International forskning

Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial


Libat Weizman # 1, Haggai Sharon # 1 2 3 4, Lior Dayan 4, Joumana Espaniol 5 6, Silviu Brill 4, Hadas Nahman-Averbuch 7, Talma Hendler 1 2 3 8, Giris Jacob 9 10 11 12

  • 1Sagol Brain Institute, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • 2Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
  • 3School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 4Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • 5Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • 6Recanati Autonomic Dysfunction Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • 7Division of Clinical and Translational Research, Department of Anesthesiology, Washington University Pain Center, Washington University in St Louis School of Medicine, St Louis, MO, USA.
  • 8School of Psychological Sciences, Tel Aviv University, Tel-Aviv, Israel.
  • 9Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. jacob.giris@gmail.com.
  • 10School of Medicine, Tel Aviv University, Tel Aviv, Israel. jacob.giris@gmail.com.
  • 11Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. jacob.giris@gmail.com.
  • 12Recanati Autonomic Dysfunction Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. jacob.giris@gmail.com.

Affiliationer

Background: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain.

Methods: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo.

Results: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. Conclusions: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation.