Strong reasons make strong actions: medical cannabis and cancer—a call for collective action

Logo of curroncol“Call it cannabis, not marijuana or weed.

It has been more than 17 years since the Canadian prohibitory regulations on the use of medical cannabis began to ease and more than 17 weeks (more than 6 months by the time of publication) since the Cannabis Act (Bill C-45) became law. Cannabis use for medical purposes has been part of the historical record and medical writings for millennia. However, it is only in the last 30 years that the workings of the human endocannabinoid system have been described and its receptors discovered. Amazing as all of those developments have been, the challenge of reintegrating cannabis into the science of modern medicine—and particularly care for patients with cancer—is a need whose time has come.

Surveys inform us that patients with cancer are using cannabis to manage symptoms related to cancer and cancer treatment. More concerning is that their use is for a medical need occurring outside the confines of modern cancer care, with patients accessing their cannabis from friends and family, and often from casual or unlicensed suppliers. Beliefs in the benefits of cannabis—for its yet unfounded therapeutic potential—are commonly held or supported by poor-quality evidence. Patients and their caregivers are inundated with media stories about a budding industry and its mergers and acquisitions while it grows to meet a need for what is regarded by some as overlooked and undertreated ailments. How should oncologists and the oncology team, trusted as the informed and compassionate advocates for their patients, reconcile the overwhelming public attention being given to this product—growing more, creating new routes of administration, and reaching for new uses—with the work needed to further the science of cannabis as it pertains to cancer care?

The onus is on us, the community of cancer care providers, to act.

Therapeutic and clinical developments in oncology are resulting in improvements in the survival of many patients. Costly immunologic therapies are promising and are being implemented for a variety of cancers. New science about the microbiome, about cancer detection, and about targeted therapies are being researched. And yet, contrasted against those celebrations of scientific ingenuity are the glaring gaps in the work pertaining to cannabis to settle unsubstantiated claims and anecdotal observations of this elixir for the ages. As clinicians and scientists, we must work to generate the needed evidence-based outcomes and to document or dispel the potential interactions and sequelae between cannabis and prescribed cancer treatments. “There are in fact two things, science and opinion, the former begets knowledge, the latter ignorance”.

The frameworks to lead this charge are ours to create. The current legal framework is focused on issues of access and control to regulate production, distribution, and sale. The medical framework for cannabis research is more tenuous, concentrated in silos of expertise as a result of the previous prohibitory environment. The study of cannabis is ripe for development, but even intra-institutional endeavors require help. The machinery of science requires some assembly and repurposing to address the new challenges.

If the current and future oncology landscape is a challenge for those working in cancer care, we must remember that patients deserve our compassion as they attempt to navigate this emotional journey with or without cannabis. More importantly, they need our support and deserve to see us take leadership in cannabis research. Oncologists who have expertise in both the clinical and scientific worlds must inform the necessary work. We must be the architects of its design, building bridges to industry and patients, while engaging our academic institutions.

“Coming together is a beginning, staying together is progress, and working together is success”.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588059/

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

 “Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray’s competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients.

Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved.

People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.”

https://www.ncbi.nlm.nih.gov/pubmed/31286317

https://link.springer.com/article/10.1007%2Fs10461-019-02585-7

Isolation, Synthesis And Structure Determination Of Cannabidiol Derivatives And Their Cytotoxic Activities.

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“In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (1) with acid catalyst POCl3 afforded a new derivative 6 along with six known molecules 2  57 and, 8. The structure of 6 was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data. All the compounds (2  8) were evaluated for their cytotoxic potential against a panel of eight cancer cell lines. Compounds 457, and 8showed pronounced in vitro cytotoxic activity with IC50 values ranging from 5.6 to 60 μM. Out of the active molecules, compounds 4, and 7 were found to be comparable to that of the parent molecule 1 on the inhibition of almost all the tested cancer cell lines.”

https://www.ncbi.nlm.nih.gov/pubmed/31282748

https://www.tandfonline.com/doi/abs/10.1080/14786419.2019.1638381?journalCode=gnpl20

Employment and Marijuana Use Among Washington State Adolescents Before and After Legalization of Retail Marijuana

 Journal of Adolescent Health Home“The purpose of the study was to describe associations between employment and marijuana use among adolescents 2 years before passage of 2012 ballot initiative and 2 years after the implementation of retail recreational marijuana sales took place in Washington.

Working adolescents in all grades had higher prevalence of recent marijuana use compared with nonworking adolescents.

Working youth were more likely to use marijuana before and after Washington’s legalization of retail marijuana.”

https://www.jahonline.org/article/S1054-139X(19)30020-5/fulltext

“Study shows working teens more likely to try marijuana. Employed adolescents are more likely to use marijuana than those who don’t work, according to a study recently published in the Journal of Adolescent Health.”
“Teens with jobs are more likely to use cannabis than those who aren’t employed: study” https://www.thegrowthop.com/cannabis-news/teens-with-jobs-are-more-likely-to-use-cannabis-than-those-who-arent-employed-study

Association of Marijuana Laws With Teen Marijuana Use

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“In the United States, 33 states and the District of Columbia have passed medical marijuana laws (MMLs), while 10 states and the District of Columbia have legalized the recreational use of marijuana.

A 2018 meta-analysis concluded that the results from previous studies do not lend support to the hypothesis that MMLs increase marijuana use among youth, while the evidence on the effects of recreational marijuana laws (RMLs) is mixed.

Here, we report estimates of the association between the legalization of marijuana and its use, simultaneously considering both MMLs and RMLs.

Consistent with the results of previous researchers, there was no evidence that the legalization of medical marijuana encourages marijuana use among youth.

Moreover, the estimates reported in the Table showed that marijuana use among youth may actually decline after legalization for recreational purposes.

This latter result is consistent with findings by Dilley et al and with the argument that it is more difficult for teenagers to obtain marijuana as drug dealers are replaced by licensed dispensaries that require proof of age.”

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2737637?guestAccessKey=5e4e41eb-ec96-4641-86f9-b5c89cc7cc48&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=070819

“New JAMA study shows legalizing pot might discourage teen use”  https://www.cnbc.com/2019/07/08/new-jama-study-shows-legalizing-pot-might-discourage-teen-use.html

“Recreational marijuana legalization tied to decline in teens using pot, study says”  https://www.cnn.com/2019/07/08/health/recreational-marijuana-laws-teens-study/index.html

“Recreational marijuana legalization tied to decline in teens using pot, study says”  https://wtvr.com/2019/07/08/recreational-marijuana-legalization-tied-to-decline-in-teens-using-pot-study-says/

Model-based analysis on systemic availability of coadministered cannabinoids after controlled vaporised administration.

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“The most important two medicinal cannabinoids are Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD).

The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the ‘real world’ setting.”

https://www.ncbi.nlm.nih.gov/pubmed/31264294

https://onlinelibrary.wiley.com/doi/abs/10.1111/imj.14415

Distinct Functions of Endogenous Cannabinoid System in Alcohol Abuse Disorders.

British Journal of Pharmacology banner

“Δ9-tetrahydrocannabinol (Δ9 -THC), the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signaling by binding to cell surface receptors. CB1 receptors (CB1 s) are present in both inhibitory and excitatory presynaptic terminals. CB2 receptors (CB2 s) found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both pre- and postsynaptic terminals.

Subsequent to endocannabinoid (eCB) system discoveries, studies have suggested that alcohol alters the eCB system and that the eCB system plays a major role in the motivation to abuse alcohol.

Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and CB1 expression in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31265740

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14780

“Cannabis and Alcohol: From Basic Science to Public Policy.”  https://www.ncbi.nlm.nih.gov/pubmed/31265135

Distinct inflammatory profiles in HIV-infected individuals under ART using cannabis, cocaine or cannabis plus cocaine.

Image result for AIDS. Publish Ahead of Print():, JUNE 2019

“Cannabis use lowered the percentages of inflammatory, non-classical, activated-classic, and activated-inflammatory monocytes.

In HIV infection the use of cannabis induces predominantly an anti-inflammatory profile.

The use of cocaine and cannabis-plus-cocaine showed a mixed pro- and anti-inflammatory profile, with predominance of inflammatory status.”

https://www.ncbi.nlm.nih.gov/pubmed/31259759

https://insights.ovid.com/crossref?an=00002030-900000000-96891

Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury.

Publication cover image“The present study investigates the potential effect of a Cannabis sativa L. ethanolic extract standardized in cannabidiol as antiinflammatory agent in the skin. The extract inhibited the release of mediators of inflammation involved in wound healing and inflammatory processes occurring in the skin. Cannabis extract and cannabidiol showed different effects on the release of interleukin-8 and vascular endothelial growth factor, which are both mediators whose genes are dependent on NF-κB. Our findings provide new insights into the potential effect of Cannabis extracts against inflammation-based skin diseases.” https://www.ncbi.nlm.nih.gov/pubmed/31250491

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6400

“The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/

“The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders” https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

Cannabinoid system in the skin – a possible target for future therapies in dermatology.”   https://www.ncbi.nlm.nih.gov/pubmed/19664006

“Extracts of the hemp plant cannabis are traditionally used as a popular remedy against inflammation.” https://medicalxpress.com/news/2007-06-cannabinoids-human-body-anti-inflammatory-effect.html

Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary

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“Cannabis has been used for pain relief and to promote sleep for thousands of years. Over the past several decades in the United States (U.S.), a therapeutic role for cannabis in mainstream medicine has increasingly emerged. Medical cannabis patients consistently report using cannabis as a substitute for prescription medications. Both pain relief and sleep promotion are common reasons for cannabis use, and the majority of respondents who reported using cannabis for these reasons also reported decreasing or stopping their use of prescription or over-the-counter analgesics and sleep aids. While adult-use laws are frequently called “recreational,” implying that cannabis obtained through the adult use system is only for pleasure or experience-seeking, our findings suggest that many customers use cannabis for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/31264536

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1626953

“Cannabis Is An Effective Treatment Option For Pain Relief And Insomnia, Study Finds” https://www.inquisitr.com/5509672/cannabis-pain-medications-sleep/

“Marijuana Could Be The Alternative Pain Reliever Replacing Opioids”  https://www.medicaldaily.com/marijuana-alternative-pain-reliever-replacing-opioids-437974