Synthetic Cannabinoids: Information and Guidance for Clinicians

Coordinator:
Thank you for dialing into today’s conference call. All lines are on listen-only as we begin our conference for today. During the Q&A session of our call you will be prompted to press Star 1 on your touch-tone phone. Please be sure to unmute your line to record your name so that I may introduce you to ask your question. Our conference is being recorded. If you have any objections you may disconnect at this time. I will now turn the conference over to our host Mr. Ibad Khan. Sir you may proceed.

Ibad Khan:         
Thank you Jill. Good afternoon. I’m Ibad Khan and I’m representing the Clinician Outreach and Communication Activity, COCA with the Emergency Risk Communications Branch at the Centers for Disease Control and Prevention. I am delighted to welcome you to today’s COCA call, Synthetic Cannabinoids Information and Guidance for Clinicians.

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At the conclusion of today’s session the participant will be able to describe the epidemiology and clinical effects of synthetic cannabinoid use, discuss recent clusters of severe disease associated with synthetic cannabinoid use in the US, identify opportunities for clinicians to support surveillance and response efforts.

Today’s first presenter is Dr. Amelia Kasper. Dr. Kasper is currently a second-year EIS Officer with the National Center for Environmental Health Health Studies Branch. She received a Masters of Health Sciences Degree in Environmental Health Sciences and Medical Training at St. Louis University. She completed her internship and residency in Internal Medicine at Barnes Jewish Hospital Washington University in St. Louis followed by a postdoctoral scholarship in epidemiology at the Yale School of Public Health.

Our second presenter is Dr. Robert Galli. Dr. Galli graduated from Yale University School of Medicine, where he completed his internal medicine residency. At UCLA Medical Center he completed his emergency medicine residency in medical toxicology training. Under his direction emergency medicine was established as a formal department at the University of Mississippi Medical Center in 1994 and includes air care medical toxicology in the same program.

Today’s third presenter is Dr. Justin Arnold. Dr. Arnold is a Medical Toxicologist and Emergency Medicine Physician with the University of Alabama at Birmingham School of Medicine.

Dr. Arnolds – Arnold- completed his residency in Emergency Medicine at Lehigh Valley Health Network in Allentown, Pennsylvania and a fellowship in medical toxicology at Emory University and the Centers for Disease Control in prevention in Atlanta, Georgia. Dr. Arnold has participated in field investigations pertaining to the epidemic use and health consequences associated with synthetic cannabinoid use.

Additionally he serves as Associate Medical Director for Alabama’s only poison center at the Regional Poison Control Center at Children’s of Alabama where he provides medical oversight for centers operation.

At this time please welcome Dr. Kasper.

Dr. Amelia Kasper:  
So hi everyone. Okay so to get us started this afternoon I’m going to provide a brief overview of synthetic cannabinoids, their emerging threat to public health and a bit about what we do and don’t know about them at this time. And then finally I’ll discuss potential future directions for public health and the health care community to work together to address this threat.

Dr. Galli will be going into more detail about the specifics later in this call but briefly synthetic cannabinoids, or SCs, are a family of man-made chemicals that bind to the same receptors as THC, the major psychoactive component of marijuana. I do want to stress at this time that these – ca- products are not in any way related to marijuana.

Synthetic cannabinoid products are readily available and can be purchased through dealers, convenience stores or on the Internet. The chemicals are generally manufactured overseas and then sent to the US for processing into the final product and packaged. The empty packets can be purchased on eBay as you can see here as a variety pack with different product names included. This is important because just because the packet says Crazy Monkey on it doesn’t mean that it’s the same Crazy Monkey that you had yesterday. In reality the contents of these packages are completely unregulated. It can contain one SC, many SCs, or even other hazardous substances of completely unknown concentration.

These packets are often printed with Not for Human Consumption to get around certain laws. However, many states now have general laws banning the manufacture, distribut-distribution, or possession of SCs regardless of what is listed on the package. The handful of SCs have been placed into Schedule I as a Federal Controlled Substances Act. And again Dr. Galli will be covering this in more detail later.

I’d now like to present a timeline of the emergence of SCs as a public health threat. SCs are first synthesized in the 1960s around the same time that the active ingredients in marijuana were being isolated. Research into these compounds as possible therapeutic agents for multiple sclerosis, cancer and other diseases began to gain traction in the 1980s which led to a better understanding of cannabinoid receptor - receptors structure and the pathways involved.

In 1986 the Controlled Substance Analog Enforcement Act also known as the Federal Analog Act was signed into law in an attempt to address designer drugs just hitting the market at that time. There are multiple loopholes in this law however, including one that I mentioned on the last slide. To be considered a controlled substance analog under this act a substance needs to be made for human consumption.

So continuing on our timeline in 2004 the first reports of SCs being sold online in Western Europe arose. And by-of- November of 2008 distribution was confirmed in the US with a seizure of a shipment in Dayton, Ohio. In 2009 Germany became the first country to criminalize SCs specifically banning two individual compounds. Manufacturers quickly circumvented this legislation by slightly changing the chemical composition and introducing a new compound into the market.

And in 2011 in light of increasing use nationwide the US Drug Enforcement Administration placed five SCs in Emergency Schedule I of the Controlled Substances Act therefy-thereby making it illegal to manufacture, distribute and possess these SCs. Schedule 1 drugs have no known accepted medical use and have a high potential for abuse.

In 2012 51 new SCs were identified compared to new- two new SCs in 2009. And in this year the Synthetic Drug Abuse Prevention Act which is part of the FDA Safety and Innovation Act of 2012 banned five different structural classes of SCs. In spite of increased legislation the use of SCs continued to increase - as well. And in 2015 a multistate outbreak of adverse events from SCs occurred which in some places continues to this day. This outbreak has been linked to the novel SC called MAB-CHMINACA.

So to reiterate synthetic cannabinoid use has become widespread over the last five years or so. Now I’ll talk about why this is a problem. First the number of reports of adverse events related to these substances has increased reaching an all-time high in 2015 with outbreaks of these adverse events recorded in multiple states.

The number of exposure calls to poison centers jumped from 2700 in 2013 to 7800 in 2015. Because of the unpredictable nature of the contents and the constant introduction of new SCs in the market, the clinical effects of SCs are not consistent and can be severe. For example SCs have been linked to acute kidney injury, cardiac events, psychosis, and seizures.

Though unpredictable, it appears that over time the severity of illness associated with SCs has been increasing. There are a number of theories of why this might be happening including simply an increased awareness and reporting of these adverse events. Another thought is that since newer SCs are being developed so rapidly there hasn’t been time to learn about their pharmacokinetics or how they bind to the cannabinoid receptor. So it’s possible that these newer compounds cause more severe health effects.

One reason for the increase in use is that there is widespread misperception about the safety and legality of these substances not only among the general public but also among the medical and public health community. And finally, one particular challenge faced by both public health and the medical community is that the contents of these products are completely unpredictable. The concentration of the active ingredient can vary significantly between batches or even within the same batch. These products can contain novel SCs, blends of SCs, or other psychoactive substance such as PCP or toxic chemicals such as formaldehyde.

To better illustrate this problem I’d like to discuss four recent outbreaks. First an outbreak in multiple states occurred in February 2012. In this outbreak the Wyoming Department of Health was first made aware of four previously healthy individuals who developed acute kidney injury after smoking SC products. The state launched a multistate collaboration between public health officials, laboratorians, toxicologists, and health providers to further investigate ultimately identifying 16 individuals who developed acute inj-kidney injury in six states.

These patients initially presented with flak-flank pain, nausea, and vomiting. Ultimately an SC called XLR11 was detected in eight of 16 of these patients. Two outbreaks in the fall of 2013, one in Colorado and one in Georgia, were both linked to an SC called ADB-PINACA. In Colorado, 221 people with agitated delirium linked to synthetic cannabinoid use were seen in EDs throughout the state. Ten of these individuals were ultimately admitted to the ICU. And in Georgia, 32 patients were seen in a single emergency department for agitated delirium with six eventual ICU admissions. Neither of these outbreaks were associated with any deaths.

And then in the spring of 2015, a multistate outbreak of adverse events related to SCs affected over 700 people in at least six states. This outbreak was unprecedented in-in terms of size and severity. In Mississippi alone, over 700 people including nine deaths were linked to SC use.

Going back to data from poison centers from this time calls-calls for SC exposures nationwide jumped 330% between January 2015 and April 2015. Typical adverse events were altered mental status specifically agitated delirium, confusion and somnolence. The predominant SC identified in this most recent outbreak was MAB-CHMINACA however, in Mississippi 44% of patients who tested positive for SCs tested positive for multiple SC compounds suggesting that blends of SCs are common.

So what do we know at this time? These products are generally smoked but there are reports of vaping, ingesting, or snorting them in powdered form. And why do people use these products? Well first they’re generally cheaper than marijuana. A gram of SCs cost somewhere between 5 to 10 dollars compared to a starting price of about $20 per gram of marijuana. While they’re generally no longer openly displayed at convenient store or head shop counters SCs are so readily available oftentimes behind the counter at these same stores as well as online or through dealers.

SCs do have psychoactive effects and the desire for a novel high is cited as a reason for using them. Anecdotally some users seek out SCs reported to have severe health effects with the thought that there may also be associated more desirable psychoactive effects as well. The pervasiveness that these products are legal has led to the mis-belief that somehow SCs are as safe or even safer than marijuana. And finally these products are not detected on standard urine immunoassays making them an attractive option for people who want to use a psychoactive substance while evading standard drug testing.

We’ve seen use of these substances in both rural and urban areas throughout the country. Users are predominantly young men in their 20s and 30s. Previously published literature has shown that the people who use these substances frequently use other drugs including marijuana. And while use has been reported in all socioeconomic and racial groups, clusters of illness have been re-recently reported in adolescents, in the prison population, the military, and the homeless. The lower cost and the desire to avoid positive drug tests make synthetic cannabinoid products attractive alternatives to marijuana in these populations.

At this time there are many gaps in our knowledge. First we don’t know what the baseline number of SC users and the patterns of use are. Next the health effects of new SC compounds that are being continuously introduced into the market have proven to be unpredictable. The effects are for the most part nonspecific and no particular tox-toxidrome has emerged making it challenging to diagnose intoxication based on clinical effects alone.

Further complicating matters, only a couple of specialized research labs in the US have the capability to detec-detect novel synthetic cannabinoids in either product or biological samples. And as I mentioned before, a rapid diagnostic test for SCs that is - that are already known isn’t available either.

Treatment options are largely supportive at this point. There are no anecdotes or specific therapies. We don’t know enough about the pharmacology or pharmacokinetics of these drugs to be able to provide specific patient care recommendations. And finally we don’t know what the long term effects of using these drugs are. It does appear that some users describe a sort of dependence to these drugs and have withdrawal symptoms when they try to stop use but this has not been well described. Also standardized recommendations for counseling and treatment have not been made.

So what are our next steps? Continued collaboration and communication between poison centers, state and local health departments, the CDC, healthcare facilities, law enforcement and the DEA is critically important in order to understand and mitigate the public health impact of SCs.

Case clusters are expect-expected to continue to occur in developing baseline understanding of the extent of SC use and a better understanding of the typical clinical effects of SCs would help alert medical and public health professionals to a cluster of illness or a new clinical effect. Healthcare providers should be encouraged to report suspected clusters which will help inform medical and public health professionals of evolving outbreaks.

The more we learn about synthetic cannabinoids and their use, the more equipped we will be to develop informed diagnosis and treatment guidelines. And finally we also recommend targeted messaging for high-risk populations and healthcare providers to increase awareness of this problem and to ultimately improve patient care.

One message to healthcare providers would be to consider SC intoxication in patients with mental status changes who have negative drug screens. Also reporting illnesses that you suspect are linked to SCs to your local poison center or health department will help public health identify clusters of illness quickly and rapidly respond if needed. And Dr. Arnold will be talking more about the importance of a close collaboration between healthcare providers, public health and poison centers in his talk.

And that is all I have for you this afternoon. And I’ll pass the podium on to Dr. Galli.

Dr. Robert Galli:
Well thank you very much. I’m at the University of Mississippi Medical Center and as was mentioned by Dr. Kasper there was a significant outbreak in our state and probably the best catalogued event that we have to date. It started in early April when I received a call. I was on call for the poison center. We had four patients in our emergency department all screaming that they were on Spice. And while we see Spice on a regular basis it was really nothing super special except the numbers. And in fact within the next couple of weeks we had greater than 400 patients reported statewide. And our biggest concern of course was that six potential deaths were associated with that. I’ll give you the final numbers as we get towar-towards the end.

There were a lot of rumors around the state as to what this could be. Was this bath salts? And some coroner said MDMA and Spice. MDMA of course is Ecstasy. People were wondering how they could control patients and they wanted to take them down with a ketamine dart which was really which you use for elephants.

And more importantly I want to be able to emphasize the –the term synthetic marijuana really is a misnomer as Dr. Kasper had suggested. These are cannabinoids. They have nothing to do with marijuana. They are dangerous drugs that are really quite different. The formula you see on the left is what real THC is. That’s what mother-nature has made. And it’s been a relatively safe drug throughout the eons. I’m not a great chemist myself but I can certainly recognize that the formula on the right-hand side is certainly not the same thing. And that is a synthetic cannabinoid. That is the original Spice JWH018.

Mother-nature makes a couple of different chemicals. The one on the left again is THC tetrahydrocannabinol. The one on the right is cannabidiol which is a chemical that’s now being studied with no psychological effects but perhaps very effective in controlling intractable seizures in children in particular.

So let’s look at some of the drugs that we have that are out in population. Tobacco deaths almost half a million a year. And we know that tobacco is a problem legal as it is. Alcohol similarly, 27,000. Now these are numbers from 2011 and I will tell you that 2011 is kind of a hallmark year and it’ll come up several times during the talk.

Twenty-seven thousand alcohol deaths not from car wrecks but just from the alcohol effects itself. Prescription painkillers back then was 17,000. We know it’s a lot higher than that, cocaine perhaps about stable. Heroine deaths at 4000 we know is a lot higher now, but notice marijuana deaths. Year after year there have been no reported deaths associated with marijuana which I could confidently talk about up until this last year when some jerk was being followed by the cops and he swallowed his bag of weed and choked to death on it. So I’m not so sure that’s a direct effect of marijuana. But in general marijuana is a pretty safe drug, not so with synthetic cannabinoids.

THC is a partial agonist co-combining with or connecting to the cannabinoid binding Site 1 in the CNS. These are full agonists which means they are anywhere from ten and 200 times stronger than THC. First developed as was mentioned way back into the 80s, there were several different series of these. And these were put together by drug companies and by college university chemists.

JWH018 is the first Spice and called Spice only cause it was packaged in a little container that somebody made the name up. But this was John William Huffman, hence JWH. And 018 was the first one that was discovered in this bag of potpourri.

AM2201 Alexander Makriyannis is a chemist who put together the first K2. But notice there’s several of the series. Again these were drugs that were being studied carefully by university and-and pharmaceutical chemists who were trying to come up with precursors of drug that could potentially be used for analgesics, for muscle spasms of multiple sclerosis, maybe as anti-nausea agents for chemotherapy patients. And so there were significant studies looking at the pharmacokinetics of these drugs because the understanding was that these would be consumed by human beings. That has substantially changed.

So here’s JWH018. That’s Spice on the left, and on the right you’ll notice that is K2. The slight difference that you’ll find is that there’s a fluoride group versus the methyl group, and that really is the only difference in these two chemicals when they were first introduced. Again they were labeled as not for human consumption but it was only up until two thousand and eight when they were studied in Europe that it was determined that these little bags of potpourri were actually basically vehicles for drug use.

This is a little bit blurry but in the United States in 2010 we had 3000 calls to poison centers across the country. That doubled in 2011 to just a little under 6000. And we were figuring my goodness there’s something significant about this -6000 calls that’s dramatic, again 2010 to 2011.

Well there is a group at the University of Michigan called Monitoring the Future. And they have an annual study that they look at kids in grade school and in high school. This is a-the view of what the seniors look like in 2011. Notice that marijuana was the most commonly abused drugs among seniors in high school at 36%. But second on that list was synthetic marijuana, they called it unfortunately, but that’s 11%. That’s 11% of 3.5 million seniors. So that’s 375,000 people that are using or were using in 2011 synthetic cannabinoids and those are only seniors in high school. So you can imagine that this has been under the radar for quite some period of time. As it turns out, I am told that the reactions from smoking marijuana are dry mouth, increased breathing rate, increased appetite, relaxation and synthetic cannabinoids do essentially the same thing.

Marijuana also from the psychological effect is meant to be a feeling of relaxation. People do recreational drugs not because they want to get naked and run in the street. They want to have some sense of a good effect of a relaxing effect. Paranoia and anxiety of course happens when you see the blue lights in your rearview mirror. But in essence the synthetic cannabinoids do exactly the same thing. But unfortunately what we’re seeing in them now is ten to 200 times stronger. So again synthetic cannabinoids have a similar desired effect as THC.

In 2010, David Mitchell Rozga unfortunately, a teen from Iowa shot himself in the head and his friends admitted that he had been smoking K2 the hour before that so the association was fairly obvious. That similar – right after that Chuck Grassley, his State Senator introduced legislation that Dr. Kasper referred to and that made Schedule 1 drugs out of the synthetic cannabinoids with which we were familiar.

In 2012 it was understood that there were a heck of a lot more of these and so they were all included under Schedule 1, which means if you smoked them, if you sold them, if you bought them and you were caught you’d go to jail. Unfortunately it also meant that researchers would have a really hard time trying to be able to get a hold of them to look at some of the effects that they were having. It also meant that if these were illegal, then modifications were going to be made and they were made by rogue chemists, typically in China, which adjusted the formulation of these drug somewhat.

And so what we’re seeing over the years here’s JWH018 and you can see how that modified AM2201. We talked about this one little fluoride change. Through the years the chemicals change rather substantially but each time only a modest change. Dr. Kasper membered – mentioned ABD–PINACA of late AB-CHMINACA and MAB-CHMINACA are the key drugs.

AB-CHMINACA was popular on the streets in October of 2014. It was reported that across the country there were some 200 exposures and six deaths associated with it. The DEA did what was called a fast tracking maneuver in order to be able to make that illegal and as a result technically that was now Schedule 1.

What we found was a slight change. Instead of this, we had this, which is a methyl group hence the MAB-CHMINACA. And each of the-the letters in each of these names are associated with a part of the chemical themselves. And it turns out this was the new drug that came out in April of this last year. So while you might have certain effects from the-the true tetrahydrocannabinol what we are seeing now was much higher levels of hypertension and tachycardia. Deaths were probably associated with dysryths-dysrhythmias. We had one reported case and again this was now the beginning of April of last year so just about a year ago.

The – and the ambulance people mentioned to me that they had had a death, that there was one guy who was in a club who took one hit off of somebody’s pipe, dropped dead on the floor. Literally you’d have to assume that that would be some type of a dysrhythmia. What we started seeing quite more frequently however, with the psychological effects, which was hallucinations and psychosis that were really quite substantial.

This was from the cover of the New York Times and this unfortunately is what happens to the end result of an awful lot of our players who come in just so agitated that in order to control them and to protect the healthcare workers they really need to be sedated. These are the chemists the put these chemicals together unfortunately and there was one arrest that was made in Jackson at around that same time. What they used was something that was called fumaric acid but that we know was not and it came in a 2 kilo bag and it was mixed with Damiana leaf. Basically the process here is to have some type of herbal so that you can douse this. You can see that we have all of these plastic bins and so the Damiana leaf is put in the bins and it is dissolved in acetone. This is probably the equivalent of what they used for a fan in the hood. You can tell this was not really very sophisticated.

So here in the bucket you’ll find the chemical. It is hydrophobic which means you cannot dissolve it in water and so acetone is used. And a couple of gallons of acetone would now dissolve the chemical which is then sprayed on the Damiana leaves and now you have your product. In one place in order to try to get some quality control they used a cement mixer to make sure that it was evenly distributed. Packaged in bags like this or even in just regular plastic bags it is sold on the street quite inexpensively.

When we noticed this outbreak in our state we asked all the hospitals to try to collect some samples to us. We sent over 200 to UCSF where they were able to determine that 64% were MAB-CHMINACA which was this new chemical that now had finally hit the street. But it was not isolated to just MAB-CHMINACA. They found all of these other chemicals as well associated with samples that we collected across the state either from blood and urine or from actual herbal samples themselves.

So what are they - what do we see? In particular this is important for people in the EMS field. It’s going to be agitation and it can be really quite severe. We found that Zyprexa and Geodon were probably the best drugs in order to be able to control them. Elevating creatinines were common once we got them into the emergency department. And just like with PCP when they are really using their muscle incredibly they are breaking down some muscle tissues and you’d see it a lot.

In many cases they came in totally fine. We had one mom who saw her son was a little bit altered and heard all the news that they-he- he had this horrible chemical. Basically she just ruined his high as far as he was concerned. But in most other cases when they present to the healthcare providers they are going to be significantly agitated. And if severely agitated really the only way to be able to control them is with paralysis and intubation once you get them to the emergency department.

To give you an idea how things changed for us you can see here that from January until the end of March we would see in the state of Mississippi – and these are data from the entire state of EMS runs – 0 to 5 cases a day. It was only with this outbreak of MAB-CHMINACA that we’re getting as much as 24 cases in a single day across the state. The numbers eventually came to 1263 cases in the state of Mississippi that we were able to catalog in an eight week period of time, 14% of those were treated and released in the emergency department, almost 60% required at least 23 hour observation admissions. Full admissions were 22% many of those associated with psychiatry service and 5% of those were - had to be in the intensive care unit. Unfortunately we had as many as 17 people who died in our state. And that really is what’s so problematic about this.

Right now where we go? Well the DEA and the Mississippi Bureau of Narcotics are surveying the Internet to try to see what’s going out on –on the a- the Web these days. And there are several new chemicals that apparently are in the pipeline. As was mentioned CDC, public health really want to be able to catalog this. And Dr. Arnold’s going to be discussing that to a greater degree.

And I’m just going to throw this out is-as perhaps blasphemous but I have a colleague who graduated here and is now doing a medical toxicology fellowship in Colorado. And as you’re well aware they have legalized marijuana in the state of Colorado. As I mentioned this horrible outbreak that we had and the deaths associated with he said he’s not seen any Spice whatsoever. That’s because everybody’s buzzed up on marijuana, the relatively safe drug. And they had none of the similar complications that we were seeing.

Oregon, Alaska, DC are the areas that are now starting to do this. I think we need to watch tentatively as to what happens. But there is no question that the synthetic cannabinoids right now particularly when they are just being ad lib changed and thrown onto the populace are really quite the dangerous set of chemicals. And with that I will pass this on to Dr. Arnold.

Dr. Justin Arnold:    
Okay. So I’m going to talk a little bit about the interaction between practitioners, poison centers, and public health and how we can all work together to-to further address these issues. So a little bit of history, I think most people are pretty familiar with poison centers as a resource for poisonings and overdoses. But I kind of want to delineate how poison centers have also evolved to really serve in a broader public health capacity.

Originally poison centers were developed out of Chicago in 1953. They kind of quickly expanded to offering their services to public and layperson callers. At one point by - in the 1970s we were seeing as many as 600 poison centers across the country. The American Association of Poison Control Centers or AAPCC, then began to regionalize these services. And then we saw a pretty impressive consolidation of these centers as well as a-a more consistent services that they provided throughout the 1980s and 1990s.

There were two things that were really significant in the early 2000s that really I think pushed poison centers to be able to help in the public health effort, one being the Amendment of Title 12 of the Public Health Services Act in 2003 which allowed poison centers to function as a public health capacity. And then two in 2006 the - there was information about a Web based electronic reporting system for all poison centers. And we’ll talk more detail about that and how we can use that for both epidemiologic purposes as well as research purposes.

Poison centers today;- there are 55 poison centers as of 2014 across the United States. They’re seeing over 2.1 million calls for human exposures, over 56,000 calls for animal exposures and about 600,000 calls for information - questions about drugs, medications and safety. Additionally, poison centers were also reporting about 2.6 million outgoing calls where poison centers were following-up on patients and that they-they were called on initially.

You can see the dots kind of scattered throughout the United States. And like I said it does cover all 50 states as well as Washington DC, Puerto Rico, the US Virgin Islands, Guam, American Samoa, and the Federated States of Micronesia. Now this number’s also if you look at this national base this is-this is a call every 14.6 seconds that the poison centers are receiving. Poison centers are also staffed 24 hours a day every day of the year and the services are both free of charge to the end-user as well as confidential.

The -again we managed exposure calls so if you’ve had exposure to a medication or information calls if you have a question about a medication or drug. And again we do field calls as well to kind of close the loop with these individuals. Again the poison centers today address both the lay public as well as medical professionals and you’ll see there’s a significant amount of overlap so the communication is oftentimes communicated a little bit differently.

Lay public can call regarding accidental poisonings, ingestion as well as envenomations. They can call for information on pill identification. Poison centers also provide education to their communities and some, though not many poison centers, also provide pet calls. Medical professionals when they call, can also address some of the same issues but will get more specific treatment recommendations, again pill identification. And most poison centers offer- also offer consultation with medical toxicologists. So there’s medical professionals at the physician levels who have a significant amount of expertise in the field of toxicology can offer that to the a- the caller.

There are also public health benefits. And if you look at poison centers this is really delineated into five different key functions. First poison centers are accessible and affordable. There’s no direct cost to end-user. Information is only a call away and people know how to reach the poison center. Second there is also large reductions in healthcare costs associated with poison centers. There’s been estimates in 1997 that the poison centers across the country decreased ED visits by roughly three-350,000 visits for non-toxic exposures. And that correlates with a total cost savings in 1997 of more than $310 million. It also has been known to decrease length of stay.

There’s also Toxico and public health surveillance efforts and we’ll talk about more of this in just a moment. Fourth there’s also a focus on education for both the lay public as well as the medical profession for medical education, teaching, nursing and pharmacy students, medical students, residents and medical toxicology fellows. And then finally there’s also research, and we’ll talk again a little bit about this and how that Web-based electronic recording system has really kind of pushed the research efforts further along.

At poison centers if we talk about organization, poison centers are going to be led by both a managing director who is usually a pharmacist or a nurse with a- the certification by ABAT which is the American Board of Applied Toxicology as well as a medical director who’s a physician who’s board certified in medical toxicology.

The core of really a poison center is the SPIs which is a Specialist in Poison Information. These are the front-line call takers who have received special training oftentimes only available at the poison centers. Most of these will be pharmacists or nurses. And for – there’s a select group of SPIs that kind of have an additional amount of training as well as the certification called a CSPI, a Certified Specialist in Poison Information. And they receive a significant amount of education again logging more than 2000 calls, more than 2000 hours on the phones with poison centers and a rel- relatively difficult examination.

This graph shows the number of calls per day and I apologize a little bit small on the screen here. The number of calls per day of human exposures are in red. In blue are the number of information calls and the line on the bottom that’s green are the number of animal calls. You can see that there is seasonal variation where we see peak calls in the summer and trough calls in the winter. And you can also see there’s an overall slightly downward trend in the number of calls for exposures the poison centers are getting that we know the a- the number from healthcare providers as well as the complexity of the calls are going up. And if you look here you’ll see of all the calls that poison centers do receive still over 93% of them originate from-from individual residences and not necessarily for healthcare providers. So this is significant because what this really tells us is that-that patients, individuals and the lay public know that we’re around and they know how to reach us.

The National Poison Data System is the Web-based tool that was introduced in 2006 that I mentioned earlier. And it’s a very significant tool that exists. This is something that is the only real – pardon me, the only near real-time public health surveillance tool that exists in the United States at this time. It actively monitors – it’s actually monitored by the AAPCC as well as the CDC and some public health departments for anomalies that may rise to the level of being a public health threat. And again some poison centers and health departments also use this for –for anomaly identification.

It also serves as a repository for all the data obtained by the US poison centers. So every poison center across the country automatically uploads their cases on real –on near real-time every eight minutes. So it’s very easy to really get a very good grasp and you’re only eight minutes potentially behind on real-time national data.

This flowsheet shows us how information goes into the NPDS system as well as the end-users and what you can see is the boxes that are shaded gray are going to be entities that put information into NPDS while the white boxes are going to be the end-users. And you can see the general public as well as healthcare professionals and practitioners will call the poison centers, the poison centers upload the information to NPDS and NPDS is accessed by regional poison centers, CDC, the AAPCC surveillance team, as well as again some state and local health departments.

And what’s interesting about this-the NPDS system again is –the data is continuously monitored using very specific surveillance algorithms. So these algorithms look for things like the total human call volume over a certain time. It looks for clinical effects, total numbers over a certain number of time, as well as case based specific volumes. So if we’re looking for a specific exposure to a substance, ricin would be a good example, we would want to know every time one case of ricin is reported. But we may also want to know like in this case if marijuana or synthetic cannabinoids are being reported above a determined threshold.

And the way that this does - the way we do this is the NPDS actually is based on historical averages from the same location in the same time period using previous NPDS data. So it’s- it’s so many standard deviations above what the average norm was for the same time in the same place that the data is being uploaded from.

And again once somebody reaches the level of an anomaly that’s going to get reported automatically and alert the APCC surveillance team, the CDC Health Studies Branch as well as a designee for the poison center as well and the-the state public health department. This is an example of 11 of the case based definitions the CDC uses to identify these anomalies. And some of these you can see are very simple. For example if you look down to ciguatera, ciguatera is simply an-an exposure that’s reported and logged as an exposure of ciguatera will generate an alert. Other things like ricin for example, if ricin is recorded that will also generate an alert. But we also use syndromic surveillance as well for something like ricin. So if an individual calls the poison center and says that they’re hypotensive, they’re in renal failure, they’ve got it increased CK and they’re not a mushroom ingestion that will trigger a potential alert for ricin. And then that would end up being reviewed further in detail to see if this really was a case of ricin or not.

So again when you look at that NPDS dat-data flow the information that does come in really is critical to get back to the practitioner. So we really see that state and local health departments once they use this information to identify public health threat will turn around and implement public health interventions, HAN alerts - different things like that back to the practitioners. So it really is the data coming in is really important so that the data that goes out can be helpful to the end-users and that particularly would be the health professionals.

So poison centers do have an expanded role in the public health threat- threats particularly in augmenting the response. So we can customize surveillance definitions based on the current threat as well as access and share the information and also look at national aggregate data as well. So- so this information can be shared with public health, regulatory agencies, government agencies as well so- so that everybody’s kind of on the same page and really looking at real-time relevant information.

The other thing that poison centers really have - are in a good position to- to expand on is that they’re always staffed. So some states currently are using poison centers with additional funding to do things like public health after hours lines to assist in outbreak information and messaging and monitoring, and a good example like that would have been Ebola and flu. Many poison centers had a hotline that would answer questions and direct patients on questions with people in flu.

And again it also serves as a centralized data repository. So NPDS is excellent at really collecting that information in near real-time and getting it quickly to the end-users. And this is what actually was the really probably the strongest thing that we saw with the synthetic cannabinoid outbreak in April of 2015. So again the key collaborations I think going forward to- to rapidly collect the data, interpret the data and integrate it, it really is important that we have practitioners playing a key role in reporting cases, reporting symptoms accurately. We- we need to have the state and local health departments in a position to really receive this information, use this information and put the information back out to the practitioners. And poison centers again I think have to maintain a degree of flexibility and I think there are- are well prepared to and adapt to response to the public health emergencies.

So again the synthetic cannabinoid outbreak in Mississippi, was a great example of the collaboration with contributors and end-users of poison center data. So initially in this outbreak the Mississippi Department of Health reached out to practitioners using a data collection tool and a HAN message. That data was collected by the Mississippi Department of Health as well as the Mississippi Poison Control Center.

It was entered into NPDS and then the NPDS data was used to look at identification of new cases, demographics, clinical features as well as the severity of cases and outcomes. And that was also compared to national data that the CDC provided for us and allowed us to kind of track this - this outbreak across country. And then in the end what that really translated to was the Mississippi Department of Health was able to provide guidance and public health interventions, resources and tools to the practitioners that were actually on the front lines managing this. So again this is really I think an importance emphasis here on the collaboration between practitioners, poison centers and health departments going forward especially in outbreaks just like this. And these are my references and I’ll turn it back over to Mr. Khan.

Ibad Khan:         
Thank you presenters for providing our COCA audience with such a wealth of information. We will now open up the lines for the question and answer session. Questions are limited to clinicians only. For those who may have media questions please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. If you are a patient, please refer your questions to your healthcare provider. When asking a question please state your organization and also remember you can submit questions through the Webinar system as well. Jill please open the line for questions and answers.

Coordinator:       
Thank you so much. At this time if you’d like to ask a question over the phone please press Star 1 on your touch-tone phone, please record your name and organization to be introduced into the call. Once again it is Star 1 at this time.

Ibad Khan:         
While we’re waiting for the first question on the phone I would like to pose a question to the presenters that we received through the Webinar system. The question states the SCs that can be ingested or snorted by the individual- have you seen any increased adverse effects with one route over the other?

Dr. Robert Galli:
This is Dr. Galli speaking. From the clinical perspective no. Most all the time though they are either smoked or vaped and it seems to be the most popular route of administration. Again we don’t know how many of them are getting the intended high. All we see is the people - are the people who wind up having an adverse outcome.

Dr. Amelia Kasper:  
And this is Amy Kasper. Yes to reiterate- reiterate that definitely the majority of the reports that come out say that people are mostly smoking these substances, I-  the ingestion and the snorting are very rare. And we really don’t know much- they’re so rare we don’t really don’t know what the effects of that are.

Ibad Khan:         
Thank you. Jill, do we have a question on the phone?

Coordinator:       
We have one question it’s from Sylvia Nye. Ms. Nye please state your organization.

Sylvia Nye:          
Oh. Thank you very much. It’s been answered.

Coordinator:       
Thank you ma’am. One moment please.

Ibad Khan:         
While we’re waiting for the next question

Coordinator:       
We have another ca-

Ibad Khan:         
We have another question in the Webinar

Coordinator:       
Wait.

Ibad Khan:         
system I would like to ask. This question is directed towards Dr. Kasper. How is CDC working with public health departments on this issue?

Dr. Amelia Kasper:  
So thank you. This is Amy Kasper. Yes so we are available to- at any point if anyone has any questions or would like technical assistance our branch is happy to provide that. We have had experience with multiple health departments over the past year who have reached out to us to ask about what - how best to respond to the outbreaks that they’re experiencing in their states.

We’re also going to be having a- a panel discussion at the upcoming Council for State and Territorial Epidemiologist Conference in June. So we can all get together, CDC and state and local health departments to discuss what tools we need to develop that would be useful for people at the state and local level to better address the threats. So nothing specific right now but they are- there are discussions involving a toolkit perhaps with questionnaires. And again we’re happy to provide technical assistance to anyone who would like some.

Ibad Khan:         
Thank you. Jill, do we have a question on the phone?

Coordinator:       
We have a question from Carol Burley. Ma’am please state your organization.

Carol Burley:      
Mojave Mental Health Clinic. My question is how long does the psychosis last usually or what’s the longest it’s lasted?

Dr. Robert Galli:
I’ll give that a stab this is Bob Galli. We found that most patients even those that were requiring intensive care admissions the drug would probably clear between six and 16 hours which is why the 23 hour hospitalization was the most common.

And while that was a quote psychotic reaction it was typically associated with the drug itself. It was the rare patient where this set off a true psychiatric event that required hospitalization on our psych floors.

Carol Burley:      
Thank you.

Ibad Khan:         
Jill, do we have another question on the phone?

Coordinator:       
We have no more questions at this time Mr. Kahn. Once again please press Star 1 and record your name to ask a question.

Ibad Khan:         
While we’re waiting for more questions on the phone I do have another question through the Webinar system that I would like to pose to our presenters. This question, to give context, seems to allude to some international drug safety consideration.

The question is, is there any international pressure to stop the manufacturing and/or importing of these products that you’re aware of?

Dr. Robert Galli:
I can address that. This is Bob Galli once again. I have had reasonable contact with one the Mississippi Bureau of Narcotics but more importantly the DEA. Most all of this is now coming from China. The United States manufacture of the actual chemicals has been close to eliminated.

Of course once the drug is sent here it does need to be mixed up in order to be able to be used and distributed and so the - each statewide agency is working on that. But, you know, the interaction with China is really the most important thing.

I don’t know if anyone has seen it but I would recommend that you do go to HBO’s presentation of a show called Vice where they literally toured one of the chemical manufacturers in China to see how these things were made.

There is a lot of interdiction of drug is being sent from China to the United States by DEA. But in order to put pressure on their country to stop this, you know, that gets into a relatively high negotiating political level.

Ibad Khan:         
Thank you sir. Jill, do we have a question on the line?

Coordinator:       
We have one from Lafonda Pluff. Please state your organization ma’am.

Lafonda Pluff:    
Yes ma’am I’m with the city of Texarkana, Texas.

Coordinator:       
Go right ahead ma’am.

Lafonda Pluff:    
Okay. My question is, is there a specific drug screen that will detect these chemicals?

Dr. Robert Galli:
So this is Bob Galli once again. That’s kind of the reason why this is used. There isn’t. If you look at something like marijuana there is really one active ingredient and that is THC.

In order to develop some kind of a- a testing device an awful lot of research needs to go into what in order to do that in relatively quick fashion. We use urine drug screens for a variety of chemicals but these are stable chemicals that are the same chemical each time and so therefore it’s relatively easy to process.

The synthetic cannabinoids number into the many hundreds of chemicals. And so they would have to be developed a separate chemical test for each and every one of those. As you saw from the screen that I showed when we had 200 samples sent in there were probably as many as 30 different chemicals that were identified. And in order to do that it’s really hard.

The classic example is one guy who we had EMS was called as well as the police because he was out on the streets of Jackson with no shirt on and his pants and underwear down to his ankles. He was flopping around in the grass with about 15 people videotaping him. EMS was able, to since he had an exposed buttock, to give them a hit of Geodon and he came in.

Looking through his clothes trying to identify him in one pocket I found a paystub which was- showed that he was a security guard which meant that he was going to be drug tested relatively frequently. So if he used synthetic cannabinoids he would test negative.

In his other pocket was a Mississippi Department of Corrections probation officer. He was in the early release program, once again tested frequently. There just is no way to be able to do this unless you’re in a super-sophisticated lab that most hospitals just cannot do.

Dr. Justin Arnold:    
And this is Dr. Arnold as well. I’ll just also add the- the other challenge and there is - there are a few commercial labs that are starting to develop assays for this. But the challenge is gonna- again going to be understanding the - that specific drug screening and what it does and does not test for and the-the-the rapid evolution of the-of the different iterations of these drugs.

And so if there is a commercial assay you test the patient if- if it does result positive for one of the drugs that they test that’s- that’s – that may be helpful. If it tests negative it’s still- it still is very difficult to interpret that because you don’t know if- if it’s testing negative because the drug is not there or it is testing negative because this is a new iteration of a drug that isn’t part of that panel yet.

So even as you start to come to market which I anticipate they probably will at some point, interpreting these drug screens is not going to be as simple as a- a positive or a negative result.

Lafonda Pluff:    
Okay.

Dr. Robert Galli:
This is Dr. Galli again. In Mississippi in particular the first generation drugs can be tested for. But that would be the Spice and K2. And we almost never see that on the streets anymore.

Lafonda Pluff:    
But they don’t see that very much anymore. They’re- they’re progressing them.

Man:                    
(Unintelligible). They’re progressing them. That’s what they want (unintelligible) to pick that up anymore.

Lafonda Pluff:    
Okay.

Ibad Khan:         
Thank you so much. Jill, do we have another question online?

Coordinator:       
We have no further questions at this time sir.

Ibad Khan:         
Okay. While we’re waiting to see if we have any more questions I will do one more question from the Webinar system and this goes along with the previous question. Dr. Kasper are you aware of the CDC developing any methods to measure or analyze these chemicals in clinical specimens?

Dr. Amelia Kasper:  
Thank you for that question. No there is no current plans to do that at this time though it is - that is something that we would like to explore at some point that’s- that’s not being discussed right now.

Ibad Khan:         
Thank you Dr. Kasper. Jill, do we have any questions on the phone line?

Okay hearing none, I would like to on behalf of COCA thank everyone for joining us today with a special thank you to our presenter’s doctors Kasper, Galli, and Arnold.

We invite you to communicate with our presenters after the Webinar. If you have additional questions for today’s presenters pea-please email us at coca@cdc.gov, that’s coca@cdc.gov.

Put March 31st COCA call in the subject line of your email and we will ensure that your question is forwarded to the presenters for a response. Again that email address is coca@cdc.gov.

The recording of this call and the transcript will be posted to the COCA Web site at emergency.cdc.gov/coca within the next few days.

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Coordinator:       
That does conclude today’s conference call. We thank you all for participating. You may now disconnect and have a great rest of your day.