In an exploratory randomized, double-blind, placebo-controlled, cross-over study, psychoactive doses of intravenous delt
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ORIGINAL INVESTIGATION
In an exploratory randomized, double-blind, placebo-controlled, cross-over study, psychoactive doses of intravenous delta-9-tetrahydrocannabinol fail to produce antinociceptive effects in healthy human volunteers Emmanuelle A. D. Schindler 1,2 & Ashley M. Schnakenberg Martin 3,4 & R. Andrew Sewell 4,5 & Mohini Ranganathan 4,5 & Anna DeForest 1,2 & Brian P. Pittman 4 & Albert Perrino Jr 6,7 & Deepak C. D’Souza 4,5 Received: 23 December 2019 / Accepted: 17 June 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Rationale Animal studies and anecdotal human reports suggest that cannabinoids have antinociceptive effects. Controlled human studies have produced mixed results. Objectives We sought to reduce existing variability by investigating the effects of intravenous delta-9-tetrahydrocannabinol (THC) in several pain paradigms within the same human subjects, addressing some of the limitations to the published literature. Methods In this exploratory randomized, double-blind, placebo-controlled, cross-over study, healthy human subjects received 0.01 mg/kg or 0.03 mg/kg intravenous THC or placebo (ethanol vehicle) infused over 10 min on three test days, each separated by at least 72 h. Capsaicin (250 μg) was injected intradermally to induce chemical pain and hyperalgesia. Four other forms of acute pain were induced: mechanical (von Frey filament), hot and cold (thermode), and electrical (pulse generator). Pain ratings were obtained before drug administration, at peak drug effects, and 2 h after drug administration and included both objective and subjective measures. THC drug effects and vital signs were also collected during experimental sessions. Nonparametric analysis with repeated measures was performed. Results THC induced euphoria, perceptual and cognitive alterations, and tachycardia in a dose-related manner, but failed to have significant effects in experimentally induced acute chemical, mechanical, thermal, or electrical pain and capsaicin-induced hyperalgesia. Conclusions In this exploratory controlled study, intravenous THC lacked significant antinociceptive properties in experimental models of acute pain and capsaicin-induced hyperalgesia in healthy human subjects. Continued study of THC and other cannabinoids through high-quality, controlled studies in both healthy volunteers and patients with pain conditions is warranted to inform the growing demand for the clinical application of cannabinoids in pain management.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05595-9) contains supplementary material, which is available to authorized users. * Emmanuelle A. D. Schindler [email protected]
3
Psychology Service, VA Connecticut Healthcare System, West Haven, CT, USA
* R. Andrew Sewell
4
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
5
Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, U
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