Medical Marijuana Workshop – Part 3/3 (Audio)

so I want to tell you my story from a personal perspective because of course throughout my career recent career in this field often people get misapprehensions or miss impressions about where I’m coming from so I’d like to begin actually in 1996 at that time course proposition 215 had just been passed and unfortunately that year I was diagnosed with hepatitis C and don’t know where I got it from never been IV drug user but anyways there I was and so in 1997 I entered a clinical trial at the Veterans Hospital here in San Francisco for pegylated interferon which was the new standard of care at that time and of course i interferon has a large impact on one’s immune system there’s many side effects from that medication including lack of appetite insomnia skin rashes psychological issues in terms of clinical depression never been a depressed today in my life until I started shooting interferon right but that certainly brought me to that point so my sought out to a medical marijuana you know to mitigate those symptoms of course proposition 215 had just been passed and it was available legal on the state level at that time and I certainly sought it out of course I i I’ve been using marijuana since nineteen sixty seven so I you know I was experienced with it knew what it was all about so it wasn’t a problem for me to get it or to make it available to myself to mitigate those symptoms the problem was that interferon caused me to be immunocompromised and you know my immune system was just like going right down the tubes I wasn’t that happy in terms of the level of microbiological contaminants and possible adulterants that might be found in medicine and I was able to access at that time and I was concerned you know in terms of my own safety and I knew everything that I could get would certainly be efficacious but in terms of its quality profile and its sanitation given the resume no compromise I had a lot of concern right so unfortunately that year of treatment in those drug trials failed and didn’t work and so you know I couldn’t put all that aside right well speed up to 2000 for a second drug had been improved called ribavirin for a dual a drug combination therapy that back really increased the side effects of the treatment all right these are 48 week treatment protocols so it’s not like your feelings of chemotherapy type drug so it’s not like chemotherapy or did you do for three months but your it’s a whole year all right so first year was already done second year tried it with the two drugs and of course i was using medical cannabis again to mitigate those symptoms after 50 weeks of treatment my immune system collapsed i developed epididymitis if you all know what that is I wouldn’t describe it to you the position is no rush to the emergency room you know put on morphine all that kind of stuff and again I I still it was not able to access a quality of medical cannabis different than what I was accessing in 97 so you know my background throughout the I was involved in international aid development programs i went to school here in berkeley and studied political sciences matter of fact and then international management doctor then worked for various nonprofit international aid organizations throughout the 80s and so I was an internationalist in perspective if you will and was a generalist in the sense that I was sent in to different countries or political conflict and have to build industries either cottage industries or medium scale industries and supply chain solutions so in 1990 I got involved in the kashmir industry and develop some companies there and had a lot of experience in natural product manufacturing and whether it’s cashmere or cannabis or Chanel or chocolate all of those natural products share something in common in terms of the manufacturing process in any case I was following very closely the work at CMC are and the work of maps because I felt those two organizations were doing a really good science work as best as they could under the circumstances so after reviewing all the information a few years later in 2007 I decide to go to wh 0 in Geneva to visit a gentleman by the name of dr.William Shelton and I am back to our Dutch friends here in the audience no real years he was the first director of the office of medicinal cannabis of the Dutch Health Ministry and we’ll have been seconded to wh 0 to work on their office of controlled medicines which their brief is to get morphine to people who don’t acro can access morphine because of regressive drug laws you know there came about is the enabling legislation of the international treaties so will a directed me to the Hague to his colleagues are at his replacement dr.Marco van de Velde the office of medicinal cannabis and he passed me along to bed Rukia and a very well-known chemist by the name of dr. Arnold has comp who’s done a lot of very good work and so during that time of course we were just in a discussion period between 2007 2009 we got to know each other really well I was very excited about their work because you know a burglar cam was a little bit different than the other two nationally licensed sources of research grade material those other two sources being the University of Mississippi and nida and of course Prairie plant systems under health canada in canada so the difference between those is that NIDA and has Canada own the proprietary rights of those cultivars they essentially own what’s being done in Mississippi and Health Canada owns what Prairie plant systems does so there’s no commercial path if you will in spite of Rick’s great work in great efforts you know to bring cannabis through the FDA drug approval process and I might say if it was in this room he would tell you as he’s told me many times he believes in the drug approval process and the clinical trial process is being a valid methodology to determine you know the kinds of medicines that people have access to not that there shouldn’t be other points of access and community access and on all of that but in terms of the clinical trials and the science and methodology he agrees with that and so do i and that’s why I studied Rick Rick was doing very very closely with every transcript and everything that he wrote everything was written about maps one thing I discovered was in terms of the night of Monopoly and I think Ellen will bear this out because we’ve gone through the the legal analysis there one thing I discovered and brought up to Rick and Alan was that the monopoly and the PHS review committee only come to bear when one relies upon night of material from the national drug supply program and during the federal hearings however mix that wick so based applications Stephen Gus doctor dust from NIDA who was in charge the national drug supply program basically came out and said that as long as you don’t ask for our material you don’t have to go through the PHS review committee well that was a startling little tidbit of information in my mind because if that’s the case well then why can’t we just import research grade material from the Netherlands right because they were manufacturing it there and also it wasn’t under a lock box by the Canadian government or the US government well forward a little bit to 2009 and the election of President Obama and the Ogden memo that kind of gave the the folks of beggary can the space you might say the political space to call me up and say let’s form a joint venture and see if we can project our knowledge into other jurisdictions right and that’s what we did we formed the company called bedrich an international all right and essentially the admission of that company was to seek license to manufacture medicinal cannabis in any jurisdiction globally outside of the EU we’re better cam BB was already well positioned there so for number of years I traveled around the world in terms of looking at different locations and jurisdictions like Canada Israel Brazil various other countries that might either have medicinal cannabis programs or might be putting them in place in the near future so that we could seek out the ability to manufacture in those countries at the same time we will vary interested in clinical trial work so during the pursuit of that especially in Canada we prepared a clinical trial application for Health Canada and went ahead and submitted what’s called a pre CTA document same as a pre-ind document in that document you and this was done with a professor dr.Mark we’re from mcgill university i’m sure many of you have heard of him he is the preeminent canvas researcher in candid just as may be daunted as our preeminent researcher here in the in the u.s. so mark also receive funds from the Canadian government about 1.7 million dollars of the 7 million dollars that the Canadian government allotted for research they couldn’t actually put out all that money all at 1.7 million was Norris used up by mark and there were any other applications to get that money and so any case we filed in 2010 a pre CTA document in fact Health Canada said oops I think one of the best CTA documents they’ve ever seen cannabis or no cannabis and this is cannabis as a botanical drug not pharmaceutical eyes not extracts but cannabis flowers cannabis floss all right that is the essential medicine and that’s why we sought to do that and essentially the outcome of that submission was that Health Canada gave us the green light in the big conference room in Ottawa when we did our presentation when Mark went through the science and I went through some of the commercial and political aspects of what might be required officials in Health Canada were relieved you could just see a big sigh of relief that somebody was finally stepping forward to address the science questions here and not leave physicians and other healthcare professionals trying to prescribe an unapproved drug product they didn’t have enough data on right so I found great encouragement by the attitude of those officials in Canada unfortunately at the same time or just before that time there was a change of government in the Netherlands and you know this way so the Christian Yeah right the Christian Democrats were elected and many of you might have heard about the anti cannabis campaign that they were on you know close the coffee shops but they want a declare cannabis that’s fifteen percent THC or above to be a hard drug in the same category as heroin or cocaine and they eventually turn their attention to the medicinal cannabis program so of course we were having discussions all over the world and I was giving presentations and state legislatures and meeting with folks in the industry here on the state level not to do business per se you know because of course as a nationally licensed entity bedre can could not get involved in any activity that was in not in compliance with federal law because it would be blowback and problems for them problems for the dutch government but eventually I did very you guys probably ever heard of me because a very low profile kind of person but I did do a few press interviews that got the attention of the health ministry and basically they told edgar can that well either you guys back out of the US and forget about this or we’re going to cancel your contract and so when you only have one customer that’s that’s an existential threat and so when my dutch colleagues met me in ottawa we had to drop the hammer on me and in spite of our great investment both financially and timewise essentially they said to me hit that time Michael so sorry nothing we can do about it and you know what that was ok I mean that’s how things work out after all the model the baby can had was this is cannabis right so you can’t expect anything to kind of flow in the normal regular way that their things normally do so that disappeared for me and I decided to go back into treatment again on May twenty-fourth of 2011 FDA approved a third drug for hepatitis C a protease inhibitor called in civic and now as a three-drug combination I was the first person at kaiser to get access to that went to another year of treatment from summer of 2011 2012 and it worked this time and I was cured and so thanks thanks so thought was a net experience was a also left a strong impression on me in terms of medical science and the drug approval process in the guy who started the company in vertex he spent 20 years to bring in civic through the process raised seven billion dollars to do that there’s a long run but he is saving millions of lives as a result of that because when i started in ninety-seven eleven to fifteen percent curate and 2004’s ended up to thirty percent now it’s up to eighty-five ninety percent and they’re going to get rid of interferon and so the disease cured right for the world so although yes I totally support community based medicine and believe there should have a place still just as weak and other colleagues and scientists would say clinical trials and going through the rigors of those trials does have a place a place as well as some statements that Donald made at one point to me was that the only way this was going to make progress was when legalization took place so that’s certainly caught my attention right because I listened to my gurus and so in that sense you know I felt that the legalization of cannabis could facilitate it given the overwhelming a political opposition that we were seeing so just to move to the end of my story here because I’m probably about out of time a few months ago I received a call from a company called boat or analysis corporation and though tech analysis corporation is run by a gentleman a professor at UCLA by the memeber professor mark kleiman water broke marijuana legalization a couple years ago mark is a policy person thank you and as you might have heard there was an RFP put out by the state of Washington after the election last November to bring a group of consultants to advise the liquor board there to get some expertise in-house about the English through net RFP had fur categories to a product in industry and I was brought in as the team leader of that team and the second category was quality and testing David lamp at from steep hill labs here in Oakland is leading that team the third team is on consumption validation and that’s being run by the guys from RAND Corporation and the last team is on regulation and policy and that’s being run by dr.Kleinman and number of other guys from land and others so yes we would be raw brought into place to revise the board and part of the agenda up there you know is how to incorporate the state level medical marijuana system into the wider field of general adult use legalization I’m no longer with Bowtech although they got the contract I declined to sign a contact contract with them for a number of reasons I might not get into here but some of them have to do with policy disagreements with dr. Kleinman in terms of the risk evaluation of cannabis and a number of other factors as well so on now I saw that’s what I’m saying i have no no pony in this race here i don’t company now at all but where I’m focused right now actually is back up in Canada again because I don’t know if you folks have heard what’s going on there the restructuring medical cannabis system there are they’re going to allow commercial production facilities to come into place next year those who are facilities will operate under the authority of Health Canada the same standards that PPS is being held to right now will also be applied to those organizations but there will be competition between those commercial producers and those commercial producers would be able to sell directly to patients all right so they can achieve a low price point and affordability that way I don’t agree with everything the health canyon is doing up there for example it withdrawing personal production licenses from patients that don’t think that they should do that but you know that’s the decision they’ve made because of pressure from provincial and local government there there’s also no space really for the compassion clubs because of course the distribution system that they’re standing up is a direct sale from the factory right to the patient so although that’s helpful for the patient in terms of prices those patients can have access to a community-based organizations for all the other services that they might provide but again the constituency of the compassion clubs and the constituency of personal producers right I would say are a smaller burden and a smaller constituency than the patient’s themselves right and it’s also about the doctors you know because it was a big resistance in Canada from the physicians community about prescribing there that’s always been a really really big problem but the outcome of this new system will be now the monopoly will be and I’m looking forward to hear responsive my other presenters here because you know several years ago when I was pointed out to a learning to Rick that why are you persisting in annual trying to obtain material from nada you can’t take it to the drug approval process you’re very clear with everyone that that is your objective is the FDA drug approval process as right on the website there right so if you cannot use that material to go through the drug approval process why don’t we just bring your material from the Netherlands that’s commercially available for drug development but you know there are other motivations of course you know the in terms of overcoming the political log jam making a point with the deeply whatever those those reasons are those issues are now behind this Maps has now come to an end both both administratively and in terms the federal court system that I don’t think talking to Rick liberators and I’m further joy there so in terms of the future I hope that what we can do in Canada and I plan to participate up there is to produce a supply chain of medicinal cannabis that is research played that is pharmacy grade that can be distributed by a compassion clubs as well if they have the appropriate licenses to do so I see this as a game changing event in Canada because it’s going to be outside of the main patient basis will be ordinary prescription Health Canada really has the intention of treating this like any other medicine and the fact that we can create in a commercial framework will create the funding that will allow us to bring this from an unapproved drug product into an approved drug product at least for those people like myself rappin to need it on that quality control so thanks very much so what I’d like to do is just review some of the work that we’ve done and end by telling you some of the work I hope to do because probably since the last time you heard me I haven’t done anything new in this field but I do have a few irons in the fire so again as we all know from the story it was Rick Doblin sending a letter to the age program in 1992 after Mary Rothman AKA brownie mary was arrested in in Sonoma for making brownies for AIDS patients that inspired me through Rick’s persistence to take on the challenge of trying to investigate cannabis as medicine and this is a headline from one of our local gay papers back in 1994 which really is again what prompted this work because so many of the patients with hiv/aids that I was caring for were using cannabis so Rick the first effort that we tried to collaborate on was a forearm comparative outpatient evaluation of three different strengths of an alt H see that he was going to get from the netherlands vs dronabinol in patients with the AIDS wasting syndrome and of course that opened up all sorts of cans of worms because we couldn’t import cannabis from across international borders without the u.s.Saying it was okay and they wouldn’t say was okay until the Dutch said it was okay to export it so it was a big catch-22 that wasn’t going to work at all and then ultimately Alan leshner said that this the science was not there and that if we propose something that was favorably peer-reviewed he would consider providing cannabis for it so we did another much more study that we submitted tonita in 1996 which is when I finally learned that NIDA has a congressional mandate to only study substances of abuse as substances of abuse so as long as I was going to request to study cannabis for its potential therapeutic effectiveness they couldn’t fund it which is what I was asking for but they could probably give cannabis to another source so in 97 when the terrain changed in HIV when we got the availability of protease inhibitors which were effective drugs a new window of opportunity opened as Clint called it the other night he said I did a Trojan horse proposal with protease inhibitors there was an early report that somebody died of an overdose of ecstasy mixed with the protease inhibitor because they’re both metabolized by the same pathway in the liver and in checking cannabinoids are also metabolized by the same liver enzyme system so we proposed the study in 97 tonita to look at the safety of using inhaled cannabis in patients on protease inhibitors and we were going to compare that to the oil drain a banal which was licensed and available then it does turn out that the particular protease inhibitors that we were saying we wanted to investigate back then which are really no longer used anymore were metabolized by the same enzyme systems that metabolize some of the cannabinoids in cannabis so the original objective of our first study that we ever did back in 97 was to determine the safety and the toxicity of cannabinoids in patients with HIV on protease inhibitors asking the question whether there was a metabolic interaction between the cannabinoids and the protease inhibitors or possibly between the cannabinoids and the patient’s immune system that might alter the level of the AIDS virus in their bloodstream after 21 days of exposure and if there is such a difference does it matter whether the cannabinoids are inhaled or ingested by mouth and as long as we’re going to have patients in our clinical research center basically incarcerated for 25 days we were going to look at some effectiveness endpoints as well including caloric intake body weight etc so this was a prospective randomized partially blinded placebo-controlled trial in that patients who were smoking cannabis knew that they were smoking a real cannabis cigarette patients receiving a pill didn’t know if they were getting the dronabinol two and a half milligrams or the drune a banal placebo and they were exposed to whichever arm they were randomized to three times a day for 21 days and at the end of the well again what we looked at was the level of the AIDS virus the level of the protease inhibitors and immune function doing probably the most sophisticated battery of immune tests in response to cannabis that’s ever been done and the activity parameters again as I mentioned were things that we sort of snuck in there just to see if there was any potential benefit now all the all the cannabis that comes from NIDA comes pre rolled in Pall Mall rolling papers they each weigh about a gram each of the cigarettes and they’re there they’re sent to us in a sort of a coffee tin standing upright and they’re not twisted off at the end the cannabis is freeze-dried so it sort of flakes out and but it’s a bit it’s close to the gram that they thought they were and to standardize inhalation we use the famous Fulton puff procedure which you see here because we do want to you know have the benefit of appearing that we’re using and this is the standard sort of procedure that’s suggested to use in studies of inhaled cannabis and then we have a nurse who views the patient usually with the blind up in the in the room in our clinical research center we have the room is vented to the outside with a fan but unfortunately this is San Francisco General Hospital so the door in the hallway is about an inch off the floor so the nurses would roll up blankets and put them outside the patient’s door while they were smoking sort of the opposite of college is where every six so at the end of the day I don’t know is this a pointer no at the end of the day you can see the top line is the level of the patient’s viral load the change in their rival load and in all three arms there is no change in the level of the AIDS virus in the patient’s after 21 days of exposure interestingly those cd4 cells which are the helper T lymphocytes the cells that get infected by HIV and diminished actually increased in the cannabinoid groups both in the marijuana and in the dhryn a banal the cd8 cells which are the suppressor cells which fight virally infected cells and cancer cells were markedly increase statistically so in the cannabis group also increase in the dhryn a banal group but not as much and in contrast to the prior study of june a banal which showed that it increased appetite but not wait our patients after 21 days gained three point two kilos a kilo being 2.2 pounds so about seven pounds and the cannabis group gained a little over six and a half pounds whereas the placebo group also gained weight but not as much as the group receiving the cannabinoids so we concluded from that study that cannabinoids both smoked an oral didn’t alter levels of the AIDS virus and was on no a significant adverse effect on the immune system if anything there might have been a benefit and no clinically significant interaction between cannabinoids and the protease inhibitors and we saw the significant weight gain so the next we’ve heard from Senator John the Center for medicinal cannabis research was funded and founded much gratitude for the work that he did to get that done and the real goal of that Center was to make it easy for us to be able to jump through all the hoops that we needed to jump through that I had trouble with in my first study to obtain cannabis and approvals from all the regulatory agencies we needed to deal with and so with funding from the center for medicinal cannabis research I conducted I was awarded four different clinical trials and only completed two of them because for some reason I’ve had difficulty enrolling cancer patients in cannabis clinical trials in San Francisco why that is is we can discuss perhaps later but but the study that were very proud of was a study looking at cannabis in patients with HIV related painful peripheral nerve damage or peripheral neuropathy this was a problem in the past due to infection with the virus itself and the drugs that we use to treat it opiates were generally ineffective many people were treated with anticonvulsant switch also had side effects and might interfere with the HIV meds then we knew two things number one from an animal model of neuropathic pain which is the so-called rat tail flick model that can effective in that model of neuropathic pain and we also got from patients reports that G cannabis seems to work in this condition so first we did a 16 patient open-label study where we brought patients to our clinical research center and everybody smoked real cannabis three times a day for a week and we found that it decrease their pain so with that information we were able to calculate calculate the sample size that we would need to do a follow on placebo controlled trial where half of the patients smoked cannabis and the other half smoked cannabis placebo both from NIDA now how could you blind cannabis one would ask now remember the strength of the potency of night is cannabis is three-point-five percent THC so that’s a bit low and the cannabinoids are removed but the terpenoids and flavonoids which provide much of the smell remain so just smelling it you can’t really tell and second of all if you just do the Fulton tough procedure yourself inhale for five hold it for ten and repeat that a few times you get a little something just by doing that so you know we did do this clinical trial in a double-blind fashion and my colleagues from a pain Clinical Research Center felt that we needed to have a more objective anchor of the patients pain besides their report of their peripheral neuropathy pain because people who are you know reviewing our manuscript would say well gee you you allowed a lot of we want to see cannabis become a medicine and they’re going to be able to tell if they’re on placebo or real so the real people will say oh my pain went down and the placebo people say I have no effect so we did an experimental pain model to do something more objective we heated the forearm a patch with a thermode to 40 degrees Celsius for 15 minutes and then applied capsaicin cream which is the ingredient in chili peppers to the same heated patch and that creates an area of funny feeling and hypersensitivity around that rectangle that you can map out while the person is looking off in another direction before and after exposure to the analgesic and you can assess by how big the area of hippest Eva and allodynia are whether or not your intervention has been effective so we use this experimental pain model but in our study as well the results of this study was shown here patients were asked to keep a diary of their pain for the week before they came into the hospital they’re paying averaged about 60 on a scale of 0 to 100 and for the first two days they were just in the hospital without any smoking and their plane went down a little bit so it was about 52 and 53 in the placebo and the cannabis groups the bottom line is what happened when patients smoked the cannabis and you can see what we chose as a evidence that the drug was working was a reduction of thirty percent in their pain level and fifty-four percent of the cannabis smokers had that thirty percent reduction compared to twenty four percent of the participants who smoked placebo the top left shows you what happened after smoking the first cannabis cigarette to the neuropathic pain the placebo group had a nineteen percent decrease in their pain the group smoking cannabis had a seventy-four percent decrease and the bottom two panels show what happened to that area of funny feeling in the experimental pain model the top line is the placebo group and you can see that the area either stayed the same or actually increase whereas the bottom line was the group smoking cannabis then you can see that in the experimental pain model that also was reduced about thirty percent the same as what we saw in the peripheral neuropathic pain so we concluded that smoked cannabis is an effective treatment in patients with painful HIV related peripheral neuropathy and remember the definition of a schedule 1 substance is it has no reported medical use the CMC are funded three other studies looking at smoked cannabis in peripheral neuropathy and all of them demonstrated the same improvement and what’s more interesting is that to calculate the magnitude of the pain reduction we calculate something called the number needed to treat so how many people do we need to treat for one to have a benefit and for cannabis and peripheral neuropathy from our study it’s 3.6 from two other studies in HIV peripheral neuropathy it was 3.5 and 3.7 so that’s really consistent for studies done in three different places in three different populations of patients so I think that you know cannabis for peripheral neuropathy is definitely something that works and Mark where previously mentioned has done a study in Canada in patients with post-traumatic neuropathic pain and finds is the same so the next study we did was to address the concern of the Institute of Medicine work marijuana as medicine that came out in 1999 that said there is data that suggests that cannabis has some utility but studies should be done to develop of a non smoked rapid onset cannabinoid delivery system so we took that to heart and the Center for medicinal cannabis research then funded us in looking at the vaporization of cannabis through the volcano vaporizer this is basically a heating device with the fan the cannabis is put in the chamber and it blows up that balloon which can then be inhaled and vapors are cooler pure and probably less toxic than smoke and there may be more psycho activity as less of the THC is combusted so this is very busy but this was the easiest study I’ve ever done we in load 25 to 40 year-old chronic marijuana smokers we put them in our general Clinical Research Center for six days and on each of those six days they either vaporized or smoked half of an idle cigarette of three different strengths one point seven three point four and six point eight percent THC this first panel is the level of THC in the bloodstream you can see that they’re super imposable the second panel shows expired carbon monoxide which is a measure of exposure to noxious gases the bottom line that doesn’t change is the vaporize group the top line where you do have increased expired carbon monoxide other people smoking the cannabis cigarette the last panel shows the patients reported high and the the journal almost didn’t want to publish this because they wanted to know how I elevated that scale which was very difficult but you can see that the reported highs are also super imposable so we concluded that vaporization of cannabis is safe and effective the plasma THC levels are comparable the physiologic effects are comparable and expired carbon monoxide is decreased and when we ask patients which day they preferred 14 out of 20 chose a day where they actually vaporized and that could be because the night of cannabis is dehydrated needs to be rehydrated and is very harsh when smoked as a cigarette so our next studies then are all going to use the vaporization as a delivery system as opposed to combustion so the last study that I want to report on is is one that I think is very important and it’s looking at the potential interaction between cannabinoids and opioids because in mice and rat THC greatly enhances the analgesic effect of morphine in a synergistic fashion so one plus one equals five not to and cannabinoids and opioids interact with different receptors in the brain to bring about decrease pain so there is a possibility if you add cannabinoids to opioids that you can get away with a lower dose of opioids for a longer period of time and gets the same pain relief so the study we did we enroll patients with chronic pain on a stable dose of sustained release morphine or sustained release oxycodone in our general clinical research center and on the first day we drew their they’re opiate and then on the next day they were able to inhale cannabis vaporize three times a day and on day five the last day of the study we redrew the level of the opioids in their bloodstream we enrolled ten patients on the sustained release morphine and 11 on oxycodone to do a pharmacokinetic interaction study you don’t need more than 10 patients the average dose of morphine was 60 milligrams twice a day the oxycodone the sustained release was 50 milligrams twice a day and you can see the pain scores were slightly lower in the morphine cohort compared to the oxycodone group now this shows the level of the morphine in the blood the top line is the first day and the second line is after exposure to cannabis and you can see that the plasma level of the morphine is actually slightly decreased the this curve shows the oxycodone then you can see that over the course of the five days or that between day 1 and 5 there’s no real change in the level of oxycodone so with the potential decrease in the blood level or the same level you would expect that pain would either go up or stay the same and what we actually saw was overall patients came in with an average pain score of 40 and it dropped to 29 that’s a twenty-five percent reduction in that was statistically significant the pain reduction was greater in the morphine group where it was thirty-three percent reduced than it was in the oxycodone group where was twenty percent but the the numbers here are too small to really say anything about pain but we did conclude that co-administration of vaporized cannabis with oil sustained-release opiates is safe and appears to enhance the analgesic effect and if that happened it’s not a pharmacokinet interaction that is it’s not through increasing the plasma levels of the opiates it’s a so-called pharmacodynamic interaction and I believe that this small study actually changed some policy because prior to this study I’m aware that the VA and the Department of Defense would not provide chronic pain patients with opiates if they had a positive test for cannabis in their urine whereas now they do in fact they might not even test i’m not sure but i was happy with that so what’s next on the wish list actually i was visited by a basic science investigator from the university of minnesota about two years ago who has a mouse model of sickle cell disease and she said these mice are very responsive to cannabinoids with regards to decreasing pain inflammation and progression of disease and so she wanted to submit a large grant to the National Heart Lung and Blood Institute and she asked if I would write a human clinical trial to be part of this submission and we did and National Heart Lung and Blood Institute wanted to fund seven centers and she got the third best score and we had a phone call with nhlbi program people asking if who could perhaps get less money so that they could fund more centers and the council met and we were just about to get funded starting on April first when sequestration happened so in this study I’m hoping to do use a CBD THC blend and I’ve called NIDA and dr.L sulay and they do have about five percent THC five percent CBD blend that we using the study because I’m not sure if it’s THC or CBD that’s going to be working the best here with one of my neuro oncologists this is in the ocean disease paper sort of two steps ahead of where we are in reality but he and I that one of the neuron colleges at UCSF says the only thing that that unifies all of his long-standing glioblastoma multiforme II or brain tumor patients is that they all use cannabis so we are going to propose a clinical trial looking at cannabis oil to see if there’s an interaction between cannabis oil and the chemotherapy that we use in treating brain tumors that study again is just in the development phase again they do have cannabis oil at night and now because dr.L sulay from Mississippi donated some so that we could use it for our study but as yet that cannabis oil has not been used in humans so whether or not I’m going to have to jump through hoops to show that cannabis oil is safe when everybody in California and Colorado and everyplace else is already using it is something that that I don’t know then we need to do the definitive cannabinoid opioid interaction study with pain as the end point not the opioid levels and finally I cure many patients with cancer who remain disabled because they have peripheral neuropathy from the chemotherapy we use and one of my colleagues Andrea at the University of Indiana has a mouse model of chemotherapy-induced peripheral neuropathy that sensitive to cannabis that is cannabis not only treats it but seems to protect the mice from developing it so if I wasn’t having difficulties in rowland cancer patients in clinical trials i would have done this one quite a long time ago so that’s my wish list for the upcoming years i’m still going to continue to do this in answer to sort of michael’s questions why do this if it’s not going to be developed as a drug i think it’s to develop the database that shows that we in fact help people and as a doctor as an oncologist that’s sort of my credo that’s what i need to do and first do no harm so thank you for your attention thank you all for coming on this really exquisitely beautiful bay area day it’s good to see a nice gathering like this and I’d like to thank maps for inviting me to speak about marijuana and better health I think I start out talking about cancer and then maybe move into all sunders and a couple of other things if there’s time because this is really a fascinating field is so amazing what we’re learning when you look back at the point we’ve come from say during the 68 60s through the 70s when there was a little respite in the war on drugs and cannabis to the 80s when Reagan relaunched the Nixon’s war on cannabis and drugs in general with renewed gusto and through that whole time and then Bush and Clinton to hear what’s really amazing is what the sciences started telling us about this plant and what it does with human biology how it interacts with us because there’s 1,000 plus year history thousands of years plus history of using this plant as a medicinal agent for a whole host of ailments that have plagued humanity and that was dismissed through prohibition and they tried to bury it but it wouldn’t go so we’ve revived it and we’ve established a whole new branch of biological science that has arisen from studying what cannabis does for human health to human by a biological organism back in the early 70s there was a study that was done it was actually about 74 and this was at uva university of virginia charlottesville and it was an effort to sort of find out how carcinogenic marijuana is how dangerous THC is and to in general I suspect to generate propaganda to use to justify the war on cannabis and the results were pretty shocking it was a Munson at our was Vincent was the lead researcher and what they found was that when they implanted rats and mice were the lung tumor cells and then dosed them with a variety of cannabinoid CB n THC CBD in general the dose rats and mice had a longer survival rate and had a proportionate decrease in tumor viability this is pretty shocking because they had anticipated i think in finding the opposite and there is also some other changes that seemed to suggest that the cannabinoids might inhibit certain types of leukemia oh this was a pretty amazing study and unfortunately because of this whole marijuana phobia you that were entrenched in men it was dropped it was never taken and exploited and pursued and when we stop and think about that 1975 to today all the misery and suffering and possible premature deaths that have resulted from that it just seems like such a terrible terrible example of human folly so basically nothing really happened with cannabis and cancer other than innuendo and deceit being promulgated by the anti-drug agencies that claim that causes lung cancer destroys the immune system which will promote all forms of cancer and then sort of simultaneous to the mapping the discovery and mapping of the Indo cannabinoid receptors the first receptor was discovered in 1988 the cb1 receptor and that was plotted by Mary in the central nervous system and then there was another cannabinoid receptor located and found to be expressed in primarily immune to issue an organ tissue and I believe it was about 95 that it was found in spleen tissue and I actually remember when that study came through because it was very confusing we didn’t expect to find a cannabinoid receptor in spleen tissue and so that was all going on in this whole new pursuit was being followed this whole new line of research into where these receptors are whether expressed and what they do in conjunction with human health and biology and so in Madrid there was a researcher there is a researcher Manuel Guzman and his team and they were researching the metabolism of brain cells and what different compounds due to brain cell metabolism and because the cb1 receptor had been found in bone tissue that was one thing they wanted to look at what THC does two brain cells now to buy brain cells that are harvested from rats and mice astrocytes is incredibly expensive because they have to be harvested from these rats and preserved and transported whereas if you have astrocytoma which are brain the form of brain cancer cells they rapidly proliferate and you can get a line of these cells and basically produce your own research material without having to keep paying for newly harvested one so you have a nice regular supply of research material so they were using these astrocytomas to try and see how THC affected brain cell metabolism but as they said they couldn’t do a single study because every time they expose these cancer cells to THC they all died they were you know you wanting to do your research you start to do it boom your research material dissipates dies off collapses and so very intelligently and admirably they dropped the metabolism research and shifted right over into cancer research to see what this is about why is this happening and they went they looked at the the research material the previous body of data and the only thing they could find was the Munson study that was published in 75 so they started pursuing this line and looking at what THC and CBD and synthetic cannabinoids do in terms of these brain cancer cells and they were looking at glioblastoma cells too and they found that it’s quite amazing that THC attacks selectively the brain tumor cells and changes basically the signaling it would in the cell to change its viability it seems that THC is someone set a circuit breaker it interpolates in with the signaling process and reverses the production of pro cancer chemicals and increases the production of on antitumor chemicals so that the cells collapse and die and this is selective to the tumor cells so this research was pretty amazing they continued to look at this and pursue this and see how it works and then other researchers decided to pick it up and started looking at other forms of cancer and throughout the world research has been done in Italy Israel Germany very many places and what Thailand they have found is that a very effective and kreative tumor cells colon cancer cells breast cancer cells bile duct cancer cells and melanoma cells so there is this really amazing effect of cannabinoids selectively attacking cancer cells triggering what’s called apoptosis which is the dying off process and actually it possibly even enhancing the health of the surrounding tissue so this material has been growing and growing and growing and researchers have been exploiting it and on the other hand they’re sort of the guerilla movement of people having heard that this is happening that these compounds have anti-tumor effects and beginning to try and see if they could use them for health and there’s some interesting pathology coming out it’s all anecdotal at this point and it’s all underground because this research can’t really be done very easily and it’s certainly not being facilitated in the way it should it’s being suppressed but there’s a lot of anecdotal stories coming up with people who are using cuts and traded cannabis oils where a massive amount of cannabis is concentrated in to viscous thick oil and you’re able to dose yourself regularly with it and flood your system with these cannabinoids and really let let them have the ability that there’s enough volume to attack the cancer cells and either slow tumor growth stuck tumor growth or even reverse tumor growth and in the hashanah sees paper which is available here at the back there’s the story of Michelle Aldridge and she seems to have complete remission using cannabis oil and some dietary changes from lung cancer and the more and more of these stories coming up by now on rather than another patient who had a remission surprising omission using our grain of cannabis oil rice grain size dose in the evening and so this is something I think we really need to talk about and get out and push because there’s no reason we shouldn’t have something akin to a Manhattan Project to establish what the appropriate dosages how the deliverer no of cannabinoids works best for what cancels and stop alleviating so much human misery and grief because these things really do seem to have potential now it’s also interesting is that some of the actions of cannabinoids against cancer involve reducing inflammation attenuating the production of compounds in the body that produce inflammation like cytokines and nitric acid and as I said stimulating the production of more healthful nurturing chemicals in the body and this also involves the decrease of harmful oxidation and another aspect where cannabinoids work is in modulating our immune response sort of them almost acting like a referee to regulate how our immune system responds to different challenges that we have in day-to-day life and through our genetics and that’s also interesting is that it seems that cannabinoids are we were beginning to understand that they actually influence the expression of genes and this is why I want to get more into this and learn more about it but it kept a genetic on influence on our biology so that’s another avenue to think about but what we see with this reduction in inflammation and oxidation and also the immune modulation is that it does to work with cancer this is apparently the foundation of many of the illnesses from which we’re suffering and one of those as Alzheimer’s and other forms of dementia which can result from a variety of causes but primarily aging perhaps genetic influences but the destruction of our cognitive ability three dimension 3 Alzheimer’s does involve information and oxidation and so there’s a growing body of evidence that cannabinoids stop these processes that they by intercalating with our cannabinoid receptors and matching up and adjusting the activity of them that they lower the activity that leads to Alzheimer’s and protects us from the cellular changes and we also have seen that these changes also seem to work in rats and mice that they see the default perform better cognitively when they receive cannabinoids and dr.Gary link has been doing a lot of this research and i love the progression of his his conclusions because initially he downplayed the idea that someone might be able to use marijuana to protect themselves from Alzheimer’s disease and then he did more research and he began to come around to live a says oh it might be possible that someone could use THC marijuana if they have a family history to protect themselves now he’s gone so far as to say a puff is enough one puff of marijuana every day is enough to offer significant protection from the degenerative process that accompanies the aging brain that leads to dementia through Alzheimer’s disease and his lab actually has a t-shirt not that they wear that says a puff is enough and so that’s their motto and I’m willing to go with the doc and so there’s this huge wave of dementia that’s facing America and is coming at us and it makes you know it’s a form of mental illness to pretend that this evidence doesn’t exist and it’s not something that we should explore and embrace and exploit to help ourselves and our fellow human beings because Alzheimer’s dementia is really I think one of the worst things that can happen to someone my mother is experiencing it and you just lose your ability to have reference points for the incidents that happened in your life the people you interact with what your passions what your skills will all dissolve the way until you lose your ability to function and usually they people die from choking on their own saliva or from bed sores from being and it’s a terrible terrible illness for the patient and for the families and it is hugely expensive to manage this disease and it makes me crazy that I am too scared of going to prison in North Carolina to send my mother a box of marijuana cookies or jar of tincture and you know have to deal with it there’s no reason that we shouldn’t be able to provide this for our loved ones and it’s criminal the people who oppose us I think of just scoundrels so in the less you miss ahead i also just wanted to mention that one thing i find really interesting what wasn’t presented to my agenda is diabetes those recent studies coming out that show that chronic long-term marijuana smokers have a significant reduction in their incidence of diabetes compared to people who don’t use marijuana once again diabetes a product of abnormal inflammation harmful inflammation and oxidation these processes attack the cells that are responsible for modulating the production of response to in sugars with insulin production and in this in this realm it’s also interesting that there’s significant evidence that our long-term chronic marijuana smokers have a significant protection from obesity much lower rates of obesity significant obesity in the general public which speaks to the ability of cannabinoids to modulate our immune response to modulate how our body actually processes sugars and deals with excess oil and how it affects our health to shield us from the harm that these substances causes and that’s what we see again and again and again is that THC CBD and the other cannabinoids along with the flavonoids and the terpenes make this really amazing natural cocktail of healing protective compounds but enhance not only our health but also our experience of life you know our opponents often talk about these horrible looks at it causes depression and lack of focus and disorientation you know what that is the rare exception there’s a reason we call it getting high because it elevates mood and it elevates health and we’re just not going to get away from this the studies are going to keep coming in which show that you have a lower rate of cancer you have low movies you have lower rates of Alzheimer’s disease if you use cannabis marijuana on a regular basis and the harms that result from that are just not going to turn out to be significant enough to keep us from embracing it as an effective medicine and protective agent thank you all right hi guys I’m you soon Cicely I’m a physician from Arizona and among faculty of the movie universe opposing the College of Medicine and one of my academic pursuits there’s I am a principal investigator on a marijuana study looking at combat veterans who have PTSD and I’m going to fly through these slides and try to get to you know because i know we’ve covered a lot of this material about the night of monopoly and i want to talk about about what we’re doing to try to get around that so just fill disclosure I don’t have any personal experience of marijuana not part of the industry I don’t wait certifications I’m squarely focused on trying to do marijuana research and we talked a lot about the scheduling of drugs I wanted to dig a little bit deeper with you because we all know that schedule one means no medical value hi addiction potential what’s interesting though the schedule for the guys more clear schedule for presumably then is is high medical value and video abuse potential and you can see the schedule for you got ambien and xanax and all these drugs that we all know ur but hugely addictive and so it just prints to the absurdity of the scheduling and the problem with having law enforcement defining the scheduling is is really on is really ridiculous and we know that if medical professionals were doing this it would be scheduled a lot different way this is when we talk about the night of monopoly it’s this is a very frustrating obstruction that has limited our ability to implement this study that I’m going to be describing to you and what’s with surprising that marijuana is the only schedule one drug that has to endure the second review by so if you want to do a study on LSD and then you just get on with FDA approval and IRB approval we move forward so if neither besides not to sell you study drug they effectively derail your study you just can’t you can’t implement it and a lot of people don’t know is it when I send a study design of FDA they have to respond in a 30-day timetable but neither has no such timetable so they can take ten months or ten years and that’s a way they can kind of put your study in a permanent review process and it never emerges and that’s a this is I wanted to just mention how much mainstream media attention we’re getting around this issue now a lot of the media is paying attention the fact that the study is being suppressed and they will be doing a nice job of highlighting the injustice a rat the reason we wanna study buses because we know how many people in in the US are plagued by PTSD we know how many combat bats are coming back with PTSD and we know see here the amount of disability pay outs just for 2010 and in 2012 we’re expecting this number to be much much higher so it’s clearly a big economic issue for the u.s.Also and this is showing media is really starting to point up the problems that you know that’s are not responding to conventional meds that we’re offering them they’re still agonizing within very very symptomatic because you need to fda approved meds for PTSD is a left and pack so we all know how disappointing those meds are they have ton of side effects including sexual dysfunction and waiting and for vets who are trying to reintegrate into normal family life that can be terribly onerous for them so what spurred the study on more than anything that was the unbelievable the manatee of anecdotal reports that we were getting from our veterans who are talking about what excellent experiences they are having with communities and many of them were able to walk away from their old fda-approved meds that weren’t working for that and so it’s been really heartening to see how many vets are going on record and talking about their experience now if they’re having the courage to step out of the shadows and say publicly that this is the only thing that has helped them all these painkillers and antidepressants that we’re pummeling the North have done nothing and suddenly they’ve discovered commun abyss and it’s been really life changing for them and there are no other randomized controlled trials looking at treating combat vets with PTSD and human subjects it’s this would be the first and only one of its kind so we’re really excited to be able to get this going eventually and this is just for those you who haven’t seen the timeline of how these studies get implemented on this study was approved exactly two years ago so the FDA gave it its stamp of approval two years ago and it’s still just sitting in the pipeline waiting moving the same day we got FDA approval we submitted to the DEA and the Public Health Service for they review moves still I’m trying to get the green light from them this is dr.Else away without who runs the neither production facility at the University of Mississippi and got his hand in a you know a bill of ground-up marijuana and that’s exactly what they do they will take the entire plant throw it in a grinder and what we’re left with then of these rolled up cigarettes and if you dump out the contents you’ll see that it’s mostly stems sticks and leaves there’s not a lot about you know for pubic bubna tools so a lot of people argue that you’re trying to do an efficacy study like what we’re doing but this kind of art of sabotage is it right from the beginning because you’re stuck with you know cigarettes get mailed out to investigators by rate so you can imagine if each cigarette is about a gram and half of the cigarette is is a bunch of extraneous material it doesn’t not really highly therapeutic it will can sabotage your results right away so our hypothesis of course is it read the read marijuana bill ease the symptoms of PTSD in a dose-dependent manner so the higher the dose of the active ingredient the better the patient’s response and we also think that there’s one on the study that looks at six percent THC and six percent CBD and that was a really important part of what we were challenging night out to see if they could produce that and we’re really excited to see the results of that arm of the study so this is the breakdown on what the study looks like so you can see there’s five different dosage arms it includes up to some bacon troll lobby guys might not know that they actually night offers a placebo control 0% THC that is that alcohol watch out rotc it looks indistinguishable from the real plant and and then what’s going to happen to they have all these other dosage arms that they might be randomized into the highest one you can see is twelve percent THC and then we have the six percent THC six percent CBD so what’s going to happen is these patients are gonna be allowed to the basically going to be enrolled into a full rank home south administration period here so they’ll get randomized into one of these dosages and they will be able to titrate the dose at harm to manage their symptoms nobody’s arguing that marijuana is a cure for PTSD we’re simply arguing that it’s a very effective symptom control and that’s the idea is if we differ enforced people you know patients in the study to take the third dose every day that might be really unethical for patients who might be marijuana naive if they get randomizing there twelve percent THC and they’re required to smoke a third two cigarettes a day we want people to have the power to manage old dos we want this to be like a real world study that’s part of the pushback that we’re getting from neither than just you know one of the big criticisms as they don’t want this better want patients to have the power to adjust their own dose they don’t want it to be an option environment because I think that’s really dangerous that the drug might actually get devoted and we all know there’s no marijuana anywhere except in this study so it’s really scary if it got out and then do after after they finish the four weeks of stage one they get the governor to wreak abstinence period where they actually we’re going to be continuing to monitor their symptoms activate with the cap scales and all these different measurement tools that we have will be met monitoring their can have a dial blood levels will be checking their young drugs free to make sure they’re not using any other illicit drugs and then they’ll go back or be randomized into stage two which is another four weeks of home self-administration but the good thing this time is it there were maybe randomized into some higher dosages so if they got randomized into two percent THC and they didn’t have any response then the beauty is that they’ll get randomized what they begin to twelve percent teach you will be able to analyze all that data later and see who did well getting we randomized and and so this crossover is really important I can see they’re actually going to be also randomizing to two different delivery methods right so they even be a smoke delivered lized and basically you know the vaporizer doing they’re going to dump the cigarette material into the vaporizer and we’re hoping to get a better understanding of how patients are going to work with the vapor this is um I’ll show you the safety the safety parameters that the FDA asked us to implement so we basically are going to be giving everybody a rock back so that we require to store their study drug in this rock box then it didn’t get a video camera and we’re going to ask each participant to have a secondary verify where they’ll be videotaping each session of the drug delivery and will be required to review all the video to ensure that no study drug is debated at boy 2 concessions and then um and and then what’s going to happen is we showed us all well actually let me this level 2 so this was really these words some of the concessions that we made to get FDA approval and seem really simple things that we could do simple interventions to make them happy it made our IRB happy so the institutional review board at the University of Arizona after about you know five six months of back and forth wrangling questioning those parts of the protocol Vader to prove the study so now we have FDA approval will have University IRB approval and we’re just waiting for night at the cellar study drug so which frustrating is we all know how important the study is we all want this to be implemented but we just keep banging our head against is neither monopoly and so in an effort to try to get some you know somewhat empowered and feel like we can change public policy a little bit we’ve decided to create this pack called Americans for scientific freedom and what we’ve done over the last year’s really try to work with elected build relationships with elected officials by selectively targeting those lawmakers who could help us with this with this movement and sober squarely focused on alumina those two marijuana research and i’ll give you some examples of some initiatives that we’ve been working on over the last year so last year in Arizona for instance which has happened in many other states now is that marijuana has been banned from all the university campuses and and it was sort of maybe an unintentional consequence that they also Bay and marijuana research then if you’re not allowed to have marijuana on campus you also shut down any potential to do research so we submitted this bill worked with all the public and legislators in Arizona to get them to support this concept and are requesting an exception to the ban for marijuana research that’s been FDA approved IRB approved approved so that we can bring that back on campus because what happened was after they banned marijuana and we were looking for a new home for this research I went around to all the you know landlords in the private sector asking hey can we do marijuana research here and they kind of you can imagine the response was not warmly embraced everybody’s terrified of hosting a study like this even though they don’t realize that you know federally regulated study is rigo they don’t see it as any different than the medical marijuana program so so hopefully this book’s of this bill is going to pass in the governor of has already gone on record to say she will sign it so it’s already passed the Senate it’s flying through the house right now it looks good so this is one of our efforts just so you oh yeah thank you guys thank you and so just so you guys know we actually we have a decent funding base for this pack already but our problem is that we can’t give at the level that will attract attention of elected officials unless we become a super PAC so we’re trying to let everybody know that if you’re into if you care about this issue anything you can the best thing you can do to help it will go on our website and if you need to collect ten dollar donations 500 separate donations of 10 bucks apiece and we become a super PAC and then we can give at a much higher level and so that that would be a big started we be the first you know marijuana research back to become a super PAC this is what the website look soap if you get a chance to hop on there and this is another after we’ve been working with organized medicine in Arizona which is really conservative doctors from all over the state that are you know we’re slowly moving the needle with them where they didn’t even understand the importance of marijuana research until our medical marijuana program got approved in Arizona and suddenly they were stuck as gatekeepers for this program that they have no clue how to counsel patients about and so they pass this resolution saying that all basically eliminate to marijuana research and so that was a big achievement and shows a huge culture change with physicians in Arizona and you can see how detailed this resolution is it’s not just eliminate barriers they basically say that the neither a monopoly should be overturned that we there should not be a second redundant review by Public Health Service NIDA when it comes to me and maybes can say sell marijuana at cost to any FDA / dep investigators so that is a big achievement and if you think this quote by dr.Savory well sums up the best that you know if we know that there’s a plant it has potential to reduce human suffering we have a duty to demean that this plant is studied properly and i think that this is a good example of how giving money to elected officials works because when we started writing checks and making good you know solid political contributions we were able to get our entire arizona congressional delegation to pay attention and we got our area Medical Association to write this letter to them and attach this ladder which maps road so Rick and his team they’re put together this letter for our congressman explaining how you’re basically outlining the problem with this second we’ve done the review and I de monopoly is so damaging and the congressmen are preparing to submit this letter to HHS within the next couple of weeks so this was a big a big solid victory and I’ll just give you a couple of glimpses of some other things that just I thought you might be curious about this is so Arizona our medical marijuana program is starting you know it’s gathering a lot of media attention and we now have about 30,000 card holders in Arizona and we’ve raised a ton of money so even though our program hasn’t really been implemented yet what we don’t have are there any dispensaries up and running yet that will happen this summer but we already have a seven million dollars surplus and we have no no real program in place yet so this is really excited because what happens in Arizona will have a voter Protection Act and it says that that money cannot be swept by the legislature so the money’s just sitting there at the Health Department waiting to be days out somewhere and we’ve been arguing than day one that that money should go to research and we haven’t been able to make any headway until we started contributions and now suddenly they are actually meeting with us and we had a good meeting with the Attorney General and he’s willing to rethink the language of the law the language of pop culture says that but money and surplus money can only be used for admin of the program to administer pop to a tree and so we’re trying to argue that administering the program will include to research because they are required to record to adjudicate qualifying diagnosis every six months and they really don’t have a lot of randomized controlled trials looking at adding these different diagnoses so we’re hoping that that’s going to come about but I just wanted to answer because I think that a lot of medical marijuana states probably have the surplus and it takes demanding that information or you won’t find out because we know but you advertise is that right we had to insist and keep insisting and the public records requests and all that until we finally got them to to announce that so I would encourage anybody with a medical marijuana state to try to find out if you have surplus money and demand that be used for science and this is just I wanted to show you that an exhibit these are the qualifying diagnosis for us PTSD is not on there you can see chronic pain is the big one that that we’re all contending with now because what happens is it’s a big political problem for us to get buy-in from our elected officials we want to try to get to quantify what that chronic pain really looks like and so what we’re doing is to get around the night a monopoly until night agrees to sell a study drug we’re going to do just a purely observational study looking at PTSD and chronic pain and so hopefully by next year although over the give you guys some bad on just launching that right now and I’m really excited to see but we can what what kind of science we can collect on that and this is just an example of the breakdown I know all the states are probably billing with this same thing we’re trying to get more md’s and do is to understand the importance of participating in our program you can see that it’s pretty unbalanced right now but what we’re doing is we’ve launched a big PR campaign to work with our kind of mainstream docs to get them to understand why this is so important for their patients and so we’re hoping that that’s going to help so I think that’s about it thank you so much you guys you