While more patient-facing medical research to date has been done with synthetic cannabinoids, across the medical community, there has been an increased understanding of and interest in whole-plant cannabis as a distinct entity. The question we need to ask as clinicians is whether isolates work as well as whole-plant-based therapies.
Of note, there is a third class of nonregulated, synthetic cannabinoids that have no medically recognized benefit and are typically linked to illicit use. The drugs in this class are commonly referred to as “K2” or “Spice.” While these drugs are outside of the current discussion, increased awareness that these drugs exist and are available is prudent, as unsuspecting patients may not know the difference between illicit and legal substances.6
Whole-Plant Cannabis Compared With Isolates: Do We Have Enough Evidence About How They Differ?
A meta-analysis of cannabinoids for medical use, both isolated synthetics as well as plant-based versions, was published in JAMA in 2015.7 This analysis included more than 6000 patients across 79 trials.
Specific to cancer were questions posed about chemotherapy-induced nausea and vomiting as well as cancer-related pain, both neuropathic and nonneuropathic. The majority of trials assessed whether dronabinol or nabilone (both synthetic isolates) compared with either placebo or alternative non-cannabis-based therapies were effective.
Nausea and vomiting due to chemotherapy was assessed in 28 studies. All studies suggested a greater benefit of cannabinoids compared with both alternative antiemetic regimens and placebo, but this result did not reach statistical significance across all studies. Based on the GRADE approach, the evidence to suggest either dronabinol or nabilone in the treatment of chemotherapy-related nausea and vomiting is of low quality.8 There were not enough clinical data to even make a recommendation about plant-based cannabis from this meta-analysis.
There was only moderate evidence to suggest the use of cannabis for cancer-related pain, both neuropathic and nonneuropathic. In addition, there is an increased short-term risk of adverse events with synthetic isolates (dronabinol and nabilone). The primary conclusion by the authors of the JAMA review was that further studies evaluating cannabis itself are required because there is very little evidence about the effects and the adverse events associated with plant-based cannabis.
A novel development in this area is the development of nabiximols, a plant-based isolate of 2.7 mg of THC and CBD per 100 mcL in an oromucosal spray format. A study published in 2010 looked at 177 patients with intractable cancer-related pain.9 This 2-week (2-day baseline and 2-week treatment), multicenter, double-blind, randomized, placebo-controlled, parallel-group study evaluated the efficacy of THC:CBD extract (nabiximols), THC extract alone, and placebo. Patients treated with the THC:CBD oromucosal spray showed an improvement in the Numerical Rating Scale (NRS) score that was statistically significantly when compared with placebo or THC alone. However, a later study of nabiximols did not show significant improvements in cancer pain compared with placebo.10
While closer to the whole plant, nabiximols (Sativex®) is comprised of only 2 plant-based chemicals among the hundreds of chemical entities found in whole-plant cannabis that could have potential therapeutic value.