatments.
We should be more concerned about an autistic individual’s quality of life instead of preventing them from being born.
Listen to self-advocates and learn about neurodiversity. Include the organized community of autistic adults when it comes to making legislation regarding their quality of life.
Positive behavioral supports aimed at stopping harmful behaviors while respecting natural differences are a great way to help autistic people achieve quality of life.

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Sage advice?: NC to join 13 states in outlawing Salvia divinorum

ResearchBlogging.orgSalvia divinorum (Salvia, Magic Mint) is a plant used for entheogenic purposes by the Mazatec people of Mexico. A relative of the common garden plant “scarlet sage” (Salvia splendens), S. divinorum contains several hallucinogens that include salvinorin A, the first non-nitrogenous agonist known for kappa opioid receptors (KOR).
I had known of salvinorin A since a highly-cited 2002 Proceedings of the National Academy of Sciences paper by Bryan Roth, Richard Rothman and colleagues (full text here). At that time, I had read several anecdotal reports (that I cannot locate now) that the hallucinations rendered by Salvia ingestion or smoking were so bizarre and disturbing that 8 of 10 first-time users declared they would not use it again. Hence, I never really thought that Salvia would become much of a public health problem or be embraced by recreational hallucinogen enthusiasts.
However, just Google “Salvia” and take a gander at the ads on the right sidebar.
I’m still not certain if Salvia is enough of a public health problem to warrant legislation but we just learned this week that North Carolina will join 13 other US states in criminalizing possession and use of the plant or extracts made thereof:

A bill that would outlaw the psychoactive herb Salvia divinorum has passed the state Senate, prompting consumers to rush to buy it legally.
Senate Bill 138, sponsored by Sen. Bill Purcell, D-Laurinburg, would prohibit the “manufacture, sale, delivery, or possession” of Salvia divinorum. The law calls for a fine for the first two offenses and misdemeanor charges for subsequent offenses. Purcell stressed that North Carolina’s law would not be as strict as those of 13 states, which made Salvia divinorum a drug on par with heroin.

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