Case-Based Review
continued
table vomiting with stomach upset for the past 1.5 years, leading to 4 hospitalizations in the previous 6 months for cyclical vomiting syndrome. Neither ondansetron nor metoclopramide mitigated these symptoms. Symptoms peaked in the morning and were alleviated by repeated hot showers and heating pad applications. The symptoms subsided earlier in the year when he stopped using marijuana for 2 months, but returned upon reinitiating use. He denied fevers, chills, sick contacts, hematemesis, melena/hematochezia, diarrhea, trauma, unusual food ingestion, recent travel, and use of any prescription, over the counter, or other herbal agents. No immediate family members or acquaintances were similarly affected. • Social history: EtOH negative, tobacco negative, marijuana positive o Marijuana use on and off for 8 years o Smoked 6 joints/day and intermittently vaped and consumed marijuana products • No known drug allergies • Physical exam unremarkable (soft, non-tender, non-distended abdomen, with normal bowel sounds) • Hemodynamically stable • Labs normal (no electrolyte/acid-base abnormalities, normal hepatic and pancreatic enzymes) • Urine toxicology (+) Cannabidiol
• Imaging studies ruled out gastric etiologies Diagnosis: CHS Drug information Marijuana is a product of the Cannabis plant (sativa, indicia, ruderalis) and has a myriad of phytocannabinoids and active cannabinoids.3,6 Variations in Cannabis chemovars (i.e. chemical varietals), formulations, usage techniques, and general dietary considerations impact the pharmacologic and pharmacokinetic properties of the product (Table 1). Marijuana is metabolized via the CYP450 enzymatic system to its primary active metabolite, delta-tetrahydrocannabinol (∆-THC), responsible for mediating psychoactive and gastrointestinal effects, and cannabidiol (CBD), responsible for mediating analgesic, anti-inflammatory, anti-anxiety, and antipsychotic effects via pre-synaptic involvement of the endogenous cannabinoid receptors, CB-1 and CB-2. THC and CBD work synergistically and should, preferably, be used in conjunction. Optimal cannabinoid dosing has not been firmly established and is highly personalized. Generally, the “start low and go slow” approach is implemented and usually results in therapeutic efficacy, with minimal adverse events. As cannabis has a high potential for dependence, tolerance, and addiction, users and clinicians should be aware of the utility of implementing a drug holiday, as well as the withdrawal symptoms associated with cannabis abstinence, such as anxiety, depression, decreased appetite/nausea, headaches, insomnia, irritability, and vivid dreams/nightmares.
Table 1: Marijuana Pharmacokinetics (Adults)3,6 Route
Absorption
Peak Concentration
Bioavailability
Inhalation/smoking
Rapid drug delivery to brain
22 min Duration: 2-4 hours
Variable, 2-56%
Oral
Slow
1-2 hours, up to 8 hours Duration: 6-8 hours
10-20%
Sublingual
Fast
30 min Duration: 6-8 hours
10-20%
Rectal
Fast
15 min
20-40%
Transdermal
Slow
2 hours, maintained for 48 hours
10%
Distribution
Metabolism
T1/2
Elimination
Highly lipophilic Large Vd
CYP450 2C9, 2C19, and 3A4
Infrequent users: 31.2 hours Men: 14.9 hours ±3.7 L/hr Frequent users: 5-13 days Women: 11.8 hours ±3 L/hr Feces: 65%, urine: 20%
Synthetic Forms Dronabinol (Marinol®), nabilone (Cesamet®), cannabidiol (Epidiolex®)
12
Semi-Synthetic Forms Nabiximols (Sativex®, Europe; 1:1 THC:CBD ratio)