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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.

SUBMITTER: Wilsey BL

PROVIDER: S-EPMC5012851 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Wilsey Barth L BL Deutsch Reena R Samara Emil E Marcotte Thomas D TD Barnes Allan J AJ Huestis Marilyn A MA Le Danny D

Journal of pain research 20160831

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. ...[more]

PMID: 27621666

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Project description:Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% ?(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r?0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd.

Project description:Traditionally, smoking has been the predominant method for administering cannabis, but alternative routes of administration have become more prevalent. Additionally, research examining urinary cannabinoid excretion profiles has primarily focused on 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH), a metabolite of ∆9-tetrahydrocannabinol (∆9-THC), as the primary analyte. The aim of the current study was to characterize the urinary excretion profile of ∆9-THC-COOH, ∆9-THC, ∆8-tetrahydrocannabinol (∆8-THC), 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC), ∆9-tetrahydrocannabivarin (THCV), 11-nor-∆9-tetrahydrocannabivarin-9-carboxlic acid (THCV-COOH), cannabidiol (CBD), cannabinol (CBN) and 8,11-dihydroxytetrahydrocannabinol (8,11-diOH-∆9-THC) following controlled administration of both oral and vaporized cannabis. Participants (n = 21, 11 men/10 women) who were infrequent cannabis users ingested cannabis-containing brownies (0, 10 and 25 mg ∆9-THC) and inhaled vaporized cannabis (0, 5 and 20 mg ∆9-THC) across six double-blind outpatient sessions. Urinary concentrations of ∆9-THC analytes were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity and agreement between the three immunoassays (IAs) for ∆9-THC-COOH (cutoffs of 20, 50 and 100 ng/mL) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyses (confirmatory cutoff concentrations of 15 ng/mL) were assessed. Urinary concentrations for ∆9-THC-COOH, ∆9-THC, 11-OH-∆9-THC, THCV, CBN and 8,11-diOH-∆9-THC all peaked at 5-6 h and 4 h following oral and vaporized cannabis administration, respectively. At each active dose, median maximum concentrations (Cmax) for detected analytes were quantitatively higher after oral cannabis administration compared to vaporized. Using current recommended federal workplace drug-testing criteria (screening via IA with a cutoff of ≥50 ng/mL and confirmation via LC-MS-MS at a cutoff of ≥15 ng/mL), urine specimens tested positive for ∆9-THC-COOH in 97.6% of oral sessions and 59.5% of vaporized sessions with active ∆9-THC doses. These data indicate that while ∆9-THC-COOH may serve as the most consistent confirmatory analyte under the current drug-testing guidelines, future work examining 11-OH-∆9-THC under similar parameters could yield an alternative analyte that may be helpful in distinguishing between licit and illicit cannabis products.

Project description:ImportanceVaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns (>30 days since last use) are needed.ObjectiveTo evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods.Design, setting, and participantsThis within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster.InterventionsCannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant.Main outcomes and measuresChange from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration.ResultsThe sample included 17 healthy adults (mean [SD] age, 27.3 [5.7] years; 9 men and 8 women) with no cannabis use in the prior month (mean [SD] days since last cannabis use, 398 [437] days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean [SD] ratings on a 100-point visual analog scale, smoked: 46 [26]; vaporized: 69 [26]) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean [SD] ratings, smoked: 66 [29]; vaporized: 78 [24]), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average.Conclusions and relevanceVaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure.Trial registrationClinicalTrials.gov Identifier: NCT03676166.

Dataset Information

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

Publications

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

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