Evaluating the Evidence: Cannabis and Psychosis, Part II

March 26, 2019 / Carey S. Clark, PhD, RN, AHN-BC, RYT, FAAN / 1 Comment

As promised, I am back with more of the analysis. Before I jump into the findings, I do want to let you know I have been ruminating a bit about the issue of cannabis testing.

To attempt to state my thoughts succinctly here, until we start testing the cannabis that patients in these types of studies are using, we won’t be doing good science. Granted, we know that THC is responsible for many of the side and and adverse effects of cannabis, but to state that the issue with the cannabis is that it has become so high in THC% is far too reductionistic. There is no specific proof that this one cannabinoid alone is the issue when it comes to the relationship between cannabis and new onset of psychosis. The researchers did state that they opted not to test patients’ cannabis because it provides only a snapshot of a moment of cannabis use in the person’s history.

However, relying on reports of what cannabis is available in the area, because it still in my mind, when I think of the wide variety of cannabis strains available, leaves too much of a gap in getting a handle on what patients are actually consuming. Cannabis is a complex plant with over 500 chemicals, but a few simple tests could provide a wealth of information when it comes to determining if high potency THC cannabis truly does play a role in onset of psychosis, or if something else is going on here.

If a similar study were run again, I would suggest testing the actual cannabis that these psychosis patients had used. Those tests should minimally include the cannabinoid and terpene profiles, in addition to testing for heavy metals and pesticides. While this would have some associated costs, it may at least let the researchers know if the profile of the last cannabis used, which could be very enlightening.

Another consideration with testing cannabis: there is a long history of concern when it comes to the role of heavy metal ingestion and the onset of psychiatric symptoms (Attademo , Bernardini , Garinella , & Compton 2017; .Orisakwe, 2014 ). Cannabis plants can easily become contaminated with heavy metals when grown in soils containing heavy metals. Pesticides can also contaminate cannabis, and the consideration of pesticides as both endocrine disruptors and a possible contributing factor to schizophrenia/.psychosis has also been researched over the years (Maqbool F¹, Mostafalou S², Bahadar H³, Abdollahi M^{4,, ,}2016). What if what we really need to regulate or worry about is not the cannabis plant and THC potency so much as what contaminants are in the plant? In my thought process, this really becomes an ethical question of what we are researching, and what might actually bring harm to patients and vulnerable populations. One of the issues around the end of cannabis prohibition and the beginning of regulation of cannabis should be that people have access to a an herbal medicine that is tested and safe, so people know what they are consuming. Beneficence and autonomy come to mind.

This would encourage cleaner product to be produced and help support people with their own healing quests and/or help them to be a more informed consumer. While I don’t particularly care to draw analogies to alcohol (which comes with its own costly public health concerns namely that alcohol is potentially deadly and cannabis is not), imagine buying alcohol without knowing how strong it is, what is really in it, and so forth. Remember the days of prohibition of alcohol and all of the issues with people making “moonshine”?

And now I will continue to look at the findings.

Participants: Theres seems to be a good split between male/female, with the median age of 36 for control and 31 for case. The median age coupled with the wide range of ages (18-64) included in the study was just a bit concerning, because we know that first time psychosis tends to happen in the early-mid 20’s. The vast majority of all participants were white with at least some college or vocational training and full time employment. It was also clear between case and control, there was much more use of cigarettes, cannabis, and other “drugs” (stimulants, hallucinogens, ketamine, etc) by the case group. Alcohol was not included the summary data table, but in the body of text it states there no difference in alcohol consumption amongst the case vs control groups. And this points to another issue, that it’s really hard to control these types of studies, because most people who are using “drugs” tend to use many different types of substances and it is hard to determine which is having the impact, particularly as we know their can be short term and long term implications. I began to question the issue of poly substance abuse perhaps being a greater issue here then just looking at the % of THC in cannabis, and that lead me to this research….

The International Early Psychosis Association published research by Neilsen et al (2016) that found that alcohol, cannabis, and other drugs increase risk for developing schizophrenia later in life. This was a large retrospective study with the Danish population. The full paper can be accessed here: https://pdfs.semanticscholar.org/1d58/2eaad2f2f9b61f5952f2ecf696bb81a55c7e.pdf Actually, as I ruminate and dig deeper into the Neilsen et al study, I discover it’s having the diagnosis of substance abuse that is correlated with the risk for being diagnosed with schizophrenia 6 fold. Indeed both cannabis and alcohol greatly increased the risk for diagnosis, but Neilsen et al are careful to state that they cannot say alcohol and substance abuse caused the schizophrenia.

Let’s keep in mind with the study being analyzed DiForti et al (hopefully you aren’t getting lost as I move between the primary study and supporting studies I have included!) also found in their population that most people who have a substance abuse disorder do not use one substance alone. In fact the case participants in most of the drug categories used nearly twice as much as the control groups. So is poly substance abuse a factor here?

And that brings me to my next thought: Self-medicating. I don’t see this addressed at all in this article, but were the participants asked about why they used cannabis? Seeing as most people with psychosis have at least 1 year of symptoms prior to being diagnosed with the new onset psychosis, during that time they may be self-medicating or abusing many different substances. My mind starts to question: What if cannabis is actually helping them manage their symptoms, and they would actually would be worse off without it?

And then I come along this little article, that although it’s not in a peer reviewed journal, it clearly explains a possible link between THC, reduction in glutamate, lowered NMDA, weakened CB1 receptors, dopamine receptor D2 being elevated….all this comes together to create hypersensitivity in the limbic system, which may create an environment where schizophrenia could occur. I didn’t see any of this info in the article be analyzed, f I missed it, somebody let me know! There is conflicting research on whether CBD might help with schizophrenia as it changes/modulates CB1 receptors, but we can ‘t forget that CBD % is an important consideration when looking at cannabis plant profiles. https://www.leafly.com/news/health/link-between-cannabis-and-schizophrenia

The leafy article also linked me out to another article looking at causation between cannabis use and psychosis. The authors Louise Arseneault ^(a1), Mary Cannon ^(a2), John Witton ^(a3) and Robin M. Murray

in their meta analysis of five other research articles found that while youthful cannabis use may create a two fold a risk factor for psychosis, and may be responsible for up to 8% of the worlds schizophrenia diagnoses, it also is just one part of a “complex constellation of factors”, and of course vulnerable youth should avoid use of cannabis.

What if people with mental health issues find some relief, for some period of time, from cannabis, that they don’t find from other medications or activities? Why are there so few qualitative studies around cannabis use and self-medication? And why do we have such a stigma associated with self-medication, in much the same we have a stigma around being diagnosed with a mental health issue? The questions go on and on in my mind.

Overall Findings: Okay, let’s get down to the meat of the findings here. The statistical analysis seem logical and well run (I am not a statistician, in fact I found a statistician to work with as I am doing my own quantitive study on an unrelated topic at this time.).

Simply stated, the findings correlate starting use of cannabis before age 15, using high potency cannabis (>10% THC), and daily use as seeming to have the greatest correlation to psychosis (keep in mind causation is not proven here, and almost all of the case participants had also indulged in other substance use at much higher rates than the control group, the issue of possible contamination of ingested cannabis, the lack of knowledge around the full cannabinoid and terpene profile of the cannabis used, and so on).

Conclusions: For me personally, this study did little to change my mind about cannabis and its safety profile, nor change my overall thoughts on safe use of cannabis, including the idea that cannabis should likely not be used recreationally by young people in their teens and early 20’s.

For most people using cannabis medicinally, a high potency THC cannabis is likely not needed, but having safe tested cannabis helps people to make informed decisions about the quality of cannabis they are ingesting and the amount of THC they are consuming. High potency THC cannabis or escalating doses of THC may indeed be risky for some people, most likely young people, those with a predisposition to addiction or history of familial psychosis episodes, those with childhood trauma, those with familial history of substance abuse, and those who currently are poly- substance users.

Avoid using cannabis (and really all “drugs” and alcohol) until one is in the mid-20’s and the brain is well developed. This does not account for the idea that teens will use substances, so I would say avoid poly-substance use, and cannabis is still generally safer than alcohol (psychosis risks aside). Alcohol is far more readily available for teens to access, also it too is a significant risk factor for psychosis (and of course immediate death if one becomes extremely intoxicated….you can’t die from cannabis ingestion).
Use tested cannabis that is free from heavy metals, pesticides, fungus, and mold.
Know the potency of the cannabis medicine you are using. Avoid long term use of “high potency THC cannabis”, or better yet know your THC consumption in mg and limit it to 15 mg max/ day (divided into TID doses), balanced with CBD (up to 20 mg/ day) and terpenes from whole plant medicine (MacCallum & Russo, 2018).
Take regular cannabis breaks (for the recreational user, avoid daily use and avoid regular use of high potency THC strains; for the medicinal user, consider working with your healthcare provider to determine what a break schedule might look for you, and use lower THC strains if they are still effective at managing symptoms). The website www.healer.com has great info about dosing.
Medicinal users of cannabis: start low, go slow with the THC dosing. One does not need to be “high” in order to feel relief of symptoms, and with cannabis being a biphasic medication, sometimes less is more. For specific dosing guidance, see MacCallum & Russo (2018).
For researchers: as prohibition ends and we move toward an era of regulation, let’s find ways to create the best body of evidence available when it comes to the benefits and risks associated with this herbal medication. Let’s base our public policy and educational efforts in sound science. Let’s not jump from correlation to causation, which means we will have to approach the study of this plant with a complexity lens.

References:

Arseneault, L. ^(a1), Cannon, M., ^(a2), Witton, J. ^(a3) & Murray, R.M. ^{(a4 .}

(2004). Causal association between cannabis and psychosis: Examination of the evidence. The British Journal of Psychiatry, 184(2), 110-117. https://doi.org/10.1192/bjp.184.2.110

Attademo L¹, Bernardini F², Garinella R³, & Compton MT⁴.(2017). Environmental pollution and risk of psychotic disorders. Schizophrenia Research, 18, 55-59.

MacCallum, C.A.. & Russo, E.B. (2018). Practical considerations in medical cannabis administration and dosing. European Journal of Internal Medicine, 49 , 12–19.

(Maqbool F¹, Mostafalou S², Bahadar H³, Abdollahi M^{4,, ,(}2016). Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms. Life Sciences, 145, 265-273.

Nielsen, S.M., Toftdahl, N.G., Nordentoft, M., & Hjorthoj, C. (2016). Association between alcohol, cannabis, and other illicit substance abuse and the risk of developing schizophrenia: A nationwide population based register study. Retrieved from https://pdfs.semanticscholar.org/1d58/2eaad2f2f9b61f5952f2ecf696bb81a55c7e.pdf

Orisakwe O. E. (2014). The role of lead and cadmium in psychiatry. North American journal of medical sciences, 6(8), 370-6.

Evaluating the Evidence: Cannabis and Psychosis, Part I

March 21, 2019 / Carey S. Clark, PhD, RN, AHN-BC, RYT, FAAN / 7 Comments

Over the last few days on facebook and across social media platforms, there has been the evocation of fear based in the findings from a new study around the evidence that high potency cannabis used daily may cause increase the risk for psychosis. While alarming at first glance, as someone who understands the endocannabinoid system and the benefits of cannabis, and as an advocate for patients’s rights to access this herbal medicine, I feel obligated to take a closer look at the evidence as presented in The Lancet. So feel free to join me on this journey of evaluating the evidence (or perhaps for those of you with advanced research analysis skills, take a look at the article yourself and see, regardless of your stance on cannabis, what the researchers did well and where they might be flawed). As President of the American Cannabis Nurses Association, my bias toward being pro-cannabis is clear, but I am also pro-patient and pro-safe use of cannabis, so I will do my best to provide an honest analysis. My approach here is the same that I would use in my work with my RN-BSN students, going through each area of the research, and using an approach to express my concerns that all levels of educated healthcare professionals can understand.

The full text article can be found here: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30048-3/fulltext

(Be sure to download the appendix as well, if you are following along!).

My thoughts are in blue font.

Title: The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): A multi center case-control study. (long title, but fairly clearly depicts what the study is about). The article is open access, which I like.

Journal: Lancet Psychiatry (reputable!)

Authors:Lots of good credentials here; a mix of MDs and PhDs. There are over 30 authors, which I find interesting. Sometimes this is a good thing, sometimes it doesn’t mean much. In the field of nursing, 30 authors would be quite large; in the world of physics hundreds to even thousands of authors can get credit…but are they really authors? Here is a link that looks at this issue (if you care or if your dare!), but this seems reasonable in this case: https://physicstoday.scitation.org/doi/10.1063/PT.3.1499

Funding: This was funded by the Medical Research Council, the European Community’s Seventh Framework Grant, Sao Paulo Research Foundation, the National Institute for Health Research Biomedical Research Center, Maudsley NHS Foundation Trust (South London and University College London), Kings College London, and Wellcome Trust.

At least five of the authors report funding from pharmaceutical companies, though stating that they were funded for other studies, not this study. Check out the full list at the end of the article. Getting funded is part of people’s jobs within research. Its just one of those little tidbits, to keep in mind, that certain loyalties and biases may be playing a part in the research here. “Big pharma” can be viewed as having vested interests in people using cannabinoids (which they may eventually be producing medicines for us all to use someday) or people sticking with their traditional allopathic medicines (I won’t get into the poly pharmacy issue and all of those implications) or even creating pharmaceuticals that help people managing psychosis.

Problem: In the beginning of the article, the authors state that with legalization movements, we may have “an increase in cannabis use and associated harm, even if the later only affects a minority of patients” (p. 1) and they go on to state that several studies “support a causal link between cannabis use and psychotic disorder”(p.1). Ideally I would have time to thoroughly analyze each of the 5 cited studies in the first paragraph, but seeing as nobody is paying me to do this work, I instead decided I would check out at least one of the articles cited. I went to the fifth article cited because of the researchers’ claim that the research may “support a causal link” (which was very concerning to me, because I keep running around saying “correlation is not causation…!” and people don’t seem to get that).

And it turns out that key word “support” is very important: when I reviewed the cited study by Gage, Hickman, and Zammit (2016) entitled “Association Between Cannabis and Psychosis: Epidemiological Evidence”, their conclusions lead me to believe that they did not determine causation. Gage at al basically looked at the evidence from longitudinal studies, and in their findings, they distinctly refrain from making a “causal” statement: “Overall, evidence from epidemiological studies provides strong enough evidence to warrant a public health message that cannabis use can increase the risk of psychotic disorders. However, further studies are required to determine the magnitude of this effect, to determine the effect of different strains of cannabis on risk, and to identify high-risk groups particularly susceptible to the effects of cannabis on psychosis”. When people read articles like this one we are analyzing here, it’s just too easy to assume that somehow causation has already been proved, when it clearly has not.

The authors in the introduction go on to state that there is a rising incidence of schizophrenia in the world. “Differences in the distribution of risk factors for psychosis, such as cannabis use, among the populations studied might contribute to these variations” (p. 1). Hmm, well, this might be related to cannabis use, but when I checked out the articles cited, they had more to do with income, urbanicity, migrant status, age, race/ ethnicity, and whether or not the person owned their home. I think we just have to be careful as readers and consumers of evidence to pay very close attention to the subtle nuances. What the researchers are saying is that they think cannabis should be examined in light if rising schizophrenia diagnoses (though some of the literature I read as part of this process stated that schizophrenia is not rising, rather its falling as we do a better job of differentiating and diagnosing). More on this later…

In a pink box on page 2, the authors summarize some of the previous work done in this area I found their review of the literature (I think that is part of the purpose of this box?), a bit compelling, though they only found 3 articles that matched their criteria for psychotic disorders in combination with specific terms like “high potency cannabis””skunk-super skunk” or “high THC cannabis”. Two of the articles were their own work, and the third article was much older, going back to 1965-1999 London where increasing rates of schizophrenia “might be related” to cannabis use in the previous year.

I couldn’t find the authors of this rise in schizophrenia article cited on the reference list, so I asked Dr Google for some help. I did eventually find the article and review the abstract…it then lead me to wonder about the idea of increasing diagnosis of schizophrenia during this time period, which then lead me to stumble upon a major issue with the criteria for schizophrenia, how it was historically diagnosed, and the argument that there may be some big issues around valid DSM criteria for the various types of schizophrenia (rabbit hole alert, check it out, check it out…https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103459/). Though I worked in psychiatric nursing a few eons ago, I am clearly not up-to-date on all of the controversies that the DSM seems to spark.

As near as I can tell, “psychotic disorders” are pretty much undifferentiated, and this is why the authors used this term vs chasing a more definitive diagnosis like perhaps bipolar or schizophrenia, which may be more difficult to make and of course may take time to differentiate. According to the NIH/NIMH, “psychosis” describes conditions where the person has a mind condition, and they have lost contact with reality: it can be a sign of a mental illness or physical illness, it can be caused by medications/ alcohol/drug abuse, 3% of the population experiences it, and symptoms include hallucinations, delusions, paranoia, and disordered thoughts/speech. Studies show that is common for people to have symptoms for more than a year prior to diagnosis.

https://www.nimh.nih.gov/health/publications/raise-fact-sheet-first-episode-psychosis/index.shtml

This is extremely important to note because the researchers here looked at cases of first-psychosis, but there appears to be no follow-up regarding if these were “temporary” diagnoses, or if they persons were eventually diagnosed with schizophrenia or bipolar. They did use ICD-10 criteria to define the population eligible for the study : https://www.icd10data.com/ICD10CM/Codes/F01-F99/F20-F29/F20- but it remains vague to me as far as differentiating this population and they simply lumped all psychotic disorders together.

It is known that adverse effects of cannabis can be things like hallucinations and paranoia, so I started to worry a bit and wonder if these folks were high at the time of intake into the ER, and if they were experiencing adverse effects vs a mental health diagnoses. Thankfully, I do see some distinction of this in the article: if the symptoms were from acute intoxication, the person was not included in the study. Phew! I can assume they knew how to differentiate this.

Participants: Participants were people age 18-64, they were diagnosed using the ICD-10 criteria for psychosis (which envelops a lot, check out link above). Control groups were apparently randomly selected from the same area using postal address, age, race, gender, ethnicity, and lack of psychotic symptoms as the control criteria. The researches had participants in the 17 areas of England, France, the Netherlands, Italy, Spain, and Brazil. The researchers were striving to assess 1000 first time psychosis and 1000 controls. I did not see in the study that cannabis use was ever confirmed by a urinalysis or blood test. This seems obvious to me, but since they are looking a year back, maybe it’s not needed? I really would have liked to have known their current status of testing positive for cannabis.

The n for each group was good: control = 1237, cases= 901

Methods:

The researchers asked the participants about 6 measures of cannabis use: lifetime use (whether or not they ever used cannabis), current use, age at first use, lifetime frequency (pattern or most consistent use), money spent weekly (or during most consistent use period), The researchers then used data from the European Monitoring Centre for Drugs and Drug Addiction 2016 report to determine cannabis potency by THC. (download it, you’ll like it, it’s fascinating: http://www.emcdda.europa.eu/publications/edr/trends-developments/2016_en) , however, I actually ended up finding the data elsewhere on the website, where they have info about potency. The data available now is from 2018, I am assuming the researchers used 2016 data http://www.emcdda.europa.eu/data/stats2018/ppp_en.

Okay, wait, what, don’t tell me…they didn’t ask the patients what specific strain they were using, nor actually test the cannabis strains the patients used, they conjectured from the data? I think I would have felt more comfortable if they would have collected some kind of data from patients beyond frequency of use that demonstrated that they were actually, truly consuming high potency cannabis. Additionally, I had to dig around the website to find the potency, and the data is not well labelled.

Also, another discovery in the EMCDDA report (figure 2.1) tends to show a downtrend in cannabis use in Europe, particularly in the 3 countries that previously were high prevalence countries such as Germany, Spain, and the UK. So while cannabis may be getting stronger, it’s use sure has dropped off greatly since the year 2000 in these 3 countries (which perhaps goes against the researchers thoughts that cannabis use is on the rise and posing a greater risk for psychosis).

EMCDDA (2016).

Back to the Methods. I am directed to the appendix to further investigate how they determined “high potency”. I am feeling frustrated, because there is no appendix on the pdf I downloaded, and luckily I did find it on the main page. The appendix has lots of great further details and I am left to wonder why the editors had them put this crucial data in the appendix.

Based on the data, low potency cannabis was <10% THC and high potency cannabis was >10% THC. Participants were asked to report the type of cannabis used, in their own language, and potency was estimated based on the data from EMCDDA. The participants seemed to give what I can only categorize as broad terms for the cannabis they were using, including UK home-grown skunk/sensimilla UK Super Skunk, Italian home-grown skunk/sensimilla , Italian Super Skunk, the Dutch Nederwiet, Nederhasj and geimporteerde hasj, the Spanish and French Hashish (from Morocco), Spanish home-grown sensimilla, French home-grown skunk/sensimilla/super-skunk, and Brazilian skunk. (To clarify, in the UK “skunk” is a term used for all high THC % cannabis plants, but I could not find a clear definition for “skunk” in terms of strains or exactly what the cut off is for a plant to be called skunk). https://www.independent.co.uk/news/uk/home-news/uk-cannabis-market-skunk-drug-strength-weed-spice-street-sales-dealers-a8231426.html

This process of asking data based questions of patients experiencing first time psychosis brings up red flags for me: firstly, asking patients who are in first time psychosis what “type” of cannabis the participants were using seems highly unreliable to me. The problems with patients and participants self-reporting data are well known, and yet this whole study is about self report, I get it…we may not have better ways to collect the data (yet), but it remains an issue for me. They did also have some other questions around intoxicants, which is good, but I will get back to that with results.

Secondly, the actual cannabis was never tested for true potency (back to the idea of the researchers claiming these patients used high potency cannabis, but the only evidence of them doing so was that they may have consumed cannabis in a geographical area where high potency cannabis is available), nor was there any indication that the patients were tested for THC (granted they could have tested negative and last use could have been some months before the episode).

What about the actual findings????

Hang on for Part II of the analysis! The findings and conclusion analysis coming up in Part II!

References:

European Monitoring Centre for Drugs and Drug Addiction. (2016). European Drug Report 2016: Trends and Development. Retrieved from http://www.emcdda.europa.eu/publications/edr/trends-developments/2016_en

Forti, M.D., Quattrone, D., Freeman, T.P., Tripoli, G., Gayer-Anderson, C., Quigley, H….et al. (2019). The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. The Lancet, Psychiatry. Open Access. DOI:https://doi.org/10.1016/S2215-0366(19)30048-3

A Nurse’s Perspective on Cannabis (Marijuana), Legalization, and Safety.

October 16, 2016December 21, 2017 / Carey S. Clark, PhD, RN, AHN-BC, RYT, FAAN / Leave a comment

I am a Registered Nurse with 22 years of experience, and I have had an anti-prohibition stance in regards to marijuana (cannabis) for 30 years. I was fortunate that when I moved from California to Maine 6 years ago, I was introduced to Maine’s amazing medical cannabis program. I have also been able to study and learn more about the medicinal benefits of this sacred herb through my involvement with the American Cannabis Nurses Association (I now sit on ACNA’s board of directors) and by going to cannabis clinician conferences, such as Patients Out of Time.

Cannabis is on the ballot in 9 states this November, for either legalization for adult use or medicinal consideration. As nurses, we are often concerned with safety, so the following are my thoughts on safety issues and the end of prohibition of cannabis. If you are unfamiliar with how cannabis works in the body and why it such a safe herbal medicine, I suggest you first visit my blog posting on what nurses need to know about cannabis: https://nursemanifest.com/2015/07/14/the-endocannabinoid-system-what-nurses-need-to-know-an-introduction/.

Let’s consider the following issues:

Access: The idea of increased access for adults over age 21 is compelling on many levels. As many have stated before me, all cannabis use is medicinal due to the way the herb interacts with the body’s own endocannabinoid system. (http://thejointblog.com/all-marijuana-use-is-medicinal/; https://halcyonorganics.com/all-cannabis-use-is-medical/). Patients who cannot access cannabis legally to support their healing because they did not have a documented qualifying condition may now have access to this safe effective herbal medicine. Sites like http://www.drugguardians.com are being created with impunity and are helping the population become informed by third parties, decentralizing the source of knowledge about drugs. As legal access increases, black market issues will likely dissipate which creates a safer environment for all citizens. Meanwhile, we know that in legalized states, teen cannabis use drops significantly, effectively decreasing access for younger folks, which is often a concern for those who are considering legalization or medicinal programs (http://www.usnews.com/news/articles/2014/08/07/pot-use-among-colorado-teens-appears-to-drop-after-legalization).

Quality: In Maine, our ballot calls for testing and proper labeling of cannabis products sold at both recreational stores and recreational cafes. This is a major step forward to ensuring safe use of quality cannabis products for both patients and recreational users. Many patients now are being encouraged to start low and go slow with their dosing of their medication, and proper labeling will help to ensure that people can use cannabis with comfort knowing the relative psychoactive effects increase as THC levels of the cannabis products increase. Additionally, products will be tested for pesticides and contaminants, further ensuring the medicine and products people are accessing is safe.

Smoking: I often hear that medical providers are very concerned with the idea that smoking cannabis may be harmful to the person. While there may be some minimal changes to lung structures, there is no strong correlation with COPD and lung cancer in cannabis smokers (http://www.ncbi.nlm.nih.gov/pubmed/23802821; http://www.ncbi.nlm.nih.gov/pubmed/21859273). However, there are many ways to ingest cannabis, and vaporizing cannabis is a way to inhale the medicine without having contact with some of the combustive byproducts that are related to any perceived risk of smoking cannabis. For more therapeutic effects, regular users of cannabis and those seeking its healing properties are generally encouraged to use edibles and tinctures, as they target whole body homeostasis more effectively.

OUI/ DUI: Driving under the influence of any psychoactive medication is obviously an issue. However, levels of THC in the body do not directly equate to impaired driving in the same way that alcohol does, secondary to the way THC is metabolized in the body and how it remains in the body due to it being a fat soluble substance (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3456923/). “Stoned drivers” do not pose the same risk to the public’s well-being as “drunken drivers” do; indeed “stoned” drivers tend to drive more slowly. Researchers from UCLA have called for more efforts to be made around lowering acceptable blood alcohol levels to truly curb issues around impaired driving (http://www.nytimes.com/2014/02/18/health/driving-under-the-influence-of-marijuana.html?_r=0), as being at .08 BAL leads to an eleven fold increase in the risk for being in a car accident, while driving under the influence of cannabis leads to a two-fold increase of being in an accident (texting while driving has a two fold increase and talking on the phone while driving has a 3 fold increase in risk for car accidents) (http://www.huffingtonpost.com/sam-tracy/putting-marijuana-dui-in-_b_6023136.html). Driving or operating machinery while under the influence of cannabis is unacceptable and indicates a risk, however in Colorado since legalization of recreational use of cannabis was initiated, DUI fatalities have decreased (https://www.washingtonpost.com/news/the-watch/wp/2014/08/05/since-marijuana-legalization-highway-fatalities-in-colorado-are-at-near-historic-lows/?utm_term=.64fa02a0cc5e). It should be noted that Colorado made a concerted effort to promote safer driving conditions and decreasing driving while intoxicated once they ended cannabis prohibition. all states should be making efforts to combat intoxicated and unsafe driving practices.

Children: When cannabis was made recreationally available in Colorado, it appeared that more children were being accidentally exposed to cannabis (http://www.usatoday.com/story/news/nation/2014/04/02/marijuana-pot-edibles-colorado/7154651/). I would posit however that once the plant became legal, more parents were willing to seek medical attention if their child had accidentally ingested cannabis infused edibles or other cannabis products. Additionally, the relative number of cannabis ingestion issues versus other toxic substances truly remains quite low in Colorado at 6.4% of all “poisoning” cases treated within the pediatric population (http://www.cnn.com/2016/07/27/health/colorado-marijuana-children/index.html). There has not been a single reported death from a child (or any person) ingesting cannabis (unlike other ingested toxins, such as laundry pods: http://www.cnn.com/2014/11/10/health/laundry-pod-poisonings/index.html). So while we will need to educate consumers about the risks of pediatric access and ingestion of cannabis, the risks remain relatively low. In most cases, children recover quickly from cannabis intoxication, with hospitalization for supportive care only, which generally lasts 1-2 days and generally leads to no lasting side effects (http://health.usnews.com/health-news/news/articles/2013/05/27/kids-poisoned-by-medical-marijuana-study-finds
). Both the states and the individual companies who will be selling cannabis should be responsible for educating the public around ensuring pediatric safety should a state chose to legalize. Ideally some of the tax dollars generated from cannabis sales would be geared toward education of the public on safe cannabis consumption and storage.

Teen Use: Teen cannabis use has actually declined as more states legalize or become medicinal cannabis states (https://www.washingtonpost.com/news/wonk/wp/2014/12/16/teen-marijuana-use-falls-as-more-states-legalize/). This in part may be due to tougher regulations making it harder for teens to access cannabis, and a decrease in black market availability of cannabis.

Pregnancy: Dr. Melanie Dreher, the Former Dean of Rush University school of nursing, is a nurse who researched the Ganga culture in Jamaica for over ten years, and determined that there were no adverse outcomes to the fetuses who were exposed to cannabis (https://www.youtube.com/watch?v=K9WorIM0RhA; https://www.youtube.com/watch?v=RDV5HhmP4UI). A recent study also reported that cannabis use is safe during pregnancy (though caution may still be advised)(http://www.scienceworldreport.com/articles/47194/20160910/marijuana-safe-during-pregnancy-experts-encourage.htm) and breast feeding while using cannabis also appears to have minimal risks (http://cannabisclinicians.org/breastfeeding-and-cannabis/).

Harm Reduction: Cannabis has been studied as a harm reduction tool, particularly when it comes to addiction and treating folks for pain related issues. Physicians have called for neuropathic pain to be treated with cannabis instead of opioids (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295721/). We also know that cannabis can decrease the need for escalating doses of opioids, and assist people who are opioid dependent in either decreasing thier doses of opiates or completely overcoming their addiction (http://nationalaccesscannabis.com/press-release/opiate-study-press-release/).
For an overview of the body’s endocannabinoid system and the issue of biological harm reduction, please see here: http://harmreductionjournal.biomedcentral.com/articles/10.1186/1477-7517-2-17

Overdoses with opioids have fallen in states where medicinal and legal cannabis are available (http://www.nytimes.com/roomfordebate/2016/04/26/is-marijuana-a-gateway-drug/overdoses-fell-with-medical-marijuana-legalization; and https://www.drugabuse.gov/news-events/nida-notes/2016/05/study-links-medical-marijuana-dispensaries-to-reduced-mortality-opioid-overdose). With high rates of opioid addiction plaguing our country, it makes sense to legalize cannabis now to help address this issue.

Self-Medicating: People self-medicate with substances on a daily basis; from alcohol to caffeine to tobacco. People self-medicate with herbs as well from turmeric to Echinacea, to vitamins and natural thyroid supplements. With legalization and regulation, people have a better chance of using safe, monitored, quality herbal cannabis medicine. For most of our recorded human history, cannabis was used as a healing herb. This came to a halt when cannabis prohibition became a global stance. Additionally, legalization opens the door for more open discussions between healthcare providers and patients. Healthcare providers such as nurses and doctors must become educated around the body’s endocannabinoid system and the therapeutic use of cannabis to create homeostasis and support healing.

Pathways for New Healing Products: Currently, many new cannabis products that are available in legal states are not available to medicinal patients in states where only medicinal cannabis is legal. For instance, various teas, salves, edibles and patches that are available in Colorado, Washington, or Oregon are not yet always available for medicinal patients in other states. Once states have a legalized cannabis regulation processes in place, it may be that people can access items such as a topical sub-dermal patches to deliver cannabis medicine or specific cannabinoids. A person may be able to use a CBD (a non-psychoactive cannabinoid) only patch during the day to help with issues like, pain, anxiety, nausea, and depression, and a CBN patch (another non-psychoactive cannabinoid) at night to help with sleep. In this example, the person would have minimal if any exposure to the psychoactive effects of THC in cannabis, and yet they may experience a greater quality of life. From a justice perspective, people deserve to make choice around the medicines they would like to utilize for their own healing, particularly when the medicines are safe.

Social Justice Issues and Policing: Recently, the chiefs of police in Maine came out against the yes on 1 ballot initiative to legalize marijuana in Maine. It is interesting to me that this organization stated they are “unprepared to address legalization issues,” when certainly looking at the legalization issues in Colorado and Washington should provide plenty of data and solutions to common issues. I would posit that there would be fewer marijuana trafficking issues and convictions, and the police could turn greater attention to bigger and more harmful issues in Maine, such as the opioid crisis and OUI related to alcohol ingestion. Additionally, cannabis legalization is a step toward social justice given the illogical, irrational, and unsuccessful war on drugs (http://www.sfgate.com/opinion/article/Marijuana-legalization-a-step-toward-social-5848468.php, http://theweek.com/articles/542678/why-pot-legalization-also-fight-social-justice). Legalizing cannabis should free up our law enforcement agencies to fight crimes that cause greater damage, even as it lowers the need for them to be addressing black market cannabis issues.

I would like to close with my final thought:

All cannabis is medicinal. Our bodies have our own endocannabinoid systems; we make our own endogenous cannabinoids. However when we become deficient in these cannabinoids, we may become ill and need to seek exogenous sources of cannabinoids, or support our own bodies in creating more endocannabinoids. Cannabis is a safe effective medicine with a low rate of addiction and minimal if any withdrawal symptoms, similar to caffeine. Ingestion of cannabis itself has never lead to a death (unlike many prescription and OTC drugs, alcohol, and nicotine products), and it is time we begin to move beyond the government’s ineffective “prohibition of marijuana” stance and take steps toward effective access for all adults.

In the states where cannabis is a ballot initiative, I urge us as nurses and other healthcare providers to explore the data around cannabis as a medicine and consider our roles as advocates for patient access to the healing support this medicine can provide.

The Endocannabinoid System: What Nurses Need to Know, An Introduction

July 14, 2015December 15, 2017 / Carey S. Clark, PhD, RN, AHN-BC, RYT, FAAN / 11 Comments

Medical cannabis is now legal in 23 states and Washington DC, along with recreational cannabis also being legal in several states. Many patients and families are now relocating to Colorado and Washington State as “marijuana refugees” (http://www.nbcnews.com/business/consumer/marijuana-refugees-looking-new-homes-pot-legal-states-n22781), knowing they can freely and safely access cannabis as medicine in these recreational cannabis states. Nurses may still wonder, how is cannabis “medicine”?

As nurses we have a lot to learn about cannabis, including how it works in the mind-body-spirit system, and how we can best advocate for and support patients who could or do benefit from this medicine. Last spring, I witnessed a brief presentation being given to nurses around medical cannabis use, and it was obvious from the questions asked by many of the nurses that the social stigma around “marijuana” was alive and well. Would these nurses be so reluctant to accept and support medical cannabis use if they truly understood the endocannabinoid system (ECS)?

The ECS was discovered some time ago, with Dr. Ralph Mechoulam (Faukner, 2015) being a pioneer in this area in the mid-1990’s. There are 20,000+ scientific articles written about the endocannabinoid system (ECS). Though it has been many years since the discovery of this body regulatory system, most nurses likely know very little, if anything, about the ECS. Truly, this is a problem, nurses are more likely to know the xarelto lawsuit phone number by heart over the benefits of ECS.

A functioning ECS is essential to our health and well being. Endocannabinoids and their receptors are found throughout the body; in the brain, organs (pancreas and liver), connective tissue, bones, adipose tissues, nervous system, and immune system. We share this system in common with all other vertebrate animals, and some invertebrate animals (Sulak, 2015). Cannabinoids support homeostasis within the body’s system; the ECS is a central regulatory system, cannabinoid receptors are found throughout the body, and they are believed to be the largest receptor system in our bodies. Cell membrane cannabinoid receptors send information backwards, from the post-synaptic to the pre- synaptic nerve. CB1 (found primarily in the brain) and CB2 (mostly in the immune system and in the bones) are the main ECS receptors (Former, 2015), though several more are currently being studied. The exogenous phytocannabinoid THC, or the psychoactive compound in cannabis, works primarily on CB1 receptors (hence the “high feeling” in the brain), while the cannabinoid CBD works primarily with the immune system and creating homeostasis around the inflammatory response through CB2 receptors and does not have psychoactive effects. Other cannabinoids and their actions are still being studied, such as the non-psychoactive cannabinoids CBN and CBG, also found in cannabis. Our bodies react to both our own production of endogenous cannabinoids and to the ingestion of phyto-cannabinoids found in the cannabis plant, and other non-pyschoactive plants such as Echinacea. To read more about the science behind the ECS and endocannabinoid receptors, the following are excellent resources:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/

http://www.ncbi.nlm.nih.gov/pubmed/16596770

Endogenous Cannabinoids: Endocannabinoids are the chemicals our own bodies make to naturally stimulate the cannabinoid receptors; anandamide and 2-arachidonoylglycerol (2-AG) are two well known endocannabinoids (Sulak, 2015) that are produced by the body as needed, though not stored int he body. The body produces these endocannabinoids in a similar fashion to how it produces endorphins (Pfrommer, 2015), and activities such as exercise support the endogenous production of cannabinoids. Endocannabinoids are also found in breast milk and in our skin. Alcohol interferes with endogenous cannabinoid production.

Phytocannabinoids: In general, we think of the cannabis plant as the generator of exogenous cannabinoids that we can ingest in a variety of ways, namely psychoactive THC (works with the CB1 receptors in the brain- and also in the gut) and non-psychoactive CBD (works with the CB2 receptors in the immune system and the gut). Other plants such as Echinacea also produce non-psychoactive cannabinoids and work with the ECS to support health and well being through homeostasis (Sulak, 2015).

Cannabinoid Deficiency Syndrome: It should be clear that everybody makes cannabinoids and everybody needs cannabinoids to function. People who do not make enough cannabinoids need to supplement with exogenous cannabinoids through cannabis ingestion, in much the same way that an diabetic needs insulin supplementation making it a “Natural Energy Powder,” in which it is good for your health. Dr. Ethan Russel’s (2004) publication on Clinical Endocannbinoid Deficiency explains this particularly well: http://www.nel.edu/pdf_/25_12/NEL251204R02_Russo_.pdf

Homeostasis:

Cancer: “Cannabinoids promote homeostasis at every level of biological life, from the sub-cellular, to the organism, and perhaps to the community and beyond. Here’s one example: autophagy, a process in which a cell sequesters part of its contents to be self-digested and recycled, is mediated by the cannabinoid system. While this process keeps normal cells alive, allowing them to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products, it has a deadly effect on malignant tumor cells, causing them to consume themselves in a programmed cellular suicide. The death of cancer cells, of course, promotes homeostasis and survival at the level of the entire organism” (Sulak, 2015, paragraph #7). Cannabinoids support apoptosis and suppress cancer tumor angiogenesis (McPartland, 2008).

Heart disease: Additionally, it has been stated that the ECS plays an important function in protecting the heart from myocardial infarction and cannabinoids can have anti-hypertensive effects (Lamontagne et al, 2006).

Inflammation: When inflammation occurs, the ECS helps to stop the process, similar to applying the brakes on a car. This is why cannabis is proving to be good medicine for inflammatory related illness. “Activation of CB₂ suppresses proinflammatory cytokines such as IL-1β and TNF-α while increasing anti-inflammatory cytokines such as IL-4 and IL-10. Although THC has well-known anti-inflammatory properties, cannabidiol also provides clinical improvement in arthritis via a cannabinoid receptor–independent mechanism” (McPartland, 2008).

PTSD: “This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories. The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress. Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.” (Passie et al, 2012).

Seizures: Most hopeful, cannabis has been used to support pediatric treatment-resistant epilepsy, and while more research needs to be done in this area, many parents are becoming medical marijuana refugees by moving to states where they can procure cannabis for their children who suffer from seizures.

Co-agonists:Cannabis increases the pain relieving effects of morphine, as discovered by researchers at UCSF. The two medications are synergistic, and this provides great hope for patients suffering intractable pain at end of life, chronic pain suffers, and opiate addicts. (http://www.maps.org/research-archive/mmj/Abrams_2011_Cannabinoid_Opioid.pdf)

For Nurses: So as nurses, what do we need to know to support patients who use cannabis?

Legal issues: If you live or work in a state that has legalized medical or recreational use of cannabis, familiarize yourself with the laws in that state, as well as your own workplace policies around supporting patient’s use of medical cannabis. Patients may have questions and as a patient advocate, your responsibility is to support patients with their knowledge and use of this medicine within the confines of your practice setting and state laws. You should also be aware of constraints around your role as a nurse in supporting patient use of medical cannabis. For instance, Kaiser patients in some states are likely to be removed from chronic pain patient programs if they test positive for cannabis. Nurses with knowledge around the benefits of medical cannabis can also advocate to support shifts in such policies will no longer align with the emerging ECS science.

Safety: This goes along with the legal aspects; medical cannabis patients should be supported in how to manage and store their medications with safety. While cannabis is known to be extremely safe (far safer than opiates and alcohol), cannabis consumers still need to store medication out of reach of children and pets. They should be supported in knowing the safety of driving or operating machinery if they consumer THC- based cannabis medicines. They also may need information on cannabis testing for both THC: CBD ratios, pesticides and/or other hazardous materials. Many patients need assistance with the basics around medical cannabis use, such as dosage, ratios of THC: CBD, strain information, and ingestion methods.

Overcoming Stigma: Unfortunately, a stigma was created around around cannabis during the process of prohibition in the 1930’s, which was largely financially and racially driven. Contradictory state and federal laws, and the stigma around smoking cannabis (though many cannabis patients can now get relief from vaporizing using the best vape pen for oil, drinkable tinctures, topicals, wearable patches, and edibles), along with a clear ignorance around the body’s ECS, serve to further the stigma associated with medical cannabis. Educate yourself on the roots of the prohibition of the medicine:

http://origins.osu.edu/article/illegalization-marijuana-brief-history

And other issues around stigma and cannabis myths:

http://alibi.com/feature/48426/Erasing-Stigma.html

http://sandiegofreepress.org/2014/05/12-of-the-biggest-myths-about-marijuana-debunked/

http://www.huffingtonpost.com/mary-hall/weed-the-people-movie-loo_b_5501864.html

American Cannabis Nurses Association: There are many nurses actively involved in supporting the use of medical cannabis and the defining the nurse’s role in this process. The ACNA has a mission to advance excellence in cannabis nursing practice through advocacy, collaboration, education, research, and policy development. http://americancannabisnursesassociation.org/

In Israel, nurses actively support patients in cannabis consumption from the process to the dosage.

http://www.tabletmag.com/jewish-news-and-politics/137423/medical-marijuana-kibbutz

Nurses’ supporting patients healing process through cannabis medications may someday be common place in the USA as well.

References:

Lamontagne, D., Lepicier, P., Lagneux, C. & Bochard, J.F. (2006). The endogenous cardiac endocannabinoid system: A new protective mechanism against myocardial ischemia. Arch Mal Coeur Vaiss.,99(3), 242-6.

McPartland, J.M. (2008). The endocannabinoid system: An osteopathic perspective. The Journal of the American Osteopathic Association, 108, 586-600. Retrieved from http://jaoa.org/article.aspx?articleid=2093607

Passie, T, Emrich, H.M., Karst, M., Brandt, S.D., & Halpern, J.H. (2012).Mitigation of post traumatic stress symptoms by cannabis resin: A review of the clinical and neurobiological evidence. Drug Test Anal. 2012 Jul-Aug;4(7-8):649-59. doi: 10.1002/dta.1377. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22736575.

Pfrommer, R. (2015). A beginner’s guide to the endocannabinoid system: The reason our bodies so easily process cannabis. Retrieved from http://reset.me/story/beginners-guide-to-the-endocannabinoid-system/.

Russel, E. (2004). Clinical Endocannabinoid Deficiency (CED): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome, and other treatment resistant conditions? Neuroendocrinology Letters(25), 1-2, 31-40.

Sulak, D. (2015). Introduction to the endocannabinoid system. Retrieved from http://norml.org/library/item/introduction-to-the-endocannabinoid-system.