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 Table of Contents  
LETTER TO THE EDITOR
Year : 2019  |  Volume : 33  |  Issue : 3  |  Page : 174-175

Cannabis derivatives in chronic pain: Is it legitimate?


1 Department of Anaesthesiology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Anaesthesiology, Sancheti Hospital, Pune, Maharashtra, India

Date of Web Publication5-Dec-2019

Correspondence Address:
Dr. Abhijit S Nair
Department of Anaesthesiology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad - 500 034, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpn.ijpn_45_19

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How to cite this article:
Nair AS, Diwan S. Cannabis derivatives in chronic pain: Is it legitimate?. Indian J Pain 2019;33:174-5

How to cite this URL:
Nair AS, Diwan S. Cannabis derivatives in chronic pain: Is it legitimate?. Indian J Pain [serial online] 2019 [cited 2020 Feb 29];33:174-5. Available from: http://www.indianjpain.org/text.asp?2019/33/3/174/272379

Dear Editor,

Cannabis plant contains more than 100 phytocannabinoids which possess analgesic properties. However, the most important and clinically useful are cannabidiol (CBD) and tetrahydrocannabinol (THC) [Figure 1].[1]
Figure 1:(a) Structure of cannabidiol (Image source: National Center for Biotechnology Information. PubChem Database. Cannabidiol, CID=644019, https://pubchem.ncbi.nlm.nih.gov/compound/644019 [accessed on April 25, 2019]); (b) Structure of tetrahydrocannabinol (Image source: National Center for Biotechnology Information. PubChem Database. Dronabinol, CID=16078, https://pubchem.ncbi.nlm.nih.gov/compound/16078 [accessed on April 25, 2019]

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THC has cannabinoid (CB) 1 and CB2 agonist activity and leads to psychomimetic effects, which has made cannabis notorious and thus regulated in many countries. CBD has minimal CB agonist properties and is used for clinical practice. CBD-based oil preparation is not regulated and is commercially available over the counter because, unlike THC, CBD does not have any psychoactive properties. CBD has been used for treating epilepsy, for anxiolysis, as an antipsychotic, antiemetic, and anti-inflammatory agent (in acute and chronic, especially neuropathic pain of varied etiology). CBD is mostly extracted from the stalk of the hemp plant solely for its CBD content as hemp plant contains less THC (up to 0.3%).

Injured nerves and surrounding nonneural tissues release endocannabinoids, which are arachnoid acid derivatives that alleviate inflammation and sensitization, via CB receptors, namely CB1 and CB2. These receptors are present in the dorsal root ganglion, trigeminal ganglion, cells such as macrophages, mast cells, and epidermal keratinocytes.[2]

Endocannabinoids bind to CB receptors, and this mechanism helps in alleviating somatic, visceral, and neuropathic pain. CB1 and 2 agonists have been used as antinociceptive, with CB2 agonists, especially effective against centrally mediated neuropathic pain.[3] Anandamide (arachidonoyl ethanolamide) and 2-arachidonoyl glycerol are the two predominant endocannabinoids release endogenously.

Cannabis products are commonly used via inhalation (smoking), but this is the most commonly used route for recreation. Wallace et al. had however used vaporized cannabis in patients with refractory diabetic neuropathic pain and found a dose-dependent reduction in otherwise untreatable pain. However, the safe and effective dose by this route has not been described yet.[4] Other routes of administration are transdermal (patches, gel/oil, needles), nasal sprays, oromucosal, and rectal. The pharmacokinetics and dynamics depend on the route of administration.

THC is considered responsible for abuse potential and psychotomimetic effects. However, certain THC molecules have been approved for use in certain clinical situations.

Dronabinol, a THC molecule extracted from the resin of cannabis, and Nabilone, a synthetic THC derivative, are approved by the U.S. Food and Drug Administration (US-FDA) for the treatment of chemotherapy-induced nausea and appetite stimulation in patients with AIDS. Nabiximols is an oromucosal spray containing equal concentrations of THC and CBD derived from the cannabis plant (plus minor quantities of other cannabis constituents), which has been approved by the US-FDA for the treatment of cancer pain and multiple sclerosis. Epidiolex, a liquid formulation of CBD derived from the cannabis plant, has been approved for treating two difficult-to-treat epilepsy syndromes such as Lennox–Gastaut syndrome and Dravet syndrome, in patients of 2 years of age and older.[5]

Mücke et al. performed a systematic review that was published in the Cochrane Database of Systematic Reviews.[6] This included 16 studies which involved 1750 participants using cannabis-based medications for 2–26 weeks long. Authors concluded that potential benefits of cannabis-based medicine in chronic neuropathic pain are outweighed by their potential harms, such as sedation and psychosis. Cannabis products can be considered as the third or fourth line of therapy in treating chronic neuropathic pain. Along with several states in the USA, cannabis derivatives are approved for managing chronic pain in several European countries and Israel for symptom control in palliative care. The cost of medications is covered by the health insurance companies also. Many countries including India have not made cultivation and production of cannabis and its derivatives for medical use legitimate. Clinicians and researchers in India have approached government on several occasions to have regulated growth and production of cannabis-based products so that patients suffering from chronic ailments, such as cancer and epilepsy, can benefit from regulated use.

In conclusion, there is no high-quality evidence demonstrating both efficacy and safety of cannabis-based medications in chronic neuropathic pain. Use of cannabis-based medications can be considered legitimate and can be kept as a reserve for difficult to treat chronic pain when all the approved medications, including opioids, have been used up to maximal dose. Well-designed randomized studies and robust data are required to establish the efficacy of cannabis-based medications for clinical use in pain management. Patients on cannabis-based medications should be monitored for possible adverse effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Urits I, Borchart M, Hasegawa M, Kochanski J, Orhurhu V, Viswanath O. An update of current cannabis-based pharmaceuticals in pain medicine. Pain Ther 2019;8:41-51.  Back to cited text no. 1
    
2.
Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry 2016;79:516-25.  Back to cited text no. 2
    
3.
Darkovska-Serafimovska M, Serafimovska T, Arsova-Sarafinovska Z, Stefanoski S, Keskovski Z, Balkanov T. Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. J Pain Res 2018;11:837-42.  Back to cited text no. 3
    
4.
Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain 2015;16:616-27.  Back to cited text no. 4
    
5.
Romero-Sandoval EA, Kolano AL, Alvarado-Vázquez PA. Cannabis and cannabinoids for chronic pain. Curr Rheumatol Rep 2017;19:67.  Back to cited text no. 5
    
6.
Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2018;3:CD012182.  Back to cited text no. 6
    


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