Medicinal cannabis for patients with chronic non-cancer pain: analysis of safety and concomitant medications

Abstract

Objectives This study aimed to explore the incidence of adverse events (AEs) reported by patients when initiating medicinal cannabis treatment for chronic pain, and the association of cannabis constituents, dose and concomitant medicines with AE incidence. Methods Patient demographics, cannabis products and AE data were collected as part of the Cannabis Access Clinics Observational Study, and concomitant medicines were obtained from patient health summaries provided by referring doctors. Cannabis products were grouped by their constituents as either cannabidiol-only or containing both cannabidiol and Δ-9-tetrahydrocannabinol. Key findings From a total of 275 patients, each had a median of six concomitant medicines, with opioids (n = 179; 65%) the most common. A total of 35.6% patients took 10 or more other medicines, and they were associated with a 3.6 times higher likelihood to report the AE of fatigue (P = 0.048). Patients who received concomitant gabapentinoids were 2.4 times more likely to report dizziness (P = 0.036), patients on tricyclic antidepressants were 1.8 times more likely to report somnolence (P = 0.034) and 3.4 times more likely to report anxiety (P = 0.04), when compared with patients who were not prescribed those classes of medications. Those patients who were prescribed products containing both cannabidiol and Δ-9-tetrahydrocannabinol were 1.5 times more likely (P = 0.004) to have experienced an AE when compared with those prescribed only cannabidiol. Conclusions These findings show that certain concomitant medications and cannabis constituents may be associated with AE incidence when initiating medicinal cannabis. These potential pharmacokinetic and pharmacodynamic interactions require further study to develop guidance for prescribers and pharmacists.

Differences in prescribed medicinal cannabis use by cannabinoid product composition: Findings from the cannabis as medicine survey 2020 (CAMS-20) Australia-wide study

“…Unlike CBD, THC is well known for its increased risk of impairment [ 44 , 45 ], particularly when combined with other sedatives [ 20 ]. Nonetheless, our analyses revealed that patients on prescribed opioids and/or antipsychotics, drugs with sedating properties, are significantly more likely to be receiving THC-dominant or T+C products (70%) than CBD-dominant (30%) products, OR = 2.2 (1.0,4.6); perhaps suggesting a failure to investigate safer alternatives or inadequate attention to potential drug-drug interactions.…”

“…Nonetheless, our analyses revealed that patients on prescribed opioids and/or antipsychotics, drugs with sedating properties, are significantly more likely to be receiving THC-dominant or T+C products (70%) than CBD-dominant (30%) products, OR = 2.2 (1.0,4.6); perhaps suggesting a failure to investigate safer alternatives or inadequate attention to potential drug-drug interactions. Conversely, the primary concern with CBD is its risk of interaction with CYP450 metabolised drugs, particularly those engaging CYP3A4, CYP2C9 and CYP 2C19 [ 20 , 21 , 44 , 46 , 47 ]. CYP3A4 enzymes [ 21 ] are responsible for the metabolism of benzodiazepines including alprazolam, midazolam and clobazam; and for part of the metabolism of other benzodiazepines including diazepam and flutrinazepam [ 48 ].…”

“…With THC, there is low to moderate evidence of benefits in treating nausea and vomiting, muscle spasms, and cachexia [11,14]. There is also moderate evidence that THC can reduce non-cancer related pain including moderate to high quality evidence in favour of nabiximols (a combination THC and CBD in a 1:1 ratio) [14,[18][19][20].…”

The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study

“…The most common AEs reported in this study were dry mouth, somnolence, fatigue, and dizziness; consistent with other studies. 29 An Australian study that recruited 1302 participants who had been taking medicinal cannabis and reported AEs found that the most common AE was increased appetite, followed by somnolence, ocular irritation, and a lack of energy. 30 The incidence of AEs was much higher in this sample; however, the most common AEs were similar to those observed in our study.…”