Therapeutic potential of cannabis in pain medicine

Neurology Research Group, Peninsula Medical School, Plymouth, UK.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 08/2008; 101(1):59-68. DOI: 10.1093/bja/aen119
Source: PubMed


Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has
elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived
from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Δ9-THC) was isolated in 1964 and the first CB receptor (CB1R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids
are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB1Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB2 receptors (CB2R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs
play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical
trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia
have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have
variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can
be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB1R and CB2R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic
science and clinical aspects of CB pharmacology with a focus on pain medicine.

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    • "When activated, CB2 receptors can affect the release of chemical messengers (i.e., cytokines by immune cells) and can modulate immune cell trafficking ([7–11] for reviews). In both clinical and preclinical studies, cannabis has been shown to have analgesic effects at central and peripheral levels [12, 13]. "
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    ABSTRACT: Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study, in vitro and in vivo tests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and then in vitro toxicity was evaluated in fibroblasts and astrocytes. In the in vivo tests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administered per os in almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counteracted by DHA coadministration. In the in vivo tests, pain responses were significantly decreased in the BCP and BCP+DHA groups with respect to OIL after 1 and 2 weeks of treatment. Estradiol and testosterone levels were increased only in the BCP group. In conclusion, BCP alone or at lower concentration in combination with DHA was efficacious in modulating pain, showing a clear analgesic activity.
    Full-text · Article · Jul 2014 · Evidence-based Complementary and Alternative Medicine
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    • "More than 60 C terpenophenols derived differently from one another in their chemical structure by location and number of carbons have been isolated from Cannabis sativa [2]. In the early 1990s, the endocannabinoid derivatives of arachidonic acid, which bind to cannabinoid receptors in the body, were located. "
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    ABSTRACT: Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6-8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P < 0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P = 0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients.
    Full-text · Article · Jul 2013 · Evidence-based Complementary and Alternative Medicine
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    • "One of the main indications for its use is neuropathic pain [5], for which cannabis is generally seen as acceptable third-line treatment [4]. Cannabinoids are agonists for the central and peripheral cannabinoid receptors , CB1 and CB2, both playing an important role in pain modulation [6] [7]. Ketamine acts on the N-Methyl-Daspartate (NMDA) receptors, which, as with the cannabinoid receptors, are located centrally and peripherally [8]. "

    Full-text · Article · Feb 2012 · Journal of clinical anesthesia
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