Cannabinoids Effect on Central and Peripheral Pain Modulation in Fibromyalgia

Fibromyalgia is a syndrome characterized by widespread chronic pain involving all musculoskeletal systems, accompanied by chronic sleep disorders, fatigue, memory problems, and more. Despite the advancement in the understanding of pain mechanisms thanks to various innovations in neuroscience and pain medicine, the syndrome's treatments are not satisfying, even in the presence of optimal multidisciplinary therapy, and many patients continue to suffer from chronic pain and associated symptoms. Although the pathophysiology of Fibromyalgia is not fully understood, there is evidence supporting the involvement of several mechanisms, including central sensitization, descending pain modulation pathway deficiency, and autonomic dysfunction, confirmed by physiological and functional imaging studies. Following the above reasons, there is great importance in understanding the effect of new treatments on pain mechanisms in Fibromyalgia syndrome. In the past few years, more and more research is providing evidence for cannabis analgesia in chronic pain syndromes, with an emphasis on Tetrahydrocannabinol (THC). However, only a little research has examined its efficacy in random double-blind experiments. Thus, testing the effect of THC in experimental clinical pain models could give a hint to our understanding of the pain regulation system in Fibromyalgia. The current research will study the effects of the cannabinoid THC component on pain regulation in Fibromyalgia in a double-blind controlled design. For that matter, the investigators will perform different peripheral physiological tests and functional magnetic resonance imaging. Additionally, the investigators aim to disclose the neural mechanisms underlying pain-autonomic interactions in Fibromyalgia patients.

The participants will arrive twice to Tel Aviv medical center, in each meeting they will receive either THC oil or Placebo (all participants will receive the drug at some point). The participants will go through quantitative sensory tests (offset analgesia and conditioned pain modulation), functional magnetic resonance (fmri) scan, and autonomic measurements at rest and after the Valsalva maneuver test.

Neither the investigator nor the participant will know which drug they are receiving. The participants will be "deceived" as they think they will get drug at both meeting (to avoid order effect). Helsinki ethics committee has approved this mask. All participants will recieve the drug at one of the meetings.

Functional connectivity change in pain descending pathways at rest, and under offset analgesia test will be measured between both arms

blood oxygenation levels and functional connectivity from the fmri scan (main regions of interest are insula and anterior cingulate cortex) under an emotional task and in resting state

Inclusion Criteria: Diagnosed with fibromyalgia for over 3 months according to American college of rheumatology Do not respond well to analgesic medications and or have severe side effects Medium to high level of pain (over 40 on visual analogue scale scale) Does not have other pain-related syndromes Not treated regularly with cannabis. Is ready to stop taking central nervous system medications 3 days prior to the experiment. Exclusion Criteria: alleviated levels of anxiety (above 52 in STAI) Psychiatric medications due to psychiatric diagnoses (depression, bi-polar syndrome, etc.). Cardiovascular problems Neurological diseases (other than migraine). Pregnancy or breastfeeding Alcoholism or substance abuse Cancer Blood pressure problems Patients that used cannabis in the past month Illegibility to MRI