Show Notes

Disclaimer: This is the unedited transcript of the podcast. Please excuse any typos.

Jeff:  Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta and we’ll be taking you through the August 2018 issue of Emergency Medicine Practice.

Nachi: This month’s topic is one that Jeff has significant personal experience with from his college days. We’re reviewing Cannabinoids -- and emerging evidence in their use and abuse.

Jeff: Um… that is definitely not true. I was actually a varsity rower in college... Are we still reviewing talking points together before we start recording these episodes?

Nachi: Sometimes…

Jeff: This month’s issue was authored by Mollie Williams, who is the EM residency program director at the Brooklyn Hospital Center. It was peer-reviewed by Joseph Habboushe, assistant professor at NYU and Nadia Maria Shaukat, director of the emergency and critical care ultrasound at Coney Island Hospital in Brooklyn, New York.

Nachi: We’re going to be talking about the pathophysiology of cannabinoids, clinical findings in abuse, best practice management, differences between natural and synthetic cannabinoids, and treatment for cannabinoid hyperemesis syndrome. So buckle up and get ready.

Jeff: As you’re listening through this episode, remember that the means that we are about to answer one of the CME questions from the end of the print issue. If you’re not driving while listening, be sure to jot down these answers and get your CME credit when we’re going through this issue..

Nachi: As of June 2018, there are 31 states, the District of Columbia, and 2 US territories that possess state and local-level laws allowing the use of cannabis medicinally or in recreational formulations. Marijuana actually maintains the highest lifetime use of an illicit drug used within the US.

Jeff: There are a shocking 22 million past-month users of marijuana in the US, followed by pain relievers at 3.8 million, and cocaine at 1.9 million. Clearly, an important topic worth discussion, especially as synthetic products have become more widely available.

Nachi: And worth noting -- Colorado, where medicinal and recreational marijuana use has been decriminalized and later legalized, has shown a nearly 2-fold increase in the prevalence of ED visits, which may be related to marijuana exposure.

Jeff: Medicinally, cannabinoids are currently used in the treatment of chronic pain syndromes, complications of multiple sclerosis and paraplegia, weight loss due to appetite suppression in HIV/aids, chemotherapy-induced nausea and vomiting, seizures, and many other neuropsychiatric disorders. In fact, cannabis use has been documented for medical use dating as far back as 600 BC in West and Central Asia.

Nachi: All of that being said though, there is an absence of high-quality reviews and evidence to support the use of cannabinoids for any of the indications you just mentioned. And the US DEA maintains cannabis as a Schedule I substance.

Jeff: This DEA designation limits the ability to do research and obtain federal funding for such research. General lack of federal regulations on chemical content also leads to product variation, which may be a cause of increased incidences of accidental overdoses.

Nachi: To attain the most up to date information for this article, Dr. Williams searched the PubMed and Cochrane Databases from 1950 to 2018. This produced predominantly case reports and retrospective studies. There were just a few randomized prospective studies -- not surprising.

Jeff: Let’s get started with the pathophysiology. There are 3 cannabis species to be aware of: Cannabis sativa, cannabis indica, and cannabis ruderalis. Within these species, over 545 active cannabis-derived components have been described.

Nachi: There are ten main constituents of cannabis sativa. Of these, 9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) are found in the greatest quantities. The neuropsychiatric and addictive properties of cannabis are due primarily to the delta-9-THC.

Jeff: THC and other cannabis derivatives work through the endocannabinoid system and other neuroregulators. The endogenous cannabinoid system has 4 components: (1) endogenous endocannabinoids, (2) receptors, (3) degradation enzymes, and (4) transport mechanisms.

Nachi: There are two endogenous endocannabinoids to know about: anandamide (AEA) and 2-arachidonoyl-glycerol.

Jeff: Cannabinoid receptors are broadly dispersed through the central nervous system, and to a lesser degree, also to other organ systems.

Nachi: Because CB receptors are concentrated within the central nervous system, they exert the majority of their effects on the neuropsychiatric systems. And   -- yes that’s a double ding -- the cannabinoid 1 (or CB1) receptor is most responsible for cannabis-induced neuropsychiatric effects.

Jeff: Interestingly, the anti-emetic effects and possible palliative properties of cannabis derivatives are thought to be secondary to the inhibitory effects on serotonin receptors and the excitatory effects on the transient receptor potential vanilloid 1 (or TRPV1).  More on TRPV1 later...

Nachi: So far we have been talking about cannabinoids from the cannabis plant, but with cannabis being illegal in many states, there has been a growing emergence of synthetic cannabinoids. Synthetics were initially developed in the 1980s largely for research purposes.

Jeff: Because the current DEA controlled substances schedule designations are based on original chemical names, synthetics have gained popularity as manufacturers are able to produce newer compounds and circumvent DEA designation as well as routine urine drug screening tests.

Nachi: You may be familiar with some of the street names for synthetics -- like spice, K2, scooby snacks, black mamba, kush, and kronic. These can often be purchased over the internet or through specialty smoke shops.

Jeff: Scooby Snacks, what a fantastic name, mooovingggg on… Synthetic cannabinoids often have greater affinity for the CB1 receptor than naturally occurring cannabinoids -- and synthetics can produce 100 times the effect. As a result, the presenting symptoms with synthetic intoxication can be difficult to differentiate from crystal meth or bath salt abuse.

Nachi: Manufacturers sometimes use solvents and other contaminants. Clusters of toxic ingestions and deaths have occurred. Emergency clinicians need to be aware of this and should report suspicious events immediately.

Jeff: For more on synthetic intoxications in the ED, be sure to take a look at the recent May 2018 issue of Pediatric Emergency Medicine Practice on Synthetic Drug Intoxication in Children if you haven’t already read it. Also, just a quick FYI - If you’re not a current subscriber to Pediatric Emergency Medicine Practice, we’re giving away a free copy of the issue specifically for our listeners. Just head over to ebmedicine.net/drugs for the PDF of the issue.

Nachi: A free issue for our listeners, that’s nice! Let’s move on to a discussion about current indications for cannabinoids. So, there is no clear consensus on these indications, but there is some research of varying quality that supports the treatment of some chronically debilitating diseases with cannabinoids.

Jeff: A systematic review and meta-analysis from 2015 found low-quality evidence to support cannabis therapy for appetite suppression in HIV and aids patients; moderate-quality evidence for treatment of chronic pain and spasticity; and also moderate quality evidence for some chronic debilitating diseases.

Nachi: While talking about evidence-based medicine here, another review by the National Academies of Science, Engineering, and Medicine on possible associations between cannabis and cancers arising in the lungs, head, and neck, or testicles -- showed no statistically significant associations exist.

Jeff: So in case that wasn’t clear - the overall evidence to support cannabis therapy, in general, is weak. Also, be aware that there are various formulations of cannabis that allow for different routes of administration. We’re talking oils, tinctures, teas, extracts, edibles like candies and baked goods, parenteral formulations, eye solutions, intranasal, sublingual, transmucosal, tablets, sprays, skin patches, topical creams, rectal suppositories, and capsules -- just to name, a few.

Nachi: A few! That seems pretty complete to me. Basically, any way you can imagine, it seems like a route of administration has been explored. But of importance, these formulations have different absorption times -- as you might expect. The shortest duration to peak plasma levels of delta-9-THC is through the inhalation route, which can produce effects within 3 minutes. On the longer end, rectal cannabis administration can take up to 8 hours to reach peak plasma concentrations.

Jeff: Let’s talk about some of the clinical findings and systemic effects associated with cannabis use. First up is the link between cannabis use and stroke or TIA. Cannabis users wh...