Ketamine & Mental Health: What We Know Already

A very good friend sent me a landmark study surrounding Ketamine a little while ago.  In drug research, big effects and powerful findings are usually accompanied by tiny sample sizes and weird statistics magic to rig the findings. So when I read the meta-analysis and systematic review published in The American Journal of Psychiatry, I was heartened. This is serious science and serious stats, with 167 patients evaluated across multiple studies. Also, the reporting scales (MADRS, HAM-D, QIDS-SR & the BDI) are well understood, robust and respected in the field. All of this adds up to this results abstract being very, VERY important:

Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen’s d=0.48–0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine’s effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms.
~The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review & Individual Participant Data Meta-Analysis (Wilkinson et al)

That’s a dense couple of sentences, so let me explain why it’s so earth shattering. Suicidal thoughts, (known as suicidal ideation in clinical psychology) and depressed feelings are very difficult to get rid of, especially for depressed people. Treatment-resistant depression is a term associated with someone who has attempted multiple types of treatment for their Axis I disorder, but it hasn’t gotten better. After trying multiple types of interventions with no success, people slide quickly into hopelessness and thoughts of self harm. Up until now, depression treatments like SSRI drugs and Cognitive Behavioral therapy take time to work, sometimes more than a month. If you’re not in a good place right now, these things can’t help you. Ketamine infusions help immediately, and the change is apparent both to the patient and to the interviewing physician afterwards. This bit is huge, as most drug research relies heavily on self-report, which leads to bias and distorted findings. But, people are already talking to the press swearing by it, and it’s getting quite a lot of press, so here’s what they’re talking about.

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Morphine, Myth & The Civil War: Before Cause and Effect

Editorial by Terry Gotham

Last week, we spoke about the gendering of drug use in America and how that may have led to the original wave of drug prohibition laws. This was one example of the  many times where drug use was distorted as a justification for it to be outlawed. One of the biggest myths associated with heroin usage was that the Civil War “created 500,000 addicts.” This is of course not the case, so let’s unpack the various reasons brought up to justify this erroneous attribution. An exceptional paper published in War In History by Jonathan Lewy of Harvard University helps to round up the main reasons this assumption is wrong, which I’ll be quoting from liberally.

One of the easiest ways people explain the deluge of opiate & whiskey addicts during the last quarter of the 19th century & the first 2 decades of the 20th was the invention of the hypodermic syringe. The Civil War doctor did use opium for much more than just killing pain. Opium was used for diarrhea, dysentery, stomachache, gallstones, hemorrhoids, tetanus, typhus, syphilus & “neuralgia” (an anachronistic diagnosis that loosely translates to peripheral neuropathy today). But, remember, it’s 1860. Opium powder was usually sprinkled on top of the wounds suffered by soldiers in the field. By the end of the Civil War, a little over 2,000 hypodermic syringes had been fabricated & distributed to the 11,000 surgeons employed by the Union Army, which is one of the pieces of evidence used to support the claim that the modern heroin addict was created by the Civil War.

There’s one crucial difference between a modern syringe & those that were used, especially at the beginning of the Civil War. The first syringes were dull. That’s right, doctors had to puncture your skin first using a lancet (yes, that’s where the journal name comes from), before using the dull and large gauge syringe to deliver the medicine. So, the most hyperbolic claim, that soldiers were shooting up because they were taught to do so at field hospitals and by doctors, can immediately be dismissed. If any of you had nightmares that involved Requiem For A Dream and civil war uniforms, you can put that aside.

Not only was injection drug use essentially impossible, Confederate surgeons had little to no access to spare opium. The Confederacy attempted to grow poppy fields to supply their armies with opium. This sounds like a good idea in theory, but resulted in exceptionally poor quality poppy crops and an inferior supply of pain killers for the Confederate Army. Resulted in the Confederacy relying on smugglers & blockade runners to bring it down from the North, as one of the first examples of drug running in the USA.  The North was buying opium on the world market, as their Navy gave them access to trade with Europe. And boy did they take advantage of that. The Federal Army consumed 10 million opium pills and 80 tons of opium powder & laudanum tinctures before the surrender at Appomattox was signed.

People weren’t converting pills into inject-ready substance in the field, and the Confederacy couldn’t even get its hands on syringes and medical staff/training using them. When you’re taking a small pile of opium and spreading it over a wound with a knife, the person receiving care doesn’t know they’re “doing heroin.” It’s hard to develop a drug habit when you don’t know what drug you’re craving.

There were anecdotal cases of physicians becoming addicted to the morphine, but as a record, this was always classified as misuse, not addiction. General Benjamin Butler discovered one such doctor, and relieved him of his duty. However, no note of addiction, health problems, or vice was mentioned, merely a note of dereliction of duty. This is corroborated by The Medical & Surgical History of the War of the Rebellion, a six-volume epic tome documenting the case histories of the various field surgeons across the US Army. 13 years of records were submitted, accounting for all of the ailments, diseases and afflictions that these doctors, surgeons and field hospital directors encountered. Zero cases of addiction, or anything resembling the modern, conventional definitions of substance abuse/addiction appear.

This isn’t to say that the maladies associated with excess substance use weren’t known. But the idea that the substance use, if continued, would cause dependence or other negative consequences, hadn’t entered the greater medical world, and wouldn’t for years. The Manual of Military Surgery, introduced in 1861, noted that morphine & laudanum (tincture of 10% opium in alcohol) should be used in managing pain and amputation-related hardship. Interestingly, and without further definition, the reader is warned to not abuse the drugs “lest they induce fatal oppression of the brain.” For serious, no other context is given, you can see for yourself on page 50:

“Reaction must be promoted by the cautious use of stimulants ;while pain is allayed by morphia orlaudanum given with more than ordinary circumspection, lest it induce fatal oppression of the brain.” ~Samuel Gross

Could “fatal oppression” be like our modern definition of “brain death?” You betcha. Will we ever know if it was, definitively, and not the fog, memory loss or other neurological side effects of opiate use described at the time? No, which is a huge problem. It’s really easy to assume, but we need confirming evidence and there simply isn’t any. And, to put this lack of information in context, in the late 19th Century, the closest thing to “addiction” most people were aware of was the “habit” (Source Bias warning: Vaguely pearl clutchy, but still relevant historical portrayal of the time).  Alcohol had been seen to be habit forming as early as 1819, but morphine wasn’t seen in the same light. Using opium was seen as roughly equivalent to swearing, paying for sex, gambling and gossiping. If you couldn’t resist the temptation of drink or poon or dope, you were a sinner, or morally weak, not sick. But in 1877, 12 years after the end of the Civil War, that changed. Die Morphiumsucht was published by Eduard Levinstein, connecting drug use with a craving for more drugs, for the first time in the wider, respected medical literature. And I do really mean for the first time. Between 1864 & 1875, when Levinstein lectured publicly on the topic for the first time, only 24 articles discussed pathology stemming from drug use. In the decade after? Over 230. It’s kind of hard to have a mass of people “addicted to drugs” when they couldn’t access the drugs, and “addiction” wasn’t a word at the time. Oh, and the people weren’t there either.

The USA documented approximately 10,000 habitual opium uses (referred to as habitues) in 1842, with that number peaking at 313,000 in 1896, according to some. However that number gets turned on its head when it’s documented in the same source that there were more women habitues than men. Grief caused by becoming a widow explains why all the women are getting high, but, if all of the soldiers are dead, where is the epidemic of strung out veterans? They weren’t in the Sanatoriums, as a casual review of the Second Annual Report to the Citizens in the Delaware County American shows. Even back in 1868, right at the end of the war, when soldiers were most vulnerable to opiates, 2 out of 26 under his care, were there for opium. The rest? Booze. Additionally, they were in there because of social use or physician prescription, not because they even fought in the war. In the “National Homes” in and around Milwaukee,  only one veteran was admitted to the entire system for non-alcoholic drug use between 1867 & 1872. To put that in perspective, 36 people have died from Fentanyl overdoses alone in Milwaukee this year

Were there people who developed habits? Absolutely. The Confederate vet Doc Pemberton was wounded at the battle of Athens, Georgia and became addicted to cocaine after being given it on the battlefield. After the war, as an unemployed chemist, he created a brew of cocaine and kola nut extract, as an attempt to keep up with the hooch being slung at the saloon across the street. Were there a giant pile of strung out drug addicts walking around after the war? No. What were there? A bunch of wounded veterans.

Lewy really does sum it up quite nicely in his conclusion, so I won’t try to out do his words:

Some contemporaries claimed their experience in the war prompted their addiction. A few decades later, Crothers and other physicians supported the notion that the war caused addiction, but not based on fact, at least statistical fact, but was due to the understanding that wars caused trauma. One can only assume that, with the amount of drugs consumed by the armies of the Civil War, a few soldiers and perhaps even a General or two became addicted to drugs, but it would be next to impossible to determine how many (were), and whether this was, indeed, a historical trend. Especially since addiction was only recognized as a full fledged disease several decades after the war.
~
Johnathan Lewy, The Army Disease: Drug Addiction and The Civil War (2013)

Finally, it’s important to note that this fear of drug zombie veterans have been used as a justification for drug laws ever since. A heroin resurgence coincided with the end of World War II, the Korean war sparked rumors that Communists were attempting to dope American youth to beguile them, Vietnam managed to vilify drafted soldiers, decrying their drug habits before they even returned, and the war in Afghanistan is already being blamed for heroin use among soldiers. There will always be people attempting to justify drug prohibition using the trope that veterans would be the most vulnerable of American citizens. Yet, this continues not to be the case, even to this day. Don’t believe the hype. Drug use is an ineffective, yet popular way to cope with trauma, whether you were part of a unit that saw incoming fire at the Battle of Gettysburg or if you’re just growing up in rural America after Bain Capital sent all of the jobs in your town away.

War on Drugs Leads to Wholesale Rainforest Destruction

Photograph by Luke Duggleby www.lukeduggleby.com

Photograph by Luke Duggleby http://www.lukeduggleby.com

By Terry Gotham

I usually talk about how to reduce the damage drugs can do to people, but today I want to switch it up a little bit. I’m going to tell you about the Mreah Prew Phnom trees of Asia, the Sassafras trees of America, and how our voracious appetite for drugs is hurting them. This isn’t a story about water usage or gang violence, but of appetites. The explosion in popularity of MDMA has ensured one of the trees that produce a precursor substance, safrole oil, is now critically endangered. It’s estimated (not verified) that more than 5 million trees have been destroyed over the last 10 years.

Photograph by Luke Duggleby www.lukeduggleby.com

Photograph by Luke Duggleby http://www.lukeduggleby.com

 

 

Formally named Cinnamomum parathenoxylon, the tree grew in Bhutan, India, Indonesia, Laos, Malaysia, Myanmar, Nepal, Pakistan & Vietnam, but is currently most often found in Cambodia. The remaining population is clustered in the Phnom Samkos Wildlife Sanctuary, as cultivation of the tree is increasingly restricted. When the roots are chopped up and processed, safrole, an essential oil is produced. This stuff has been an herbal remedy, a critical part of perfumes, soaps & can be used to make MDMA.

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Benzodiazepines : Socially Acceptable Drowning

As many people reading this have been with their families long enough at this point to start taking sedatives or hypnotics to cope, I figured that Black Friday’s harm reduction post should focus on benzodiazepines. They were developed early in the history of pharmaceuticals, with the first going on sale in 1960, becoming the most prescribed medication in 1977, with numbers dropping since.Benzos have a long  history. Which I have no part in, so I won’t be taking time to explain it here. As some of the people reading this have giant chunks of those memories voided by said benzos. Continue reading

Miss Molly Goes to War

by Whatsblem the Pro

CJ Hardin has gone from PTSD to MDMA to A-OK

CJ Hardin has gone from PTSD to MDMA to A-OK

CJ Hardin first went to Burning Man in 2006; when he can make it to Black Rock City he volunteers as a medic. He spins fire staff, and is learning ball poi.

Outside Black Rock City, CJ Hardin is a soldier whose three tours in Iraq and Afghanistan left him an alcohol-soaked, suicidal wreck peppered with physical, emotional, and psychological trauma. The physical damage wasn’t much – some minor injuries, a touch of tinnitus – but the PTSD he suffered picked him up by the scruff of the neck and took him right out of his life.

Michael and Annie Mithoefer are burners, too, and more formally known as Dr. Michael Mithoefer, MD, and his co-therapist, Annie Mithoefer, BSN. The couple run a well-regarded internal medicine practice in Mount Pleasant, South Carolina.

The Mithoefers are currently conducting clinical trials as part of a ten-year, $15,000,000 project that intends to transform MDMA — sometimes sold under the street names Molly, Ecstasy, or X, among others — from an illegal street drug into an FDA-approved prescription medicine. CJ Hardin is a patient in one of those trials.

The project is being administered by a non-profit organization called MAPS, or the Multidisciplinary Association for Psychedelic Studies. MAPS, currently the only organization in the world funding clinical trials of MDMA-assisted psychotherapy, has earned a solid reputation in the scientific community by doing peer-reviewed work on the legitimate medical uses of psychedelics and marijuana since 1986.

To a non-profit organization like MAPS, exploring the medical uses of MDMA makes good sense, because the patent on the drug has expired. This being the case, the for-profit pharmaceutical industry has little or no interest in testing and developing the drug into a product. Once someone like MAPS does it, the for-profit big boys in the big league may manufacture their own version and sell it alongside the patented products they own, but since they can’t hold a monopoly on the drug, there’s no money to be made in doing the groundwork that must come first. This is part of the reason why MDMA has remained on the government’s Schedule 1 list of substances that supposedly have no medicinal value.

All the drugs that MAPS works with either have expired patents, like MDMA, or are unpatentable, like marijuana; once the research allows products to be manufactured from them, nobody – not even MAPS – will have a monopoly on making and selling them, and thus they will likely remain cheap or even free to the people who need them most.

I interviewed CJ Hardin about his progress with the Mithoefers’ MDMA-assisted psychotherapy on Tuesday, November 26th, 2013.

Whatsblem the Pro:
CJ, you’re a burner, right? How did you find your way to Black Rock City the first time?

CJ Hardin:
I went with friends in 2006, after my second Iraq deployment. I really didn’t know much, other than that it was a huge party with cool music and art in the desert. We rented a bus and really kinda glamped it. I didn’t know that it was such a participatory event, but I really started to enjoy it once I began talking to fire spinners, since I had done fancy drill teams with rifles in the JROTC. I had a great time, but also gained a deeper appreciation for the burner community. I really appreciated how Burning Man set itself apart from music festivals I had been to, like the Family Values Tour, and Bonaroo.

Whatsblem the Pro:
How long have you had PTSD, and how long have you been doing the MDMA therapy?

CJ Hardin:
I got deployed in 2003 during the initial push to Baghdad, and served three tours in Iraq and Afghanistan. I started to really feel it after the second deployment.

I’ve been in the MDMA study since midsummer of 2013, and I’m about to do my third MDMA session, on December 3rd. If I haven’t been getting the higher of the two doses they’re testing, I’ll get another five sessions with the high dose after this.

Whatsblem the Pro:
This is a horribly rude question that I wouldn’t ask under other circumstances, but would you mind telling me something about the experiences you had that left you with PTSD?

CJ Hardin:
Well, I’ve been hit by two IEDs while in armored vehicles, but I wasn’t seriously injured, just some hearing loss. I was hit by a bullet fragment from friendly fire that made me think I was shot. . . and pretty much every day we were being targeted with mortar and rocket fire, so we could never really feel safe. On top of that, I was a member of a command team, so I got to see all the operational stuff and the casualties. There was a lot of gory stuff, and friends getting injured and killed. . . and of course never knowing whether a mortar was going to drop on you in your sleep or on the shitter was a really bad feeling that dissociates you from the real world. All of it combined was the problem.

Whatsblem the Pro:
What sort of symptoms did you develop?

CJ Hardin:
Any sudden noise, change of air pressure in the room, motion. . . I’d get hyper-vigilant. Rapid pulse, crippling anxiety. Depression. A need to avoid crowds. Driving became impossible; I’d swerve to avoid anything near the road because it would remind me of IEDs. I got into some major alcohol abuse to keep my mind off stuff. Insomnia. Lack of a sex drive. Thanks to the IEDs, I’ve also got permanent tinnitus, which is a ringing in the ears.

I got to the point where I stayed home and never went out. I didn’t even try to work really, just did odd jobs. I had a lot of suicidal thoughts.

Whatsblem the Pro:
How has the therapy you’ve been doing with the Mithoefers affected all this?

CJ Hardin:
Working with them and with the MDMA has vastly reduced all the symptoms. Some are gone totally. I go out and hike and drive now; I don’t jump as much at all at sudden things; I’m much better with crowds now. Essentially, I realize on a gut level that I’m not at war any more, and I’m safe.

Whatsblem the Pro:
All that, with just two sessions?

CJ Hardin:
Two sessions with the MDMA, and some therapy sessions in between, yes. I’m about to do the third MDMA session.

Whatsblem the Pro:
It sounds like you got your life back.

CJ Hardin:
I did get my life back! There was a profound difference after the first session. . . and my girlfriend benefits by having a sane boyfriend. Did I mention that I lost my marriage due to the PTSD?

Whatsblem the Pro:
I’ve read that a single dose of MDMA might be worth years of psychotherapy.

CJ Hardin:
Oh, yeah. . . eight hours of therapy with MDMA feels like three years of therapy without it.

Whatsblem the Pro:
What went with the MDMA? Were you guided through any particular experience with it, or did they just give it to you and babysit passively?

CJ Hardin:
Oh no, I was totally guided. The doctor and his wife, who is a nurse, were with me the whole time. There was soft music playing, and they gave me a sleeping blindfold in case I wanted to “go inside.” My girlfriend was there for most of the time, too. They let me talk about whatever. Sometimes they would remind me of what I was saying or get me back on a train of thought.

Whatsblem the Pro:
They told you to go inside yourself?

CJ Hardin:
Yep. After I’d talk about something a little more intense, they’d suggest that I go inside and try to feel where I felt the feelings. . . then breathe through it. To dwell on it, kind of.

Whatsblem the Pro:
I can see that happening at a theme camp at Burning Man, too.

Thank you, CJ. This is fascinating research, and from what you’re telling me it seems very promising. Is there anything the community can do to get involved and help?

CJ Hardin:
Actually, yes. . . the study I’m taking part in right now needs funding to continue. It’s all non-profit, and runs on donations, so there’s an Indiegogo campaign that you can give money to. You can read all about the clinical trials and the science and everything there, too.

I really believe that the work the Mithoefers are doing is going to end up helping a lot of people who need help badly and can’t get it because MDMA is illegal. It’s helping me, and I’m very grateful. Please give generously!

Whatsblem the Pro:
Good luck, CJ! We’re rooting for you.