Several Major Universities To Offer Cannabis Courses and Even Grow Some on the Side!

In a previous blog post I wrote that several community colleges and lesser know universities were offering summer and/or continuing education classes about cannabis.  While these course offerings were impressive, most were community-based and specifically designed to support local cannabis growers and the emerging cannabis business in these locales.

More recently, however, several major universities including Ohio State University, the University of Washington, the University of Vermont and the University of California-Davis announced that they will offer courses designed to provide students and healthcare professionals with an understanding of the physiology, medical and legal implications of cannabis use.

And, quite surprisingly, Louisiana State University has entered into a private agreement with a Las Vegas-based biopharmaceutical pharmaceutical company GB Sciences to cultivate and supply cannabis for disease indications that the company plans to treat including chronic pain, arthritis, cardiovascular problems, asthma and inflammatory bowel disease. While LSU entered into this agreement, it is not clear whether or not it relationship with GB Sciences may affect its sources of federal funding because cannabis is still illegal at the federal level.

Nevertheless, it is becoming abundantly clear that academia sees an opportunity to get into the cannabis business one way or the other. Below is a sampling of the cannabis courses and seminars that are currently being offered.

The University of Vermont offers a medical marijuana and cannabis certification course for clinicians who want the latest information regarding medical cannabis and possible healthcare applications of the plant.

The Moritz College of Law at Ohio State University offers a seminar style course on the legalization of cannabis that will examine the social and historical backdrop of intoxicant prohibition, and assess the legal reforms and political debates now having an impact on the control and regulation of marijuana distribution and use.

The University of Washington offers a course for healthcare professionals on the use of medical cannabis to treat chronic pain.

The University of California-Davis will offer a course to biology majors that will cover the biology of cannabis and cannabinoids as well as their physiological effects in multiple systems, underlying mechanisms and therapeutic values. It also will survey the history of cannabis use, cover the endocannabinoid system and discuss potential medical targets for cannabis and their relative effectiveness.

Finally, there is a big push at University of California at Los Angeles to create a research center to study the medicinal effects of cannabis on a variety of disease indications.

References

  1. http://cannabisscienceblog.com/2017/06/15/69/ accessed September 25, 017
  2. https://www.businessreport.com/article/lsu-finalizes-medical-marijuana-agreement-gb-sciences/ accessed September 25, 2017
  3. http://learn.uvm.edu/com/program/cannabis-science-and-medicine/ accessed September 25, 2017
  4. http://moritzlaw.osu.edu/academics/course-explorer/category/criminal-law/ accessed September 25, 207
  5. http://adai.uw.edu/mcacp/ accessed September 25, 2017
  6. http://www.ucdmc.ucdavis.edu/physiology/ accessed September 25, 2017
  7. http://dailybruin.com/2017/05/23/editorial-ucla-must-build-marijuana-research-center-study-effects-of-legalization/ accessed September 25, 2017

Cannabis Pharmacokinetics, Metabolism and Detection

THC (Δ-9-tetrahydrocannabinol) is the main psychoactive cannabinoid found in cannabis and the primary molecule used for detection among cannabis users. Therefore, it is important to understand THC’s pharmacokinetics (distribution in the body), its metabolism (how it is broken down by the body) and the basis of the laboratory tests used for its detection.

The primary routes of administration of cannabis include smoking/vaporization and ingestion. Not surprisingly, the route of administration affects the absorption characteristics of THC. When cannabis is smoked or vaporized, there is a rapid onset of action (within minutes) with absorption of roughly 10%-35% of available THC in the product (1). THC is mainly absorbed through the bloodstream (2).

Peak THC plasma concentrations (blood levels) occur within 8 minutes after smoking or vaporization (1). In contrast, onset of action following ingestion occurs within 1-3 hours with 5%-20% absorption of THC (1). Peak plasma levels are observed after 2-6 hours after ingestion (1).

THC is primarily metabolized via the liver cytochrome P450 (CYP) system into a psychoactive compound, 11-hydroxy-THC (11-OH-THC) (2). 11-OH-THC is further metabolized into several inactive forms with 11-nor-9-carboxy-▵ 9-tetrahydrocannabinol (THC-COOH) as the dominant inactive metabolite (2). Because THC is highly lipophilic (fat-loving) it is mainly distributed in adipose (fat) tissue, liver, lung and spleen (1, 2).

THC’s elimination half-life —50% elimination of the initial absorbed dose of THC—can range from 2-57 hours following inhalation. The half-life of 11-OH-THC (the active metabolite of THC) is 12-36 hours (1, 2). Twenty (20) percent of THC is excreted in the urine whereas up to 65% is eliminated in feces (2). Within 5 days, nearly 90% of THC is eliminated from the body (2).

Urine immunoassays are typically used to detect THC-COOH in persons being tested for cannabis consumption. After a single use, THC can be detected in the urine for up to 7 days. With chronic cannabis consumption, THC can be detected in urine for 10-30 days. A sensitive test called enzyme-multiplied immunoassay technique (EMIT) can detect urine levels as low as 20-100 ng/ml.

Results from these screening tests indicate prior cannabis exposure but they cannot determine the amount used or degree of clinical effects after use. At present, detection of 50 ng/mL is considered positive for employees undergoing drug testing.  False-positive results can occur with ibuprofen, naproxen, dronabinol, efavirenz, and hemp seed oil. False-positive test results are unlikely from second-hand smoke inhalation, unless this exposure occurs in an unventilated space (1).

Blood tests can also be used to detect THC; however, detected levels cannot be associated with clinical effects. Hair sampling tests that use gas chromatography and mass spectrometry assays are available for cannabis screening. These screening methods can be used to test for multiple cannabinoids, including THC, THC-OH, THC-COOH, CBN and CBD (3). Cannabinoids enter the hair through capillaries and sweat and can be detected up to 3 months after exposure (3, 4). However, detection depends on heaviness of use and potency of marijuana consumed (4). 

References

  1. Russo L, Caneva D Cannabinoid poisoning. http://emedicine.medscape.com/article/833828-overview#a5  Accessed Aug. 9, 2017
  2. Sharma P, Murthy P, Srinivas Bharath MM Chemistry metabolism and toxicology of cannabis: clinical implications Iran J. Psychiatry 2012; 7:149-156
  3. Huestis MA, Mitchell JM Cone EJ Detection times of marijuana metabolites in urine by immunoassay and GC-MS J Anal Toxicol 1995; 19:443-449.
  4. Taylor M, Henderson R, Lingford-Hughes A, Macleod J, Sullivan J, Hickman M Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev. 2017; 36-220-226.

The Number of Legal Cannabis Jobs in the US Grew Over 20% Last Year

While the data are difficult to come by, a recent survey by Leafly (1) determined that the number of legal fulltime Cannabis jobs in the US grew from 122,814 job in 2016 to roughly 149,304 in 2017; a gain of 22%. Of course, not all of these jobs are directly related to Cannabis cultivation and production. These estimates include electricians, plumbers, greenhouse builders, insurance brokers, software developers, realtors and bankers.

Not surprisingly, the growth of legal US Cannabis jobs was not uniform throughout the country (8 states and the District of Columbia have legalized recreational adult Cannabis use and medical Cannabis and 23 medical Cannabis only).

Among the recreational use states, Alaska exhibited the greatest job increases (252%), followed by Maine (100%), and Nevada.  Florida (1,743 %) and Hawaii (1,692%) were the clear leaders in the medical cannabis states. It is important to note that percentages can be deceiving because they don’t represent raw job numbers. For example, if Nevada had 2 full time Cannabis jobs in 2016 and 4 in 2017 that would represent a 50% annual increase. To that point, the actual 2017 job leaders in the recreational use states are California (47,711), Colorado (26, 891), Washington State (26,556) and Oregon (10,843). Likewise, medical cannabis state job leaders in 2017 were Michigan (12,515), Arizona (6,520), Illinois (1,352) and New York (1,341).

Because of legal and political ramifications, the actual number of jobs in the US Cannabis industry is very difficult to quantify. That said, the number of full time jobs is certain to rise as the industry continues to mature in recreational use states.  Likewise, as more research and information about the therapeutic use of Cannabis become available (and mainstream physicians buy into these effects), the number of jobs in the medical cannabis will also grow. However, the 22% increase in the number of fulltime cannabis jobs over the past year suggests that the industry continues to remain strong despite an uncertain political and legal future.

References

  1. https://www.leafly.com/news/politics/cannabis-jobs-count-legal-marijuana-supports-149304-americans?mc_cid=071453b259&mc_eid=510390e56d Accessed September 13, 2017

Anticancer Properties of Cannabis and Cannabinoids

The anticancer effects of cannabis and individual cannabinoids are thought to be mediated via interaction of these compounds with their cognate receptors; cannabinoid receptor 1 (CB1) and CB2). CB1 receptors are widely distributed in the central nervous system (CNS) and brain whereas CB2 receptors are mainly found in the immune system with much lower and more restricted distribution in CNS (1,2)

Early in vitro studies using tumor cell lines and tumor xenograft mouse models suggest that cannabinoids can inhibit solid tumors and hematologic malignancies including  gliomas (brain tumors), adenocarcinomas of the lung, breast, colon, pancreas and melanoma and also myeloma and lymphoma (3-5).

Although not completely elucidated, the mechanism of action of cannabinoids as anticancer agents has been attributed to induction of programmed cell death or apoptosis (via interaction with CB1 receptors), inhibition of angiogenesis or blood vessel growth (reduction in the expression of endothelial growth factor and its receptors) and a decrease in the activity of matrix metalloproteinase 2 which can lead to decreased tumor cell invasiveness and metastasis (6-8).  In addition, cannabinoids possess potent anti-inflammatory and antioxidant properties that can also help to combat cancer (9). Finally, cannabinoids administered in combinations with conventional chemotherapy agents or radiation treatment have been observed to enhance antitumor activity (10-12).

While these preliminary findings are encouraging, much more basic research must be performed to identify the actual anticancer/anti-tumor action of cannabinoids and the individual cancer indications that would benefit most from their use. Once these things are established, large scale controlled human clinical trials will be necessary for regulatory approval of these agents as cancer treatments.

References

  1. Howlett AC. The cannabinoid receptors. Prostaglandins Other Lipid Mediat 2002; 68-69: 619–31
  2. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N,Makriyannis A, Piomelli D, Davison JS,Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005; 310: 329–32
  3. Velasco G, Galve-Roperh I, Sanchez C, Blazquez C, Guzman M. Hypothesis: cannabinoid therapy for the treatment of gliomas? Neuropharmacology 2004; 47:315–23.
  4. Velasco G, Sánchez C, Guzmán M. Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer 2012; 12:436–44.
  5. McAllister SD, Soroceanu L, Desprez PY. The antitumour activity of plant-derived non-psychoactive cannabinoids. J Neuroimmune Pharmacol 2015; 10:255–67.
  6. Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anti cancer drug. Br J Clin Pharmacol 2013; 75:303–12.
  7. Chakravarti B, Ravi J, Ganju RK. Cannabinoids as therapeutic agents in cancer: current status and future implications. Oncotarget 2014; 5:5852–72.
  8. Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther 2015; 97:575–86.
  9. Abrams, DJ. Integrating cannabis into clinical cancer care. Curr Oncol. 2016; 23:S8-S14.
  10. Donadelli M, Dando I, Zaniboni T, et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ros-mediated mechanism. Cell Death Dis 2011;2:e152.
  11. Torres S, Lorente M, Rodriguez-Fornes F, et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 2011;10:90–103.
  12. Scott KA, Daigleish AG, Liu WM. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther 2014;13:2955–67.

Treating Patients: Integrating Cannabis into Clinical Cancer Care

There is a growing body of evidence that cannabis and certain cannabinoids may offer potential therapeutic benefits to cancer patients (1). Mainly, cannabis may be beneficial in the management of a wide range of cancer-related symptoms including neuropathic pain (2-4) chemotherapy induced nausea and vomiting (CINV; 5-9), anorexia (10), insomnia (11) and depression (12,13).

Unfortunately, most oncologists trained during the era of cannabis prohibition (1930s to present) have no knowledge of how to use cannabis and its products in routine medicine practice or clinical care.  More problematic is the lack of research and clinical data on which oncologist can base treatment decisions or make care recommendations. That said, what must be done before oncologists and cancer care professionals can feel comfortable using cannabis in cancer care and treatment?

First, rigorous basic research must be performed to clearly demonstrate that cannabis and cannabinoids indeed possess anticancer/antitumor properties. This will require a clear understanding of the mechanism of action of these compounds and the identification of the receptors/transcriptional factors etc that mediate their anticancer effects.

Second, once preclinical data are confirmed, rigorous double-blind, placebo controlled human clinical trials (with sufficient numbers of participants) must be performed to confirm or refute the effects of cannabis/cannabinoids on recognized and clearly defined  oncology indications  e.g., solid tumors, blood malignancies, etc.

Third, if cannabis and cannabinoids are to used for adjunctive cancer care and disease management purposes, than other large scale, well-designed clinical trials must be performed to demonstrate the safety and efficacy of these treatments.  Anecdotal evidence and results from small clinical studies are not sufficient for regulatory approval nor widespread acceptance of the use of cannabis and cannabinoids for cancer/chemotherapy symptom management.

Finally, for all of this to happen, cannabis and its products must be rescheduled from a Schedule 1 drug (illegal with no recognized therapeutic value) to either a Schedule 2 or Schedule 3 classification.  This would effectively decriminalize cannabis at the national level and allow federal funds and resources to be leveraged for basic research and clinical testing of cannabis and its products.

If all of these things should come to pass, then oncologists may be able to add cannabis and cannabinoids to treat and care for patients living with cancer.

References

  1. Abrams, DJ. Integrating cannabis into clinical cancer care. Curr Oncol. 2016; 23:S8-S14
  2. Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: systematic review or randomized controlled trials. Can Fam Physician 2015; 61:e372–81
  3. Andreae MH, Carter GM, Shaparin N, et al. Inhaled cannabis for chronic neuropathic pain: a meta-analysis of individual patient data. J Pain 2015; 16:1221–32.
  4. Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain 2015; 16:616–27.
  5. Chang AE, Shiling DJ, Stillman RC, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Ann Intern Med 1979; 91:819–24
  6. Duran M, Perez E, Abanades S, et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 2010; 70:656–63
  7. Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001; 323:16–21.
  8. Machado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl) 2008; 17:431–43.
  9. Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev 2015; 11:CD009464.
  10. Strasser F, Luftner D, Possinger K, et al. on behalf of the Ca nnabis-In-Cachex ia-Study-Group. Compa rison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia–cachexia syndrome: a multicenter, phase iii, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 2006; 24:3394–400.
  11. Russo, EB, Guy GW Robson PJ. Cannabis pain and sleep: lessons learned from therapeutic clinical trials of Sativex®, a cannabis-based medicine. Chemistry and Biochemistry 2007; 4:1729-1743
  12. de Mello Schier AR, de Oliveira Ribeiro NP, Countinho DS, et al. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compounds of Cannabis sativa. CNS Neruol Disord Drug Targets 2014; 13:953-960
  13. Bricker JB, Russo J, Stein MB, Sherbourne C, Craske M, Schraufnagel TJ, Roy-Byrne P Does occasional cannabis sue impact anxiety and depression treatment outcome?  Results from a randomized effectiveness trial. Depress Anxiety 2007; 24:392-398

Cannabis and PTSD: A Clinical Trial Update

The Marijuana for Symptoms of PTSD in US Veterans clinical trial being conducted by the Multidisciplinary Association for Psychedelic Studies (MAPS, a Santa Cruz-based 501 (c)(3) a private non-profit research organization)  is believed to be the first randomly controlled clinical trial to evaluate medical marijuana as a treatment for post-traumatic stress disorder (PTSD) in US military (1).  Officially, the study title is “Placebo Controlled, Triple Blind, Randomized Crossover Study of the Safety and Efficacy of Four Different Potencies of Smoked Marijuana in 76 Veterans with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)”.  The study protocol with inclusion and exclusion criteria can be found here .

The principal investigator of this federally-approved study is Sue Sisley, MD with help from Marcel Bonn-Miller, MD (coordinating PI formerly of the University of Pennsylvania) and co-investigator Paula Riggs, MD (University of Colorado) and the project is funded by a $2, 156, 000 grant from the State of Colorado. Although the project was approved in 2014, it has been plagued by a variety of political and legal issues.

First, the National Institute on Drug Abuse (NIDA) which is the only legal source of marijuana for federally sanctioned research in the US has been unable to provide the Cannabis required for the study. Incidentally, the only legal grower of Cannabis in the US is the University of Mississippi. The university was awarded that license in 1968. However, recent reports suggest that the Cannabis provided by the university is contaminated with lead, yeast and mold which could raise concerns about efficacy and safety if used in the trial (2). Also, the university has not established testing guidelines for the Cannabis that is produces.

Second, the study was initiated in Phoenix, Arizona because the city’s VA hospital has a very high density of treatment resistant PTSD patients (those who continue to experience symptoms despite undergoing VA-sanctioned treatment and/or therapy) and Dr. Sisley was on the faculty at the University of Arizona. Unfortunately, Dr. Sisley was fired from the university for political reasons. This delayed the start of the study and has subsequently slowed its progress.

Finally, Phoenix VA hospital administrators have been slow and unwilling to provide Dr. Sisley with the data that she and her team need to identify patients to complete enrollment for the study. At present, 22 patients have been enrolled and treated. Investigators must screen 6,000-8,000 veterans to identify the remaining 54 patients to complete the study (3).

The MAPS trial has the support of most veteran groups including the American Legion, Iraq and Afghanistan Veterans of America, Veterans of Foreign Wars and Disabled American Veterans.  However, the Trump administration has clearly its distaste for all things Cannabis and, despite anecdotal evidence that Cannabis can help treat PTSD and traumatic brain injury (4), the current political climate has made it difficult to conduct this very important clinical trial.  According to Dr. Sisley, “All we get from them [VA hospital administrators] is polite responses about marijuana being federally illegal.” (3)

To put PTSD in perspective, America loses an estimated 15,000 veterans each year to drug overdoses and suicide. It is a shame that the federal government will not allow a scientifically-designed clinical trial to be conducted to help determine whether or not Cannabis is a safe and effective treatment for PTSD.  Thankfully, PTSD can be treated with Cannabis in many states that have already legalized medical marijuana.

References

  1. http://www.maps.org/research/mmj/marijuana-us
  2. http://www.pbs.org/newshour/updates/scientists-say-governments-pot-farm-moldy-samples-no-guidelines/
  3. http://www.thecannabist.co/2017/08/29/veterans-administration-ptsd-marijuana-study-enrollment
  4. https://www.nytimes.com/2017/09/01/opinion/marijuana-legalization-veterans.html?ref=todayspaper