A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis

Abstract

A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its nonpsychotropic metabolite, 11-nor-9-carboxy-THC, were related to percent change from baseline of several descriptors (eg, itching, burning, and deep pain). However, given the large number of multiple comparisons, false-discovery-rate-adjusted P-values were not significant. Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids. Such an appraisal of descriptors might contribute to the identification of distinct pathophysiologic mechanisms and, ultimately, the development of mechanism-based treatment approaches for neuropathic pain, a condition that remains difficult to treat.

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects

“…The high variability in the PK of CBD and its metabolites in this trial is common with other cannabinoids . During validation of the bioanalytical method to quantify CBD and metabolite plasma concentrations, recovery of CBD was low at 45.4%‐48.8%; however, recovery levels were consistent across the assay range and sufficient to achieve adequate method sensitivity.…”

A Phase 1, Open‐Label, Parallel‐Group, Single‐Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment

“…The large total subject variability in this trial is common with cannabinoids, and similar levels of variability have been previously reported in other trials with cannabinoids. 23,24 Although the PK of CBD and its metabolites have been explored following a single administration in this trial, exposures have been reported following multiple bidaily administration; results show there is no significant time dependency in the PK other than accumulation approximating to 3-fold for the parent drug CBD. 25 It is anticipated this single-dose assessment would predict the extent of change in drug clearances observed following multiple administration.…”

Medical Marijuana Use in Older Adults

“…Growing evidence suggests that MM is useful in the treatment of neuropathic pain . The majority of these studies used inhaled marijuana.…”

“…15 There is little good-quality evidence studying the role of MM in depression specifically, although some trials investigating synthetic cannabinoids in pain assessed mood as a secondary outcome, and these did not suggest an effect on depression. 33,34 Nociceptive pain 22 Weak Neuropathic pain [17][18][19][20][21] Moderate Spasticity 23 Moderate Nausea and vomiting 9,15,29 Moderate Anorexia 9,30 Moderate Neurological and psychiatric illness 9,15,[31][32][33][34] Mixed (see text)…”