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Pain is the intense feeling that arises due to the activation of nociceptors, sensory neurons which provide signals of pain to the brain in case of damaging stimuli. If pain lasts for more than 12 weeks, then it is considered to be chronic pain. In chronic pain, pain signals are generated without physiologic significance and the pain relieving mechanism may be defective or deactivated due to this pain lasting longer than usual. Donald Abrams, MD, defined the relationship of marijuana for pain as, “Pain is one of the major functions of the [body’s] endocannabinoid and cannabinoid receptor system, so it makes sense that cannabis is useable for pain syndromes” 
Prevalence of the use of Marijuana for Pain:
Chronic pain is widely distributed and it is estimated that approximately 38 million people in the U.S. suffer from chronic pain out of which 12 million have used cannabis in its treatment .
Endocannabinoid (EC) System:
The Endocannabinoid system in the body regulates the internal system related to pain, inflammation, chronic neurological conditions and immune responses. Two types of receptor systems are present in the Endocannabinoid (CB1 and CB2) that regulate a variety of functions as described in the following diagram [3, 4].
Mechanism of Cannabis action:
CB1 receptors present in the central and peripheral systems regulated by neurons and CB2 receptors present in central and peripheral systems having non-neuronal tissues like an immune system. Activation of these receptors decrease the perception of pain due to deactivation of nociceptors or antinociception activity and block the EC system signalling to the brain and spinal cord (Figure 1). In the case of chronic pain the activation of these receptors are diminished due to physiological changes and the perception of pain remains for a longer duration. Cannabinoids present in cannabis act as agonists of these receptors and activate them to decrease the perception of pain .
Figure 1: Schematic representation of supraspinal structures involved in cannabinoid-mediated antinociception: Simplified connection pattern between supraspinal structures involved in EC modulation of the nociceptive signal and the spinal cord.
Cannabinoids Useful in Pain Management:
The most useful cannabinoids in chronic pain management is tetrahydrocannabinol (THC) due to its increasing ability to activate the CB1 and CB2 receptors. The other common cannabinoids also show activity on cannabinoids receptors are cannabidiol (CBD) and cannabichromene (CBC). These cannabinoids are also active, but less potent in nature. They show better activity for CB1 receptors, but less than THC . Beta-caryophyllene, not only present in cannabis, but also in other plants, has anti-inflammatory and pain management properties with no side effects . Beta-sitosterol, a non-cannabinoid component present in cannabis also show activity in pain and inflammation .
Uses of Cannabis in Various Form of Chronic Pain:
Cannabis is useful in different forms of chronic pain as described below :
- HIV-related peripheral neuropathy
- Diabetes related neuropathy
- Orthopedic injuries
- Central pain syndrome
- Neuropathic pain syndrome
- Rheumatoid arthritis
- Spinal cord injury
- Phantom pain
- Malignant pain
- Fibromyalgia syndrome
In the case of HIV-related neuropathy, chronic pain results due to the damage of the nerve supply to peripheral tissues. The inhalation of cannabis is useful in this condition because of its immediate absorption and effects on specific peripheral CB1 receptors. Cannabis also providesimmune modulation in HIV due to its agonist action on CB2 receptors associated with the immune system. Similar types of effects seen in case of diabetic neuropathy by cannabis inhalation, which is a very common pain syndrome now-a-day affecting nearly 600,000 people in U.S. .
Chronic type of pain is present in migraines which are effectively treated by the use of the active ingredient in cannabis (THC) by the activation of CB1 receptors [8, 9]. In inflammatory disorders like rheumatoid arthritis, Beta-caryophyllene, is an effective component because of its dual action. It decreases the perception of pain due to its action on CB1 and decrease the inflammation due to its action on prostaglandin receptors (PGR). Using marijuana for pain is superior than other form of treatments first because of its effective pain and inflammation management and secondly due to its less side effects like nausea, vomiting and dizziness mostly associated with opioids .
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- American for Safe Access. Chronic Pain & Medical Cannabis. 2013; Available from: http://www.safeaccessnow.org/chronic_pain_booklet.
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- Gómez, M.A., et al., Study of the topical anti-inflammaotry activity of achillea ageratum on chronic and acute inflammation models. Zeitschrift für Naturforschung C., 1999. 54(11): p. 937-941.
- Greco, R. and A.S. Mangione, Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model Journal of Headache Pain, 2014. 15(1): p. 14.
- Greco, R., et al., The endocannabinoid system and migraine. Experimental Neurology. Experimental Neurology, 2010. 224(1): p. 85-91.