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Cannabinoid Therapy for Pain

Pain and inflammation are the body’s physiological responses to tissue injury, infection and genetic changes. These responses can be divided into two phases: acute and chronic. The acute phase is the early, non-specific phase and is characterized by increased blood flow to the localized area, increased inflammation, and edema, which is swelling caused by excess fluid trapped in your body’s tissues. Pain is produced by pro-inflammatory agents that also lead to an increased sensitivity to feeling pain and an extreme response to pain, or hyperalgesia. 


If the condition that causes the damage is not resolved, the inflammatory process progresses towards subacute/chronic inflammation. Chronic inflammation plays a critical role in the onset of classic inflammatory diseases such as arthritis, but also of various other conditions such as cardiovascular and neurodegenerative diseases, diabetes, cancer, and asthma.


The chronic pain state, including neuropathic pain, is a leading health problem worldwide as it causes one to suffer beyond the resolution of the pain source and can deeply impact quality of life. Unlike physiological pain, in which tissue injury and/or inflammation can induce reversible adaptive changes in the sensory nervous system leading to protective sensitization, changes in sensitivity become persistent or chronic in neuropathic pain


To date, there is no one designated clinical treatment for chronic pain. Adequate pain relief may be achieved using drugs with adverse effects on the central nervous system side. The quality of life of those with chronic pain is often aggravated by comorbidities such as sleep disorders, depression and anxiety.


Endocannabinoid System and Pain Management


Findings on the endocannabinoid system have opened up a new era for cannabinoid research, discovering and evaluating various therapeutic uses. Specific CB2 agonists have shown considerable efficiency in a variety of neuropathic pain preclinical models. Increasing amounts of evidence, derived from both clinical and observational studies, have confirmed the potential of the endocannabinoid system in providing benefits for individuals with chronic pain and chronic inflammatory diseases. Preclinical studies have shown that cannabinoid receptor agonists block pain in various acute and chronic pain models and that inflammation is reduced. 


Data from clinical trials on synthetic and plant-derived cannabis-based medicines have suggested that they are a promising approach for the management of chronic neuropathic pain of various origins. It is also hypothesized that cannabis reduces the negative effects that chronic pain can have on cognitive performance.


Currently, individuals with chronic arthritic and musculoskeletal pain are reported among the most prevalent users of therapeutic cannabis products.


Synthetic Cannabinoid Studies


Dronabinol is a semi-synthetic form of THC, which is available in capsule form and as a solution, that has been approved by the FDA for appetite stimulation and the treatment of chemotherapy-induced nausea in patients with AIDS. A published study that compared the oral solution and capsule forms of dronabinol under fasting and fed conditions, found Dronabinol exerted a modest, but clinically relevant, analgesic effect on central pain in the pain treatment of patients with multiple sclerosis. Although the proportion of patients that showed adverse reactions was higher in dronabinol-treated than in placebo-treated patients, it decreased over the drug’s long-term use.


Using THC for pain


Cannabis use for pain can be traced back thousands of years. In 2900 B.C. ancient Chinese texts show written records of cannabis as a medicine, recommending cannabis for constipation, rheumatic pain, female reproductive tract disorders, and malaria. It was also used in conjunction with wine to anesthetize patients during surgical procedures. The Chinese mostly used cannabis seeds containing very low levels of THC. From there, use spread of varying preparations and potencies across and to India, however it wasn’t until the early 19th century that cannabis started to be explored in Western medicine. 


More recent studies with medical cannabis (THC)


Bringing it to more recent times, here are a few studies looking to THC use for pain and pain-related conditions. 


Patients with cancer enrolled in Minnesota’s Medical Cannabis Program self reported after 4 months of beginning medical cannabis that there was a significant reduction in the severity of symptoms across all eight measures included in the study (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) compared with baseline.


In another study that took place in Israel, a total of 128 individuals over the age of 50 with chronic pain and sleep issues were recruited. Medical cannabis use was associated with less problems waking up at night compared with non-medical cannabis use showing that medical cannabis use may have an overall positive effect on maintaining sleep throughout the night in chronic pain patients. 


Opioids and cannabinoid use


With increased access to cannabis and more conservative opioid prescribing, evidence suggests that patients are substituting cannabis for opioids. For example, opioid analgesic prescriptions filled by Medicare Part D enrollees fell significantly in states with medical cannabis laws, and patients with chronic pain report over 60% reduction in their opioid use in these states. Some pain patients reported that cannabis increased the analgesic effects of their opioids or decreased the opioid dose needed for therapeutic effect. 


The demonstration of analgesic effects of cannabinoids in those taking opioids for chronic pain suggest that cannabis may increase the pain-relieving properties of opioids, therefore decreasing the total dose, or provide enough pain-relieving qualities on its own to serve as a substitute. However, there are no data from placebo-controlled studies directly addressing whether cannabis can decrease the effective analgesic doses of opioids. Additionally, to date, no studies have investigated the impact of opioid-cannabinoid drug combinations on abuse liability, a critical aspect when considering the therapeutic utility of two drugs that may have significant abuse liability when administered alone.


Researchers of these studies suggest that a pharmacotherapeutic strategy that capitalizes on THC’s potential to decrease opioid use while also minimizing its intoxicating effects should be prioritized. For example, oral THC produces analgesic effects that are longer lasting than smoked cannabis while eliciting lower ratings of intoxication and positive subjective effects.


CBD applications


To date, the widespread use of medical cannabis is still controversial, mostly because the plant produces both therapeutic and psychoactive effects. There is strong evidence suggesting that the non-intoxicating cannabinoids, such as CBD, could also alleviate chronic inflammation and pain in animals. Several clinical studies have demonstrated that a THC to CBD combination can be an effective therapeutic option for individuals with neuropathic pain, as well as other types of chronic pain. However, researchers point to the need to improve the efficacy of these cannabinoids in targeting chronic pain. One obstacle is the uncertainty of the molecular targets for cannabinoid-induced analgesic effects. Recent studies have shown that glycine receptors (GlyRs) are an important target for cannabinoids in the central nervous system. One study with rodents showed that glycinergic cannabinoids, such as CBD, are ideal therapeutic agents for inflammation and neuropathic pain as they can suppress both without causing significant intoxicating side effects or analgesic tolerance. 


There has been accumulating evidence through observational trials and animal studies that CBD presents an opportunity for the treatment of intractable chronic pain for which primary treatments are insufficient or not possible. Since the early 2000s, clinical trials involving CBD for chronic pain have shown effects ranging from placebo-equivalent to highly effective among patients suffering from multiple sclerosis, spinal cord injury, brachial plexus injury, limb amputation, fibromyalgia, and kidney transplantation. 


Observational studies have consistently shown improvements among self-reported quality of life and quality of sleep. More recently, cannabis users in one observational study reported lower past-month average pain relative to controls. 




For some who are in the acute phase of chronic pain, or who are not quite ready to take cannabinoid therapy orally, topical products may offer relief. Topical administration is potentially ideal for localized areas, such as those found in dermatological conditions and arthritis but also in peripheral neuropathic pain. Topicals may be best for acute flare ups and administration throughout the day. 



Starting your cannabinoid therapy journey


If you are wondering if cannabinoid is right for you on your wellness journey, our care specialists are here to talk with you one-on-one. Reach out by calling 719-347-5400 or emailing






The Realm of Caring Foundation specifically invokes the first amendment rights of freedom of speech and of the press without prejudice. These statements have not been evaluated by the food and drug administration. the products discussed are not intended to diagnose, cure, prevent or treat any disease. Realm of Caring always recommends when and wherever possible that licensed local healthcare professionals be consulted.


The Realm of Caring Foundation is an independent nonprofit with its own governing board. We do not produce or sell cannabinoid products, nor do we receive funds from the sale of other company’s products.