Applied Evidence

Medical Cannabis: A guide to the clinical and legal landscapes

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If your patient expresses interest in medical marijuana, you’ll find evidence on maximizing benefit while minimizing risk. But be cautious: Data are often contradictory.


› Educate patients about the effects of the physiologically active therapeutic compounds in Cannabis; this is critical to prevent overconsumption of products with high levels of tetrahydrocannabinol. B

› Screen patients for serious mental health concerns before recommending or certifying medical Cannabis; this is essential because the rate of psychiatric hospitalization is increased in bipolar disorder and schizophrenia patients who use Cannabis heavily. B

› You can recommend medical Cannabis and certify patients for its use with the certainty that the risk of overdose or serious adverse effects is exceedingly low. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series




Barry S, a 45-year-old man with a new diagnosis of non-Hodgkin’s lymphoma, recently started induction chemotherapy. He has struggled with nausea, profound gustatory changes, and poor appetite; various antiemetics have provided only minimal relief. He tells you that he is hesitant to try “yet another pill” but has heard and read that marijuana (genus Cannabis) is used to alleviate disruptive chemotherapy-induced adverse effects. He asks if this is a treatment you’d recommend for him.

As Mr. S’s physician, how do you respond?

Understandably, some family physicians are hesitant to recommend an unregulated, federally illegal substance characterized by conflicting or absent evidence of safety and effectiveness.1 Nevertheless, throughout history and in the current court of public opinion, medical Cannabis has overwhelming support,2 leading to legalization in most of the United States.

As with many traditionally accepted therapies (whether they are or are not supported by substantial evidence), physicians are expected to provide individualized guidance regarding minimizing risk and maximizing benefit of the therapeutic use of Cannabis. The rapidly growing scientific and commercial fields of medical Cannabis guarantee that information on this topic will constantly be changing—and will often be contradictory. In this article, we review the most common concerns about medical Cannabis and provide up-to-date evidence on its use.

The pharmacology of cannabis

Cannabis sativa was among the earliest plants cultivated by man, with the first evidence of its use in China, approximately 4000 BC, to make twine and rope from its fibers.3 Records of medicinal Cannabis date back to the world’s oldest pharmacopoeia, a written summary of what was known about herbal medicine through the late 16th century.4

Common forms of plant-based Cannabis include leaf that is smoked or vaporized, oral tincture, pill, and oil concentrate that can be vaporized.

The 2 principal species of Cannabis are sativa and indica. There is no good medical evidence to separate the impacts of either strain; however, a staggering amount of lay information exists about the reported differing effects of each strain.5

Chemical constituents. Phytocannabinoids derived from C sativa are the plant’s best-known proteins, constituting a complex lipid-signaling network involved in numerous physiological processes. There are more than 100 known phytocannabinoids, the most well-recognized being Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Additional sources of cannabinoids include endogenous cannabinoids, or endocannabinoids, and synthetic cannabinoids.

The endocannabinoid system, comprising cannabinoid receptors, endocannabinoids, and their specific enzymes, is a potential therapeutic target for a variety of pathologic processes.6,7 The 2 most well-studied targets for cannabinoids in the human body are the cannabinoid receptors CB1 and CB2, found throughout the body: CB1, predominantly in the central and peripheral nervous system, and CB2 in a more limited distribution in the immune and hematopoietic systems. Other pathways activated or antagonized by THC and CBD exist, but are less well-mapped than CB1 and CB2.

Continue to: Botanical or synthetic?


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