K2, Spice and How Drugs Won the Drug War

A few nights ago I was working the Emergency Department when the ambulance brought in two teenagers. Both had smoked "Spice" - a chemical purchased at a local store. One was clearly high, dissociated, and hallucinating, but he was medically stable. The older boy was in much worse shape. His heart rate was greater than 140 at rest, his blood pressure was elevated and he was unable to sit still. His hallucinations were apparently unpleasant and he required one-to-one staffing just to keep him from pulling his IVs out. 

Many of my coworkers hadn't heard about Spice or bath salts, but we've actually had quite a few teenagers in the ED with this over the past year or so. Spice and similar products use analogs of JWH-018 -- the chemical components of marijuana and other illegal drugs. 

It is just one example of the new and profitable front of legal highs being exploited by chemists who are staying one -- or several -- steps ahead of the law. Marketed in stores as bath salts, potpourri or incense, these drugs are often labeled "not for human consumption" as a way to avoid any regulation.  

As WIRED magazine reported: 

During the last several years, the market for legal highs has exploded in North America and Europe ...
Active ingredients in the drugs are compounds originally synthesized by institutional researchers whose esoteric scientific publications were mined by as-yet-unidentified chemists and neuroscientists working in Asia, where most of the new drugs appear to come from.
One class of popular cannabinoid mimics, for example, was developed by respected Clemson University organic chemist John Huffman, who sought to isolate marijuana’s chemical properties for use in cancer research. Other “legal high” ingredients have similar pedigrees, with designers including researchers at Israel’s Hebrew University and the pharmaceutical giant Pfizer.

Researchers say these are much more potent that pot. (I can't remember the last time I had an ED patient in for simple marijuana consumption. ) 

What I have seen with these patients is mirrored in the literature -- often extreme tachycardia, hypertension, hallucinations, sweating. I've also treated a girl who came in with what is called “couchlock” or the inability to move.  Numbness, blackouts, headaches, anxiety are also often reported. This kid the other night was actually very similar to those presenting with Meth Induced Psychosis. 

“The results are toxic and very dangerous, especially for vulnerable people — people with previous psychotic episodes — and the young,” said Liana Fattore, a chemist at Italy’s Institute of Neuroscience told WIRED. 

Fattore studies the latest wave of THC and cannabis analogs. It is a wave of products that are successfully staying ahead of legal controls. In 2010, laws were passed banning the synthetic stimulants, but when researchers looked at the products on the market today, 95 percent did not fall under the ban. Overseas chemists had altered the substance at the molecular level to be different enough to skirt the law, but still perform the same psychopharmaceutical role. 

“If you want any evidence that drugs have won the drug war, you just need to read the scientific studies on legal highs,” wrote Vaughan Bell at neuroscience blog MindHacks.

If you’re not keeping track of the ‘legal high’ scene it’s important to remember that the first examples, synthetic cannabinoids sold as ‘Spice’ and ‘K2′ incense, were only detected in 2009. Shortly after amphetamine-a-like stimulant drugs, largely based on variations on pipradrol and the cathinones appeared, and now ketamine-like drugs such as methoxetamine have become widespread. Since 1997, 150 new psychoactive substances were reported. Almost a third of those appeared in 2010.

From a "get this junk off the streets" standpoint, the problem is almost insurmountable. Lawmakers would have to understand enough chemistry to ban classes of chemical compounds. Moreover, there is little agreement on what kinds of compounds and analogs would be included.  Finally, there are decades of research and scores of chemical compounds know to create stimulant and psychoactive substances out there to be put on the market the instant another ban is put in place. 

The problem is that we have a market that wants a legal high and a world full of knowledge to serve that market without scruples. 

"The drug war isn’t only being lost," Bell concludes "it’s being made obsolete."

-30-

Guess What? Smoking Pot, Meth Bad for your Asthma

So the last case of the morning yesterday was a 24 year old male in respiratory distress. He got duoneb breathing treatments and a magnesium drip in route and the paramedic was still coming code 3 so we knew he was struggling. The patient arrived drenched in sweat and pale with resps about 40 a minute. 
He looked sick and was wearing out.  The MD ordered BiPap for him, but he was barely tolerating the nebulizer mask. He had that hypoxic anxiety that is common in older COPD patients who feel like they are drowning and you just can't convince them that they are getting enough air even after you fix them. 
Yet this kid seemed to have something else going on too. We asked him if he had smoked. He nodded his head "yes" to smoking meth and pot over the past two days. 
He was too wound up to tolerate the BiPap mask and was getting increasingly agitated. His ABGs were horrible. We intubated him. 
The social worker came back from the family waiting room and said his girlfriend was out there and appeared to be tweaking on meth too. The social worker asked us about the effect of meth on the lungs - on top of asthma.  
"Well, they clean up meth labs in hazmat suits if that tells you anything," I said. "Smoking pot isn't good for your lungs either."
One of the ED techs was standing next to me and protested.
 "There's never been any study that has proven pot is bad for your lungs," she said.
 I get a lot of pot-apologists in the 20-30 year age range - after all their parents and grandparents often smoked in their presence and so I'm sure they've all been indoctrinated about the overkill warnings in Reefer Madness. In isolation, I agree that it is a much more benign drug than meth - or even alcohol for that matter. 
Yet her assertion that smoking pot was not harmful to the lungs of an asthmatic seemed pretty counterintuitive to me. Taking smoke into your lungs and holding it in as long as possible just seems like something an asthmatic wouldn't want to do. 
Moreover, I used to tell my oncology patients that if they needed marijuana to help their appetite, they should bake it rather than smoke it. I'd seen many cases where COPD exacerbations were set off by smoking pot.
Indeed, smoking pot rapidly accelerates the progression and development of some lung diseases. A 2008 study found that "the development of bullous lung disease occurs in marijuana smokers approximately 20 years earlier than tobacco smokers." Published in the journal Respirology, the authors found that CT scans revealed the progression of bullous lung disease in pot smokers. 

Patients who smoke marijuana inhale more and hold their breath four times longer than cigarette smokers. It is the breathing manoeuvres of marijuana smokers that serve to increase the concentration and pulmonary deposition of inhaled particulate matter – resulting in greater and more rapid lung destruction. Science Daily reported.

Moreover, other research has supported a significant increase in COPD development if a patient smokes pot and cigarettes -- a synergistic effect greater than either alone. Some studies indicate that exposure to pot smoke at a young age helps predispose patients to COPD development later in life. It certainly kills cilia and damages airways - which of course predispose repeated upper respiratory infections and chronic bronchitis.
Of course, it is hard to due randomized controlled trials on an illegal substance, even if that substance is the second most smoked product on the planet. As a 2009 review of the links between Pot and COPD concluded:

"Firm conclusions cannot be drawn about the association between use of marijuana and COPD based on the limited and inconsistent data available. The studies that address this topic are limited by their small numbers of participants and by the uncertain accuracy of self-reported use of marijuana, particularly in view of its illegality and the difficulty of accurately recalling amounts previously used. Nevertheless, the consistency of some aspects of the available data allows us to more firmly conclude that smoking marijuana by itself can lead to respiratory symptoms because of injurious effects of the smoke on larger airways."

Note the part there about the trouble with pot smokers having trouble remembering...
Marijuana has become more and more accepted in society and these days medical pot dispensaries are opening up faster than Starbucks stores. A few years ago it was estimated that  11 million people smoked marijuana during the last month, and approximately 20% of these smoke almost daily. These smokers -- even if they don't smoke tobacco -- report chronic bronchitis, frequent phlegm, shortness of breath, frequent wheezing, chest sounds without a cold, and pneumonia, according to a 2004 study. 
Moreover, other studies have found significant damage at the cellular level and may predispose patients for lung cancers. It disrupts the immune response in the lungs as well, predisposing patients to respiratory infections. 

"Regular marijuana smoking produces a number of long-term pulmonary consequences, including chronic cough and sputum, histopathologic evidence of widespread airway inflammation and injury and immunohistochemical evidence of dysregulated growth of respiratory epithelial cells, that may be precursors to lung cancer. The THC in marijuana could contribute to some of these injurious changes through its ability to augment oxidative stress, cause mitochondrial dysfunction, and inhibit apoptosis."

Another study found that pot delivers different doses and chemical changes compared to tobacco: Each joint delivered five times the increase in carboxyhemoglobin levels compared to tobacco. Toking delivers three times as much tar to the lungs versus smoking.
What about meth? Well there's pulmonary hypertension, but so far I didn't find a lot of controlled studies on it. It's a drug that has been around since 1919,  but has become wildly popular only in the last 20 years or so and so the research is more focused on the more obvious health effects.


So, if you have asthma don't smoke meth and don't think that pot is healthy just because you got a script for it.