https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660: The endocannabinoid system is tonically active in control of pain, as demonstrated by the ability of SR141716A (rimonabant), a CB1 antagonist, to produce hyperalgesia upon administration to mice (Richardson et al 1997). As mentioned above, the ECS is active throughout the neuraxis, including integrative functions in the periacqueductal gray (Walker et al 1999a; Walker et al 1999b), and in the ventroposterolateral nucleus of the thalamus, in which cannabinoids proved to be 10-fold more potent than morphine in wide dynamic range neurons mediating pain (Martin et al 1996). The ECS also mediates central stress-induced analgesia (Hohmann et al 2005), and is active in nociceptive spinal areas (Hohmann et al 1995; Richardson et al 1998a) including mechanisms of wind-up (Strangman and Walker 1999) and N-methyl-D-aspartate (NMDA) receptors (Richardson et al 1998b). It was recently demonstrated that cannabinoid agonists suppress the maintenance of vincristine-induced allodynia through activation of CB1 and CB2receptors in the spinal cord (Rahn et al 2007). The ECS is also active peripherally (Richardson et al 1998c) where CB1 stimulation reduces pain, inflammation and hyperalgesia. These mechanisms were also proven to include mediation of contact dermatitis via CB1 and CB2 with benefits of THC noted systemically and locally on inflammation and itch (Karsak et al 2007). Recent experiments in mice have even suggested the paramount importance of peripheral over central CB1 receptors in nociception of pain (Agarwal et al 2007)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280: Management of severe chronic pain is best done by a multi-pronged approach, individualizing it not just according to the disease but also according to patient preferences and their side effect profiles. Currently there is intriguing evidence from animal studies showing efficacy of cannabinoids as antinociceptive agents, however data from human studies is still emerging. Cannabinoids may form a useful adjunct to current analgesic drugs in many conditions, especially in low doses incapable of inducing hyperalgesia or other side effects. They can also be used as rescue drugs when opioid analgesia is ineffective or inadequate, or as opioid sparing agent. They also appear to antagonize several side effects of opioids, and the opioid-cannabinoid combination may become a very useful agent in the long-term management of severe pain. Preclinical data also suggest a beneficial effect of cannabinoids on the disease process in HIV, cancer, and MS. While smoked marijuana tends to be a controversial territory, evidence points to significant multi-symptom relief from it especially in HIV patients. Cannabis derived medications deserve to be investigated in rigorously designed studies so that their role in managing severe and chronic pain in various conditions can be more clearly defined. The legalization of medical marijuana would also enable more clinical trials in humans, and development of cannabis-derived drugs for multiple disease processes, in addition to treating severe pain. Moreover, examination of cannabinoids and their receptors may potentially lead to a new understanding of disease processes as well. Thus, the medical, as well as the general community, need to move beyond preconceived notions about cannabis, and focus on its potential advantages in treating a host of conditions, including severe pain.
https://www.ncbi.nlm.nih.gov/pubmed/25635955: Cannabis-based medicinal extracts used in different populations of chronic nonmalignant neuropathic pain patients may provide effective analgesia in conditions that are refractory to other treatments. Further high-quality studies are needed to assess the impact of the duration of the treatment as well as the best form of drug delivery.
https://www.ncbi.nlm.nih.gov/pubmed/12185373: The results of this self-selected case series must be interpreted with caution. Small doses of smoked cannabis may improve pain, mood and sleep in some patients with chronic pain. Clinical trials are warranted to test these effects. Further prospective studies should examine the patterns and prevalence of cannabis use among chronic pain populations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692: Pain severely impairs quality of life. Currently available treatments, generally opioids and anti-inflammatory drugs, are not always effective for certain painful conditions. The discovery of the cannabinoid receptors in the 1990s led to the characterisation of the endogenous cannabinoid system in terms of its components and numerous basic physiologic functions. CB1 receptors are present in nervous system areas involved in modulating nociception and evidence supports a role of the endocannabinoids in pain modulation. Basic research on how cannabinoid receptors and endocannabinoids intervene in pain mechanisms is progressing rapidly. Clinical progress, however, is advancing slowly. Cannabinoids have antinociceptive mechanisms different from that of other drugs currently in use, which thus opens a new line of promising treatment to mitigate pain that fails to respond to the pharmacologic treatments available, especially for neuropathic and inflammatory pains. The combination of cannabinoids with synergistic analgesic substances is interesting because it may improve the efficacy and safety of treatment. One of the drawbacks of investigating cannabinoids is their typification as substances of abuse. However, compounds blunting severe pain allow patients to perform daily activities more easily, so the potential benefits should be weighed against possible adverse effects. Our current understanding of the physiology and pharmacology of the endogenous cannabinoid system has motivated cannabis-based therapeutic drug design, in which attempts are being made to synthesise compounds with the desired therapeutic actions but without psychoactive adverse effects. Medications prepared with cannabinoid receptor agonists or with drugs that enhance endocannabinoid function (by either increasing release or diminishing reuptake of endocannabinoids) may afford the novel therapeutic approaches demanded by disorders in which pain is a prominent symptom. Clinical trials seem to indicate that either extracts of the Cannabis sativa plant containing known amounts of the active compounds (mainly THC and CBD) or diverse synthetic derivatives of THC are promising treatments for painful conditions that do not respond to available treatments, such as neuropathic, inflammatory and oncologic pain. Specifically, cannabis extracts have shown effectiveness to relief some symptoms of the patients with multiple sclerosis, mainly for pain and spasticity. Pharmacologic manipulation directed to elevate endocannabinoids levels like, for example, with anandamide reuptake inhibitors, or by inhibiting the enzyme fatty acid amide hydrolase (FAAH), which is responsible for intracellular anandamide degradation, may well become a valuable therapeutic tool. CB2 receptor selective agonists with no central effects are other promising pain treatment under investigation. Adequately sized and designed, doubleblind placebo-controlled clinical trials are needed to evaluate the potential applications of cannabis-based medications as novel and effective therapeutic drugs for controlling different types of pain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101100: The mechanism of action of CBD is multifold.1–3 Two cannabinoid receptors are known to exist in the human body: CB1 and CB2 receptors. The CB1 receptors are located mainly in the brain and modulate neurotransmitter release in a manner that prevents excessive neuronal activity (thus calming and decreasing anxiety), as well as reduces pain, reduces inflammation, regulates movement and posture control, and regulates sensory perception, memory, and cognitive function.a2 An endogenous ligand, anandamide, which occurs naturally in our bodies, binds to the CB1 receptors through the G-protein coupling system. CBD has an indirect effect on the CB1 receptors by stopping the enzymatic breakdown of anandamide, allowing it to stay in the system longer and provide medical benefits.4 CBD has a mild effect on the CB2 receptors, which are located in the periphery in lymphoid tissue. CBD helps to mediate the release of cytokines from the immune cells in a manner that helps to reduce inflammation and pain.2
Other mechanisms of action of CBD include stimulation of vanilloid pain receptors (TRPV-1 receptor), which are known to mediate pain perception, inflammation, and body temperature.5 In addition, CBD may exert its anti-anxiety effect by activating adenosine receptors which play a significant role in cardiovascular function and cause a broad anti-inflammatory effect throughout the body.5 At high concentrations, CBD directly activates the 5-HT1A serotonin receptor, thereby conferring an antidepressant effect.6 Cannabidiol has been found to be an antagonist at the potentially new third cannabinoid receptor, GPR55, in the caudate nucleus and putamen, which if stimulated may contribute to osteoporosis.7
Cannabis is an extremely safe and effective medication for many patients with chronic pain. In stark contrast to opioids and other available pain medications, cannabis is relatively non-addicting and has the best safety record of any known pain medication (no deaths attributed to overdose or direct effects of medication). Adverse reactions are mild and can be avoided by titration of dosage using smokeless vaporizers.
More research needs to be pursued to discover degrees of efficacy in other areas of promise such as in treating anxiety, depression, bipolar disorder, autism, nausea, vomiting, muscle spasms, seizures, and many neurologic disorders. Patients deserve to have cannabis released from its current federal prohibition so that scientific research can proceed and so that physicians can prescribe cannabis with the same freedom accorded any other safe and effective medications.
Cannabis -vs- Chronic Pain